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Introduction: Snakebite envenomation can lead to prolonged disruption of hemostasis, neuromuscular paralysis, myolysis (muscle degeneration) followed by release of damage associated molecular patterns, acute kidney injury and hypovolaemic shock due to underlying cytokine storm. Extracorporeal cytokine adsorption device can be used to address the cytokine storm. Patients and Methods: A 40-year-old male patient underwent hypotensive and circulatory shock post viper snakebite making it difficult to maintain mean arterial pressure (MAP) >65 mmHg. Standard of care was ensured. Further, the patient progressed towards septic shock and multi organ failure, starting with acute respiratory distress syndrome followed by acute kidney injury. Inflammatory markers were indicative of cytokine storm. Considering the severity, extracorporeal cytokine adsorption device (CytoSorb) was initiated along with hemodialysis for 8 hours. Results: Post CytoSorb, noradrenaline dose was reduced and eventually terminated. The ventilation support was weaned. Circulatory shock was restored which was evident by the normalization of hemoglobin, platelet counts and leukocyte counts. Procalcitonin dropped considerably from the baseline. Eventually Sequential Organ Failure Assessment (SOFA) score reduced significantly to 1, which, at the time of admission, was 14. Conclusions: Extracorporeal cytokine adsorption device along with standard of care appears a promising approach towards better outcome post snakebite induced multi organ failure.

ABSTRACT Background Melanoma, a highly aggressive skin cancer, is characterized by rapid progression and a high metastatic potential, presenting significant challenges in clinical oncology. A critical aspect of melanoma biology is its metabolic reprogramming, which supports tumor growth, survival, and therapeutic resistance. Objective This review aims to explore the key molecular mechanisms driving metabolic alterations in melanoma and their implications for developing therapeutic strategies. Methods A Pubmed search was conducted to analyze literature discussing key mechanisms of the Warburg effect, mitochondrial dysfunction, enhanced lipid metabolism, epigenetic modifications, and the tumor microenvironment. Results Metabolic reprogramming supports melanoma growth, proliferation, and survival. Understanding these complex metabolic dynamics provides valuable insights for developing targeted therapeutic strategies. Conclusion Potential therapeutic interventions aimed at disrupting melanoma metabolism highlight the promise of precision medicine in improving treatment outcomes in cutaneous oncology. By targeting metabolic vulnerabilities, novel treatment approaches could significantly enhance the clinical management and prognosis of melanoma.

The present article showcases a novel approach for obtaining the approximate solution of the nonlinear Burgers' equation, a frequently occurring equation in the study of wave propagation and dispersion phenomena. The Double Power Series Method, a methodology not conventionally applied to this equation, introduces a unique analytical perspective. The method's versatility in handling two independent variables makes it particularly well-suited for addressing the complexities of the Burgers' equation, providing a comprehensive representation of fluid concentration for arbitrary distances and times. Through this novel approach, we study the intricate dynamics governing the relationship between convection and diffusion forces in longitudinal dispersion. This research not only enriches the theoretical foundation of nonlinear partial differential equations but also holds promise for practical applications across fluid dynamics, environmental engineering, and beyond. Both numerical and graphical solutions are meticulously computed through MATLAB coding, facilitating a robust physical interpretation of the results. This study contributes valuable insights into the behavior of fluids in dispersion scenarios, offering a practical approach to understanding and predicting such phenomena.

Axial spondyloarthritis (axSpA) is a chronic inflammatory disease that is characterized by new bone formation in the axial musculoskeletal system, with X-ray discriminating between radiographic and non-radiographic forms. Current therapeutic options include non-steroidal anti-inflammatory drugs in addition to biological disease-modifying anti-rheumatic drugs that specifically target tumor necrosis factor-alpha (TNFα) or interleukin (IL)-17. Pain is the most critical symptom for axSpA patients, significantly contributing to the burden of disease and impacting daily life. While the inflammatory process exerts a major role in determining pain in the early phases of the disease, the symptom may also result from mechanical and neuromuscular causes that require complex, multi-faceted pharmacologic and non-pharmacologic treatment, especially in the later phases. In clinical practice, pain often persists and does not respond further despite the absence of inflammatory disease activity. Cytokines involved in axSpA pathogenesis interact directly/indirectly with the Janus kinase (JAK)/signal transducer and activator of transcription (STAT) signaling cascade, a fundamental component in the origin and development of spondyloarthropathies. The JAK/STAT pathway also plays an important role in nociception, and new-generation JAK inhibitors have demonstrated rapid pain relief. We provide a comprehensive review of the different pain types observed in axSpA and the potential role of JAK/STAT signaling in this context, with specific focus on data from preclinical studies and data from clinical trials with JAK inhibitors.

Nonsteroidal anti-inflammatory drugs (NSAIDs) are the most commonly used pharmaceuticals in both human and animal medicines for the treatment of certain conditions such as inflammation, fever, and pain. The role of validated analytical methods has become highly important in the quantification of drug substances from their pharmaceuticals as precise product quality control is required. In the present review, we have summarized various sample preparation methods and analytical methods developed for the quantification of NSAIDs during the past decade (2012-till date). Furthermore, an in-depth description of numerous techniques including chromatography (89), UV spectrophotometry (5), spectroflurometry (4), IR spectroscopy (3), electrophoresis (4), and electrochemical (9) approaches used to determine and quantify NSAIDs are provided. Based on the matrix utilized, the following details were discussed: analytical conditions, detection limits, and solvent used in sample preparation. The present compilation provides valuable insights and crucial information on quantification methods for NSAIDs and would assist the scientific community to select the best and economical method for drug analysis in pharmaceuticals and biological samples.

Given the continuous emergence of hepatitis and the associated consequences, developing effective antiviral strategies has become a major public health concern. Current antiviral strategies for the treatment of hepatitis, especially for hepatitis B virus (HBV) and hepatitis C virus (HCV), and those under discovery and development are broadly classified into two categories, i.e., biologics and small molecules. These therapeutic classes include small molecule modulators, peptides, nucleic acid polymers, small interfering RNA (siRNA), antisense oligonucleotides, monoclonal antibodies, and vaccines. To date, several small molecule antiviral agents targeting HBV and HCV have advanced into different phases of clinical investigation for monotherapy and/or combination therapy. In ongoing clinical investigations, researchers are testing small molecule-based antiviral therapies that mainly target complex molecular interactions between virus and host cells involved in viral replication. An up-to-date comprehensive analysis is required to examine the current state of antiviral drug discovery and understand the new trends in antiviral approaches. In the present compilation, we have highlighted the FDA-approved therapies for HBV and HCV with a special focus on the ongoing clinical developments of small molecules for the treatment of hepatitis.

Accurate identification at an early stage of infection is critical for effective care of any infectious disease. The “coronavirus disease 2019 (COVID-19)” outbreak, caused by the virus “Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2)”, corresponds to the current and global pandemic, characterized by several developing variants, many of which are classified as variants of concern (VOCs) by the “World Health Organization (WHO, Geneva, Switzerland)”. The primary diagnosis of infection is made using either the molecular technique of RT-PCR, which detects parts of the viral genome’s RNA, or immunodiagnostic procedures, which identify viral proteins or antibodies generated by the host. As the demand for the RT-PCR test grew fast, several inexperienced producers joined the market with innovative kits, and an increasing number of laboratories joined the diagnostic field, rendering the test results increasingly prone to mistakes. It is difficult to determine how the outcomes of one unnoticed result could influence decisions about patient quarantine and social isolation, particularly when the patients themselves are health care providers. The development of point-of-care testing helps in the rapid in-field diagnosis of the disease, and such testing can also be used as a bedside monitor for mapping the progression of the disease in critical patients. In this review, we have provided the readers with available molecular diagnostic techniques and their pitfalls in detecting emerging VOCs of SARS-CoV-2, and lastly, we have discussed AI-ML- and nanotechnology-based smart diagnostic techniques for SARS-CoV-2 detection.

Background: Most of the data on neuroendocrine tumors (NETs) are from the Western literature. Indian studies regarding clinicopathological characteristics and treatment outcomes are lacking. Methods: This is a prospective observational study of all new patients with NETs (except small-cell lung cancer) registered at our tertiary care cancer institute from November 2014 to November 2016. A total of 97 new patients were registered, of which 20 were lost to follow-up before starting any planned treatment. Epidemiological and clinicopathological features of all these 97 patients were studied, and the remaining 77 patients were analyzed for treatment response and survival analysis. Results: The median age at diagnosis was 49 years (20–74 years) with male preponderance (M: F = 1.85:1). The most common primary site of origin was pancreas (34/97 = 35%), followed by unknown primary origin (19%), small intestine (9%), and pulmonary (6%). Of 97 patients, 91 (93.8%) presented with nonfunctional symptoms, 3 (3.1%) had purely functional symptoms, and 3 (3.1%) presented with both functional and nonfunctional symptoms. The most common presenting symptom was abdominal pain (59.7%), followed by jaundice (9.3%), whereas watery diarrhea (83.3%) and flushing (66.7%) were the most common functional symptoms. Sixty-six percent (64/97) of cases were metastatic at presentation. A strong correlation was noted between the primary site of origin and metastatic presentation (P = 0.016). Chemotherapy was the most common primary therapy (40.2%), followed by surgery (28.6%), watchful waiting (15.6%), and somatostatin analogs (11.7%). The median event-free survival was highest for patients undergoing surgery (10 months). Conclusions: The clinicopathological profile of NETs in the Indian population differs from Western countries. Majority of patients present with metastatic disease, thus representing a need for creating awareness among patients and medical fraternity and formulating Indian guidelines for optimized treatment.

The “severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)” is the third member of human coronavirus (CoV) that is held accountable for the current “coronavirus disease 2019 (COVID-19)” pandemic. In the past two decades, the world has witnessed the emergence of two other similar CoVs, namely SARS-CoV in 2002 and MERS-CoV in 2013. The extent of spread of these earlier versions was relatively low in comparison to SARS-CoV-2. Despite having numerous reports inclined towards the zoonotic origin of the virus, one cannot simply sideline the fact that no animal originated CoV is thus far identified that is considered similar to the initial edition of SARS-CoV-2; however, under-sampling of the diverse variety of coronaviruses remains a concern. Vaccines are proved to be an effective tool for bringing the end to such a devastating pandemic. Many vaccine platforms are explored for the same but in this review paper, we will discuss the potential of replicating viral vectors as vaccine carriers for SARS-CoV-2.

Objective Determine differences between faculty, residents, and nurses regarding night shift preparation, performance, recovery, and perception of emotional and physical health effects. Methods Survey study performed at an urban university medical center emergency department with an accredited residency program in emergency medicine. Results Forty-seven faculty, 37 residents, and 90 nurses completed the survey. There was no difference in use of physical sleep aids between groups, except nurses utilized blackout curtains more (69%) than residents (60%) and faculty (45%). Bedroom temperature preference was similar. The routine use of pharmacologic sleep aids differed: nurses and residents (both 38%) compared to faculty (13%). Residents routinely used melatonin more (79%) than did faculty (33%) and nurses (38%). Faculty preferred not to eat (45%), whereas residents (24%) preferred a full meal. The majority (>72%) in all groups drank coffee before their night shift and reported feeling tired despite their routine, with 4:00 a.m. as median nadir. Faculty reported a higher rate (41%) of falling asleep while driving compared to residents (14%) and nurses (32%), but the accident rate (3% to 6%) did not differ significantly. All had similar opinions regarding night shift-associated health effects. However, faculty reported lower level of satisfaction working night shifts, whereas nurses agreed less than the other groups regarding increased risk of drug and alcohol dependence. Conclusion Faculty, residents, and nurses shared many characteristics. Faculty tended to not use pharmacologic sleep aids, not eat before their shift, fall asleep at a higher rate while driving home, and enjoy night shift work less.

Background. Screening for unhealthy alcohol and drug use in the emergency department (ED) can be challenging due to crowding, lack of privacy, and overburdened staff. The objectives of this study were to determine the feasibility and utility of a brief tablet-based screening method in the ED and if patients would consider a face-to-face meeting with a certified alcohol and drug counselor (CADC) for more in-depth screening, brief intervention, and referral to treatment (SBIRT) helpful via this interface. Methods. A tablet-based questionnaire was offered to 500 patients. Inclusion criteria were age ≥18, Emergency Severity Index 2–5, and English comprehension. Subjects were excluded if they had evidence of acute intoxication and/or received sedating medication. Results. A total of 283 (57%) subjects were enrolled over a 4-week period, which represented an increase of 183% over the monthly average of patients referred for SBIRT by the CADC prior to the study. There were 131 (46%) who screened positive for unhealthy alcohol and drug use, with 51 (39%) and 37 (28%) who screened positive for solely unhealthy alcohol use and drug use/drug use disorders, respectively. There were 43 (33%) who screened positive for combined unhealthy alcohol and drug use. Despite willingness to participate in the tablet-based questionnaire, only 20 (15%) with a positive screen indicated via the tablet that a face-to-face meeting with the CADC for further SBIRT would be helpful. Conclusion. Brief tablet-based screening for unhealthy alcohol and drug use in the ED was an effective method to increase the number of adult patients identified than solely by their treating clinicians. However, only a minority of subjects screening positive using this interface believed a face-to-face meeting with the CADC for further SBIRT would be helpful.

The improving cure rate of childhood acute lymphoblastic leukemia (cALL) is considered as success story in the field of oncology. It has become possible due to progressive refinement of treatment over the period of years. Assessment of minimal residual disease (MRD) is one such tool to further refine and personalize treatment of cALL. Assessment of MRD is no longer a research tool; it has become an integral part of comprehensive management of cALL. Prognostic importance of MRD in cALL is well accepted, but translation of this new information in improving therapy has just begun especially in developing countries like ours. There is increasing understanding among clinicians regarding importance of MRD assessment in day to day clinical practice. Still, there are many issues and lack of clarity with respect to MRD assessment. We are making an attempt in this review to address such issues faced during practical implication of MRD assessment.

Background and Aim: Percutaneous nephrolithotomy (PCNL) is a common for managing renal calculi. Pain in the initial post operatie period is relieved by infiltration of local anaesthetic around the nephrostomy tract.We aimed to compare the analgesic efficacy of bupivacaine and ropivacaine. Methods: A total of 100 adult patients undergoing elective PCNL- under balanced general anaesthesia were randomly divided into bupivacaine group (Group B) and ropivacaine group (Group R). After completion of procedure, 23G spinal needle was inserted at 6 and 12 O′clock position under ultrasonic guidance up to renal capsule along the nephrostomy tube. A volume of 10 ml of either 0.25% bupivacaine or 0.25% ropivacaine solution was infiltrated in each tract while withdrawing the needle. Post-operative pain was assessed using visual analogue scale (VAS) and dynamic visual analogue scale (D-VAS) for initial 24 h. Intravenous tramadol was given as rescue analgesia when VAS >4. Time to first rescue analgesic, number of doses and total amount of tramadol required in initial 24 h and side-effects were noted. Results: Visual analogue scale and D-VAS at 6 h and 8 h in Group B was significantly higher than Group R. Mean time to first rescue analgesia in Group R was significantly longer than Group B. Mean number of doses of tramadol and total consumption of tramadol in 24 h was less in Group R, though not statistically significant. Conclusion: Peritubal infiltration of 0.25% ropivacaine infiltration along the nephrostomy tract is more effective than 0.25% bupivacaine in alleviating initial post-operative pain after PCNL.

In a developing country such as India, deceased donor renal transplantation (DDRTx) accounts for only about 1% of all renal transplants (RTx). Our institute initiated an intercity DDRTx in the year 2006, which significantly increased the number of RTx. We retrieved 74 kidneys from 37 deceased donors from various cities of Gujarat from January 2006 to December 2009. We transplanted the allografts in 66 recipients and a retrospective analysis of the donor profile and management and recipient outcome was performed. The mean age of the donors was 43.3 ± 18.8 years. The causes of death included road traffic accident in 51.35% of the donors and cerebrovascular stroke in 48.65% of the donors; 83.78% of the donors required ionotropes for hemodynamic stability in addition to vigorous intravenous fluid replacement. The average urine output of the donors was 350 ± 150 mL. The organs were perfused and stored in HTK solution. The mean cold ischemia time (CIT) was 9.12 ± 5.25 h. The mean anastomosis time in the recipient was 30.8 ± 8.7 min. 57.6% of the recipients established urine output on the operating table and 42.4% developed delayed graft function. At the end of 1 month after transplantation, the mean serum creatinine was comparable to the Ahmadabad city DDRTx, although the CIT was significantly longer in the intercity patients. Intercity organ harvesting is a viable option to increase the donor pool. Distance may not be an impediment, and good recipient outcome is possible in spite of prolonged CIT in case of proper harvesting and preservation.