Ensemble for evaluating diagnostic efficacy of non-invasive indices in predicting liver fibrosis in untreated hepatitis C virus population.

BACKGROUND: Hepatitis C virus (HCV) infection progresses through various phases, starting with inflammation and ending with hepatocellular carcinoma. There are several invasive and non-invasive methods to diagnose chronic HCV infection. The invasive methods have their benefits but are linked to morbidity and complications. Thus, it is important to analyze the potential of non-invasive methods as an alternative. Shear wave elastography (SWE) is a non-invasive imaging tool widely validated in clinical and research studies as a surrogate marker of liver fibrosis. Liver fibrosis determination by invasive liver biopsy and non-invasive SWE agree closely in clinical studies and therefore both are gold standards. AIM: To analyzed the diagnostic efficacy of non-invasive indices [serum fibronectin, aspartate aminotransferase to platelet ratio index (APRI), alanine aminotransferase ratio (AAR), and fibrosis-4 (FIB-4)] in relation to SWE. We have used an Artificial Intelligence method to predict the severity of liver fibrosis and uncover the complex relationship between non-invasive indices and fibrosis severity. METHODS: We have conducted a hospital-based study considering 100 untreated patients detected as HCV positive using a quantitative Real-Time Polymerase Chain Reaction assay. We performed statistical and probabilistic analyses to determine the relationship between non-invasive indices and the severity of fibrosis. We also used standard diagnostic methods to measure the diagnostic accuracy for all the subjects. RESULTS: The results of our study showed that fibronectin is a highly accurate diagnostic tool for predicting fibrosis stages (mild, moderate, and severe). This was based on its sensitivity (100%, 92.2%, 96.2%), specificity (96%, 100%, 98.6%), Youden's index (0.960, 0.922, 0.948), area under receiver operating characteristic curve (0.999, 0.993, 0.922), and Likelihood test (LR+ > 10 and LR- < 0.1). Additionally, our Bayesian Network analysis revealed that fibronectin (> 200), AAR (> 1), APRI (> 3), and FIB-4 (> 4) were all strongly associated with patients who had severe fibrosis, with a 100% probability. CONCLUSION: We have found a strong correlation between fibronectin and liver fibrosis progression in HCV patients. Additionally, we observed that the severity of liver fibrosis increases with an increase in the non-invasive indices that we investigated.

Clinical and Histopathological Characteristics in Women With Postmenopausal Bleeding: A Study of 120 Women in a Tertiary Care Hospital in Punjab.

Background Postmenopausal bleeding (PMB) is defined as blood loss from the genital tract occurring 12 months or more after an individual's last menstrual period. It is important for women to recognize abnormal symptoms during menopause, with PMB being one of the most critical. PMB is a common clinical presentation and can be indicative of endometrial carcinoma. A thorough clinical assessment and endometrial histopathology can ensure early diagnosis and treatment of malignancy in high-risk patients. Materials and Methods This study included 120 women with PMB. Their clinical and histopathological characteristics were studied, and correlations between the characteristics were investigated. Patients were evaluated according to their age, parity, duration of menopause, and socioeconomic status. Various comorbidities such as diabetes mellitus, hypertension, and obesity were noted. Results The patients ranged in age from 45 to 80 years, with a mean age of 54.97 ± 5.86 years. Fifty-nine (49.16%) of the patients presented with PMB within 3 years of menopause. PMB was seen most commonly in patients with parity 3, accounting for 37 (30.83%) of the cases. Endometrial thickness was increased in 100 (83.33%) cases. The most common causes of PMB were simple hyperplasia without atypia (SHWOA) in 36 (36%) patients and atrophic endometrium in 14 (14%) patients. Twelve (10%) of the patients had endometrial carcinoma. Benign causes of PMB were present in 91 (75.3%) cases, whereas 29 (24.1%) had a malignant cause. Weakly positive, but significant correlations (P < 0.05) were seen between the development of malignancy and increasing age (Pearson correlation coefficient, r = 0.263) parity (r = 0.244), and body mass index (r = 0.272). Conclusions PMB is considered abnormal. Benign causes are more common, but malignant causes are possible. In the current study, endometrial carcinoma was the most common malignant cause of PMB. Endometrial carcinoma incidence increased with greater endometrial thickness and more years since menopause. Histopathological examination remains the criterion standard for the correct diagnosis. Initiatives are recommended for increasing awareness about PMB to support prompt medical attention for a better prognosis.

A Comparative Study of Serum and Salivary Uric Acid Measurement in Pre-eclampsia and Normal Pregnancy in a Tertiary Care Hospital in Punjab: A Pilot Study.

Background Pre-eclampsia is a multisystem progressive disorder associated with significant maternal and neonatal morbidity and mortality. It is essential to identify the potential indicators of associated complications in pre-eclampsia to improve pregnancy outcomes. Serum uric acid (UA) levels are increased in pregnancies complicated by pre-eclampsia. This study was performed to validate salivary UA as an alternative non-invasive biomarker to serum UA in pre-eclampsia. Methodology A total of 150 pregnant women were enrolled in the study. They were divided equally into three groups with 50 participants in each group. Group 1 included healthy normotensive pregnant women as control, group 2 included participants with non-severe pre-eclampsia and group 3 included participants with severe pre-eclampsia. Both salivary and serum UA were estimated in all the study participants and comparative analyses were done. Results Serum UA was elevated in 33(66%) and 48(96%) of participants in groups 2 and 3 respectively while saliva uric acid in 30(60%) and 43(86%) as compared with healthy controls who had serum UA raised in 14(28%) and salivary UA in 12(24%) with a significant p-value of 0.0001. The mean values of serum and salivary UA in group 1 were 4.5 ±1.16 mg/dl and 4.11±1.74 mg/dl respectively whereas in group 2 these were 6.12±1.86mg/dl and 5.96±1.90mg/dl and in group 3 these were 8.24±2.31mg/dl and 8.17±3.31mg/dl respectively. There was a significant correlation between serum and salivary UA values in groups 1 and 2, groups 1 and 3, and groups 2 and 3 with a p-value of 0. 001. The serum and salivary UA levels showed an increasing trend from healthy controls (group 1) to non-severe pre-eclampsia (group 2) with the highest values in severe pre-eclampsia (group 3). Oligohydramnios was present in 10(20%) cases in group 1 whereas 24(48%) cases in group 3. The appearance, pulse, grimace, activity, respiration (APGAR) score at 1 and 5 minutes was abnormal in 5(1.23%) and 7(1.33%) cases in group 1, 6(1.26%) and 7(1.29%) cases in group 2 and 5(1.73%) and 6(1.53%) cases in group 3. The area under curve (AUC) in group 2 was 0.778 for serum UA and 0.779 for salivary UA. In group 3, the AUC for serum UA values was 0.938 and for salivary UA 0.882. A statistically significant correlation between serum and salivary UA values in group 2 (non-severe pre-eclampsia) was found with a p-value of 0.001 and Pearson's correlation coefficient r of 0.738. Conclusions Serum and salivary UA levels correlate with the severity of pre-eclampsia with maximum levels in severe pre-eclampsia (group 3) followed by group 2 (non-severe pre-eclampsia) with the lowest levels in group 1 (healthy controls). The authors are of the opinion that a non-invasive salivary UA test can replace the serum UA test and can be a useful supplementation for conventional pre-eclampsia prediction.

To Compare the Maternal and Fetal Outcomes of COVID-19-Affected Expectant Mothers During the First and Second COVID-19 Waves: Data From a Tertiary Care Referral Hospital in Punjab.

BACKGROUND: Coronavirus 2019 (COVID-19) infection, declared pandemic in March 2020 by the World Health Organization, paved the way for newer research in the field of medicine. The second wave, beginning in March 2021, appeared to be more devastating. The purpose of this study is to evaluate the clinical characteristics, effects of COVID-19 infection in pregnancy, and obstetric and perinatal outcomes in the first and second waves. MATERIALS AND METHODS: This study was conducted from January 2020 to August 2021 at the Guru Gobind Singh Medical College and Hospital, Faridkot, Punjab. The patients were enrolled immediately after each infected woman was identified as per the inclusion and exclusion criteria. Demographic details of the patients, associated comorbid conditions, intensive care unit (ICU) admission, and treatment details were noted. Neonatal outcomes were recorded. The testing of pregnant women was done as per the Indian Council of Medical Research (ICMR) guidelines. RESULTS: There were 3421 obstetric admissions and 2132 deliveries during this period. Group 1 had 123 COVID-19-positive admissions, while group 2 had 101 admissions. The incidence of COVID-19 infection in pregnancy was 6.54%. In both groups, the majority of patients were between the ages of 21 and 30. About 80(66%) of the admissions in group 1 and 46(46%) in group 2 were in the gestational age of 29-36 weeks. Multiparity was more common in both groups, with 58% of cases in group 1 and 79% of cases in group 2. Obstetric comorbidities were common in both groups, seen in 46% of cases in group 1 and 78% of cases in group 2. The majority of patients were asymptomatic in group 1, with an 89% incidence, whereas only 33% of patients in group 2 were without symptoms. In biological data, D-dimers, prothrombin time, and platelet count were altered in 11%, 14%, and 17% of cases, respectively, in group 2, with almost normal data in group 1. Most cases in group 2 (52%) were critical cases in the moderate and severe categories requiring intensive care unit (ICU) treatment, whereas there was only single ICU admission in group 1. The overall case fatality rate (CFR) in group 2 was found to be 19.8(20/101).  Delivery by cesarean section was done in 38.2% of cases in group 1, while in 33% of cases in group 2, with a significant p-value of 0.001. About 29% of cases in group 1 and 34% of cases in group 2 underwent vaginal delivery. The rate of abortion was almost similar in both groups. Only two cases in group 1 and nine cases in group 2 had intrauterine fetal death. Observations of neonatal outcomes suggested that five cases in group 2 and two cases in group 1 had severe birth asphyxia. Only one case in group 1 and four cases in group 2 had positive COVID-19 status. Maternal mortality was significantly higher in group 2 with 20 cases, while only one case was in group 1. Anemia and pregnancy-induced hypertension were the chief comorbidities in this group. CONCLUSION: COVID-19 infection during pregnancy may be associated with maternal mortality while having a minimal effect on neonatal morbidity and mortality. The possibility of maternal-fetal transmission cannot be ruled out completely. The severity and characteristics of COVID-19 may vary in each wave, and we need to modify treatment strategies. More studies or meta-analyses reports are required to authenticate this transmission.

Clinicoradiological profile and outcome of cavernous sinus syndrome with coronavirus disease-2019-associated rhino-orbito-cerebral mucormycosis.

Objective: With coronavirus disease 2019 (COVID-19) pandemic across the world, there had been an exponential increase in rhino-orbito-cerebral mucormycosis (ROCM). Extension of infection to cavernous sinus leads to cavernous sinus syndrome (CSS). This study aims to describe incidence, clinicoradiological profile, and outcome of CSS positive along with comparative analysis of CSS negative COVID-19-associated ROCM. Material and Method: This was a prospective and observational study conducted from May 1, 2021, to July 31, 2021. Subjects included ROCM with active or recovered COVID-19 (past 6 weeks) and were categorized and staged. CSS was defined as involvement of two or more of third, fourth, fifth, or sixth cranial nerve with one each direct and indirect qualitative neuroradiological features. Clinicoradiological features of CSS-positive and negative COVID-19-associated ROCM groups were compared. Results: Incidence of CSS with COVID-19-associated ROCM was 28%. Mean age of subjects was 44 ± 15 years with 60% being males and 73% were proven ROCM. Significant differences seen across the CSS-positive and negative groups were ocular, nasal, and cerebral findings including eyelid and periocular discoloration, ptosis, proptosis, ophthalmoplegia, nasal discharge, mucosal inflammation, and fever. Oculomotor, trochlear, and abducens nerves were significantly involved more in CSS-positive group. Significant radiological findings across two groups included indirect features in orbit, nose, and paranasal sinuses along with direct features in cavernous sinus. Surgical intervention was more common in CSS-positive group. Mortality in CSS-positive group at 8-24 weeks was 13 and 27%, respectively. Conclusion: Extension of ROCM to CSS was more common in young males in advanced stages of proven ROCM with concurrent COVID-19. CSS-positive group had significant difference in clinicoradiological features involving orbit, nose, paranasal sinuses, and central nervous system as compared to CSS-negative group. This study highlights the need to develop an objective scoring system considering clinical and radiological features for diagnosis of CSS with COVID-19-associated ROCM.

Correlation of Surrogate Markers of Insulin Resistance with Fasting Insulin in Type 2 Diabetes Mellitus Patients: A Study of Malwa Population in Punjab, India.

Context Insulin resistance (IR) and abnormal insulin secretion play a key role for the development of type 2 diabetes mellitus (DM). Aims We investigated the surrogate markers of IR, i.e., Homeostasis Model Assessment (HOMA), Quantitative Insulin Sensitivity Check Index (QUICKI), McAuley, and Fasting Insulin Resistance Index (FIRI) in type 2 DM patients. Also, fasting insulin (FI) levels were estimated in type 2 diabetics. Further, the correlation of FI with other surrogate markers of IR in type 2 DM was done. Settings and Design A hundred newly diagnosed patients with type 2 DM from Malwa population, Punjab, were considered for evaluation. Another 100 healthy individuals (age and sex-matched) were examined as controls. Methods and Material Fasting blood glucose, FI, and lipid profile were estimated, and IR was calculated using McAuley index (McA), HOMA, QUICKI, and FIRI. Statistical Analysis Used The statistical analysis was performed on the above-mentioned clinical interpretations. The Cohen's kappa test was used to affirm the agreement. Results FI levels in patients with type 2 diabetes were significantly higher (20.8 ± 9.05 µIU/L) than controls (7.93 ± 1.01 µIU/L). IR by surrogate markers was found significant in the study group. The 76% patients with type 2 diabetes ended up as resistant to insulin by FI measurement, almost equivalent to McA, 80%; HOMA, 88%; FIRI, 88%; and QUICKI, 90%. A notable correlation was highlighted between FI and McA manifesting IR ( p < 0.01, r = -0.85). We calculated the statistical correlation of FI with HOMA, QUICKI, and FIRI indices ( p < 0.01, r = 0.93; p < 0.01 r = -0.92; and p < 0.01, r = +0.93, respectively). The agreement visible from Cohen's kappa test also affirms the same ( k = 0.9 for McA). Conclusion We concluded that all the surrogate markers for IR were specific when compared with FI, but in terms of sensitivity McA was found to be more sensitive as it includes markers of dyslipidemia, which is the precipitating factor of metabolic derangements so as the IR in type 2 DM.

Potential role of noninvasive biomarkers during liver fibrosis.

Various types of liver disease exist, such as hepatitis and alcoholic liver disease. These liver diseases can result in scarring of liver tissue, cirrhosis, and finally liver failure. During liver fibrosis, there is an excess and disorganized accumulation of extracellular matrix (ECM) components which cause the loss of normal liver cell functions. For patients with chronic liver disease, fibrosis prediction is an essential part of the assessment and management. To diagnose liver fibrosis, several invasive and noninvasive markers have been proposed. However, the adoption of invasive markers remains limited due to their inherent characteristics and poor patient acceptance rate. In contrast, noninvasive markers can expedite the clinical decision through informed judgment about disease stage and prognosis. These noninvasive markers are classified into two types: Imaging techniques and serum biomarkers. However, the diagnostic values of biomarkers associated with liver fibrosis have also been analyzed. For example, the serum levels of ECM proteins can react to either matrix accumulation or degradation. During virus-host interactions, several regulatory steps take place to control gene expression, such as the change in cellular microRNA expression profiles. MicroRNAs are a class of non-coding RNAs (18-20 long nucleotides) that function by post-transcriptional regulation of gene expression. Although various noninvasive markers have been suggested in recent years, certain limitations have restricted their clinical applications. Understanding the potential of non-invasive biomarkers as a therapeutic option to treat liver fibrosis is still in progress.

Neurenteric Cyst: Magnetic Resonance Imaging Findings in an Adolescent.

Intracranial neurenteric cysts are uncommon congenital space-occupying lesions that may be misinterpreted for other more frequent nonneoplastic cysts and cystic tumors. We discuss the imaging findings of this lesion in a 16-year-old female who presented with chronic headaches.

Evaluation of bowel wall thickening by computed tomography to differentiate benign from malignant lesions.

PURPOSE: Computed tomography(CT) is an excellent non-invasive modality to evaluate bowel wall thickening.The aim of our study was to evaluate CT appearance of bowel wall thickening due to various benign and malignant conditions taking into consideration pattern of attenuation, bowel wall thickness, extent of lesion, symmetry of lesion and other associated CT findings. MATERIALS AND METHODS: The prospective study was carried out on 50 patients who underwent computed tomographic evaluation of abdomen for suspicion of bowel pathology based on ultrasonography, barium studies and/or clinical grounds. The studies were conducted on Siemens ART and GE High speed CT scanners. The examination was performed as is done routinely for an abdominal scan with imaging done from diaphragm to pubic symphysis in supine position with the right lateral decubitus scans in selected cases for better characterization of gastric antral and duodenal lesions. Oral, rectal and intravenous (IV) contrast agents were administered. The diagnosis was confirmed by cytology or histopathology of any biopsy or surgical specimen. However, in cases where surgery was not done, diagnosis was confirmed by clinical response to medical treatment. RESULTS: Based on the various CT characteristics of abnormal bowel wall thickening, sensitivity and specificity of classifying a lesion as benign or malignant were calculated. Majority of the malignant bowel lesions were showing the following characteristics i.e. heterogeneous pattern of enhancement, marked bowel wall thickening, asymmetry of the lesion and focal/segmental bowel involvement. Overall, CT showed a sensitivity of 97% and specificity of 93% in differentiating between benign and malignant etiology of abnormal bowel wall thickening. CONCLUSION: Due to its high sensitivity and specificity, CT is an ideal imaging modality for differentiating between benign and malignant etiology of abnormal bowel wall thickening. Radiologists should be aware of the usefulness of specific CT criteria of bowel wall thickening to better differentiate benign lesions from malignant or potentially malignant lesions that warrant further diagnostic evaluation.

Acoustic radiation force impulse imaging of the liver: measurement of the normal mean values of the shearing wave velocity in a healthy liver.

AIM: To find the normal mean values of the liver elasticity/stiffness by Acoustic Radiation Force Impulse (ARFI) Elastography in healthy subjects. MATERIAL AND METHOD: This study was conducted on 137 healthy subjects without any known liver pathology or a history of jaundice by using the Siemens Acuson S2000TM Ultrasound machine with a convex probe . A routine ultrasound was also performed in each case, and the subjects with fatty liver changes or any other signs of a chronic liver pathology were excluded. In each subject, 10 measurements were taken and the median value of the 10 measurements was calculated, which was expressed in metres/sec (m/s). The inter quartile range method was used for the interpretation of the data. Only the measurements with an IQR of < 30% and a Success Rate (SR) of >60% were considered. The measurements were taken at 1-2 cm depth from the liver capsule through an intercostal approach, with the subject lying in the decubitus position. The mean ARFI values and the mean values according to the age and gender of the subjects were evaluated. RESULT: Valid ARFI measurements were taken in 108/137 patients (78.83%). The mean value of the ARFI measurements in the normal individuals was 1.197±0.25 m/s. There were no significant differences between the mean ARFI values in men vs women (1.195±.25 vs. 1.199±0.26m/s, p = 0.939), and also among the different age groups (p>0.05). CONCLUSION: In our study, the mean liver elasticity value (shearing wave velocity) which was obtained by ARFI in the healthy subjects was 1.197±0.25 m/s.