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  1. Shrestha A, Marla V, Lamsal M, Sarraf DP, Rao N
    Kathmandu Univ Med J (KUMJ), 2021 11 26;19(74):210-215.
    PMID: 34819438
    Background Tobacco consumption is a leading cause of premature death in the world. Tobaccorelated deaths are associated with cardiovascular diseases, pulmonary diseases, oral potentially malignant disorders, cancer, others. Moreover there is also associated nicotine dependence which might result to numerous tobacco-associated diseases. Objective This study was conducted to analyze the degree of nicotine dependence considering its potential health risk, in the Eastern region of Nepal. Method A descriptive questionnaire based study was conducted among current tobacco users of six districts of Eastern Nepal. Fagerstrom Test for Nicotine Dependence (FTND) and Fagerstrom Test for Nicotine Dependency for Smokeless Tobacco (FTNDST) questionnaire were used for tobacco smokers and chewers, respectively. Result Of the total participants, 836 were males and 359 females, among whom 736 were active tobacco smokers and 432 chewers, 34.8% had tried to stop consuming tobacco and 306 (25.6%) had oral lesions in white or red forms. Very low nicotine dependence was found among 244 (31.47%) tobacco smokers and 37 (8.56%) chewers whereas 36 (4.71%) smokers and 103 (23.84%) chewers had very high nicotine dependence. The mean score for FTND was 3.73±2.37 and 5.74±2.12 for FTND-ST. A significant difference in duration and age group with FTND score was observed, however not with FTND-ST. Conclusion The information regarding degree of nicotine dependence can be used as baseline information for planning of preventive strategies and implementation of tobacco cessation and control programs.
  2. Nagraj SK, Naresh S, Srinivas K, Renjith George P, Shrestha A, Levenson D, et al.
    PMID: 25425011 DOI: 10.1002/14651858.CD010470.pub2
    BACKGROUND: The sense of taste is very much essential to the overall health of the individual. It is a necessary component to enjoying one's food, which in turn provides nutrition to an individual. Any disturbance in taste perception can hamper the quality of life in such patients by influencing their appetite, body weight and psychological well-being. Taste disorders have been treated using different modalities of treatment and there is no consensus for the best intervention. Hence this Cochrane systematic review was undertaken.

    OBJECTIVES: To assess the effects of interventions for the management of patients with taste disturbances.

    SEARCH METHODS: We searched the Cochrane Oral Health Group Trials Register (to 5 March 2014), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 1, 2014), MEDLINE via OVID (1948 to 5 March 2014), EMBASE via OVID (1980 to 5 March 2014), CINAHL via EBSCO (1980 to 5 March 2014) and AMED via OVID (1985 to 5 March 2014). We also searched the relevant clinical trial registries and conference proceedings from the International Association of Dental Research/American Association of Dental Research (to 5 March 2014), Association for Research in Otolaryngology (to 5 March 2014), the US National Institutes of Health Trials Register (to 5 March 2014), metaRegister of Controlled Trials (mRCT) (to 5 March 2014), World Health Organization's International Clinical Trials Registry Platform (WHO ICTRP) (to 5 March 2014) and International Federation of Pharmaceutical Manufacturers and Associations (IFPMA) Clinical Trials Portal (to 5 March 2014).

    SELECTION CRITERIA: We included all randomised controlled trials (RCTs) comparing any pharmacological agent with a control intervention or any non-pharmacological agent with a control intervention. We also included cross-over trials in the review.

    DATA COLLECTION AND ANALYSIS: Two authors independently, and in duplicate, assessed the quality of trials and extracted data. Wherever possible, we contacted study authors for additional information. We collected adverse events information from the trials.

    MAIN RESULTS: We included nine trials (seven parallel and two cross-over RCTs) with 566 participants. We assessed three trials (33.3%) as having a low risk of bias, four trials (44.5%) at high risk of bias and two trials (22.2%) as having an unclear risk of bias. We only included studies on taste disorders in this review that were either idiopathic, or resulting from zinc deficiency or chronic renal failure.Of these, eight trials with 529 people compared zinc supplements to placebo for patients with taste disorders. The participants in two trials were children and adolescents with respective mean ages of 10 and 11.2 years and the other six trials had adult participants. Out of these eight, two trials assessed the patient reported outcome for improvement in taste acuity using zinc supplements (RR 1.45, 95% CI 1.0 to 2.1; very low quality evidence). We included three trials in the meta-analysis for overall taste improvement (effect size 0.44, 95% CI 0.23 to 0.65; moderate quality evidence). Two other trials described the results as taste acuity improvement and we conducted subgroup analyses due to clinical heterogeneity. One trial described the results as taste recognition improvement for each taste sensation and we analysed this separately. We also analysed one cross-over trial separately using the first half of the results. None of the zinc trials tested taste discrimination. Only one trial tested taste discrimination using acupuncture (effect size 2.80, 95% CI -1.18 to 6.78; low quality evidence).Out of the eight trials using zinc supplementation, four reported adverse events like eczema, nausea, abdominal pain, diarrhoea, constipation, decrease in blood iron, increase in blood alkaline phosphatase, and minor increase in blood triglycerides. No adverse events were reported in the acupuncture trial.None of the included trials could be included in the meta-analysis for health-related quality of life in taste disorder patients.

    AUTHORS' CONCLUSIONS: We found very low quality evidence that was insufficient to conclude on the role of zinc supplements to improve taste perception by patients, however we found moderate quality evidence that zinc supplements improve overall taste improvement in patients with zinc deficiency/idiopathic taste disorders. We also found low quality evidence that zinc supplements improve taste acuity in zinc deficient/idiopathic taste disorders and very low quality evidence for taste recognition improvement in children with taste disorders secondary to chronic renal failure. We did not find any evidence to conclude the role of zinc supplements for improving taste discrimination, or any evidence addressing health-related quality of life due to taste disorders.We found low quality evidence that is not sufficient to conclude on the role of acupuncture for improving taste discrimination in cases of idiopathic dysgeusia (distortion of taste) and hypogeusia (reduced ability to taste). We were unable to draw any conclusions regarding the superiority of zinc supplements or acupuncture as none of the trials compared these interventions.

  3. Shrestha N, Adhikari M, Pant V, Baral S, Shrestha A, Basnyat B, et al.
    BMC Infect Dis, 2019 Feb 19;19(1):176.
    PMID: 30782129 DOI: 10.1186/s12879-019-3793-x
    BACKGROUND: Melioidosis is a life-threatening infectious disease that is caused by gram negative bacteria Burkholderia pseudomallei. This bacteria occurs as an environmental saprophyte typically in endemic regions of south-east Asia and northern Australia. Therefore, patients with melioidosis are at high risk of being misdiagnosed and/or under-diagnosed in South Asia.

    CASE PRESENTATION: Here, we report two cases of melioidosis from Nepal. Both of them were diabetic male who presented themselves with fever, multiple abscesses and developed sepsis. They were treated with multiple antimicrobial agents including antitubercular drugs before being correctly diagnosed as melioidosis. Consistent with this, both patients were farmer by occupation and also reported travelling to Malaysia in the past. The diagnosis was made consequent to the isolation of B. pseudomallei from pus samples. Accordingly, they were managed with intravenous meropenem followed by oral doxycycline and cotrimoxazole.

    CONCLUSION: The case reports raise serious concern over the existing unawareness of melioidosis in Nepal. Both of the cases were left undiagnosed for a long time. Therefore, clinicians need to keep a high index of suspicion while encountering similar cases. Especially diabetic-farmers who present with fever and sepsis and do not respond to antibiotics easily may turn out to be yet another case of melioidosis. Ascertaining the travel history and occupational history is of utmost significance. In addition, the microbiologist should be trained to correctly identify B. pseudomallei as it is often confused for other Burkholderia species. The organism responds only to specific antibiotics; therefore, correct and timely diagnosis becomes crucial for better outcomes.

  4. Akbar SM, Al-Mahtab M, Khan MS, Raihan R, Shrestha A
    Ann Transl Med, 2016 Sep;4(18):335.
    PMID: 27761439
    Although several antiviral drugs are now available for treatment of patients with chronic hepatitis B (CHB), sustained off-treatment clinical responses and containment of CHB-related complications are not achieved in majority of CHB patients by antiviral therapy. In addition, use of these drugs is endowed with substantial long term risk of viral resistance and drug toxicity. The infinite treatment regimens of antiviral drugs for CHB patients are also costly and usually unbearable by most patients of developing and resource-constrained countries. Taken together, there is a pressing need to develop new and innovative therapeutic approaches for CHB patients. Immune therapy seems to be an alternate therapeutic approach for CHB patients because impaired or distorted or diminished immune responses have been detected in most of these patients. Also, investigators have shown that restoration or induction of proper types of immune responses may have therapeutic implications in CHB. Various immunomodulatory agents have been used to treat patients with CHB around the world and the outcomes of these clinical trials show that the properties of immune modulators and nature and designing of immune therapeutic regimens seem to be highly relevant in the context of treatment of CHB patients. In this review, the general properties and specific features of immune therapy for CHB have been discussed for developing the guidelines of effective regimens of immune therapy for CHB.
  5. Kumbargere Nagraj S, George RP, Shetty N, Levenson D, Ferraiolo DM, Shrestha A
    Cochrane Database Syst Rev, 2017 Dec 20;12(12):CD010470.
    PMID: 29260510 DOI: 10.1002/14651858.CD010470.pub3
    BACKGROUND: The sense of taste is very much essential to the overall health of an individual. It is a necessary component to enjoy one's food, which in turn provides nutrition to an individual. Any disturbance in taste perception can hamper quality of life in such patients by influencing their appetite, body weight and psychological well-being. Taste disorders have been treated using different modalities of treatment and there is no consensus for the best intervention. Hence this Cochrane Review was undertaken. This is an update of the Cochrane Review first published in November 2014.

    OBJECTIVES: To assess the effects of interventions for the management of patients with taste disturbances.

    SEARCH METHODS: Cochrane Oral Health's Information Specialist searched the following databases: Cochrane Oral Health's Trials Register (to 4 July 2017); the Cochrane Central Register of Controlled Trials (CENTRAL; 2017 Issue 6) in the Cochrane Library (searched 4 July 2017); MEDLINE Ovid (1946 to 4 July 2017); Embase Ovid (1980 to 4 July 2017); CINAHL EBSCO (1937 to 4 July 2017); and AMED Ovid (1985 to 4 July 2017). The US National Institutes of Health Ongoing Trials Register ClinicalTrials.gov (www.clinicaltrials.gov) and the World Health Organization International Clinical Trials Registry Platform were searched for trials. Abstracts from scientific meetings and conferences were searched on 25 September 2017. No restrictions were placed on the language or date of publication when searching the electronic databases.

    SELECTION CRITERIA: We included all randomised controlled trials (RCTs) comparing any pharmacological agent with a control intervention or any non-pharmacological agent with a control intervention. We also included cross-over trials in the review.

    DATA COLLECTION AND ANALYSIS: Two pairs of review authors independently, and in duplicate, assessed the quality of trials and extracted data. Wherever possible, we contacted trial authors for additional information. We collected adverse events information from the trials.

    MAIN RESULTS: We included 10 trials (581 participants), nine of which we were able to include in the quantitative analyses (566 participants). We assessed three trials (30%) as having a low risk of bias, four trials (40%) at high risk of bias and three trials (30%) as having an unclear risk of bias. We only included studies on taste disorders in this review that were either idiopathic, or resulting from zinc deficiency or chronic renal failure.Of these, nine trials with 544 people compared zinc supplements to placebo for patients with taste disorders. The participants in two trials were children and adolescents with respective mean ages of 10 and 11.2 years and the other seven trials had adult participants. Out of these nine, two trials assessed the patient-reported outcome for improvement in taste acuity using zinc supplements (risk ratio (RR) 1.40, 95% confidence interval (CI) 0.94 to 2.09; 119 participants, very low-quality evidence). We meta-analysed for taste acuity improvement using objective outcome (continuous data) in idiopathic and zinc-deficient taste disorder patients (standardised mean difference (SMD) 0.44, 95% CI 0.23 to 0.65; 366 participants, three trials, very low-quality evidence). We also analysed one cross-over trial separately using the first half of the results for taste detection (mean difference (MD) 2.50, 95% CI 0.93 to 4.07; 14 participants, very low-quality evidence), and taste recognition (MD 3.00, 95% CI 0.66 to 5.34; 14 participants, very low-quality evidence). We meta-analysed taste acuity improvement using objective outcome (dichotomous data) in idiopathic and zinc-deficient taste disorder patients (RR 1.42, 95% 1.09 to 1.84; 292 participants, two trials, very low-quality evidence). Out of the nine trials using zinc supplementation, four reported adverse events like eczema, nausea, abdominal pain, diarrhoea, constipation, decrease in blood iron, increase in blood alkaline phosphatase, and minor increase in blood triglycerides.One trial tested taste discrimination using acupuncture (MD 2.80, 95% CI -1.18 to 6.78; 37 participants, very low-quality evidence). No adverse events were reported in the acupuncture trial.None of the included trials could be included in the meta-analysis for health-related quality of life in taste disorder patients.

    AUTHORS' CONCLUSIONS: We found very low-quality evidence that was insufficient to conclude on the role of zinc supplements to improve taste acuity reported by patients and very low-quality evidence that zinc supplements improve taste acuity in patients with zinc deficiency/idiopathic taste disorders. We did not find any evidence to conclude the role of zinc supplements for improving taste discrimination, or any evidence addressing health-related quality of life due to taste disorders.We found very low-quality evidence that is not sufficient to conclude on the role of acupuncture for improving taste discrimination in cases of idiopathic dysgeusia (distortion of taste) and hypogeusia (reduced ability to taste). We were unable to draw any conclusions regarding the superiority of zinc supplements or acupuncture as none of the trials compared these interventions.

  6. Adhikaree J, Shrestha R, Bomjan P, Shrestha A, Pokharel S, Acharya R, et al.
    Post Reprod Health, 2023 Dec;29(4):195-200.
    PMID: 37907067 DOI: 10.1177/20533691231213301
    Background: The ovarian follicular cell's degradation and subsequent decrease in the synthesis of estrogen results in the decreased cardiovascular protection. As a result, the incidence of cardiovascular disease (CVD) increases in postmenopausal women and is characterized by change in lipid profile. This study sought to ascertain the extent of the impact that menstrual status might have on lipid profiles among premenopausal and postmenopausal women. Methods: A cross-sectional study was conducted with 260 premenopausal and postmenopausal women (1: 1) and serum lipid component concentrations (high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), triglycerides (TGs), and total cholesterol (TC)) were measured. A comparison between two groups was made between premenopausal and postmenopausal women, and regression was carried out to estimate the effect of menstrual status on lipid components. Results: Compared with premenopausal women, the concentrations of the lipid components (HDL-C, LDL-C, TG, and TC) were found to be significantly higher in postmenopausal women. Using the linear regression, menstruation status was able to predict 11.7%-13.3% of the lipid components (TG and TC) when age and weight were adjusted. Conclusion: The difference in lipid components between premenopausal women and postmenopausal women exists, with menstrual status explaining 11.7%-13.3% variance for the observed lipid level. The factors influencing the lipid profile beside the menstrual status should also be explored. External intervention such as estrogen replacement therapy is also recommended in case of deviation of lipid profile from the suggested normal clinical range.
  7. Adhikaree J, Shrestha R, Bomjan P, Pokharel S, Shrestha A, Siwakoti A, et al.
    J Midlife Health, 2024;15(2):81-90.
    PMID: 39145261 DOI: 10.4103/jmh.jmh_179_23
    BACKGROUND: The use of nontraditional lipid parameters for assessing clinical conditions is emerging; however, no study has identified thresholds for those parameters for the identification of cardiovascular disease (CVD) risk. The present study aimed to establish the thresholds of nontraditional lipid parameters and test its ability to identify CVD risk factors.

    METHODOLOGY: A cross-sectional study in women (n = 369, age: 46 ± 13 years, body mass index (BMI): 26.31 ± 2.54 kg/m2) was conducted. Blood samples were collected and high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol, total cholesterol (TC), and triglycerides (TGs) were estimated. Subsequently, nontraditional lipid parameters were calculated, namely non-HDL-C, Castelli's Risk Index II (CRI-II), CRI-I, lipoprotein combined index (LCI), atherogenic index (AI), and AI of plasma (AIP).

    RESULTS: Based on TC (≥200 mg/dL), the derived thresholds for non-HDL-C, CRI-II, CRI-I, LCI, AI, and AIP were 139 mg/dL, 2.29, 3.689, 58,066, 2.687, and 0.487, respectively. Similarly, based on the threshold of TG (≥150 mg/dL), the derived thresholds for non-HDL-C, CRI-II, CRI-I, LCI, AI, and AIP were 127 mg/dL, 2.3, 3.959, 58,251, 2.959, and 0.467, respectively. Out of considered five risk factors, non-HDL-C, CRI-II, CRI-I, LCI, and AI thresholds were capable in identifying four risk factors (physical activity, blood pressure, BMI, and age) and AIP was able to associate with two risk factors at most (blood pressure and BMI).

    CONCLUSION: The derived thresholds of nontraditional lipid parameters were capable of differentiating between CVD risk and nonrisk groups suggesting the possible use of these thresholds for studying CVD risk.

  8. Emiliani E, Sanz-Gómez I, Somani B, Tailly T, Castellani D, Traxer O, et al.
    Actas Urol Esp (Engl Ed), 2023 Nov;47(9):581-587.
    PMID: 37369300 DOI: 10.1016/j.acuroe.2023.06.008
    INTRODUCTION AND OBJECTIVES: As well established flexible ureteroscopy (RIRS). There is still no evidence if gender can have any influence on the outcomes and complication when performing. This study aims to evaluate the role that gender has in performing flexible ureteroscopy from a large series of patients.

    METHODS: This study retrospectively analyzed patients who underwent RIRS for renal stones from January 2018 to August 2021 within the multicentric FLEXOR registry. Demographics, stone characteristics, perioperative findings, results and complications were analyzed and compared between gender groups.

    RESULTS: A total of 6669 patients were included, 66.1% were male and 33.9% were female. Stone characteristics was comparable between groups. Female patients had significant higher fever and positive urine culture rates (12% vs. 8% and 37% vs. 34%). Also, females had a slight longer hospital stay (3.8 vs. 3.5 days; P 

  9. Snider CJ, Boualam L, Tallis G, Takashima Y, Abeyasinghe R, Lo YR, et al.
    Vaccine, 2023 Apr 06;41 Suppl 1:A58-A69.
    PMID: 35337673 DOI: 10.1016/j.vaccine.2022.02.022
    Concurrent outbreaks of circulating vaccine-derived poliovirus serotypes 1 and 2 (cVDPV1, cVDPV2) were confirmed in the Republic of the Philippines in September 2019 and were subsequently confirmed in Malaysia by early 2020. There is continuous population subgroup movement in specific geographies between the two countries. Outbreak response efforts focused on sequential supplemental immunization activities with monovalent Sabin strain oral poliovirus vaccine type 2 (mOPV2) and bivalent oral poliovirus vaccines (bOPV, containing Sabin strain types 1 and 3) as well as activities to enhance poliovirus surveillance sensitivity to detect virus circulation. A total of six cVDPV1 cases, 13 cVDPV2 cases, and one immunodeficiency-associated vaccine-derived poliovirus type 2 case were detected, and there were 35 cVDPV1 and 31 cVDPV2 isolates from environmental surveillance sewage collection sites. No further cVDPV1 or cVDPV2 have been detected in either country since March 2020. Response efforts in both countries encountered challenges, particularly those caused by the global COVID-19 pandemic. Important lessons were identified and could be useful for other countries that experience outbreaks of concurrent cVDPV serotypes.
  10. Gauhar V, Chew BH, Traxer O, Tailly T, Emiliani E, Inoue T, et al.
    World J Urol, 2023 Feb;41(2):567-574.
    PMID: 36536170 DOI: 10.1007/s00345-022-04257-z
    PURPOSE: To collect a multicentric database on behalf of TOWER research group to assess practice patterns and outcomes of retrograde intrarenal surgery (RIRS) for kidney stones.

    METHODS: Inclusion criteria: age ≥ 18 years, normal renal/calyceal system anatomy, calculi of any size, number, and position.

    STUDY PERIOD: January 2018 and August 2021. Stone-free status: absence of fragments > 2 mm, assessed post procedure according to the local protocol (KUB X-Ray and/or ultrasound or non-contrast CT scan).

    RESULTS: Twenty centers from fifteen countries enrolled 6669 patients. There were 4407 (66.2%) men. Mean age was 49.3 ± 15.59 years. Pain was the most frequent symptom indication for intervention (62.6%). 679 (10.2%) patients underwent RIRS for an incidental finding of stones. 2732 (41.0%) patients had multiple stones. Mean stone size was 10.04 ± 6.84 mm. A reusable flexible ureteroscope was used in 4803 (72.0%) procedures. A sheath-less RIRS was performed in 454 (6.8%) cases. Holmium:YAG laser was used in 4878 (73.1%) cases. A combination of dusting and fragmentation was the most common lithotripsy mode performed (64.3%). Mean operation time was 62.40 ± 17.76 min. 119 (1.8%) patients had an intraoperative injury of the ureter due to UAS insertion. Mean postoperative stay was 3.62 ± 3.47 days. At least one postoperative complication occurred in 535 (8.0%) patients. Sepsis requiring intensive care admission occurred in 84 (1.3%) patients. Residual fragments were detected in 1445 (21.7%) patients. Among the latter, 744 (51.5%) patients required a further intervention.

    CONCLUSION: Our database contributes real-world data to support to a better understanding of modern RIRS practice and outcomes.

  11. Chai CA, Teoh YC, Tailly T, Emiliani E, Inoue T, Tanidir Y, et al.
    Minerva Urol Nephrol, 2023 Aug;75(4):493-500.
    PMID: 37293816 DOI: 10.23736/S2724-6051.23.05239-4
    BACKGROUND: Retrograde Intrarenal Surgery (RIRS) is recommended as an alternative to percutaneous nephrolithotomy for stones up to 2 cm. Pre-stenting before RIRS remains controversial with various studies differing in outcomes and recommendations. We aim to understand how pre-stenting influences surgical outcomes.

    METHODS: A number of 6579 patients from the TOWER group registry were divided into pre-stented (group 1) and non-pre-stented groups (group 2). Patients aged ≥18 years old, with normal calyceal anatomy were enrolled. Patients with ureteric stones, anomalous kidneys, bilateral stones, planned for ECIRS were excluded.

    RESULTS: Patients are homogeneously distributed in both groups (3112 vs. 3467). The predominant indication for pre-stenting was symptom relief. Overall stone size was comparable, whilst group 1 had a significantly more multiple (1419 vs. 1283, P<0.001) and lower-pole (LP) stones (1503 vs. 1411, P<0.001). The mean operative time for group 2 was significantly longer (68.17 vs. 58.92, P<0.001). Stone size, LP stones, age, recurrence and multiple stones are contributing factors for residual fragments at the multivariable analysis. The incidence of postoperative day 1 fever and sepsis was significantly higher in group 2, indicating that pre-stenting is associated with a lower risk of post-RIRS infection and a lower overall complications rate (13.62% vs. 15.89%) (P<0.001).

    CONCLUSIONS: RIRS without pre-stenting can be considered safe without significant morbidity. Multiple, lower-pole and large stone is a significant contributor towards residual fragments. Patients who were not pre-stented had significantly higher but low-grade complications, especially for lower pole and large volume stones. While we do not advocate routine pre-stenting, a tailored approach for these patients should include proper counselling regarding pre-stenting.

  12. Singh V, De A, Mehtani R, Angeli P, Maiwall R, Satapathy S, et al.
    Hepatol Int, 2023 Aug;17(4):792-826.
    PMID: 37237088 DOI: 10.1007/s12072-023-10536-7
  13. Trujillo-Santamaría H, Robles-Torres JI, Teoh JY, Tanidir Y, Campos-Salcedo JG, Bravo-Castro EI, et al.
    Curr Urol, 2024 Mar;18(1):55-60.
    PMID: 38505163 DOI: 10.1097/CU9.0000000000000163
    BACKGROUND: Emphysematous pyelonephritis (EPN) is a necrotizing infection of the kidney and the surrounding tissues associated with considerable mortality. We aimed to formulate a score that classifies the risk of mortality in patients with EPN at hospital admission.

    MATERIALS AND METHODS: Patients diagnosed with EPN between 2013 and 2020 were retrospectively included. Data from 15 centers (70%) were used to develop the scoring system, and data from 7 centers (30%) were used to validate it. Univariable and multivariable logistic regression analyses were performed to identify independent factors related to mortality. Receiver operating characteristic curve analysis was performed to construct the scoring system and calculate the risk of mortality. A standardized regression coefficient was used to quantify the discriminating power of each factor to convert the individual coefficients into points. The area under the curve was used to quantify the scoring system performance. An 8-point scoring system for the mortality risk was created (range, 0-7).

    RESULTS: In total, 570 patients were included (400 in the test group and 170 in the validation group). Independent predictors of mortality in the multivariable logistic regression were included in the scoring system: quick Sepsis-related Organ Failure Assessment score ≥2 (2 points), anemia, paranephric gas extension, leukocyte count >22,000/μL, thrombocytopenia, and hyperglycemia (1 point each). The mortality rate was <5% for scores ≤3, 83.3% for scores 6, and 100% for scores 7. The area under the curve was 0.90 (95% confidence interval, 0.84-0.95) for test and 0.91 (95% confidence interval, 0.84-0.97) for the validation group.

    CONCLUSIONS: Our score predicts the risk of mortality in patients with EPN at presentation and may help clinicians identify patients at a higher risk of death.

  14. Duseja A, De A, Taneja S, Choudhury AK, Devarbhavi H, Hu J, et al.
    Liver Int, 2021 01;41(1):150-157.
    PMID: 32970356 DOI: 10.1111/liv.14671
    BACKGROUND: Metabolic risk factors may impact the severity and outcome of alcoholic liver disease. The present study evaluated this effect in patients with alcohol-associated acute-on-chronic liver failure (ACLF).

    METHODOLOGY: One thousand two hundred and sixteen prospectively enrolled patients with ACLF (males 98%, mean age 42.5 ± 9.4 years, mean CTP, MELD and AARC scores of 12 ± 1.4, 29.7 ± 7 and 9.8 ± 2 respectively) from the Asian Pacific Association for the Study of the Liver (APASL) ACLF Research Consortium (AARC) database were analysed retrospectively. Patients with or without metabolic risk factors were compared for severity (CTP, MELD, AARC scores) and day 30 and 90 mortality. Information on overweight/obesity, type 2 diabetes mellitus (T2DM), hypertension and dyslipidaemia were available in 1028 (85%), 1019 (84%), 1017 (84%) and 965 (79%) patients respectively.

    RESULTS: Overall, 392 (32%) patients died at day 30 and 528 (43%) at day 90. Overweight/obesity, T2DM, hypertension and dyslipidaemia were present in 154 (15%), 142 (14%), 66 (7%) and 141 (15%) patients, respectively, with no risk factors in 809 (67%) patients. Patients with overweight/obesity had higher MELD scores (30.6 ± 7.1 vs 29.2 ± 6.9, P = .007) and those with dyslipidaemia had higher AARC scores (10.4 ± 1.2 vs 9.8 ± 2, P = .014). Overweight/obesity was associated with increased day 30 mortality (HR 1.54, 95% CI 1.06-2.24, P = .023). None of other metabolic risk factors, alone or in combination, had any impact on disease severity or mortality. On multivariate analysis, overweight or obesity was significantly associated with 30-day mortality (aHR 1.91, 95% CI 1.41-2.59, P 

  15. Choudhury A, Vijayaraghavan R, Maiwall R, Kumar M, Duan Z, Yu C, et al.
    Hepatol Int, 2021 Oct 04.
    PMID: 34608586 DOI: 10.1007/s12072-021-10206-6
    BACKGROUND AND AIMS: Acute-on-chronic liver failure (ACLF) is a rapidly progressive illness with high short-term mortality. Timely liver transplant (LT) may improve survival. We evaluated various indices for assessment of the severity of liver failure and their application for eligibility and timing of living donor LT (LDLT).

    METHODS: Altogether 1021 patients were analyzed for the severity and organ failure at admission to determine transplant eligibility and 28 day survival with or without transplant.

    RESULTS: The ACLF cohort [mean age 44 ± 12.2 years, males 81%) was of sick patients; 55% willing for LT at admission, though 63% of them were ineligible due to sepsis or organ failure. On day 4, recovery in sepsis and/or organ failure led to an improvement in transplant eligibility from 37% at baseline to 63.7%. Delay in LT up to 7 days led to a higher incidence of multiorgan failure (p 

  16. Devarbhavi H, Choudhury AK, Sharma MK, Maiwall R, Al Mahtab M, Rahman S, et al.
    Am J Gastroenterol, 2019 06;114(6):929-937.
    PMID: 31021832 DOI: 10.14309/ajg.0000000000000201
    OBJECTIVES: Acute insults from viruses, infections, or alcohol are established causes of decompensation leading to acute-on-chronic liver failure (ACLF). Information regarding drugs as triggers of ACLF is lacking. We examined data regarding drugs producing ACLF and analyzed clinical features, laboratory characteristics, outcome, and predictors of mortality in patients with drug-induced ACLF.

    METHODS: We identified drugs as precipitants of ACLF among prospective cohort of patients with ACLF from the Asian Pacific Association of Study of Liver (APASL) ACLF Research Consortium (AARC) database. Drugs were considered precipitants after exclusion of known causes together with a temporal association between exposure and decompensation. Outcome was defined as death from decompensation.

    RESULTS: Of the 3,132 patients with ACLF, drugs were implicated as a cause in 329 (10.5%, mean age 47 years, 65% men) and other nondrug causes in 2,803 (89.5%) (group B). Complementary and alternative medications (71.7%) were the commonest insult, followed by combination antituberculosis therapy drugs (27.3%). Alcoholic liver disease (28.6%), cryptogenic liver disease (25.5%), and non-alcoholic steatohepatitis (NASH) (16.7%) were common causes of underlying liver diseases. Patients with drug-induced ACLF had jaundice (100%), ascites (88%), encephalopathy (46.5%), high Model for End-Stage Liver Disease (MELD) (30.2), and Child-Turcotte-Pugh score (12.1). The overall 90-day mortality was higher in drug-induced (46.5%) than in non-drug-induced ACLF (38.8%) (P = 0.007). The Cox regression model identified arterial lactate (P < 0.001) and total bilirubin (P = 0.008) as predictors of mortality.

    DISCUSSION: Drugs are important identifiable causes of ACLF in Asia-Pacific countries, predominantly from complementary and alternative medications, followed by antituberculosis drugs. Encephalopathy, bilirubin, blood urea, lactate, and international normalized ratio (INR) predict mortality in drug-induced ACLF.

  17. Kumar A, Arora A, Choudhury A, Arora V, Rela M, Jothimani DK, et al.
    Am J Gastroenterol, 2024 Jul 17.
    PMID: 39016385 DOI: 10.14309/ajg.0000000000002951
    BACKGROUND: The prevalence of Metabolic dysfunction associated fatty liver disease (MAFLD) and its complication, MAFLD-related acute on chronic liver failure (MAFLD-ACLF), is rising. Yet, factors determining patient outcomes in MAFLD-ACLF remain understudied.

    METHODS: Patients with MAFLD-ACLF were recruited from the AARC registry. The diagnosis of MAFLD-ACLF was made when the treating unit had identified the etiology of chronic liver disease (CLD) as MAFLD (or previous nomenclature such as NAFLD, NASH, or NASH-cirrhosis). Patients with coexisting other etiologies of CLD (such as alcohol, HBV, HCV, etc.) were excluded. Data was randomly split into derivation (n=258) and validation (n=111) cohorts at a 70:30 ratio. The primary outcome was 90-day mortality. Only the baseline clinical, laboratory features and severity scores were considered.

    RESULTS: The derivation group had 258 patients; 60% were male, with a mean age of 53. Diabetes was noted in 27%, and hypertension in 29%. The dominant precipitants included viral hepatitis (HAV and HEV, 32%), drug-induced injury (DILI, 29%) and sepsis (23%). MELD-Na and AARC scores upon admission averaged 32±6 and 10.4±1.9. At 90 days, 51% survived. Non-viral precipitant, diabetes, bilirubin, INR, and encephalopathy were independent factors influencing mortality. Adding diabetes and precipitant to MELD-Na and AARC scores, the novel MAFLD-MELD-Na score (+12 for diabetes, +12 for non-viral precipitant) and MAFLD-AARC score (+5 for each) were formed. These outperformed the standard scores in both cohorts.

    CONCLUSION: Almost half of MAFLD-ACLF patients die within 90 days. Diabetes and non-viral precipitants such as DILI and sepsis lead to adverse outcomes. The new MAFLD-MELD-Na and MAFLD-AARC scores provide reliable 90-day mortality predictions for MAFLD-ACLF patients.

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