Treatment of chronic hepatitis D with peginterferon lambda-the phase 2 LIMT-1 clinical trial.

BACKGROUND AND AIMS: HDV infection leads to the most aggressive form of human viral hepatitis for which there is no FDA-approved therapy. PEG IFN-lambda-1a (Lambda) has previously demonstrated a good tolerability profile in HBV and HCV patients compared to PEG IFN-alfa. The goal of Phase 2 LIMT-1 trial was to evaluate the safety and efficacy of Lambda monotherapy in patients with HDV. APPROACH AND RESULTS: An open-label study of Lambda 120 or 180 mcg, administered once weekly by subcutaneous injections for 48 weeks, followed by 24 weeks of posttreatment follow-up. Thirty-three patients were allocated to Lambda 180 mcg (n=14) or 120 mcg (n=19). Baseline mean values: HDV RNA 4.1 log10 IU/mL (SD±1.4); ALT 106 IU/L (35-364); and bilirubin 0.5 mg/dL (0.2-1.2). Intention-to-treat rates of virologic response to Lambda 180 mcg and 120 mcg, 24 weeks following treatment cessation were 5 of 14(36%) and 3 of 19 (16%), respectively. The posttreatment response rate of 50% was seen in low BL viral load (≤4 log10) on 180 mcg. Common on-treatment adverse events included flu-like symptoms and elevated transaminase levels. Eight (24%) cases of hyperbilirubinemia with or without liver enzyme elevation, leading to drug discontinuation, were mainly observed in the Pakistani cohort. The clinical course was uneventful, and all responded favorably to dose reduction or discontinuation. CONCLUSIONS: Treatment with Lambda in patients with chronic HDV may result in virologic response during and following treatment cessation. Clinical phase 3 development of Lambda for this rare and serious disease is ongoing.

Factors Associated with Difficulty Maintaining Insufflation of the Colon During Endoscopy.

BACKGROUND: Insufflation of the colon allows for adequate visualization of the mucosal tissue and advancement of the endoscope during colonoscopy. Most colonoscopies are performed with sedation to mitigate discomfort and enhance the colonoscopy experience for both the patient and the endoscopist. AIM: We aimed to evaluate factors associated with difficulty maintaining insufflation. METHODS: A cross-sectional study of individuals undergoing colonoscopy at the Oklahoma City Veterans Affairs Medical Center was performed. Experiencing difficulty maintaining air insufflation during colonoscopy was assessed with a questionnaire completed by the performing endoscopist at the end of procedure. Information regarding procedure times, sedation used, demographics, comorbidities, surgical history, and medications used was extracted from the medical record. A multivariate regression analysis was performed to identify factors associated with difficulty maintaining air insufflation. A P value < 0.05 was considered significant. RESULTS: 996 Patients were included for the analysis. Difficulty with insufflation was reported in 240 (24%) colonoscopies; mean age of 63.8 ± 10.4 years old and 13% were female. Fellow trainees were involved in 669 (67%) colonoscopies. Older age (OR 1.02, P 0.03, CI [1.00-1.04]), diabetes (OR 1.5, 95% CI [1.03, 2.05]), fellow's involvement (OR 2.6. (95% CI [1.68, 4.09]), total procedure time (OR 1.02, 95% CI [1.00, 1.03]), mean number of adenomas (OR 1.05, 95% CI [1.00, 1.09]), and MAC use (OR 2.6, 95% CI [1.80, 3.85]) were independent predictors for difficulty in maintaining air insufflation. CONCLUSION: Our findings suggest that endoscopists should be cognizant of colon insufflation issues in older, diabetic patients undergoing colonoscopies under deep sedation, particularly if prolonged procedure is anticipated or encountered.

Assessment of frailty in cirrhosis using bedside measures and its correlation with Child-Turcotte-Pugh, MELD & MELD-Na Scores.

Objectives: To assess frailty in cirrhotic by calculating Liver Frailty Index (LFI) using bedside clinical tests and correlate it with Child-Turcotte-Pugh (CTP), MELD, MELD Na, Fib- 4 and Transient Elastography (TE) scores. Methods: This cross-sectional observational comparative study was carried out in Dr Ruth KM Pfau Civil Hospital, Karachi from August 2020 to September 2021. Patients were subjected to three performance-based testing including dominant hand grip strength (HGS), Chair to Stand (CTS) Time & Three Position Balance (TPB). LFI was calculated using the online LFI calculator, available at http://liverfrailtyindex.ucsf.edu and classified as 'Robust' if LFI <3.2, 'Prefrail' LFI between 3.2 and 4.4, and 'Frail' as LFI ≥4.5. Correlation of frailty with MELD, MELD-Na and CTP Scores was done. Means of MELD & MELD-Na Scores and CTP scores were calculated in all 3 classes of frailty using one way ANOVA. A p-value of ≤.05 was taken as significant. Results: Out of 118 patients, 62 (52.5%) were males. Mean MELD score was 11.4 ±3.3, MELD-Na was 15.97 ±8.54, CTP 8.25 ±2.21, Fib-4 was 2.79 ±1.034 and TE score was 18.20 ±9.17. Mean LFI was 3.87 ±1.07; mean HGS was 18.12 ±4.68; mean of CTS was 9.62 ±3.55. LFI Class distribution in our cohort showed Robust were 36 (30.5%), Prefrail 34 (28.8%) and Frail were 48 (40.8%). Correlation of all these variables with LFI showed significant correlation with LFI, but highest correlation coefficient was seen with MELD-Na. Conclusion: Significant correlation between frailty score in cirrhotic with cirrhosis severity scores highlights the need for frequently assessing LFI in all cirrhotic at regular follow up visits.

Comparison of Vonoprazan and Amoxicillin Dual Therapy with Standard Triple Therapy with Proton Pump Inhibitor for Helicobacter Pylori eradication: A Randomized Control Trial.

Objectives: To compare the efficacy of Vonoprazan based dual treatment versus PPI based treatment for the eradication of Helicobacter pylori infection. Methods: A randomized controlled trial was conducted in Department of Medicine/Gastroenterology Ruth KM Pfau Civil Hospital, DMC during the period of 22 June to 21 September 2021. Sample size was calculated as 96 in each Group. All patients of age 18-75 years with Helicobacter Pylori Infection were inducted and randomly allocated to two groups. Group-A: were given Capsule Amoxicillin 1 gm; Tablet Clarithromycin 500 mg; Capsule Omeprazole 20 mg all medications were given twice daily for two weeks. Group-B were given Capsule Amoxicillin 1 gm; Tablet Vonoprazan 20 mg (Vonozon©, m/s Getz Pharma, Pakistan) twice daily for two weeks. Confirmation of Hp eradication was done by stool Hp antigen test four weeks after completion of treatment. Nine and four patients were lost to follow-up in Group-A & B respectively. Analysis was conducted on 87 patients in Group-A and 92 patients in Group-B. Results: Out of eighty-seven patients in Group-A and ninety-two patients in Group-B, 73 (83.9%) patients in Group-A and 86 (93.5%) patients in Group-B had negative H pylori result respectively after treatment (p = .042). Significantly higher frequencies of adverse events were observed in Group-A as compared to Group-B in nausea/vomiting (p = .035) and bloating (p = .045). Conclusion: VA-dual provides an acceptable eradication rate with fewer adverse events.

Are we missing varices by implementing Baveno-VI recommendation of not screening patients with Compensated Advanced Chronic Liver Disease?

OBJECTIVES: This study aimed to validate Baveno-VI recommendations for variceal screening in cACLD in our region and proposed our own cutoff values. METHODS: Prospective cross-sectional study was conducted on cACLD patients from August 2020 till April 2021. Patients segregated into Group-A, having Liver stiffness measurement (LSM) of ≥ 20 kPa and platelet of ≤ 150 × 109 cells/L; and Group-B having LSM of < 20 kPa and PLT of > 150 × 109 cells/L. Gastroscopic findings were segregated into three categories, VNT, Varices Not Needing Treatment (VNNT) and No Varix (NV). ROC plots were generated for LSM and Platelet for VNT for sensitivity, specificity, Negative and Positive Predictive Values were calculated. RESULTS: A total of 134 patients of cACLD were included. Group-A had 72 (53.7%) patients and Group-B had 62 (46.3%) patients. Group-A had 6 (8.3%) NV; 18 (25.0%) VNNT and 48 (66.7%) VNT. Group-B had 26 (41.9%) NV, 24 (38.7%) VNNT and 12 (19.4%) VNT. The sensitivity of 66.7%, specificity of 80.6% and NPV of 67.56% was obtained. Thus 19.4% VNT were missed on following Baveno VI recommendations. ROC in our study suggested cutoff value of 11.5 kPa with sensitivity of 100% and 1-sepcifity pf 78% (AUROC = 0.865; p < .001) of LSM below which screening gastroscopy could be avoided. The positive and negative predicted values for 84.85% and 100% respectively. Cut off value of platelet count for VNNT came out to be ≥ 97.5 × 109 cells/L with AUROC 0.891 (p < .001), having sensitivity of 100 % and 1-specificity of 83.3%. CONCLUSIONS: Substantial number of VNT in cACLD patients are missed by following Baveno-VI recommendations and these needs to be revised on regional basis.

Severe reinfection with severe acute respiratory syndrome coronavirus 2 in a nursing home resident: a case report.

BACKGROUND: The topic of natural immunity related to severe acute respiratory syndrome coronavirus 2 remains controversial. Although evidence suggests postinfection immunity can be achieved, there have been reported cases of reinfection with similar or milder symptoms. Information on severe disease manifestation during reinfection is not known. We present a case of reinfection with a more severe presentation as compared with the initial infection. CASE REPORT: We describe a white male patient from a nursing home who was reinfected with severe acute respiratory syndrome coronavirus 2 with severe disease manifesting as dyspnea, fevers, and encephalopathy with hypoxemic respiratory failure requiring intubation, elevated inflammatory markers, and lung infiltrates on imaging, after initially testing positive with mild symptoms 2 months prior to presentation. Notably, severe acute respiratory syndrome coronavirus 2 antibodies were detected, which indicated this was a coronavirus disease 2019 reinfection. After treatment with remdesivir, dexamethasone, and convalescent plasma, he was subsequently extubated and discharged home after 2 weeks. CONCLUSION: It is not clear whether an initial infection with severe acute respiratory syndrome coronavirus 2 and recovery provides prolonged immunity beyond 2 months. Furthermore, even if antibodies are present, it does not guarantee an attenuated course during reinfection. Therefore, vaccination plays an important role in prevention. Long-term cohort studies will be needed to study the factors behind reinfection.

Comparison of within 7 Day All-Cause Mortality among HDU Patients with Modified Early Warning Score of ≥5 with those with Score of <5.

OBJECTIVE: To compare 7-Day All-Cause Mortality among HDU Patients with Modified Early Warning Score of ≥5 with Those with Score of <5. METHODS: All patients of age more than 18 years, of either gender admitted in HDU of Medical Unit-II, CHK between September 2019 to February 2020 were included. MEWS was calculated for each patient at time of admission. Patients with MEWS score of ≥5 were allocated to Group-A and those with score of <5 were allocated to Group-B. Patients were followed for seven days and outcome status of alive, expired or discharged was noted. RESULTS: Total of 336 patients were selected out of which 168 patients was inducted in Group-A and 168 patients in Group-B. MEWS Score in patients who expired was significantly higher (Mdn=11) than in those who survived (Mdn=4), p <.001. 7-day mortality in Group-A was 62 (39.9%) while in Group-B was 40 (23.8%). ROC was plotted of MEWS Score for mortality, it showed significant area under curve of 68.4% (p <.001, 95% CI = .62 to .75). MEWS Score of 3.5 showed sensitivity of 89.2% and specificity of 65%. CONCLUSION: Our results show that MEWS has a positive trend to predict mortality. MEWS score of 3.5 is suggested cut off based on ROC in our study.

Muscle weakness assessment in non-hypoxemic COPD out-patients at tertiary care hospitals.

OBJECTIVE: To determine frequency of Muscle Weakness in Non-Hypoxemic COPD out-patients and Comparison with age matched non-COPD Controls. METHODS: This cross-sectional study was conducted at OPD of Ojha Institute of Chest Diseases and Medicine, Dow University of Health Sciences, Karachi, Pakistan, during the period 8th September 2019 till 30th May 2020. Patients of both genders aged 25-70 years who were satisfying GOLD criteria for COPD and having SpO2 ≥ 94% were included. An age matched control group was added as control. Hand Grip Strength (HGS) and Chair to Stand time (CST) were recorded. RESULTS: Two hundred fifty-six patients were inducted with aged and BMI matched group of non-COPD Control patients in ratio of 1:2 (n = 128). Comparison of HGS between Control and COPD Groups showed significant weakness in COPD group. Significant weakness in lower limbs in COPD Group with longer timings to complete the task. Mean FEV1 had significant low values in COPD Group. Age correlated negatively with HGS & positively with CST. BMI correlated positively with FEV1 and CST but negatively with HGS. HGS correlated positively with FEV1 and no correlation was found with CST. No correlation was found of CST with FEV1. CONCLUSION: Muscle weakness in COPD patients was shown by simple validated bedside tools. The older COPD patients had less HGS and were slower in doing CST whereas those COPD ones who had higher FEV1 had more HGS.

Association between insulin resistance and BMI with FEV1 in non-hypoxemic COPD out-patients.

OBJECTIVES: This study was conducted to determine the impact of insulin resistance using Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) score and BMI in non-hypoxemic out-patients with COPD on FEV1 using linear and polynomial regressions and to determine their correlation. METHODS: COPD patients of both genders were included after informed consent. Fasting blood sugar and serum insulin were done to calculate HOMA-IR, which were segregated into two groups of ≥ 3 and < 3 labeled insulin resistance present and absent, these were compared with BMI. Patients were segregated into GOLD Grade 1-4 per GOLD Guidelines and compared with HOMA-IR and BMI. Curve and linear regressions, multivariate and univariate analysis of HOMA-IR with BMI, FVC, and FEV1 were done. RESULTS: A total of 273 subjects were inducted after informed consent. There was a linear correlation between HOMA-IR and BMI (r2 0.498, P < 0.001) and nonlinear correlation between HOMA-IR and FEV1 (r2 0. 617, P < 0.001) which showed little evidence of association above FEV1 > 60 predicted, but a clear negative association below that. Significant increase in HOMA-IR was seen from GOLD-2 to 3 and from GOLD-3 to 4 classes. The impact of HOMA-IR on FEV1 was 49.9% (P < 0.001) on FVC was 43.7%. CONCLUSIONS: The results indicate that there is a high prevalence of IR in non-hypoxemic COPD. A nonlinear association is present between FEV1 and HOMA-IR which is most evident with FEV1 <60% predicted.

Frequency of silent carotid artery stenosis in diabetics and its associated factors: An analysis in tertiary care hospital.

OBJECTIVE: To estimate frequency of silent carotid artery stenosis and its associated factors in diabetic patients attending a tertiary care hospital. METHODS: This cross-sectional study was conducted in tertiary care Civil Hospital, Karachi from March 2019 to September 2019,. A total of 166 patients with Diabetes Mellitus were included in this study. Brief history was taken for the duration of DM, treatment, and smoking habits. Carotid artery stenosis (CAS) wafrs measured by Doppler ultrasound of right and left common, internal, and external carotid arteries. RESULTS: Frequency of silent carotid artery stenosis (CAS) in diabetic patients was observed in 28.92% (48/166) cases. The mean age ±SD of the patients was 54.8 ±7.96 years. 27 (22.29%) patients were smoker and all were male. Out of 166 diabetic patients, 59 (35.54%) were treated with insulin and 107 (64.46%) were treated with oral hypoglycemic. CONCLUSION: Substantial number of diabetic patients with increasing age, increased duration of diabetes and smoking habits have significant silent Silent Carotid Artery Stenosis (CAS).

Euglycemic Diabetic Ketoacidosis in a 27 year-old female patient with type-1-Diabetes treated with sodium-glucose cotransporter-2 (SGLT2) inhibitor Canagliflozin.

We are reporting a timely case of atypical euglycemic diabetic ketoacidosis in a type 1 diabetic patient treated with sodium-glucose cotransporter-2 (SGLT-2) inhibitor canagliflozin. The clinical history, physical examination findings and laboratory values are described. Other causes of acidosis such as salicylate toxicity or alcohol intoxication were excluded. Ketoacidosis resolved after increasing dextrose and insulin doses supporting the hypothesis that SGLT-2 inhibitors may lead to hypoinsulinemia. Euglycemic ketoacidosis did not recur in our patient after discontinuing canagliflozin. We recommend reserving SGLT2 inhibitor therapy to type 2 diabetics, discontinuing medication and treating patients presenting with ketoacidosis due to SGLT-2 inhibitors with higher concentrations of dextrose with appropriate doses of insulin to help resolve acidosis.

Role of multifunctional Chemerin in obesity and preclinical diabetes.

BACKGROUND: "Chemerin" is a multifuntional peptide involved in lipid and glucose metabolism. Elevated levels of this peptide have been associated with insulin resistance and systemic inflammation. This study aims to identify whether Chemerin along with other inflammatory markers (TNFα and hsCRP) can discriminate subjects with subclinical diabetes. METHODOLOGY/FINDINGS: Fifty-two asymptomatic healthy volunteers and 22 chronic diabetics (T2DM) were enrolled in a cross sectional study design. They were subjected to a 75 g oral glucose tolerance test [OGTT (2-h glucose>200 mg/dL)] and were then classified as either newly diagnosed diabetics (NDM) (n=23) or healthy controls (n=29). Our results showed a higher Chemerin level in NDM (p<0.01; MWU) compared to controls and previously diagnosed DM. Using ROC analysis, Chemerin level in NDM and T2DM had AUC of 0.963 and 0.764 respectively, compared to healthy controls. We suggest that the cut off of 13.7 ng/ml of Chemerin can discriminate 73% of NDM subjects with impaired glucose level with 91% and 96% of sensitivity and specificity respectively. Elevated serum Chemerin in NDM group is a surrogate of impairment in glucose metabolism in obese individual. CONCLUSIONS: Chemerin along with other inflammatory biomarkers suggest an ongoing inflammatory process in a high risk obese group that indicates a pre-diabetic state.

Comparison of British Thoracic Society and American Thoracic Society reintroduction guidelines for anti-tuberculous therapy induced liver injury.

OBJECTIVE: To compare the efficacy of British Thoracic Society and American Thoracic Society guidelines for reintroduction of anti-tuberculous therapy after drug-induced liver injury, and to assess the ease of administration of each guideline on a scale of 1-10. METHODS: The randomised prospective interventional study was conducted at the Department of Medicine and Pulmonology, Dow University of Health Sciences, Karachi, from December 2011 to November 2013. Patients with anti-tuberculous therapy drug-induced liver injury were selected. Hepatotoxic anti-tuberculous therapy was stopped and modified anti-tuberculous therapy was started. Patients were followed weekly till clinical and biochemical parameters got stabilised. After stabilisation, the patients were randomised to one of the two groups to receive re-introduction of anti-tuberculous therapy under the guidelines of British Thoracic Society (Group I) or those of American Thoracic Society (Group II). Means of the groups were analysed by Student's t test and proportions were compared by chi-square test. Multivariate analysis was done for age, body mass index and serum albumin for recurrence of drug-induced liver injury after the re-introduction. P value < 0.05 was taken as significant. RESULTS: Of the total 325 patients, 163 (50.15%) were in Group I, while 162 (49.84%) were in Group II. The frequency of recurrence of drug-induced liver injury in Group I was 16 (9.8%) and in Group II it was 18 (11.1%).There was no statistically significant difference between the two groups (p < 0.7). Age was positively related with drug-induced liver injury, while body mass index and serum albumin were negatively associated. CONCLUSION: There was no significant difference between the two major guidelines though the American Thoracic Society guideline was easier to follow.