Search

Management of masks disposal in the COVID-19 era is a highly ignored segment in public health management and clinical care, which might be due to the unexpected emergence of pandemic and unpreparedness of the system. Meanwhile with over time newer information has evolved, now authorities should focus on adequate management of the masks wastes, especially at community levels. Some of the hurdles and suggestions are discussed here in this article.

BACKGROUND AND AIMS: Noninvasive tools (NITs) reliably categorise patients with compensated advanced chronic liver disease (cACLD) into high-risk and low-risk group for harbouring varices needing treatment. Here, we assess the ability of these NITs to predict the need for nonselective beta-blockers at baseline based on risk of variceal bleeding (VB) on follow-up. METHODS: This was a retrospective multicentre analysis of patients with cACLD categorised at baseline into different risk groups by NITs (Baveno-VI, expanded Baveno-VI, platelet-albumin, platelet-model for end-stage liver disease (MELD) and anticipate study platelet criteria) and by endoscopy (high risk vs low risk/no varices). VB event rates on follow-up were estimated in different risk strata. Decision curve analysis (DCA) was used to estimate the benefit of administering nonselective beta-blockers (NSBB) using NITs over endoscopic classification at different threshold probabilities of VB event rates and estimating the number needed to treat (NNT) to identify one additional bleeder over endoscopy. RESULTS: A total of 1284 patients (mean age: 44.7 ± 13.5 years, 72.4% males) of hepatitis B (29.2%), nonalcoholic fatty liver disease (24.9%), hepatitis C (20.1%), and alcohol (17.5%)-related cACLD were included with 323 (25.2%) having high-risk varices. Ninety-eight (7.6%) patients developed VB over a median follow-up of 20 (9–35) months. The 1-year and 3-year rate of VB with all NITs was 5.7–7.4% and 13.2–16.4% among high-risk and 0–2.3% and 0–5% among low-risk subgroups, respectively (P

End-stage liver disease is characterized by massive hepatocyte death resulting in clinical decompensation and organ failures. Clinical consequences in cirrhosis are the results of the loss of functional hepatocytes and excessive scarring. The only curative therapy in advanced cirrhosis is orthotropic liver transplantation, but the clinical demand outweighs the availability of acceptable donor organs. Moreover, this also necessitates lifelong immunosuppression and carries associated risks. The liver has a huge capability for regeneration. Self-replication of quiescent differentiated hepatocytes and cholangiocytes occurs in patients with acute liver injury. Due to limited hepatocyte self-renewal capacity in advanced cirrhosis, great interest has therefore been shown in characterizing the possible role of hepatic progenitor cells and bone marrow-derived stem cells to therapeutically aid this process. Transplantation of cells from various sources that can be properly differentiated into functional liver cells or use of growth factors for ex-vivo expansion of progenitor cells is needed at utmost priority. Multiple researches over the last two decades have aided researchers in refining proliferation, differentiation, and storage techniques and understand the functionality of these cells for use in clinical practice. However, these cell-based therapies are still experimental and have to be used in trial settings.

Sleromyxedema is a rare disease characterised by extensive mucin deposition with fibrosis in dermis. It is often associated with monoclonal gammopathy. Its true prevalence and/or cause is unknown due to its rarity. Various extra-cutaneous manifestations can be associated with sleromyxedema such as dermoneuro syndrome, neuropathy, rheumatological problems or various malignancies. This case report showed that a patient with sleromyxedema and neuropathy had positive outcomes when treated with intravenous immunoglobulin (IVIg) and steroids pulses. The underlying cause of the patient’s condition was unknown.

Patients with cirrhosis have high prevalence of erectile dysfunction (ED). The aim of this study was to study the efficacy and safety of tadalafil for ED in patients with cirrhosis.140 cirrhotic males with ED were randomized into tadalafil 10 mg daily (n = 70) or placebo (n = 70) for 12 weeks. ED was diagnosed if erectile function (EF) domain score was 25 in International Index of Erectile Function (IIEF) questionnaire. The erectile function domain consists of six questions concerning erection frequency, erection firmness, frequency of partner penetration, frequency of maintaining erection after penetration, ability to maintain erection to completion of intercourse and confidence in achieving and maintaining erection. Primary outcome was proportion of patients having an increase in 5 points in EF domain of the IIEF. Generalized Anxiety Disorder 7 (GAD-7) questionnaire was used for screening and severity measuring of GAD. The presence of depression was screened using the Patient Health Questionnaire (PHQ-9) and the assessment of health related quality of life was done using the Short Form (36) Health Survey.At the end of 12 weeks, more patients in tadalafil group achieved 5 points increase in the EF domain of the IIEF when compared with the placebo group [44(62.9%) vs. 21(30%), p 0.001]. At the end of 12 weeks, patients receiving tadalafil had significantly more change in scores on the erectile function domain, orgasmic function domain, intercourse satisfaction domain, overall satisfaction domain, erection vaginal penetration rates and successful intercourse; significantly more decline in the GAD-7 and PHQ-9 scores; significantly more improvement in scores of five of the eight domains of SF-36 (general health perception, vitality score, social functioning, role emotional and mental health) and the mental component summary rates when compared with placebo. The development of side effects and the changes in HVPG were not significantly different between the two groups.Tadalafil therapy may enhance erectile function, improve anxiety, depression and quality of life; and is well tolerated by men with cirrhosis (CTP score 10) and ED. However, further larger and long-term studies are needed to confirm these results and look for rarer side effects of using tadalafil in patients with cirrhosis.ClinicalTrials.gov identifier number NCT03566914; first posted date: June 25, 2018.

Spontaneous-portosystemic-shunts (SPSS) in cirrhosis deprive the liver of nutrient-rich portal blood and contribute to recurrent hepatic encephalopathy (HE). We evaluated the effects of shunt occlusion and redirecting portal blood to liver on its volume and functions.Cirrhosis patients presenting with recurrent HE and having SPSS were randomized to receive standard medical treatment (SMT) or shunt occlusion (SO). The later was performed by plug-assisted or balloon-occluded retrograde transvenous obliteration. The primary endpoint was change in liver volume after a minimum follow-up of 3 months. Secondary objectives included clinical course, liver disease severity indices, arterial ammonia levels and bone density.Of 40 enrolled patients, 4 in SMT and 2 in SO group were lost to follow-up. The SO was complete in 17 and partial in one, achieving non-recurrence of HE in 17 (94.4%). In these patients, the mean liver volume increased (baseline 1040 ± 335 ml to 1132 ± 322 ml, 8.8% increase, p 0.001) and was observed in 16/18 (88.89%) patients. In the SMT group, the liver volume decreased (baseline 988 ± 270 ml to 904 ± 226 ml, 8.6% reduction, p = 0.009) during the same period. Serum albumin increased in SO group (2.92 ± 0.40 g/dl to 3.30 ± 0.49 g/dl, p = 0.006) but reduced in SMT group (2.89 ± 0.43 g/dl to 2.59 ± 0.65 g/dl, p = 0.047). After SO, the patients showed a reduction in serum-ammonia levels (181.06 ± 86.21 to 107.28 ± 44.53 μ/dl, p = 0.001) and an improvement in MELD-Na and bone density compared to SMT group. There were no major adverse events following shunt occlusion.Occlusion of large SPSS results in improving the volume and synthetic functions of the liver by restoring hepato-petal portal flow besides reducing serum-ammonia level and recurrence of HE.gov number, NCT03293459.

Sexual dysfunction (SD) is a prevalent but very commonly ignored aspect in the treatment of liver diseases and cirrhosis. The etiology of SD is multifactorial and therefore treatment strategies are complex, especially in females. Phosphodiesterase inhibitors are useful and effective in erectile dysfunction in males but in females, no single drug is available for SD, therefore multimodal treatment is required depending upon the cause. The foremost and fundamental requirement in both genders is to be stress-free and have adequate control of liver diseases. Improved quality of life is helpful in improving SD and vice versa is also true. Therefore, patients suffering from liver diseases should come forward and ask for treatment for SD, and physicians should actively enquire about SD while history taking and evaluating these patients. SD results in deterioration of quality of life, and both are modifiable and treatable aspects of liver diseases, which are never addressed actively, due to social taboos and fears of SD treatment in the presence of liver diseases. The diagnosis of SD does not require costly investigations, as the diagnosis can be established based on validated questionnaires available for both genders, therefore detailed targeted history taking using questionnaires is essential. Data are emerging in this area but is still at an early stage. More studies should be dedicated to SD in liver diseases.

Despite being one of the common diseases, the treatment options for nonalcoholic steatohepatitis (NASH) are still limited. Recently, Gawrieh et al. demonstrated significant improvement in liver enzymes and liver fat content (LFC) in nonalcoholic fatty liver disease (NAFLD)/NASH patients treated with saroglitazar (1). It's indeed an interesting attempt to exploit new avenues for treating NAFLD by using a dual PPAR-α/γ agonist, currently used in India for diabetic dyslipidemia (2). However, there are a few concerns in the current trial that require attention.

Human serum albumin is the most abundant plasma protein, and it regulates diverse body functions. In patients with advanced and decompensated cirrhosis, serum albumin levels are low because of a reduction in the hepatocyte mass due to disease per se and multiple therapeutic interventions. Because of their oncotic and nononcotic properties, administration of human albumin solutions (HAS) have been found to be beneficial in patients undergoing large-volume paracentesis or who have hepatorenal syndrome or spontaneous bacterial peritonitis. Albumin also improves the functionality of the immune cells and mitigates the severity and risk of infections in advanced cirrhosis. Its long-term administration can modify the course of decompensated cirrhosis patients by reducing the onset of new complications, improving the quality of life, and probably providing survival benefits. There is, however, a need to rationalize the dose, duration, and frequency of albumin therapy in different liver diseases and stages of cirrhosis. In patients with acute-on-chronic liver failure, potentially toxic oxidized isoforms of albumin increase substantially, especially human nonmercaptalbumin and 2, and nitrosoalbumin. The role of administration of HAS in such patients is unclear. Determining whether removal of the pathological and dysfunctional albumin forms in these patients by "albumin dialysis" is helpful, requires additional studies. Use of albumin is not without adverse events. These mainly include allergic and transfusion reactions, volume overload, antibody formation and coagulation derangements. Considering their cost, limited availability, need for a health care setting for their administration, and potential adverse effects, judicious use of HAS in liver diseases is advocated. There is a need for new albumin molecules and economic alternatives in hepatologic practice.

Massive cellular necrosis in acute liver failure (ALF) is dominantly immune mediated and innate immune cells are major pathophysiological determinants in liver damage. In fifty ALF and fifteen healthy, immune cells phenotyping by flow-cytometry, DAMPs using ELISA were analysed and correlated with clinical and biochemical parameters. ALF patients (aged 27 ± 9 yr, 56% males, 78% viral aetiology) showed no difference in neutrophils and classical monocytes, but significantly increased intermediate monocytes (CD14+CD16+) (p In conclusion, Combination of NK cell frequency among lymphocytes and lactate levels at admission can reliably predict survival of ALF patients.

Background and AimsMassive cellular necrosis in ALF is dominantly immune mediated and innate immune cells are major pathophysiological determinants in liver damage. Our aim was to investigate specific innate immune cells or damage associated molecular patterns (DAMPs) relating to the final outcome of patient.MethodsIn fifty ALF patients and in fifteen age-matched healthy controls (HC), DAMPs were measured in plasma using ELISA. Phenotypic analysis of neutrophils, monocytes, natural killer (NK) and NKT cells was done by flow-cytometry and correlated with clinical and biochemical parameters.ResultsALF patients (aged 27±9 yr, 56% males, 78% viral etiology) had MELD of 31.5±8, jaundice to hepatic encephalopathy (HE) of 4.6±3.2 days, HE grade III-IV, 82% with cerebral edema, 38% met KCH criteria, 56% had suspected sepsis. Percentage of intermediate monocytes (CD14+CD16+) was increased (p-CD16+) was decreased in ALF compared to HC. CD16+CD56+ NK cells in total lymphocytes was significantly lower in ALF patients compared to HC, but was higher in survivors {9.28% (0.5-20.3)} than non-survivors {5.1% (0.2-10.6)} (p6.7%) at admission was a good predictor of survival. Non-survivors had higher levels of serum lactate (6.1 vs. 28, Odds ratio 2.23, CI 1.27-3.94) and granzymeB positive NK cells than survivors. Logistic regression model predicted the combination of lactate levels with NK cell percentage at admission for survival (AUROC of 0.94; sensitivity 95.8%, specificity of 78.5%).ConclusionCombination of NK cell frequency and lactate levels at admission can reliably predict survival of ALF patients.KEY POINTSALF is generally immune mediated and predominantly caused by viral infections or acetaminophen toxicity.Therapeutic options are limited in ALF, important to know key immune players for their survival.CD16+CD56+ NK cells were found to be higher in survivors than non survivors.Combination of lactate levels with NK cell percentage at the time of admission can reliably predict the survival of ALF patients.

Background High volume plasma-exchange (HVPE) improves survival in patients with acute liver failure (ALF), but apprehension regarding volume overload and worsening of cerebral edema remain. Methods In an open-label randomized controlled trial, 40 consecutive patients of ALF were randomized 1:1 to either standard medical treatment (SMT) or SMT with standard-volume plasma-exchange (SVPE). SVPE was performed using centrifugal apheresis [target volume of 1.5 to 2.0 plasma volumes per session] until desired response was achieved. Cerebral edema was assessed by brain imaging. Results were analyzed in an intention-to-treat analysis. Primary outcome was 21-day transplant-free survival. The levels of cytokines, damage-associated molecular patterns (DAMPs) and endotoxins were analyzed at baseline and day 5. Results ALF patients [aged 31.5 ± 12.2 years, 60% male, 78% viral, 83% hyperacute, 70% with SIRS were included. At day 5, SVPE [mean sessions 2.15 ± 1.42, median plasma volume replaced 5.049 L] compared to SMT alone, resulted in higher lactate clearance (p = .02), amelioration of SIRS (84% vs. 26%; P = .02), reduction in ammonia levels [(221.5 ± 96.9) vs.(439 ± 385.6) μg/dl, P = .02) and SOFA scores [9.9(±3.3) vs. 14.6(±4.8); P = .001]. There were no treatment related deaths. SVPE was associated with a higher 21-day transplant free-survival [75% vs. 45%; P = .04, HR 0.30, 95%CI 0.01-0.88]. A significant decrease in levels of pro-inflammatory cytokines and an increase in anti-inflammatory cytokines along with a decrease in endotoxin and DAMPs was seen with SVPE. Conclusion In ALF patients with cerebral edema, SVPE is safe and effective and improves survival possibly by a reduction in cytokine storm and ammonia. ClinicalTrial.gov (identifier: NCT02718079 )

Pachydermoperiostosis is a rare genetic disorder which commonly presents with clubbing, bone pains and skin changes. The treatment is mostly unsatisfactory. We tried bisphosphonates in our case with encouraging results. We suggest that parenteral bisphosphonates should be tried early in treatment of Pachydermoperiostosis.

Thrombocytopenia in acute febrile illness is an alarming finding and most commonly seen in malaria and dengue patients. In the present study we evaluated and followed up 200 patient of acute febrile illness with thrombocytopenia for ten days, for changes in both clinical, biochemical and haematological parameters. Majority of cases in present study were of dengue(45%) followed by malaria (22%), septicaemia(15%) enteric fever(4%) etc. The patients of dengue presented earlier (4.11± 1.42) around 4 th day as compared to other groups. The skin rash, bleeding tendency, tourniquet test positivity and respiratory abnormalities were seen in dengue patients(p

A 22-year-old man presented with symmetric polyarthritis, pruritus and deviation of angle of mouth to the right side since the last 7 years. His symptoms were persistent despite receiving ayurvedic medications and symptomatic therapy. Examination revealed dry skin, cutaneous nodules, xanthelasma, periarticular non-tender swellings, pitting oedema of hands and feet and lower motor neuron type right facial palsy. Haematological investigations revealed eosinophilia and skin biopsy had cutaneous eosinophilic infiltration. The constellation of above findings comprises the nodules, eosinophilia, rheumatism, dermatitis and swelling syndrome. It a rare syndrome with few reported cases in literature. The patient was started on oral corticosteroids which was subsequently tapered and methotrexate therapy. His polyarthritis and skin rashes resolved with therapy. He has been followed-up for 2 years and is presently asymptomatic for the last 1 year.