A New Silicon Mold Process for Polydimethylsiloxane Microchannels.

As an alternative to SU-8 soft lithography, a new silicon mold process of fabricating PDMS microchannel chips was proposed. A picosecond laser is used to cut through a 550 µm thick silicon wafer and generate the original microchannel pattern with a 50 µm minimum feature size. This single-crystal silicon pattern, with the edge debris caused by laser cutting being trimmed off by a KOH solution and with the protection field oxide layer being removed by BOE afterwards, firmly resided on a glass substrate through the anodic bonding technique. Four-inch wafers with microchannel patterns as the PDMS mold cores were successfully bonded on Pyrex 7740 or Eagle XG glass substrates for the follow-up PDMS molding/demolding process. This new maskless process does not need a photolithography facility, but the laser cutting service must be provided by professional off-campus companies. One PDMS microchannel chip for particle separation was shown as an example of what can be achieved when using this new process.

Antibiotics With or Without Rifaximin for Acute Hepatic Encephalopathy in Critically Ill Patients With Cirrhosis: A Double-Blind, Randomized Controlled (ARiE) Trial.

INTRODUCTION: Critically ill patients with cirrhosis admitted to the intensive care unit (ICU) are usually on broad-spectrum antibiotics because of suspected infection or as a hospital protocol. It is unclear if additional rifaximin has any synergistic effect with broad-spectrum antibiotics in ICU patients with acute overt hepatic encephalopathy (HE). METHODS: In this double-blind trial, patients with overt HE admitted to ICU were randomized to receive antibiotics (ab) alone or antibiotics with rifaximin (ab + r). Resolution (or 2 grade reduction) of HE, time to resolution of HE, in-hospital mortality, nosocomial infection, and changes in endotoxin levels were compared between the 2 groups. A subgroup analysis of patients with decompensated cirrhosis and acute-on-chronic liver failure was performed. RESULTS: Baseline characteristics and severity scores were similar among both groups (92 in each group). Carbapenems and cephalosporin with beta-lactamase inhibitors were the most commonly used ab. On Kaplan-Meier analysis, 44.6% (41/92; 95% confidence interval [CI], 32-70.5) in ab-only arm and 46.7% (43/92; 95% CI, 33.8-63) in ab + r arm achieved the primary objective ( P = 0.84).Time to achieve the primary objective (3.65 ± 1.82 days and 4.11 ± 2.01 days; P = 0.27) and in-hospital mortality were similar among both groups (62% vs 50%; P = 0.13). Seven percent and 13% in the ab and ab + r groups developed nosocomial infections ( P = 0.21). Endotoxin levels were unaffected by rifaximin. Rifaximin led to lower in-hospital mortality (hazard ratio: 0.39 [95% CI, 0.2-0.76]) in patients with decompensated cirrhosis but not in patients with acute-on-chronic liver failure (hazard ratio: 0.99 [95% CI, 0.6-1.63]) because of reduced nosocomial infections. DISCUSSION: Reversal of overt HE in those on ab was comparable with those on ab + r.

Pancreatic tuberculosis mimicking as pancreatic malignancy: Surgeon's dilemma.

Pancreatic tuberculosis is a rare form of Tuberculosis (TB) which requires a high index of suspicion to diagnose. Here, we report a case of middle-aged gentleman presenting with abdominal pain and constitutional symptoms who was diagnosed with pancreatic tuberculosis on imaging, which was confirmed by Fine Needle Aspiration (FNA) from the lesion. The patient was given Anti-Tubercular Treatment (ATT) as per conventional protocol. Follow-up showed recovery from the entity. A review of patient presentation, patho-physiology, diagnosis, and management of pancreatic tuberculosis is mentioned in this article.

Safety and Efficacy of Atezolizumab-Bevacizumab in Real World: The First Indian Experience.

Background: Atezolizumab-bevacizumab (atezo/bev) combination is a recommended first-line systemic therapy for unresectable hepatocellular carcinoma (uHCC). There are no studies from India reporting the safety and efficacy of this drug in real-world settings where most patients present in an advanced stage. Methods: In this retrospective study from two centers in India, we included patients with uHCC who received atezo/bev as first-line systemic therapy. Comparison of overall survival (OS) among the different Child-Turcotte-Pugh (CTP) classes was the primary objective, while progression-free survival (PFS), radiologic response, and adverse events to the therapy were secondary objectives. Results: The median age of the 67 patients who received atezo/bev therapy was 61 (29-82) years, and 86% were males. Nonalcoholic steatohepatitis (55.2%) was the commonest cause of cirrhosis, and most patients belonged to BCLC-C (74.6%%). There were 24 patients in CTP A, 36 in CTP B, and 7 in CTP C. The median OS was 12 (95%CI, 8.16-15.83) months in the cohort. The median OS in CTP class A, B, and C was 21 (95%CI, 0-42.06) months, 9 (95%CI, 5.46-12.53) months, and 4 (95%CI, 2.14-5.85) months, respectively (P < 0.001). The median PFS in the whole cohort was 8 (95%CI, 6.03-9.96) months. The median PFS in Child A, B, and C was 18 (95%CI, 0.16-35.84) months, 8 (95%CI, 6.14-9.85) months, and 2 (95%CI, 1.77-2.23) months (P < 0.001). On mRECIST evaluation, 12.9% had achieved a complete response, 25.8% had a partial response, 27.41% had stable disease, and the rest had progressed. The objective response rate was 38.7%, and the disease control rate was 66.12%. Of the 64% who developed adverse events, 13.43% discontinued the drug. The incidence of grade ≥3 events was significantly higher in CTP C (85.7%) compared to CTP A (12.5%) and CTP B (14%) (P < 0.001). Conclusions: Atezolizumab-bevacizumab is safe and effective in uHCC in real-world settings. Candidate selection is of utmost importance in treating uHCC with atezolizumab-bevacizumab to achieve a good response. Current evidence strongly suggests limited use of atezolizumab-bevacizumab in patients with CTP C, and such individuals should not be considered for this combination therapy.

The Pattern of Alcohol Use in Alcohol-Related Cirrhosis in Indian Patients: AUDIT Indian Liver Study.

Background: Alcohol is one of the most common causes of liver cirrhosis. Yet, the pattern of alcohol consumption in cirrhosis is rarely studied. This study aims to study the drinking patterns along with the educational, socioeconomic, and mental health in a cohort of patients with and without liver cirrhosis. Methods: This prospective observational study was conducted at a tertiary-care hospital and included patients with harmful drinking. Demographic, alcohol intake history, assessment of socioeconomic and psychological status by modified Kuppuswamy scale and Beckwith Inventory, respectively, were recorded and analyzed. Results: Cirrhosis was present in 38.31% of patients with heavy drinking (64%). Cirrhosis was more among illiterates (51.76%) with early onset (22.4. ± 7.30 yrs P = 0.0001) and longer duration of alcohol (12.5 ± 6.5 vs. 6.8 ± 3.4 P = 0.001). Higher education qualification was associated with lower cirrhosis (P < 0.0001). With the same employment and education qualifications, net income in cirrhosis was lower [USD 298 (175-435) vs. USD 386 (119-739) P = 0.0001]. Whiskey (86.8%) was the commonest drink consumed. Similar median alcoholic drinks per week were consumed by both groups [34 (22-41) vs. 30 (24-40), P = 0.625], while indigenous alcohol was more consumed in cirrhosis [105 (98.5-109.75) vs. 89.5.0 (69.25-110.0) P = 0.0001]. Loss of jobs (12.36%) and partner violence were more in cirrhotic (9.89% vs. 5.80%) with similar borderline depression. Conclusion: Alcohol use disorder-related cirrhosis is present in a quarter of patients with harmful early onset and longer duration of drinking and is inversely related to the education status and affects the socioeconomic, physical, and family health of patients.

Early living donor liver transplantation for alcohol-associated hepatitis.

INTRODUCTION AND OBJECTIVES: Lately, there has been a steady increase in early liver transplantation for alcohol-associated hepatitis (AAH). Although several studies have reported favorable outcomes with cadaveric early liver transplantation, the experiences with early living donor liver transplantation (eLDLT) are limited. The primary objective was to assess one-year survival in patients with AAH who underwent eLDLT. The secondary objectives were to describe the donor characteristics, assess the complications following eLDLT, and the rate of alcohol relapse. MATERIALS AND METHODS: This single-center retrospective study was conducted at AIG Hospitals, Hyderabad, India, between April 1, 2020, and December 31, 2021. RESULTS: Twenty-five patients underwent eLDLT. The mean time from abstinence to eLDLT was 92.4 ± 42.94 days. The mean model for end-stage liver disease and discriminant function score at eLDLT were 28.16 ± 2.89 and 104 ± 34.56, respectively. The mean graft-to-recipient weight ratio was 0.85 ± 0.12. Survival was 72% (95%CI, 50.61-88) after a median follow-up of 551 (23-932) days post-LT. Of the 18 women donors,11 were the wives of the recipient. Six of the nine infected recipients died: three of fungal sepsis, two of bacterial sepsis, and one of COVID-19. One patient developed hepatic artery thrombosis and died of early graft dysfunction. Twenty percent had alcohol relapse. CONCLUSIONS: eLDLT is a reasonable treatment option for patients with AAH, with a survival of 72% in our experience. Infections early on post-LT accounted for mortality, and thus a high index of suspicion of infections and vigorous surveillance, in a condition prone to infections, are needed to improve outcomes.

Poor immune response to coronavirus disease vaccines in decompensated cirrhosis patients and liver transplant recipients.

BACKGROUND AND AIMS: Recent studies have reported poor humoral immune response to mRNA vaccines in patients with chronic liver disease (CLD). However, the immunogenicity of ChAdOx1 (vector-based) and BBV152 (inactivated virus) vaccines in patients with CLD and liver transplant recipients (LTRs) is unknown. Therefore, we aimed to assess the immunogenicity of ChAdOx1 and BBV152 vaccines in patients with CLD (including cirrhosis patients) and LTRs. METHODS: In this single-center prospective study, consecutive completely vaccinated (ChAdOx1 or BBV152) non-cirrhosis CLD patients, those with cirrhosis, and LTRs were compared with matched healthy controls for anti-spike antibody and cellular response. RESULTS: Sixty healthy individuals, 50 NCCLD patients, 63 compensated and 50 decompensated cirrhosis, and 17 LTRs were included. The proportion of non-responders was similar among the healthy control (8 %), non-cirrhosis CLD (16 %), and compensated cirrhosis groups (17.5 %;p = 0.3). However, a higher proportion of patients with decompensated cirrhosis (34 %) and LTRs (59 %) were non-responders than the healthy controls (p = 0.001). Cluster of differentiation (CD) 4-effector cells were lower in patients with non-cirrhosis CLD and compensated cirrhosis. CD4-naïve, CD4-effector, B, and B-memory cells were lower in the decompensated cirrhosis group. Although the central memory cells were higher in the decompensated cirrhosis group, they could not differentiate into effector cells. CD4- and CD8-naïve cells were higher in the marrow in the LTRs, while the CD4-effector memory cells and CD4- and CD8-effector cells were lower in the LTRs. Furthermore, B cells were more deficient in the LTRs, suggesting poor antibody response. CONCLUSION: Patients with decompensated cirrhosis and LTRs demonstrated suboptimal humoral and cellular immune responses against recombinant and inactivated COVID-19 vaccines.

Artificial intelligence: A new tool in surgeon's hand.

Artificial intelligence (AI) is the future of surgery. Technological advancements are taking place at an incredible pace, largely due to AI or AI-backed systems. It is likely that there will be a massive explosion or "Cambrian explosion" of AI in our everyday life, largely aided by increased funding and resources spent on research and development. AI has also significantly revolutionized the medical field. The concept of machine learning and deep learning in AI is the crux of its success. In surgical practice, AI has numerous applications in the diagnosis of disease, preoperative planning, intraoperative assistance, surgical training and assessment, and robotics. The potential automation of surgery is also a possibility in the next few decades. However, at present, augmentation rather than automation should be the priority. In spite of the allure of AI, it comes with its own price. A robot lacks the "sixth sense" or intuition that is crucial in the practice of surgery and medicine. Empathy and human touch are also inimitable characteristics that cannot be replaced by an AI system. Other limitations include the financial burden and the feasibility of using such technology on a wide scale. Ethical and legal dilemmas such as those involving privacy laws are other issues that should be taken under consideration. Despite all these limitations, with the way technology is progressing, it is inevitable that AI and automation will completely change the way we practice surgery in the near future. Thus, this narrative review article aims to highlight the various applications and pitfalls of AI in the field of surgery.

Stentolith in Bile Duct: A Neglected Entity-Case Report with Review of Literature.

Stentolith is a forgotten stent that acts as a nidus for stone formation leading to a stone-stent complex. Once the planned procedure is completed, these stents should be removed within 4 to 6 weeks, but if they are required for a longer period, then they should be replaced every 3 to 6 months. Devastating complications may ensue -such as cholangitis, biliary stricture, or secondary biliary cirrhosis. Management primarily comprises surgical intervention with common bile duct exploration or endoscopic clearance. The majority of patients eventually develop symptoms that lead to their diagnosis and subsequent management. This article, however, details the case of a silent stentolith and how it may have led to disastrous complications if surgical intervention was not done promptly.