UNASSIGNED: Telepathology utilizing high-throughput static whole slide image scanners is proposed to address the challenge of limited pathology services in resource-restricted settings. However, the prohibitive equipment costs and sophisticated technologies coupled with large amounts of space to set up the devices make it impractical for use in resource-limited settings. Herein, we aimed to address this challenge by validating a portable whole slide imaging (WSI) device against glass slide microscopy (GSM) using lymph node biopsies from suspected lymphoma cases from Sub-Saharan Africa.
UNASSIGNED: This was part of a multicenter prospective case-control head-to-head comparison study of liquid biopsy against conventional pathology. For the portable WSI scanner validation, the study pathologists evaluated 105 surgical lymph node specimens initially confirmed by gold-standard pathology between February and December 2021. The tissues were processed according to standard protocols for Hematoxylin and Eosin (H&E) and Immunohistochemistry (IHC) staining by well-trained histotechnicians, then digitalized the H& E and IHC slides at each center. The digital images were anonymized and uploaded to a HIPAA-compliant server by the histotechnicians. Three study pathologists independently accessed and reviewed the images after a 6-week washout. The agreement between diagnoses established on GSM and WSI across the pathologists was described and measured using Cohens\' kappa coefficient (κ).
UNASSIGNED: On GSM, 65.5% (n=84) of specimens were lymphoma; 25% were classified as benign, while 9.5% were metastatic. Morphological quality assessment on GSM and WSI established that 79.8% and 53.6% of cases were of high quality, respectively. When diagnoses by GSM were compared to WSI, the overall concordance for various diagnostic categories was 93%, 100%, and 86% for lymphoma, metastases, and benign conditions respectively. The sensitivity and specificity of WSI for the detection of lymphoma were 95.2% and 85.7%, respectively, with an overall inter-observer agreement (κ) of 0.86; 95% CI (0.70-0.95).
UNASSIGNED: We demonstrate that mobile whole slide imaging (WSI) is non-inferior to conventional glass slide microscopy (GSM) for the primary diagnosis of malignant infiltration of lymph node specimens. Our results further provide proof of concept that mobile WSI can be adapted to resource-restricted settings for primary surgical pathology and would significantly improve patient outcomes.

To study the accuracy and precision of estimating the prevalence, extent and associated risks of untreated periodontitis using partial-mouth recording protocols (PRPs) Methods: A purposive sample of 431 individuals who had never been treated for periodontal disease was recruited from screening clinics at the King Saud bin Abdul-Aziz University for Health Sciences. Data were collected using questionnaires and clinical examinations. The prevalence, extent and risk associations of periodontitis were evaluated. Three PRPs were compared to full-mouth recordings (FRPs) in terms of the sensitivity, specificity, predictive values, and absolute bias. Results: The prevalence of periodontitis was estimated with the highest accuracy and precision by examinations of the full mouth at the mesiobuccal and distolingual sites (FM)MB-DL, followed by random half-mouth (RHM) recordings. The extent of periodontitis was estimated with high precision using all the PRPs, and the absolute bias ranged from -0.6 to -2.3. The absolute bias indicated by OR for risk associations was small for the three PRPs and ranged from -0.8 to 0.8. Conclusion: (FM)MB-DL and RHM were the PRPs with moderate to high levels of accuracy and precision for estimating the prevalence and risk associations of periodontitis. The extent of periodontitis was estimated with high precision using all three PRPs. The results of this study showed that the magnitude and direction of bias were associated with the severity of periodontitis, the selected PRPs and the magnitude of the risk associations.

BACKGROUND: Saroglitazar-a unique dual peroxisome proliferator-activated receptor agonist was approved marketing authorization in India in 2013 for diabetic dyslipidemia. Postmarketing studies have additionally shown improvement in liver parameters in diabetic dyslipidemia patients with nonalcoholic fatty liver disease (NAFLD) who received saroglitazar.
OBJECTIVE: The aim of this study was to evaluate the effect of saroglitazar on liver function test, liver fibrosis score by FibroScan, lipid profiles, HbA1c in NAFLD patients with diabetic dyslipidemia in southern India.
METHODS: A prospective, interventional, pilot study was performed to study the safety and efficacy of saroglitazar in NAFLD patients having type 2 diabetes mellitus. About 97 patients were screened, of which 85 patients were involved in the study based on the inclusion criteria. The clinical parameters and liver stiffness were measured at the baseline and also after 12 weeks of treatment with administration of saroglitazar 4 mg once daily. The change in the parameters at the baseline and after the end of the treatment was measured and was subjected to statistical analysis using SPSS software.
RESULTS: The recruited patients received saroglitazar and were followed up for a period of 12 weeks. The clinical parameters such as fasting blood sugar, postprandial blood sugar, HbA1c, total cholesterol, triglycerides, SGPT, and liver stiffness showed significant difference after 12 weeks of treatment when compared with the baseline values. No adverse drug reaction was reported in patients receiving saroglitazar during the study.
CONCLUSIONS: Saroglitazar was found to show significant improvement in liver parameters in NAFLD patients with a significant reduction in liver fibrosis and triglycerides level.

UNASSIGNED: There is an unmet need for non-invasive biomarkers for the diagnosis of nonalcoholic steatohepatitis (NASH) in non-specialized settings. We aimed to develop and validate a non-invasive test for diagnosing NASH in individuals with biopsy-proven nonalcoholic fatty liver disease (NAFLD).
UNASSIGNED: We developed a non-invasive test named the acNASH index that combines serum creatinine and aspartate aminotransferase levels in a derivation cohort of 390 Chinese NAFLD patients admitted to the hepatology center of the First Affiliated Hospital of Wenzhou Medical University (China) between December 2016 and September 2019 and subsequently validated in five external cohorts of different ethnicities of patients with biopsy-confirmed NAFLD (pooled n=1,089).
UNASSIGNED: The performance of the acNASH index for identifying NASH (defined as NAFLD activity score ≥5 with score of ≥1 for each steatosis, lobular inflammation and ballooning) was good in the derivation cohort with an area under receiver operating characteristics (AUROC) of 0·818 (95%CI 0·777-0·860). A cutoff of acNASH index <4·15 gave a sensitivity (Se) of 91%, a specificity (Sp) of 48% and a negative predictive value (NPV) of 83% for ruling-out NASH, conversely, a cutoff of acNASH >7·73 gave a Sp of 91%, Se of 53% and a positive predictive value (PPV) of 85% for ruling-in NASH. In the pooled validation cohort (n=1,089), the diagnostic performance of the index was also good with AUROC=0·805 (95%CI 0·780-0·830), NPV of 93% for ruling-out NASH and PPV of 73% for ruling-in NASH. Subgroup analyses showed similar performance in patients with diabetes or subjects with normal serum transaminase levels.
UNASSIGNED: The acNASH index shows promising utility as a simple non-invasive biomarker for diagnosing NASH among adults with biopsy-proven NAFLD of different ethnicities from different countries.
UNASSIGNED: The National Natural Science Foundation of China (82070588), High Level Creative Talents from Department of Public Health in Zhejiang Province (S2032102600032) and Project of New Century 551 Talent Nurturing in Wenzhou.

Acute liver failure (ALF) is an infrequent, unpredictable, potentially fatal complication of acute liver injury (ALI) consequent to varied etiologies. Etiologies of ALF as reported in the literature have regional differences, which affects the clinical presentation and natural course. In this part of the consensus article designed to reflect the clinical practices in India, disease burden, epidemiology, clinical presentation, monitoring, and prognostication have been discussed. In India, viral hepatitis is the most frequent cause of ALF, with drug-induced hepatitis due to antituberculosis drugs being the second most frequent cause. The clinical presentation of ALF is characterized by jaundice, coagulopathy, and encephalopathy. It is important to differentiate ALF from other causes of liver failure, including acute on chronic liver failure, subacute liver failure, as well as certain tropical infections which can mimic this presentation. The disease often has a fulminant clinical course with high short-term mortality. Death is usually attributable to cerebral complications, infections, and resultant multiorgan failure. Timely liver transplantation (LT) can change the outcome, and hence, it is vital to provide intensive care to patients until LT can be arranged. It is equally important to assess prognosis to select patients who are suitable for LT. Several prognostic scores have been proposed, and their comparisons show that indigenously developed dynamic scores have an edge over scores described from the Western world. Management of ALF will be described in part 2 of this document.

BACKGROUND: To evaluate the safety and efficacy of ultrasound-guided (US-guided) omental biopsy in patients with liver cirrhosis and compare these with the noncirrhotic patients.
METHODS: We retrospectively studied the US-guided omental biopsies (73 males, 14 females with mean age 52.71 ± 15.90 y) between January 2012 and December 2018. Patients with biopsy-proven liver cirrhosis (n = 31) who underwent omental biopsy were included in Group 1, and patients without any features of the chronic liver disease (n = 56) were included in Group 2. The technical success, diagnostic parameters, complications, imaging appearance, and histopathology spectrum were compared between the two groups. Also, univariate analysis was done to evaluate the association of a parameter with histopathology.
RESULTS: The technical success, sample adequacy, diagnostic accuracy of Group 1 were 100%, 96.77%, and 96.77%, respectively, and for Group 2, these were 100%, 98.21%, and 98.21%, respectively. The sensitivity, specificity, positive predictive value, negative predictive value of Group 1 were 95%, 100%, 100%, 91.67%, respectively, and for Group 2, these were 97.92%, 100%, 100%, 88.89%, respectively. There was one complication of abdominal wall hematoma in Group 1 (3.2%), which was managed conservatively. Smudged imaging appearance and nonspecific inflammation on histopathology were more common in Group 1, and there was a significant association of increased omental thickening with specific pathology in Group 1.
CONCLUSIONS: US-guided omental biopsy in patients with liver cirrhosis is safe and effective with comparable results to noncirrhotic patients.

BACKGROUND: High-sensitivity cardiac troponin I (hs-cTnI) assays have been developed that quantify lower cTnI concentrations with better precision versus earlier generation assays. hs-cTnI assays allow improved clinical utility for diagnosis and risk stratification in patients presenting to the emergency department with suspected acute myocardial infarction. We describe the High-Sensitivity Cardiac Troponin I Assays in the United States (HIGH-US) study design used to conduct studies for characterizing the analytical and clinical performance of hs-cTnI assays, as required by the US Food and Drug Administration for a 510(k) clearance application. This study was non-interventional and therefore it was not registered at clinicaltrials.gov.
METHODS: We conducted analytic studies utilizing Clinical and Laboratory Standards Institute guidance that included limit of blank, limit of detection, limit of quantitation, linearity, within-run and between run imprecision and reproducibility as well as potential interferences and high dose hook effect. A sample set collected from healthy females and males was used to determine the overall and sex-specific cTnI 99th percentile upper reference limits (URL). The total coefficient of variation at the female 99th percentile URL and a universally available American Association for Clinical Chemistry sample set (AACC Universal Sample Bank) from healthy females and males was used to examine high-sensitivity (hs) performance of the cTnI assays. Clinical diagnosis of enrolled subjects was adjudicated by expert cardiologists and emergency medicine physicians. Assessment of temporal diagnostic accuracy including sensitivity, specificity, positive predictive value, and negative predictive value were determined at presentation and collection times thereafter. The prognostic performance at one-year after presentation to the emergency department was also performed. This design is appropriate to describe analytical characterization and clinical performance, and allows for acute myocardial infarction diagnosis and risk assessment.

OBJECTIVE: To evaluate and analyse the efficacy of computed tomography (CT) virtual cystoscopy in comparison to conventional cystoscopy for the follow-up of patients with non-muscle-invasive bladder cancer.
METHODS: The study was done over 3 years, from April 2010 to June 2013, and included 30 patients who all had non-muscle-invasive transitional cell carcinoma (Ta, T1). The patients all underwent complete transurethral resection of the tumour and presented for first follow-up check cystoscopy. The examination was performed using a 16-slice multi-detector (MD) CT scanner. The results were compared for sensitivity and specificity in relation to the site, size, and shape of the tumour.
RESULTS: In all, 20 lesions were detected by CT virtual cystoscopy in 18 patients, whilst the remaining 12 were lesion free. Conventional cystoscopy, detected 23 lesions in 19 patients. The sensitivity of the virtual images was 87%; its specificity in identifying lesions was 100%, with a positive predictive value of 100% and negative predictive value of 78.5%.
CONCLUSIONS: CT virtual cystoscopy is a promising technique for detecting bladder tumours and some other bladder lesions. However, the detection rate for recurrent NMIBC does not appear to be adequate to replace conventional cystoscopy.

OBJECTIVE: To investigate the role of an abnormal prostate-specific antigen (PSA) level and abnormal findings on a digital rectal examination (DRE) in the detection of prostate cancer in men in Qatar.
METHODS: Between June 2008 and September 2012, 651 patients had a transrectal ultrasonography-guided biopsy of the prostate (TRUSBP) at our centre. The indications for a biopsy were a high PSA level (>4 ng/mL), or an abnormal DRE result. Patients were assessed by a thorough history, clinical examination and routine laboratory investigations. Data, including age, DRE findings, TRUS findings, total PSA level, prostate volume and the pathology results, were evaluated.
RESULTS: The mean (SD) age of the 651 patients was 64.1 (7.4) years. Prostate cancer was detected in 181 men (27.8%), benign prostatic hyperplasia in 275 (42.2%) and prostatitis in 236 (36.4%). The sensitivity and specificity for detecting prostate cancer were 93.9% and 8.5% for an abnormal PSA level (>4 ng/mL), 46.1% and 84.7% for abnormal DRE findings, and 95% and 30.2% for the two combined. Using a receiver operating characteristics curve, a PSA threshold of 7.9 ng/mL had a sensitivity of 56.6% and specificity of 52.8%. When a PSA threshold of 7.9 ng/mL was used in combination with abnormal DRE findings, the overall accuracy was 76.9%.
CONCLUSIONS: The PSA threshold level of 7.9 ng/mL, determined by this analysis, has a higher likelihood of detecting prostate cancer in men in Qatar. However, it failed to detect cancer in substantially many men with statistically significant disease.