Lupine Publishers | Estimation of the Predictive Factors of Myocardial Ischemic Preconditioning in Elective Surgical Patients

 Lupine Publishers | Journal of Anesthesia & Pain Medicine

Abstract

Introduction: the physiological response to the aggression produced by the surgical trauma provides the effective treatment capacity in case of complications. Surgical intervention causes endocrine, metabolic, autonomic, immunological, and hematological changes.

Objective: to estimate the predictive factors of the second window of myocardial ischemic preconditioning in the patients proposed for elective surgical interventions.

Material and Methods: A quasi-experimental study was carried out in the period January to December 2019 at the Maria Curie Cancer Hospital in Camagüey with patients who met inclusion and exclusion criteria in preoperative consultation in the research period, to whom preconditioning was applied. Ischemic two hours before surgery. Chi squared and logistic regression was calculated as appropriate.

Results: Predictive factors such as essential arterial hypertension odds ratio 16,632, diabetes mellitus 12,157, age 60 years and over with odds ratios of 8,035, heart failure odds ratio 6,433, cerebrovascular disease odds ratio 6,135, and chronic kidney disease were estimated. Odds ratio 5,800 and chronic obstructive pulmonary disease with odds ratio 5,738.

Conclusion: the predictive factors of the second window of ischemic preconditioning were independent predictors of risk in elective surgical patients.

Keywords:Preconditioning; Elective surgical patient; Surgical stress; Predictive factors

Introduction

Knowledge of the physiological response to aggression produced by surgical trauma provides effective treatment capacity in the event of complications. Surgical intervention causes endocrine, metabolic, autonomic, immunological, and hematologic changes [1]. Somatic and autonomic afferent nerve impulses generated at the site of injury activate the endocrine response, while the inflammatory and immune response, mediated by hormones, begins to develop. and cytokines, secreted products of activated leukocytes, fibroblasts, and endothelial cells. The changes in the immune and endocrine systems in the face of surgical trauma, are objectified by the perioperative response of various markers. Surgical stress is a situation in which there is both an increase in the speed of generation of oxidizing species, free radicals (RL) and excited species, and a decrease in the activity of defense systems, resulting in higher concentrations, in the steady state of active oxygen species [2,3]. In these situations, the toxic effects of these RLs manifest and chemical reactions take place on lipids, proteins and carbohydrates inside the cells, which trigger irreversible damage and even death cellular. There are numerous diseases associated with the imbalance between oxidants and antioxidants, in the surgical patient from the preoperative period with personal pathological history, he becomes involved with the RL, through the physiological response of the diseases and the complexity of the surgical trauma as essential factors in the perioperative changes of hemostasis, the interaction of the endocrine and immune axis and of the drugs administered in the surgical anesthetic act [4]. The publication that describes the influence of anesthetics used during the perioperative period and the typical hormonal response generated by the surgical intervention and the patient is current. With modulation of adrenal response by the distribution of leukocytes and their immune functions. Anesthetics modify immune function by reducing the stress response and have a direct effect on immune cells [5]. The investigation was carried out with the objective of estimating the predictive factors of the second window of myocardial ischemic preconditioning in surgical patient’s elective for myocardial protection during major surgical intervention.

Material and Methods

General Aspects of the Study

This was a quasi-experimental investigation to estimate the predictive factors of the second window of myocardial ischemic preconditioning in elective surgical patients at the María Curie Cancer Hospital in Camagüey in the period from January to December 2019.

Definition of the Study Universe

The study population was delimited to 40 preconditioned patients 2 hours before the surgical intervention, an insufflated sphygmomanometer was placed at 200 mmHg for 5 minutes, after this time it is deflated, and 5 minutes are expected. This procedure is repeated 3 times. Blood draws are performed before and after the application of ischemic preconditioning. They are preconditioned and post conditioned patients who meet the inclusion and exclusion criteria.

Inclusion Criteria

Patients aged 20 years and over proposed for major elective surgical intervention.

Exclusion Criteria

Patients who do not offer their consent to participate in the research. Variables: age, sex, associated risk factors, antioxidant markers, discharge status, hospital stay, complications. The antioxidant markers before and after the preconditioning were determined: the concentration of reduced glutathione (GSH) by the method of Sedlak et al. [6] and malonic aldehyde (MAD).

Information Processing and Analysis Plan

Search and collection of information: A form was completed for each patient, complementing the information with data from the medical records.

Information processing: The database was compiled with the collected information, which was processed automatically using the SPSS statistical package. The information of the qualitative variables is summarized in descriptive statistics, related to the characterization of the patients operated on by the different surgical specialties, to determine the behavior of the activity of antioxidant and oxidant markers (preconditioning and postconditioning). The information resulting from applying the second window of ischemic preconditioning was processed according to the univariate and multivariate analysis for the study variables using the statistical program SPSS version 21. Implementing the chi-square test and logistic regression as appropriate. The understanding of the results obtained is facilitated through statistical tables and graphs, it was analyzed giving an answer to each proposed objective and comparing the results with those of other authors. Finally, after a synthesis work, conclusions and recommendations were issued [7].

Results and Discussion

N 40 Source: clinical history as can be seen in Table 1, most of the surgical oncology patients belong to the group of 60 years and more, for 77.5%. The evolution of the age pyramid, thanks to the increase in life expectancy and better healthcare, places cancer diseases in the forefront of surgery, influenced by the life expectancy at birth of 80.2 years for women and 76 years for the men. Cuba is among the three countries on the continent with the largest aging population, in 2000 it exceeded 1.6 million older adults and in 2014 it represented 17.9% of the total population, in 2015 the Cuban population was 18.5% and in 2018 21% of the population aged 60 and over 6.7 During the aging process, the adult heart undergoes numerous biochemical, ultrastructural, functional and anatomical changes that reshape cell structure, function and adaptive responses to stress. Histologically, a decrease in the number of myocytes and progressive hypertrophy of these are observed in both ventricles. Also, studies in humans demonstrated aging-related abnormalities in cardiac metabolism, coronary flow reserve, endothelial function. Age is an independent predictor of risk in patients with coronary heart disease, this is explained by the lack of adaptation to acute myocardial ischemia [8]. Ischemic preconditioning is a mechanism by which repetitive episodes of ischemia induce greater tolerance in the myocardium to subsequent episodes of aging as a biological process with interindividual variability leading to the progressive loss of physiological functional reserve, the alteration of these functions is not evident. in basal situation but it manifests itself in moments of stress such as illness and perioperative.

Table 1: Distribution of patients with ischemic preconditioning according to age group and sex.

Table 2: Frequency distribution of patients with ischemic preconditioning according to personal pathological history.

N 40 Source: clinical history

In Table 2, twenty-one patients out of forty preconditioned have a diagnosis of essential arterial hypertension with 52.5% followed by diabetes mellitus 42.5% and cardiovascular disease 32.5%. Comorbidity is more frequent and both cerebrovascular disease and lung processes, kidney failure, hypertension, and diabetes justify part of the increased risk of the surgical patient. However, it seems useful to recall other pathophysiological mechanisms that explain the elderly’s reduced response capacity such as endothelial dysfunction, microcirculatory disorders (rarefaction), increased precapillary resistance, and decreased ability to develop collateral circulation as clear. Limiting residual flow in the risk area and perfusion flow in the remote area [9,10]. In the myocardium, the possible loss of ischemic preconditioning, the accelerated drop in the reserve of high-energy phosphates (lower tolerance to ischemia), calcium overload and senile myomalacia are factors to consider. The primary changes of arterial aging produce important secondary changes in the heart and other terminal organs, including the brain and kidneys. The vascular aging process is accelerated by the presence of primary cardiovascular disease, including high blood pressure and atherosclerosis, as well as by other risk factors such as diabetes, smoking, and obesity. Morphological changes include a decrease in the number of myocytes, a thickening of the left ventricular wall, and a decrease in both the density of the conduction fibers and the number of cells in the sinus nodes [11]. These changes are readily apparent in terms of elevated mean arterial pressure and increased pulse pressure. Increased vascular stiffness leads to significant secondary cardiac responses, but in young people the heart pump and blood vessels are optimally coupled for maximum efficacy. The mere fact of treating the topic of aging and optimizing the preoperative period of the surgical patient with the application of preconditioning due to ischemia is the objective of the research Table 3.

Table 3: Frequency distribution of patients with ischemic preconditioning according to personal pathological history.

N 40 Source: clinical history

Interpreting the adjusted odds ratio (OR) for the variables of the equation as follows: In the estimated Logistic Regression function, the variable essential arterial hypertension had a significantly different regression coefficient of 0 (p = 0.01) and adjusted OR of 16,632 (95% CI 2,141; 20.54). In this analysis, the risk of not modulating (oxidative enzymatic response) is approximately 7 times greater in patients with positive oxidative stress markers than in negative ones, that is, the enzymatic response after preconditioning is at the expense of oxidants. The diabetes mellitus variable had a significantly different regression coefficient of 0 (p = 0.00) and adjusted OR of 12,157 (95% CI 2.487; 18.279), which implies that the risk of presenting enzymatic response to diabetes mellitus patients Oxidant expense is approximately 12 times greater than in those without a history of diabetes mellitus.
A patient 60 years and older after ischemic preconditioning is 8 times more likely to have an oxidative enzymatic response with OR (8,035) and 95% CI 2,703; 10,737. The variable Heart failure had a regression coefficient other than 0 (p = 0.00) and adjusted OR 6,433 (95% CI 2,705; 11,880), which implies the risk of presenting the oxidative enzymatic response in patients with a history of heart failure. After ischemic preconditioning, it is 6 times higher than in patients without a personal pathological history of heart failure, with a margin of 2 to 11 times. The variable cerebrovascular disease had a regression coefficient other than 0 (p = 0.00) and adjusted OR 6,135 (95% CI 2,843; 15,475), which implies the risk of presenting the oxidative enzymatic response in patients with a history of cerebrovascular disease. After ischemic preconditioning, it is 6 times greater than in patients without a personal pathological history of cerebrovascular disease, with a margin of 2 to 15 times. The variable chronic kidney disease had a regression coefficient other than 0 (p = 0.00) and adjusted OR 5,800 (95% CI 2,739; 10,270), which implies the risk of presenting the oxidative enzymatic response in patients with a history of disease. Chronic renal disease after ischemic preconditioning is 5 times higher than in patients without a personal pathological history of cerebrovascular disease with a margin of 2 to 10 times. The variable chronic obstructive pulmonary disease had a regression coefficient other than 0 (p = 0.00) and adjusted OR of 5,738 (95% CI 3,187; 11,271), which implies that the risk of presenting chronic obstructive pulmonary disease in surgical patients the oxidative enzymatic response after preconditioning being 5 times greater than in those without a personal history of chronic obstructive pulmonary disease with a margin of 3 to 11 times.

In 1986, Murry CE et al. 12. described the concept of ischemic preconditioning (PI) in dogs and since then it has been evaluated in multiple animal and human models.
PI (development of tolerance to acute ischemia) is a cellular mechanism capable of delaying, but not preventing cell death; This protection is transitory and lasts from 1 to 2 hours in anesthetized animals. During a brief episode of ischemia, adenosine, bradykinin, norepinephrine, and opioids that activate G receptors are released locally, culminating in the opening of ATP-dependent potassium channels. The signals leading to the opening of these channels are not fully defined, but include activation of phosphatidylinositol- 3-kinases, protein kinase C, and mitogen-activated protein kinase (MAPK). Multiple aging-related abnormalities at various levels of this cascade were demonstrated in animal models [13]. A clinical trial published in JAMA demonstrates a reduction in the incidence of postoperative renal failure in patients receiving IP compared to the control group (37.5 versus 52.5%) and a decrease in the need for renal replacement therapy. However, no differences were found in terms of mortality and adverse cerebral and cardiovascular events (although they were not the primary objective of the trial) [14]. Also, in 2015 two essays were published both in the New England Journal of Medicine. These are the ERICCA14 trial and the RIPHeart trial [15].
The ERICCA trial, multicentre on more than 1,000 patients, showed no difference in the primary endpoint (death, stroke, acute kidney failure or acute myocardial infarction). No differences were found either in the subgroup analyzes or in the secondary objectives (troponin values, length of stay in the Intensive Care Unit and mechanical ventilation, incidence of delirium and new atrial fibrillation). No adverse effects were observed in the intervention group [16] In the RIP Heart multicenter trial of more than 1,600 patients, no differences were found in the primary endpoint (death, acute myocardial infarction, need for revascularization or stroke), nor in the secondary endpoints (troponin elevation, acute kidney failure, need for inotropes, length of stay in the Intensive Care Unit and quality of life after the procedure). But, although PI seems to have beneficial effects, what role does it play in the case of elderly elective surgical patients in the local context? The enzymatic response obtained was oxidative in most of the elderly patients, which corresponds to 90%, showing no benefit. In a 2007 myocardial revascularization surgery study, 57 patients were randomized to receive or not receive remote ischemia-reperfusion cycles after anesthetic induction. The results showed a reduction in troponin levels at 72 hours in the treated group compared to the control group. Other trials confirm the cardioprotective effect reflected in reductions in postoperative troponin T, I or CKMB values. However, not all trials were positive in this regard and do not confirm these results. The routine uses of inhalational anesthetics or beta-blockers, which demonstrated their cardioprotective effect in several clinical trials, is very likely to mask the beneficial effects of PI. In any case, in a subsequent meta-analysis carried out by d’Ascenzo et al. A decrease in troponin values was observed in the postoperative period once possible confounding factors were controlled, such as the use of such volatile anesthetics during surgery [17]. Studies on IP, of different quality and with different objectives, conclude similarly in IP, offering benefits in terms of decreasing the values of markers for myocardial injury and incidence of kidney damage in the immediate postoperative period, but it does not seem to improve the short and medium term results when survival and cardiovascular and cerebral adverse effects are analyzed. On the other hand, cardioprotective drugs routinely used as inhalation anesthetics, beta-blockers, and anti-calcium are sufficient, without remote ischemia providing additional benefits. It is also not clear which group of patients benefits from the technique, what is the most appropriate method to perform it, and even whether or not it has no adverse effects.

Conclusion

Research suggests that the mechanism of ischemic preconditioning is diminished in elderly patients, confirming essential arterial hypertension, diabetes mellitus, age, heart failure, cerebrovascular disease, chronic kidney disease, chronic obstructive pulmonary disease as independent cardiovascular risk factors in cancer patients.

Acknowledgement

Zaily Fuentes Díaz: review, analysis and bibliographical selection; statistical processing; preparation of the final report; review and correction of the report; review and final approval. Gonzalo Fabián Orga García: field or assistance work; bibliographic review, analysis and selection; survey application, statistical processing; preparation of the final report; review and correction of the report; review and final approval. Orlando Rodríguez Salazar: review and correction of the report; review and final approval.
Jorge Lozano Casanova: sample processing and final approval. Tania Puerto Pérez: statistical processing; review and correction of the report and final approval.

Conflict of interest

The authors declare that does not exist an interest conflict.

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Lupine Publishers | Footprint Evidence Solved the Mystery in a Suspicious Death: A Rare Case Report

 Lupine Publishers | Journal of Forensic & Genetic Sciences

Abstract

Death investigation is complicated endeavours, taking an immense amount of time to take in a scene. The general rule of thumb in death investigation is that all death investigations are handled as homicide until proven otherwise. The three critical components of any death investigations are medical/social history, examination of the body and scene investigation. Sometimes in death investigation, the body posture may cause confusion or complication and difficult to explain. A death is suspicious if it is unexpected and its circumstances or cause are unexplained in the early investigation. Normally, this occurs in the context of suicide or suspected criminal activity. The following is a case report in a death scene wherein a young woman was found hanging by a rope around the neck under suspicious condition in her residence, as it was claimed to be a homicidal hanging, allegedly murdered and hanged. But the presence of dust footprint in the scene identified as suicidal hanging and solved the mystery. The fact was explained to the blood relatives in the crime scene itself by the criminalist and made them to understand. The blood relatives understood the scientific fact and accepted the forensic explanation.

Keywords:Crime Scene Investigation; Case Study; Suspicious Death; Partial Hanging; Footprint

Case report, a Real Crime Scene Investigation

Introduction

Forensic Science is an important tool for crime investigation. Scene of crime is the starting point in Forensic Science. Death investigation is complicated endeavours, taking an immense amount of time to take in a scene. The general rule of thumb in death investigation is that all death investigations are handled as homicide until proven otherwise. The three critical components of any death investigations are medical/social history, examination of the body and scene investigation. Sometimes in death investigation, the body posture may cause confusion or complication and difficult to explain. A death is suspicious if it is unexpected and its circumstances or cause are unexplained in the early investigation. Normally, this occurs in the context of suicide or suspected criminal activity.

Hanging or self-suspension is a form of ligature strangulation where the pressure is produced by the weight of the body itself [1]. The incidence of hanging cases differs as per the variation in the community, geographical location and socio-economic condition [2]. Crime scenes contain physical evidence that is pertinent to a criminal investigation. Physical evidence is any and all subjects that can establish that a crime has been committed or can provide a link between a crime and its victim or perpetrator. The successful crime investigation depends upon the recognition, collection and analysis of various kinds of evidence [3]. Footprint is a valuable physical evidence found mostly in burglary and violent crime scenes, left by the perpetrators. But some of the investigators have underestimated the value of footprint evidence and neglected to collect this evidence during crime scene search [4,5]. In Asian countries like India, Thailand, Malaysia and Indonesia, people in the rural area are still walk barefooted [6]. Researchers have proved that footprint may be used to estimate stature [7,8], body weight [9,10] and sex [11] and to solve the crime. The present case report is unique and rare case of suspicious death, wherein the manner of death (suicide or homicide) was identified in the death scene itself through footprint. Later the autopsy examination confirmed the footprint findings.

Case Study Report

A village woman aged about 25 years was allegedly murdered and hanged the body and the body was found hanging partially by a rope around her neck under suspicious condition in her residence. A case was registered by the police under section “Suspicious Death” and requisitioned the service of the field criminalist (the corresponding author while as field criminalist in India) to visit the death scene and assist the investigation. The field criminalist visited the death scene and examined the scene. The body was found hanging in kneeling position as shown in Figure 1.

Figure 1: Kneeling Position of the Deceased-Partial Hanging..

Figure 2: Observation of a dust print on the folding chair.

The house was tiled roof with wooden rafters and the body was found hanging in kneeling position. As an Indian Tamil woman, she worn saree, blouse and bangles. The rope was made of coconut fibre, normally available in all shops for the regular domestic and other uses. The position of the knot was on the left side with prominent ligature mark but non-continuous in the neck. The body did not show any injuries or bleeding but noticed faecal discharge. No struggling mark was noticed. A metal folding chair was found near the dead body and examination of chair showed the presence of right dust footprint on the seat (Figure 2). In general, before hanging, one end of rope should be tied on the wooden rafter of the roof and then another end of the rope to be used to make the ligature loop for the purpose of constriction of neck. Since the rafter was high, the person should have used the folding chair to reach the rafter to tie the one end of rope. This footprint formed a vital clue and deciding factor to fix the manner of death.

Possibility of Footprint Formation

If the death was caused by suicidal hanging, the deceased should have climbed the chair to reach the rafter to tie one end of coconut fibre rope and left dust her footprint on seat surface of chair. Since the village girl used to walk barefooted in and around the house, the feet should have been stained with dust. Or else, if the death was caused by homicide, the murderer might have murdered the woman and made her hang with coconut fibre rope and masqueraded as suicidal hanging. For that, the murderer should have used the chair to reach the rafter with one end of rope and thus dust footprint of the murderer should have been transferred. Who left this dust footprint on the chair?

The dust footprint was photographed and lifted by using “electrostatic dust print lifter” and preserved for comparison analysis. The scene was photographed. Before autopsy the footprints were collected from the deceased for comparison. As the field criminalist (author) was also a “declared footprint expert”, the footprint comparison analysis was conducted in the crime scene itself and opined that the dust footprint in the chair was left by the deceased. Also, the parents have suspected a person in this regard and his footprint was also collected and footprint comparison analysis showed that the dust foot print did not match with suspected footprint. The field criminalist also showed the comparison analysis to the parents and relatives of the deceased. In the crime itself, the field criminalist explained the parents and relatives about forensic science, footprint evidence, suicidal hanging, homicidal hanging etc. and made them to understand the fact.

The body was sent to autopsy room and the Professor of Forensic Medicine also invited the field criminalist to attend the post-mortem. The autopsy examination revealed that the death was due to suicidal asphyxia, ruled out the possibility of homicide and confirmed the result findings of footprint. The field criminalist prepared a crime scene report and handed over to the investigator and the autopsy report was also received. Thus, the keen crime scene observation, recognition, evidence collection, analysis of footprint evidence and crime reconstruction at length put an end to the suspicious death of the woman, beyond any doubt and came up with truth. The whole family members had also accepted the findings.

Discussion

Hanging is one of the commonest methods of approach in case of suicidal deaths in India [12]. Hanging is a process in which the body is suspended with a ligature around the neck, which causes constriction of air passage preventing exchange of air between atmosphere & alveoli of lungs, leading to asphyxia & death. The constriction force is either the weight of the whole body or the weight of the head alone. A weight of 2Kg is enough for death in hanging [13]. The present case report is an atypical hanging since the ligature was found on the left side of neck. The ligature mark on the neck of the woman was more detectable because the coconut fibre was narrow and hard material [14]. Broad object like cloth may not produce appreciable ligature mark. In a case report, an autopsy team have reported a suicidal hanging case wherein a 42-year-old male was found hanging by plastic rope and the rope was found attached to two suspension points and the middle part of it used for the binding of neck and blood stain was present on the floor below the dead body. Crime scene examination, police investigation and autopsy supported death due to suicide [15]. Some researchers have conducted study on different types of ligature materials used to commit suicide by hanging to understand the medicolegal significance of ligature mark [16].

Conclusion

Crime scene is a treasure of information. The investigators should apply their knowledge and skill to identify the fact in the crime scene, so that the fact may be accepted by the sentencing authorities in the court. The present case report provided valuable information in a suspicious partial hanging case and highlighted the value and importance of footprint evidence. The presence of footprint is not only aiding the burglary and violent cases but also useful in complicated investigation like suspicious deaths.

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Lupine Publishers| Acute Upper Gastrointestinal Bleeding (UGIB) In A Resource Limited Setting Highly Endemic for Viral Hepatitis B: Which Etiologies for Which Real Clinical Practices?

 Lupine Publishers| Journal of Gastroenterology and Hepatology

Abstract

Aim : To determine the aetiologies of acute upper gastrointestinal bleeding (UGIB) in a setting highly endemic for hepatitis B and to describe actual clinical practices in a resource-limited setting.

Patients and methods: This study was conducted in two parts. The first part was retrospective from January 1st 2010, to December 31st 2019 on the epidemiological profile of UGIB and the second was a prospective study from December 1st 2017 to May 31st 2018 to evaluate, in a blinded experiment, the actual clinical practices in front of an acute UGIB at the emergency units in Yaounde (Cameroon), and included: recognizing UGIB, assessing for severity, taking emergency measures and prescribing emergency Eosogastroduodenal endoscopy (EGDE).

Results : During the retrospective period, 506 patients (prevalence of acute UGIB in the services 5.6%) were included of which 71.3% were men (sex ratio 2.5). The mean age was 49.9 +/- 8 years. Haematemesis was inaugural in 350 patients (69.1%), nonsteroidal anti-inflammatory drugs were the main risk factor in 297 (43.6%), in 78 (15.4%), this was a second episode. Clinical parameters showed initial instability in 435 patients (85.9%) and haemoglobin (Hb) was <7g/dl in 359 (83.4%). EGDE was performed in 203 patients (40.2%), the main causes of UGIB were lesions of portal hypertension in 111 (44.7%), followed by peptic ulcers in 108 (43.5%). Treatment was mainly medical. However, 94 patients (84.7%) with portal hypertension lesions received endoscopic treatment, mainly by injection of sclerosing agent (69.1%), as well as 13 (1.2%) with peptic ulcers, mainly by isolated injection of dilute adrenaline (1: 10,000) in 11 (84.6%). A total of 75 patients (14.8%) died. The second part concerned 74 patients admitted for acute UGIB at the emergency services of five hospitals in Yaounde. To recognize UGIB, a digital rectal examination was done in 43 patients (58.1%), no patient received a nasogastric tube. For assessment of severity, blood pressure was taken in 73 patients (98.6%), pulse rate in 61 (82.4%), respiratory rate in 17 (23%), saturation in 17 (23%), no patient had prognostic scores in their record. For resuscitation measures, 10 patients (13.5%) received a double peripheral venous line, 20 (27%) were filled with crystalloids, restrictive blood transfusion (Hb < 7 g /dl) was carried out in 24 out of 27 patients (88.9%), 9 (12.2%) received nasal oxygen therapy. EGDE was carried out in 43 patients (60.6%), all beyond 24 hours and none had a prognostic score (Forrest or Rockall).

Conclusion: Rupture of oesogastric varices plays a significant role in the occurrence of UGIB in areas with high hepatitis B endemicity, with exceptional severity and high mortality among young people. The lack of qualified human resources and insufficient technical facilities constitute a serious problem. Locally applicable protocols are needed. In the long term, eliminating viral hepatitis B and C should reduce the prevalence of UGIB

Keywords:Gastrointestinal Bleeding; Hepatitis B Virus; Portal Hypertension; Limited Resources; Endoscopy; Clinical Practice.

Background

Acute gastrointestinal bleeding is one of the major medical and surgical emergencies whose severity should never be underestimated [1]. In approximately 80% of cases, acute gastrointestinal bleeding is of high origin, i.e. the aetiology of the bleeding is located upstream of the duodenojejunal angle or Treitz angle [2]. Acute upper gastrointestinal bleeding (UGIB) is the most frequent emergency in hepato-gastroenterology and remains a major cause of mortality, despite improvements in technical facilities, the mortality rate remains stable at about 10-15% [1-4]. The UGIB is exteriorized in 66% of cases in the form of hematemesis and the aetiologies involved are varied [2,5-7]. In the West, the proportion of peptic ulcers is significantly high. Indeed, the most common causes of acute UGIB are non-varicose (80-90%) and include gastric and duodenal ulcers in 20-50% [2,3,5-7]. Contrarily, in sub-Saharan Africa, the proportion of portal hypertension lesions is significant [8,9]. The impact of chronic hepatitis B virus (HBV) infection in this highly endemic area is significant. In highly endemic countries, ≥8% HBsAg positivity, the HBV-related disease burden is due to liver cancer and cirrhosis in adulthood, responsible for portal hypertension. The majority (80%) of the world population lives in high- or intermediate-endemic areas [10]. The way to handle acute UGIB is well codified. Gastrointestinal bleeding must be recognised, its severity assessed, and blood loss compensated. Finally, the cause of the bleeding must be found and treated [1,2,7,11]. The diagnostic approach, non-specific measures to prevent or treat haemorrhagic shock and specific haemostasis measures according to the aetiology of UGIB are often not all implemented in resources limited countries and this has an impact on evolution and prognosis. Based on data collected in the files of patients admitted in emergency and those obtained following the daily clinical practice of emergency staff, the study aimed to highlight the epidemiology and actual management of acute UGIB in our context dominated by HBV infection and limited resources.

Methods

A retrospective collection of data contained in the files of patients admitted for acute UGIB at the Yaounde Central Hospital (Cameroon) between January 1st2010 and December 31st2019, was carried out. Located at the heart of the city of Yaounde, the Yaounde Central Hospital (YCH) was created in 1930. It is the largest public referral hospital in Cameroon with capacity of …. Beds that also acts as a teaching hospital. It houses several services including the Hepato-gastroenterology service with a capacity of 34 beds, three university specialists, four general practitioners and several permanent workers and residents. This service has an upper and lower gastrointestinal endoscopy room and endoscopy equipment. The variables recorded included: demographics (age, sex); clinical and biological characteristics (onset of UGIB, history of bleeding, physical parameters of bleeding severity, and haemoglobin levels on admission); Esogastroduodenal endoscopy (EGDE) findings; specific management of the cause of the bleeding and outcomes (Table1).

Table 1: Clinical and biological parameters of 506 patients admitted at the Yaounde Central hospital for a recognized acute UGIB.

Table 2: Main causes of acute UGIB at the Yaounde Central Hospital amongst 203 patients who had an EGD.

The second component, cross-sectional and observational blinded experiments, conducted from December 1st 2017 to May 31st 2018, assessed the diagnostic approach and actual management of patients admitted for acute UGIB in five hospitals of different categories (1st to 3rd) of the Cameroonian health pyramid, in the city of Yaounde. Twenty (20) doctors and 39 nurses in the emergency service who managed 74 patients admitted for acute UGIB were followed. The elements to take care of acute UGIB included recognition of acute UGIB by placing a nasogastric tube or performing a digital rectal exam; assessment of severity by clinical criteria (taking blood pressure (BP), pulse rate (PR), respiratory rate (RR) and room oxygen saturation (SPO2), Glasgow- Blatchford score; fluid resuscitation and transfusions (double venous line, crystalloids filling, proton pump inhibitors (PPI) or vasoactive treatment, oxygenation, restrictive blood transfusion (haemoglobin (Hb) <7 g/dl), hourly monitoring of vital signs and neurological status) and finally, the performance of EGDE and the Rockall and Forrest scores.

Statistical Analysis

Data was analysed using Statistical Package for Social Sciences (SSPS Inc, Chicago, Illinois, USA) version 23.0. Means ± standard deviation was used for quantitative variables; Categorical data was expressed as numbers and proportions. A p value of less than 0.05 was considered statistically significant.

Results

During the retrospective period, 506 patients (prevalence of acute UGIB in the services 5.6%) were included of which 361 men (71.3% and 145 women (28.7 %), given a 2.5 sex ratio. The mean age was 49.9+/- 8 years (maximum 14-96 years) and the peak of bleeding was in the 55-65-year age group. Haematemesis was the initial complaint in 350 patients (69.1%), non-steroidal antiinflammatory drugs (NSAIDs) constituted the most important risk factor in 297 patients (43.6%), in 78 (15.4%). This was a second episode. On admission, clinical parameters relevant to severity were systolic BP <100 mmHg in 122 patients (39.8%); HR >100 beats/ minutes in 435 (85.9%) and RR >20 cycles/minute in 435 (85.9%). Hb was <7g/dl in 359 patients (83.4%). EGDE was performed in 203 patients (40.2%), the major causes of bleeding were: portal hypertension lesions in 111 patients (44.7%) followed by peptic ulcers in 108 (43.5%). Treatment was mainly medical. However, 94 patients (84.7%) with portal hypertension lesions received endoscopic treatment, mainly by injection of sclerosing agent (69.1%), as well as 13 patients (1.2%) with peptic ulcers, mainly isolated injection of dilute adrenaline (1: 10,000) in 11 (84.6%). A total of 75 patients (14.8%) died during hospitalization (Table 2).

The second part concerned the assessment of care offered to 74 patients admitted for acute UGIB (mean age 55 years; sex ratio 2.1). For the recognition of bleeding, digital rectal examination was performed in 43 patients (58.1%) and no patient received nasogastric tube. Regarding the assessment of severity by clinical criteria, BP was taken in 73 patients (98.6%), HR in 61 (82.4%), and RR in 17 (23%), no patient had prognostic scores in the record, including the Glasgow-Blatchford score. Only 17 patients (23%) had SPO2 measurements. Regarding intensive care measures, only 10 patients (13.5%) received a double peripheral venous line, the majority of which was a small-bore venous line. Twenty patients (27%) were filled with crystalloids; restrictive blood transfusion was performed in 24 out of 27 patients (88.9%) with Hb < 7 g / dl. Only 9 patients (12.2%) received nasal oxygen therapy. EGDE was performed in 43 patients (60.6%), all beyond 24 hours after admission and none had a prognostic score after endoscopy (Forrest or Rockall).

Discussion

The study showed that acute UGIB is an emergency with exceptional severity in our environment, as mortality is very high at around 15%. In this study, it was found that acute UGIB affected two and a half times more men than women with a mean age of about 50 years. This is the case in studies conducted in Mali (sex ratio 2.78; mean age 47.45 years), and in Côte d’Ivoire (sex ratio 3.38; mean age 47 years) [8,12]. Indeed, in the sub-Saharan African region, the occurrence of acute UGIB often involves relatively young patients. This can be explained by the fact that the causes of bleeding are often dominated by portal hypertension lesions, especially in young patients, as reported in Mali in a rural area [8]. As opposed to sub-Saharan Africa, in the West, the age of onset of acute UGIB is higher than 70 years due to the use of NSAIDs in the elderly population. Of chronic NSAID users, 25% develop an ulcer, of which 2-4% are complicated by bleeding [2,7,13,14]. The male predominance is universal, and reverses in the West after the age of 80 years due to the higher life expectancy in the female population [2,4,6-9, 11,13,14].

As in several studies reported in literature, hematemesis was the most common initial clinical presentation [2,6,7,15,16]. This initial clinical presentation can be explained by the different lesions found on endoscopy. In fact, portal hypertension lesions, led by oesophageal varices, were the most frequent, alongside peptic ulcers. The frequency of the various aetiologies varies from one region to another [5,6,8]. Thus, in the sub-Saharan African region, several studies report very high frequencies of portal hypertension lesions. This is the case of the study by Diarra et al. in Mali in 2007 [8]. The authors reported a frequency of 55.2% in favour of ruptured oesophageal varices, far ahead of peptic ulcers which represented 16%. The frequency of portal hypertension lesions is also high in Burundi (28.2%) [16] and Gabon (29.5%) [17]. These various countries have liver diseases related to chronic HBV infection in common. Indeed, sub-Saharan African countries are located in a zone of high endemicity according to the World Health Organisation (WHO), i.e. the prevalence of hepatitis B is 8-20% of the general population [10]. Cirrhosis, which causes portal hypertension, is often the result of chronic HBV infection acquired at birth or in early childhood [18]. The annual incidence of varicose veins is approximately 5% [19]. UGIB from ruptured esophageal varices accounts for 70% of gastrointestinal bleeding in cirrhosis, with an estimated overall 2-year bleeding risk of 20% [19]. The aetiological approach to acute UGIB in high- and intermediate-endemic areas where the majority (80%) of the world population lives should therefore consider this high frequency of portal hypertension lesions and bleeding complications.

Regarding the severity of the bleeding, more than 85% of patients were initially unstable with clinical and laboratory signs of severity, despite the absence of Glasgow-Blatchford and Rockall scores in their records. This initial haemodynamic instability can be explained, on the one hand, by the causes of bleeding, in particular the rupture of oesogastric varices, which are exceptionally serious, but also, on the other hand, by the late arrival in hospital structures due to distance, cultural considerations or difficulties of mobility in our country.

Treatment was essentially medical. PPI treatment was most often initiated on admission, even if this treatment did not always fully comply with current recommendations in Europe and Asia [2,7,20,21]. Contrarily, in cases of suspected acute UGIB related to rupture oesogastric varices, vasoactive therapy to reduce portal blood flow was never initiated on admission, in line with international recommendations, including those adapted by the European Society of Gastrointestinal Endoscopy to be applicable to resource-limited settings, including some African countries [2,7,22-24]. Patients with bleeding peptic ulcers have rarely benefited from endoscopic haemostasis, unlike those with portal hypertension lesions. Late arrival at hospital would explain why in sub-Saharan Africa Forrest scores IIc and III, i.e. pigmented stain or clean base of the ulcer, are most frequently found [25]. For the Forrest classification guiding the choice of endoscopic treatment modality for ulcers, there is no endoscopic treatment for these scores [2,3,7,26]. The practice of injecting adrenaline alone instead of combined adrenaline and bipolar coagulation or endoclips was inappropriate. This could be explained by factors such as excessive procedure costs, insufficient training of practitioners and limited logistic equipment.

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Lupine Publishers| Improvement of Liver Function by a Short-term Administration of Luseogliflozin in Patients with Type 2 Diabetes: A Single-arm Study and the Mini-literature Review

Lupine Publishers| Journal of Gastroenterology and Hepatology

 

Abstract

Background: Non-alcoholic fatty liver disease is not simply the hepatic manifestation of obesity and diabetes but also linked to hepatocellular carcinoma. Yet, its effective treatment has not been established. In this study, we evaluated the effect of a short-term administration of luseogliflozin to patients with type 2 diabetes having non-alcohol fatty liver disease. Luseogliflozin is a unique sodium-glucose cotransporter 2 inhibitor which is metabolized in and excreted by the liver in addition to the kidney. Therefore, the drug might possess an additional effect on other agents of the same class which are exclusively metabolized in the kidney.

Methods: Using alanine aminotransferase >20 IU/L as a diagnostic basis for non-alcoholic fatty liver disease, 19 patients, not taking alcohol, with type 2 diabetes (male/female 15/4, the median age 57 years) was treated with 2.5 mg luseogliflozin for 12 weeks.

Results: Pre- and post-treatment median values for alanine aminotransferase were 51 IU/L and 33 IU/L (p = 0.001), and the corresponding values for the fibrosis index based on the four factors [age (years) ∙ alanine aminotransferase (IU/L)] / [platelets (109/L) ∙ alanine aminotransferase (IU/L)1/2)] were 1.669 and 1.314 (p = 0.043). There was no adverse effect of the drug. Our findings were essentially compatible with the results of the previous studies reviewed.

Conclusion: We conclude that sodium-glucose cotransporter 2 inhibitor could be the choice for the pharmacological treatment of non-alcoholic fatty liver disease. Especially, a short-term administration of it is consistently effective in mild cases.

Keywords: SGLT2 inhibitor; NAFLD; Fibrosis-4 index; GPR-index; APRI.

Abbreviations: SGLT2i: sodium-glucose cotransporter 2 inhibitor; NAFLD: non-alcoholic fatty liver disease; NASH: non-alcoholic steatohepatitis; T2DM: type 2 diabetes mellitus; AST: aspartate aminotransferase; ALT: alanine aminotransferase; GGT: gammaglutamyl transpeptidase; Fib-4 index: Fibrosis-4 index; GPR-index: gamma-glutamyl transpeptidase to platelet ratio; APRI: aspartate aminotransferase to platelet ratio

Introduction

Obesity or overweight is the motherland of non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) [1]. Accordingly, with increasing trend of body weight worldwide, the number of patients with the liver problem is relentlessly increasing [2]. Recently, NASH has also been attracting the attention as a cause of hepatoma [3,4]. Under such yet, treatment of NAFLD (NASH and NAFLD are collectively called NAFLD hereafter in this communication), irrespective of presence or absence of diabetes, has not been established. Results of treatment of patients with type 2 diabetes (T2DM) having NAFLD with sodium-glucose cotransporter- 2 inhibitor (SGLT2i) appears promising [3-7], the effectiveness of a short-term treatment, such as 12 week-treatment, has not been established.
Here, we evaluated effectiveness of a short-term administration of SGLT2i, luseogliflozin, that is metabolized not only in the kidney but in the liver [8]. A mini literature review on this issue was also performed to resolve the current inconsistency. This study was approved by the Clinical Research Ethics Committee of Aizawa Hospital (No. 2019-094).

Subjects and Methods

Subjects

Consecutive 29 patients with T2DM who took luseogliflozin for 3 months or longer between January 1, 2019 to May 31, 2020 were initially registered. Because the purpose of this study was to investigate the effect of luseogliflozin on NAFLD/NASH, 8 with alanine aminotransferase (ALT) less than 20 IU/L [9], and other 2 with a habitual alcohol drinking of 20 g/day or more were excluded, and the remaining 19 were analyzed.
The study was a single-arm, add-on study. Namely, 2.5 mg luseogliflozin was additively prescribed on top of the hypoglycemic agents already taken by the patients, which are shown in Supplemental Table 1. The data before and 12 weeks after luseogliflozin administration was critically compared.

Laboratory measurements

In addition to the routine clinical chemistries, indices of the hepatic fibrosis including Fibrosis-4 index (Fib-4 index), gammaglutamyl trans peptidase (GGT) to platelet ratio (GPR-index), and aspartate aminotransferase (AST) to platelet ratio (APRI) were calculated10: the unit for AST, ALT, GGT as IU/L, platelet counts as 109/L and age as a year. Equations for each index were as follows [10].

Fib-4 = [(AST) ∙ (age)] / [(Platelet counts) ∙ (ALT)1/2]
GPR index = 100 ∙ (GGT) / (Platelet counts)
APRI = 100 ∙ (AST) / (Platelet counts)

Statistical analysis

The data were collected retrospectively and analyzed cross-sectionally and longitudinally. We evaluated the effect of luseogliflozin on the liver function tests and the indices of liver fibrosis. In addition, delta, i.e., the basal value minus 12 week-value for the indices of liver fibrosis was calculated for each study subject, and correlation between the delta values of fibrosis indices and the basal plasma glucose (PG), glycosylated hemoglobin (HbA1c), AST, ALT, GGT, body weight (BW) and body mass index (BMI) were examined. Furthermore, the delta value of the liver fibrosis indices and the delta value of PG, HbA1c, AST, ALT, GGT, BW and BMI were also examined. The statistical analysis was performed using JMP ver.15. Wilcoxon rank-sum test, Wilcoxon signed rank test and Spearman rank correlation were used as needed.

Literaturereview

Representative 10 original reports published in the English language on the treatment of patients with T2DM having NAFLD by SGLT2 inhibitors [6,7,11-18] were summarized to provide a current overview of the issue. In these literature, five kinds of SGLT2i agents were prescribed, with the number of the patients ranging from 9 to 32 and the treatment duration from 12 to 48 weeks.

Results

Baseline characteristics of the patients

Table 1. Baseline data (A), the data 3 months after the luseogliflozin treatment (B) and the difference (C) between the two (luseogliflozin- basal).

Values are median and interquartile ranges except for sex and the observation period: the latter was shown as mean and SD. sBP, systolic blood pressure; dBP, diastolic blood pressure; HR, heart rate; Hct, hematocrit; Plt, platelet count; T.Bil, total bilirubin; AST, aspartate aminotransferase; ALT, alanine aminotransferase; GGT, gamma-glutamyl transpeptidase; Al-P, alkaline phosphatase; Alb, albumin; eGFR, estimated glomerular filtration rate; HDL-C, high density-lipoprotein cholesterol; LDL-C, low density-lipoprotein cholesterol; TG, triglycerides. N.A., not applicable. *Wilcoxon signed-rank test.

The study patients were male dominant (the proportion of males, 79%), middle-aged Japanese adults with the median BMI of 28.0 kg/m2 which was larger than the representative value in the Japanese patients with T2DM in general11(Table 1A). The median HbA1c value of the entire group before luseogliflozin was 8.8% (77 mmol/mol) so that the level of glycemic control was unsatisfactory (Table 1A). Regarding the hypoglycemic agents used before subscribing luseogliflozin, Dipeptidyl Peptidase-4 (DPP-4) inhibitors and biguanide were most frequently employed (Supplemental Table 1), which was typical for the Japanese patients [19].

Supplemental Table 1: Medications before administration of luseogliflozin. 2.5 mg luseogliflozin was added in each patient on top of the medication described above.

Values are median and interquartile ranges except for sex and the observation period: the latter was shown as mean and SD. sBP, systolic blood pressure; dBP, diastolic blood pressure; HR, heart rate; Hct, hematocrit; Plt, platelet count; T.Bil, total bilirubin; AST, aspartate aminotransferase; ALT, alanine aminotransferase; GGT, gamma-glutamyl transpeptidase; Al-P, alkaline phosphatase; Alb, albumin; eGFR, estimated glomerular filtration rate; HDL-C, high density-lipoprotein cholesterol; LDL-C, low density-lipoprotein cholesterol; TG, triglycerides. N.A., not applicable. *Wilcoxon signed-rank test.

Liver function and indices of hepatic fibrosis following luseogliflozin administration

Elevated serum level of ALT was an inclusion criterion, so that the ALT was clearly elevated as a group with the median value, 51 IU/L. As well expected, administration of luseogliflozin significantly decreased PG and HbA1c (Table 1, A and B, before and after luseogliflozin, respectively). In addition, it significantly lowered the serum level of AST, ALT, GGT, and alkaline phosphatase (ALP). The degree of lowering was 12%, 34%, 35 and 42% for the respective enzyme levels. Importantly, the luseogliflozin treatment also significantly lowered the values for Fib-4 index, GPR index, and APRI (Figure 1).

Correlation between delta Fib-4, GPR index, and APRI and baseline and delta values of liver function and the body weight and BMI

Figure 1: Change of indices of liver fibrosis produced by luseogliflozin. Individual lines represent a change of the value in each person and the circles, and the vertical lines indicate the median and interquartile ranges: blue ones for before and red ones for after luseogliflozin. Wilcoxon signed-rank test was used for the statistical analysis.

The delta Fib-4 index was significantly and positively correlated associated with higher baseline AST and ALT levels; the delta GPR index was correlated with baseline AST and GGT; the greater delta APRI was associated with higher baseline AST and ALT (Table 2A). Correlation between the delta values and the baseline of liver function was absent for BW and BMI (Table 2A).
On the other hand, there was an inverse correlation between ‘delta Fib-4 and delta AST and delta ALT’, ‘delta GPR index and delta GGT’ and ‘delta APRI with delta AST and delta ALT’ (Table 2B). There was no significant correlation between delta values of the fibrosis indices and the delta of BW and BMI (Table 2B).

Table 2. Correlation between delta Fib-4, GPR index and APRI and baseline value (A) and delta (B) of liver function. Delta means the difference between the value of each test performed on the day of starting luseoglifrozin and 12 weeks later.

Values are median and interquartile ranges except for sex and the observation period: the latter was shown as mean and SD. sBP, systolic blood pressure; dBP, diastolic blood pressure; HR, heart rate; Hct, hematocrit; Plt, platelet count; T.Bil, total bilirubin; AST, aspartate aminotransferase; ALT, alanine aminotransferase; GGT, gamma-glutamyl transpeptidase; Al-P, alkaline phosphatase; Alb, albumin; eGFR, estimated glomerular filtration rate; HDL-C, high density-lipoprotein cholesterol; LDL-C, low density-lipoprotein cholesterol; TG, triglycerides. N.A., not applicable. *Wilcoxon signed-rank test.

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Lupine Publishers| Avoiding Vulnerabilities and Attacks with a Proactive Strategy for Web Applications

Lupine Publishers| Journal of Robotics & Mechanical Engineering

Abstract

As the number of users interacting with dark websites grows, it opens the door for vulnerable and malevolent actors, making web traffic unsafe and risky. To prevent such vulnerabilities and maleficent activities on dark websites the proactive strategic measures have been taken into account and the relevant hidden causes are explored that helps to overcome the security risks during various web operations. In the first step, from the dark web corpus, the web addresses have been analyzed to check the status of whether these web addresses are available or not. To prevent the web addresses mining challenges a script was designed to mines irrelevant web address URL by visiting multiple search engines based on user input. In the 2nd step, another script was designed to check those domains having chances of becoming inactive because for security reasons such as onion sites. In 3rd step, various gape has been identified in dark web hosting using crawls that create the new links from configuration files. In the 4th step, using manual and automated testing the maleficent activities were identified in web traffic. Further proceeding to the 5th step, the web address lifespan was determined which quantifies the duration between the first and last occurrences of a web address. Finally, using Fisher’s Exact Test (FET), two comparative scenarios have been developed by considering the similar attributes and the role of operating system interaction with surface and dark websites. In the first scenario for identifying the similar attributes of surface and dark websites, the role of maleficent and spammer has been investigated and found that overall, 86 and 800% of attributes of surface and dark websites are identical. Similarly, for 2nd scenario identifying how long the operating systems have interacted with surface and dark websites, it was found that windows, Linux, and android based operating systems have an incredible role and made the contents much pusillanimous which creates high chances of information leakage. In the end, up to 40 days of user interaction to surface and dark web has been analyzed and found various aggravated statistics regarding vulnerabilities involvement in network traffic such as maleficent, spammer and the information leakage. At the same time, the interaction period of operating systems with surface and dark websites such as windows, Linux, and Android is also statistically investigated. While gathering the aforementioned investigation it is observed that most of the websites use CMS, such as WordPress, Joomla, Drupal, and various forums, and are outdated with either no patching or having vulnerabilities. Since either, they hosted with old versions of the software or were not updated with the latest patches, most URLs in the dark web are vulnerable to attacks. After this study, clear and up-to-date statistics are unveiled regarding dark websites, and it is recommended that to get rid of vulnerabilities the obtained statistics can be considered before developing new applications.

Keywords: Meticulous Testing; Vulnerabilities; Webhosting; Surface Web; Dark Web; Problematic Target; CMS; Script; FET

Introduction

The dark web is a section of the internet that can only be accessed using advanced routing mechanisms. The anonymity afforded to dark web users has been abused in order to engage in illegal online activity. Considering web security is a form of deafens nowadays and helps secure websites proactively for hosting in either surface web or the dark web. Securing a website is presently one of the most critical issues because of its significance in increased cyberattacks on the surface web. A crucial truth in web applications and their security is that a hosted web server and its related system cannot be entirely trustworthy, concluding that it cannot guarantee 100% safety [1]. All Web applications have their means, such as providing information and services. Web Applications interact with their backend known as (databases) several times per client request, and if the security of such websites and web applications is compromised, there could be outcomes in the form of information loss, financial loss, lawsuits, identity theft [2]. Cybersecurity must prioritize sustaining a productive computing environment and securing various transactions. Cybercrimes are on the rise across the world, and as a result, organizations, whether it is personal, a government which means it must be critical infrastructure. Not unexpectedly, the general state of web application security is highly conducive to cyberattacks [3]. Estimates indicate a considerable number of online applications with security flaws and as a result, there have been several instances of successful security breaches and exploitations [4]. Organized crime thrives organically in this potential sector. Considering the millions worth of money made by such groups in the web’s clandestine economy [5]. Security technology is insufficient to prevent web application flaws, and practitioners should focus on assessing and ensuring their success. This unindexed portion of WWW that intentionally hidden and inaccessible by standard browsers referred to as the dark web. Some Studies state that the surface web is only 4% of web content indexed by the publicly available search engines like Google, Bing. According to TOR metrics project, more than 200K registered. Onion-based addresses as of May 2020, and on average, daily 2 million users use TOR browser [6], to access the deep or dark web. The deep and dark web provides a venue for malicious actors to coordinate cyberattacks, illicit activities such as human trafficking and terrorist activities [7]. The main reason for using the dark web is its features such as encrypted protocols, anonymity, hidden in nature. While accessing the dark web, the dark web users encouraged neither the risk of getting caught by law enforcement nor being censored by a website [8]. The IP Address identifies a system as a unique identifier during Internet communication. It also aids in determining the geolocation of any device connected to the Internet. End-to- end device communication on the dark web, on the other hand, is encrypted by enabling anonymity of end devices, routers, and communication via the dark web [9]. The Law Enforcement Agencies (LEA) showing [10], an interest in the TOR-based network and its services mainly to understand the type of data hosted and their activities for any illegal activities. As the internet community grows, so do web dangers, nowadays majority of the illegal activities happen through the dark web, and it is tough to identify the criminals behind the activity. In this work, we carried out some vulnerability assessments on the dark web initially, and we mined numerous URLs from various sources such as search engines of the dark web. We gather information about the targeted host and use various methodologies. After that, we apply various vulnerability assessment methodologies, including manual testing of the web application and automated testing of targeted web applications and the result set presented in the result analysis. Dark web is one of the most challenging and untraceable mediums adopted by the cyber criminals, terrorists, and state- sponsored spies to fulfil their illicit motives. cyber-crimes happening inside the dark web are alike the real-world crimes. however, the sheer size, unpredictable ecosystem and anonymity provided by the dark web services are the essential confrontations to trace the criminals. The LEA required opportunities for tracing such criminals by using various methods [11]. By auditing and assessing the Dark Web, we can determine the availability of website availability and the information, which is sensitive, private, or potentially damaging information about an organization and related accounts, systems, and people. There are many monitoring methods, and we considered auditing and assessing applications, i.e., hosted websites on the dark web.

The main contribution of this study includes the following findings.

• Monitoring for breached usernames, passwords and other information.

• The Business resources and secrets which are breached and put up on sale.

• Monitoring the specific websites based on technical changes, transactions in their business, and relevant illicit activities.

Rest of the manuscript is arranged as: The literature review has been placed in “Related work section, and the proposed proactive methodology has been explained in “Proposed proactive strategy” section. The section “Dark web data selection strategy” highlights the current hurdles to the webhosting system. The overall access duration with surface and dark websites has been investigated in “Comparative scenarios” section. The results have been critically discussed in “Result and discussion” section. Finally, work has been concluded in “Conclusion” section.

Related Work

Due to the increasing number of web applications in both the surface web and the dark web, the corresponding numbers in sophisticated threats are also increasing. There are requirements to understand vulnerabilities or gap areas to check about creating new tools that are efficient and accessible becomes essential. The researcher in [12], describes a validation study in which participants answered quiz questions using the tool prototype, the sample data generated using the OWASP ZAP scanner tool, and a prototype implemented and used for validation purposes. They discussed the Web forensics and legal aspects researcher collected criminal files which have been investigated with official permits and crime models that will create the database have been determined. These crime models are conventional crimes committed through web activity or cybercrimes.

Another author [13], presented an insight into various aspects of the Dark Web, such as features, advantages, disadvantages, and browsers. Further, they discussed the different types of attacks, exploits, and malware with an overview of different types of criminal activities and incidents over the dark web. Many web applications in the dark web deal with a vast amount of secure and high transactions. As a result, security plays a significant role in web application development for the dark web too. The security of any web application focuses on the data the application handles, where the Audit and Assessment of web applications in the dark web may give some idea of understanding risks, and it may help investigators trace illegal activities. Further [14], discussed the suggestions provided in this article are in line with the majority of experts. In addition to the results, there are several typical IT issues in the network security of institutions. It is important to highlight the need of performing a risk analysis before exploiting vulnerabilities. These are answers for the time being but will become weaknesses in the future, necessitating improved tactics. Defend against cyber-attacks. Another researcher [15], discussed the vulnerability assessment as it is useful since it gave information on the security of the websites that were chosen. Vulnerabilities were identified in all of the examined web servers. Some vulnerabilities were discovered across all web hosts, while others were exclusive to a single host. These revelations revealed that there are security concerns that need to be addressed across the board. On the same ground [16], discussed and suggested a unique approach for injecting realistic assaults into web applications automatically. This approach entails evaluating the web application and creating a list of probable flaws. After that, each vulnerability is injected, and numerous assaults are launched against it. Each attack’s success is automatically analyzed and reported. One of shrewd approach by [17], looked at the issue of selecting appropriate SATs for web application vulnerability detection. They proposed a method for developing benchmarks for evaluating such SATs at various levels of criticality. In four situations of escalating criticality, they use SCM to automatically arrange the workload. To rank the tools in each situation, several measures are used. Saiba nazah [18], in presented a comprehensive examination of the visible section of the darknet’s structure and content they were the first to methodically (recursively) investigate the visible darknet’s network topology. The author [19], discussed the threat landscape is complex and ever-changing. To deal with the size of the pentest, autonomous solutions are required. Autonomous Security Analysis and Pentesting (ASAP) is an effort toautomate attack analysis, attack plan generation, and validation. Future Work: Using host logs to develop the AI model and attack plans for the visible darknet’s network architecture. Similarly [20], developed MASSDEAL, a tool for the automated exploration of the Dark web that learns about new or previous unseen services and measures repeatedly across time where they collected data over more than 20 thousand dark web services sampled from September 2018 to January 2019. The performed an extensive analysis of service redundancy and measure the appearance of. onion mirrors as well as providing an estimation of the infrastructural redundancy behind those systems. Considering the same opinion, the [21], performed and analyzed the text content of 28,928 HTTP Tor hidden services hosting 21 million dark webpages and confirmed 901 phishing domains They conducted mainly an in-depth measurement study to demystify the prevalent phishing websites on the Dark Web to understand the dark web trends. This trend exacerbates the risk of phishing for their service users who remember only a partial TOR hidden service address. This study is about the auditing of websites on the dark web, in identifying vulnerabilities and gap areas, where they can support LEA for monitoring requirements to identify various activities of a website. We tried with lesser number of websites and achieved indented results for further to extend our research in building the classification framework for dark web sites.

Proposed Proactive Strategy

the proactive strategy is being conducted to analyze the impact of maleficent elements on websites hosted on the dark web. All such websites have been tested from different locations while keeping in mind that these websites were not in normal status and therefore, the alternate workstations were used in order to avoid any unusual situation as illustrated in Figure 1. During testing period, the multiple vulnerabilities were identified in various categories such as Adults, Drugs etc. Around 650 websites were tested from www web corpus and more than 60% of websites found to be vulnerable and unprotected from various attacks. During this operation, the different activities were performed in order to get the desired outcome which eventually turned the activities into a proactive strategy.

Figure 1: Proactive research methodology.

Relevant data mining

During the operation of dark web data mining, some indexing related uncouth situation was occurred because the addresses of the dark web do not appear in normal format. Further, web address belongs to dark web are exceptionally complicated and employs a more robust and modern encryption algorithm. It is much hard to recall the web address belongings to the dark websites due to URL length as 56 bytes long. These features make mining challenging; therefore, for a proactive strategy a script was designed that mines the URL by visiting multiple search engines based on user input and creating a unique result set. In addition, live activities were performed to catchup all those domains that having chances of becoming inactive because for security reasons, onion sites may become inaccessible after some time. Another script was designed to forecast the status of onion domain active or not, and also it reverts the status code (200,301,404,403 etc.), the title of the web page and saves results if the domain can redirect to some other domain [22]. Further, it is crucial identifying the gap for dark web hosting and every aspect is needed to investigate the areas which were ignored. Spiders/ crawls can use different techniques, such as brute force, to discover vital files or configuration files that have been missed or concealed. A SOCKS proxy is used to establish connections to the hidden services by the crawlers, which are written in Python. The crawler receives the first onion domains or seeds from the surface web’s publicly available directory. A separate file is created for each seed that is scraped and the new links that are discovered. The new links were crawled again to find other new links. The scraping of new link is performed two more times until no new connections can be identified. The crawler did not scrape hidden services that required user authentication or were behind subscription pay-walls. Getting the user information such as email address, phone address, how generally the users act, details about the admin, all are required and therefore, information gathering also includes looking into exposed tokens, API endpoints, API entry points, and reading the parameters. The API is used to find login information in files; client-side validation is available, although it is preferable. Having as much knowledge about the target as possible makes work more accessible and manageable. Therefore, all potential hostnames connected to target and relevant open ports have been considered. The domain-level structure of the dark web has been examined, and all sub-domains of a certain domain are aggregated under it and indicated as a single individual node of a graph. The onion possessing two sub-domains en.ABC.onion and my.IMS.onion [23], each of these sub-domains and their internal web pages are considered as a single node of graph identifiable by respected domain name. As a result, each edge in the graph connecting nodes A and B symbolizes a hyperlink inside domain A’s web page referring to a web page included in domain B.

Maleficent detection

The web maleficent detection is a complicated process of identifying vulnerabilities in web traffic; the loopholes are a significant cause of data breaches, hacking, and ransomware, among other things. The information gathered was utilized to start the maleficent detection of the web hosts Two techniques are used for this detection i.e., manual testing and automated testing. As a result of the manual testing being conducted by humans, it is essential that the testers think like a hacker. The tester examined each component of the target by hand and used a variety of methods based on his expertise of how to defend it. Automated testing makes use of scripts, tools, and software to replicate the same process by repeating defined tasks. It is handy when viewing source code since it detects weaknesses and unexpected vulnerabilities immediately. In automation testing, software such as ZAP, Burp Suite, and others are utilized [24].

Web address analysis

It has been determined that web addresses have a life expectancy, which is a novel classification. The concept of the invoked web address lifespan has been added, which quantifies the duration between the first and last occurrences of a web address in a data collection. It is related to the dynamics of content interest on the dark web. This notion is applicable to a variety of hosting considerations, as well as online cache activities. A simple parametric function closely linked to the probability density function well approximates the distribution of invoked lives. A unexpected finding was made using this model: the anticipated lifespan of a web address is asymptotically equal to the time frame of observation. It’s also surprising to see a classic and well-behaved web family of statistical distributions at all [25]. This is particularly noteworthy since a substantial volume of web addresses in online traffic are nonces inside the scope of web data corpus. Furthermore, the structure inherent in web addresses was evaluated by comparing the use of path hierarchy vs query string on a range of dark sites. Surprisingly, static material is supplied via a path-depth structure, whereas query parameters include personalized content. Despite the fact that the two morphologies are functionally similar, there is a path-depth versus query-parameter dichotomy. Also, a web address does not have to represent the content of the resource if it is not used for search and resource discovery or is handled in another way. As a result of the widespread usage of query strings in many applications, the web address is no longer viewed as a simple node in a hierarchical file system [26].

Dark Web Data Selection Strategy

While exploring the dark web for data collection, it was much hard to find the appropriate data as most of the time accessibility issue hurdles reaching to specific hosted data. An obscure part of the Internet that can only be accessed with special software is known as the dark web Although there are several dark web technologies, they all have the feature of employing encryption [27], to provide anonymity.

Dark web alive time

When it comes to selling illegal items and services, most dark web sites, also known as dark markets, are similar in functionality and structure to other well-known websites. They provide a wide range of illegal commodities and appear to cater to customers seeking specific content. As a result, one cannot be certain if the dark web will be accessible online or not because web addresses for such websites are not available throughout the session.

Maleficent detection is a time-consuming process that might take anything from many hours to several days to finish [28]. There is no guarantee that a website will be available during the maleficent assessment task. In the same way as ordinary websites, dark websites are linked to one other and to each other. When webpages did not have hyperlinks, users had to know the precise URL to find them. Thus, hyperlinks serve as the foundation for how users navigate this network, connect to domains, discover information, and interact with other users. Using social network analysis, these linkages may be examined, revealing the web’s connections [29]. In the dark network, websites with more inbound and outbound hyperlinks may be regarded more popular and significant for the dissemination of information inside the dark network, Network analysis may assist in determining not just how information is transmitted and exchanged within network structures, but also the significance of certain websites to the network. A tiny dense cluster [30], of nodes, similar to other Internet topologies, may constitute the network’s hub and direct the flow of information. Significant ramifications for how communities grow and operate might result from this, as could the tactics employed by law enforcement authorities to discover and remove unlawful users and material. Similarly, considering the web address delay response, the time it takes the web application server to complete one request is referred to as latency. Congestion has crept into the dark network [31], and the flow management system has failed to keep up with it. The issue of high latency is not the only one that has to be solved. Furthermore, the dark network is quite variable. Because queries are routed via several computers across the world, the dark network will never be as fast as the surface web. As a result, network latency will always be a problem. It took a long time to examine the endpoints and other features of websites since there were numerous instances of web address delay. An excessive amount of HTTP requests was made to the web-based application server because of this high delay rate. Further, checking some static web sites on dark web environment, Many CMS-based websites [32], are challenging to evaluate since the community is always working on security fixes and looking for new vulnerabilities. It has also been discovered that several hidden websites have not been updated.

Comparative Scenarios

In order to examine the roots of the dark web hosting script, the comparative scenarios are developed which enhanced the chances of getting accurate data and presages upcoming attacks.

(i). Similar attributes: The principles of running a web environment are the same on the surface and dark webs because Onion services are the part of the dark web, it does not expose the host’s IP address but on the surface web, the IP address is accessible to everyone, therefore a misconfiguration can reveal the server’s IP address [33]. When comparing the characteristics of the surface and dark webs, the dark web was found to be misconfigured. Exploiting a dark web site, as in the surface web, might disclose dark web users who visit the dark web site. As a result, identifying a surface web site relevant to a dark web site based on ownership and developer can increase the odds of understanding the user’s activity. The Fisher’s Exact Test (FET) [34], was used to assess the connections between surface and dark websites. The FET confirms the strong correlation between the web environment and maleficent. Unlike the dark web (1%) where this occurrence is rare, the surface web (12.2%) is more likely to experience the maleficent than the dark web (1.3%) shown in Table 1. It was discovered through a more detailed study that this relationship is only significant in paste locations. As a result of this, attackers on the dark web may be stealthier and try to avoid detection by not changing passwords on their accounts, indicating a certain degree of skill. The observed variations in the underground forums are insignificant.

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