Vonoprazan causes symptomatic improvement in non-erosive gastroesophageal reflux disease: A systematic review and meta-analysis.

OBJECTIVE: To evaluate the efficacy and safety of vonoprazan therapy as compared to conventional proton pump inhibitors (PPIs) or no vonoprazan for non-erosive esophagitis. METHODS: A thorough search was conducted across databases. The primary outcome was to determine the mean variance in the gastroesophageal reflux disease (GERD) score after vonoprazan treatment. Secondary outcomes comprised alterations in the scores for epigastric pain and post-prandial distress, the proportion of patients displaying improvement, and the occurrence of adverse events. Pooled mean differences and relative risks were determined utilizing random effects models. RESULTS: A total of 1,944 articles were screened and nine of them were included. As compared to PPI or no vonoprazan therapy, vonoprazan treatment led to a significant reduction in the GERD score [mean difference: -3.88 (95 % CI: -5.48, -2.28), p < 0.01, i2=95 %]. As compared to PPI or no vonoprazan therapy, vonoprazan treatment led to a significant reduction in the epigastric pain score [mean difference: -3.02 (95 % CI: -5.41, -0.63), p = 0.01, i2=75 %] and post-prandial distress score [mean difference: -2.82 (95 % CI: -3.51, -2.12), p < 0.01, i2=0 %] (all moderate GRADE evidence). Vonoprazan therapy was found to be safe. CONCLUSION: Treatment with vonoprazan could significantly improve symptoms in patients with non-erosive esophagitis or non-erosive GERD.

Role of semaglutide in the treatment of nonalcoholic fatty liver disease or non-alcoholic steatohepatitis: A systematic review and meta-analysis.

AIM: This systematic review and meta-analysis was conducted to evaluate the efficacy and safety of 24 weeks of semaglutide treatment in patients with non-alcoholic fatty liver disease (NAFLD) or non-alcoholic steatohepatitis (NASH). METHODS: PubMed, Embase, Scopus, Cochrane CENTRAL, and ClinicalTrials.gov databases were searched for relevant studies. The primary outcome was the change in the serum alanine transaminase level. The secondary outcomes were changes in liver stiffness, liver function test parameters, metabolic parameters, and safety. Pooled mean differences and relative risks were calculated using random-effects models. RESULTS: Six hundred studies were screened and eight were included (n = 2413). Semaglutide treatment showed a reduction in serum alanine transaminase [mean difference: 14.07 U/L (95% CI: 19.39 to -8.75); p < 0.001] and aspartate transaminase [mean difference: 6.89 U/L (95% CI: 9.14 to -4.63); p < 0.001] levels. There was a significant improvement in liver fat content [mean difference: 4.97% (95% CI: 6.65 to -3.29); p < 0.001] and liver stiffness [mean difference: 0.96 kPa (95% CI: 1.87 to -0.04); p = 0.04]. There were significant improvements in the glycated hemoglobin level and the lipid profile. However, the risk of serious adverse events [relative risk: 1.54 (95% CI: 1.02 to 2.34); p = 0.04] was high following semaglutide treatment as compared to placebo; the most common ones were gastrointestinal (nausea and vomiting, dyspepsia, decreased appetite, constipation, and diarrhea) and gallbladder-related diseases. CONCLUSION: Treatment with 24 weeks of semaglutide could significantly improve liver enzymes, reduce liver stiffness, and improve metabolic parameters in patients with NAFLD/NASH. However, the gastrointestinal adverse effects could be a major concern.

Effects of saroglitazar in the treatment of non-alcoholic fatty liver disease or non-alcoholic steatohepatitis: A systematic review and meta-analysis.

AIM: This systematic review and meta-analysis was conducted to evaluate the efficacy and safety of 4 mg saroglitazar treatment in patients with non-alcoholic fatty liver disease (NAFLD) or non-alcoholic steatohepatitis (NASH). METHODS: PubMed, Embase, Scopus, Cochrane CENTRAL, medRxiv (pre-print), bioRxiv (pre-print), and ClinicalTrials.gov databases were searched for relevant studies. The primary outcome was the change in the serum alanine transaminase (ALT) level. The secondary outcomes were changes in liver stiffness, liver function test parameters, and metabolic parameters. Pooled mean differences were calculated using random-effects models. RESULTS: Of 331 studies that were screened, ten were included. Treatment with adjunct saroglitazar showed a reduction in ALT [mean difference: 26.01 U/L (95% CI: 10.67 to 41.35); p = 0.009; i2: 98%; moderate GRADE evidence] and aspartate transaminase [mean difference: 19.68 U/L (95% CI: 8.93 to 30.43); p<0.001; i2: 97%; moderate GRADE evidence] levels. There was a significant improvement in liver stiffness [mean difference: 2.22 kPa (95% CI: 0.80 to 3.63); p = 0.002; i2: 99%; moderate GRADE evidence]. There were significant improvements in glycated hemoglobin [mean difference: 0.59% (95% CI: 0.32 to 0.86); p<0.001; i2: 78%; moderate GRADE evidence], total cholesterol [mean difference: 19.20 (95% CI: 1.54 to 36.87); p = 0.03; i2: 95%; moderate GRADE evidence], and triglyceride [mean difference: 105.49 mg/dL (95% CI: 11.18 to 199.80); p = 0.03; i2: 100%; moderate GRADE evidence] levels. Saroglitazar treatment was safe. CONCLUSION: Treatment with adjunct 4 mg saroglitazar could significantly improve liver enzymes, reduce liver stiffness, and improve metabolic parameters (serum glucose and lipid profile) in patients with NAFLD or NASH.

ZRC3308 Monoclonal Antibody Cocktail Shows Protective Efficacy in Syrian Hamsters against SARS-CoV-2 Infection.

We have developed a monoclonal antibody (mAb) cocktail (ZRC-3308) comprising of ZRC3308-A7 and ZRC3308-B10 in the ratio 1:1 for COVID-19 treatment. The mAbs were designed to have reduced immune effector functions and increased circulation half-life. mAbs showed good binding affinities to non-competing epitopes on RBD of SARS-CoV-2 spike protein and were found neutralizing SARS-CoV-2 variants B.1, B.1.1.7, B.1.351, B.1.617.2, and B.1.617.2 AY.1 in vitro. The mAb cocktail demonstrated effective prophylactic and therapeutic activity against SARS-CoV-2 infection in Syrian hamsters. The antibody cocktail appears to be a promising candidate for prophylactic use and for therapy in early COVID-19 cases that have not progressed to severe disease.

Extraintestinal manifestations in inflammatory bowel disease: Prevalence and predictors in Indian patients.

BACKGROUND: There is a paucity of reports on extraintestinal manifestations (EIMs) in patients with inflammatory bowel diseases (IBD) from Asia and India. METHODS: From May 2011 to October 2012, consecutive IBD patients underwent a detailed history and physical examination, also by trained rheumatologist, dermatologist, and ophthalmologist, about whether they experienced any EIM at the time of inclusion or in the past. The disease phenotype/severity and location was classified according to the Montréal classification. All underwent magnetic resonance imaging (MRI) of sacroiliac joints, liver function test (LFT), transabdominal ultrasound, and dual energy X-ray absorptiometry (DEXA) scanning at neck femur (bilateral) and L4-L5 spine. RESULTS: One hundred twenty patients were analyzed, 62 had Crohn's disease (CD) and 58 had ulcerative colitis (UC). Thirty-eight percent had at least one while 20% suffered from multiple EIMs. Except for uveitis and episcleritis, the frequency of individual EIMs did not differ between CD and UC patients. Twenty-three percent had peripheral arthritis, 18% had ankylosing spondylitis, and 13% had ophthalmological manifestations. Mucocutaneous manifestations, aphthous stomatitis and pyoderma gangrenosum (PG), were seen in 9%. None had erythema nodosum (EN) or primary sclerosing cholangitis (PSC). Fifty percent of patients had either osteopenia or osteoporosis on DEXA. Multivariable analysis revealed female gender, Hindu religion, severe disease, and steroid usage were significantly associated with the presence of EIMs. CONCLUSION: The prevalence of EIM is similar to that reported from Europe and USA, albeit higher than that previously reported in Asian patients. Female sex, religion, severe disease, and steroid use were associated with EIM.

Hepatobiliary tuberculosis.

Hepatobiliary tuberculosis refers to the localized form of hepatic tuberculosis and is a distinct entity in which hepatobiliary involvement overwhelmingly dominates the clinical picture. Presentations are often delayed, and manifestations can be nonspecific. Fever is the most common symptom followed by abdominal pain, and hepatomegaly is the most common abnormality found on clinical examination. Abnormalities of the liver function tests are non-specific and hence not diagnostic. Ultrasound or computed tomography reveals single or complex masses, and guided biopsy is diagnostic either by demonstrating caseating granuloma or the organism by staining and culture. Treatment is with standard first-line antituberculous drugs. Endoscopic stenting gives an excellent outcome for symptomatic biliary strictures. The outcome in patients infected with Human Immunodeficiency virus depends on the level of underlying immunosuppression.

Atypical fibroxanthoma: an unusual skin neoplasm in xeroderma pigmentosum.

Xeroderma pigmentosum (XP) is a rare autosomal recessive disorder related to defective deoxyribonucleic acid (DNA) repair. Various cutaneous manifestations related to ultraviolet (UV) damage characterize the clinical course. Primary malignant cutaneous neoplasms like squamous cell carcinoma, basal cell carcinoma and malignant melanoma have been reported. Atypical fibroxanthoma is a rare dermal neoplasm occurring in UV-damaged skin. We report an unusual case of atypical fibroxanthoma in a 20-year-old male with XP.

Hypopituitarism following poisonous viperbite.

A 28 years old male had the history of viperbite 3 years back. He has treated in a nearby rural hospital with snake venom antiserum along with other supportive therapy. He responded and discharged from hospital within a week. Three years later he had history of fever, drowsiness which progressed to unconsciousness. On examination he was found to have scanty body hairs, smooth, shiny skin with superficial oral ulcers. Serum hormone estimation confirmed the deficiency of gonadotrophins, thyrotrophin and corticotrophin while growth hormone failed to rise >3ng/ml after insulin intolerance test. MRI brain revealed loss of pituitary mass with positive infundibular sign and filling of sella with cerebrospinal fluid. He was managed with hormone replacement therapy and recovered gradually.

Gauchers disease presenting with portal hypertension.

Gauchers disease is a rare lysosomal storage disorder characterized by abnormal accumulation of lipid-laden macrophages in different organs. Though hepatosplenomegaly is commonly found, symptomatic presentation with portal hypertension is rare. We report a child with liver cirrhosis and bleeding esophageal varices who was diagnosed with Gaucher's disease.

Migration and maturation pattern of fetal enteric ganglia: a study of 16 cases.

AIMS: To study the migration and developmental pattern of ganglion cells in fetuses aged 9-21 weeks, and to document whether the migration was occurring circumferentially equally in the entire axis or if there were discrepancies in different portions at the same level. SETTINGS AND DESIGN: The hypothesis regarding the pathogenesis of Hirschsprung's disease mainly revolves around two schools. One is the single gradient migration of ganglia and the other is a dual gradient migration theory. Understanding the embryological development of enteric ganglia is necessary to study the pathogenesis of intestinal innervation disorders. MATERIALS AND METHODS: We studied the development of intestinal ganglia in fetuses aged 9-21 weeks. Serial longitudinal sections from the colon were studied, the first one including the squamo-columnar junction, for the presence and the nature of ganglion cells with Hematoxylin and Eosin, and neurone-specific enolase immunostaining. Transverse sections from proximal gut were studied in a similar fashion. Thus, we evaluated the migration pattern as well as the nature of ganglia in the fetuses. We also measured the length of distal aganglionic segment in these growing fetuses. RESULTS: We noted that ganglion cells appear first in the myenteric plexus followed by deep and superficial submucous plexus. We also found evidences in favor of dual migration theory, and the distal aganglionic segment varies around the circumference of the rectal wall. CONCLUSIONS: We got evidences in support of a dual migration pattern of intestinal ganglion cells. The level of distal aganglionic segments when measured from squamo-columnar junction varied with the age of gestation and the length was incongruous. The description of distal aganglionic segment may help surgeons while taking biopsies or during operative procedures.

Massive scapular metastasis as a presenting feature of carcinoma of the lip.

Carcinoma of the lip is a slow-growing locally-advanced disease with low metastatic potential. Distant skeletal metastasis is reported very rarely and the vertebral column is the most common site. A 58-year-old male smoker presented with pain and massive swelling of the left scapula for six months. He also noticed a slowly-growing painful ulcerated lesion on the outer aspect of the right lower lip for last two years. Biopsy from the lip ulcer, as well as cytologic smears from the scapular mass, revealed features of squamous cell carcinoma. Though no neck node was detected, patient was found to have extensive skeletal metastasis on whole body bone scan. It is rare as well as clinically appealing to have such disfiguring symptomatic massive scapular metastasis as the chief presenting feature in carcinoma of the lip.

Inherited dysfibrinogenaemia presenting with portal vein thrombosis.

A 15 years old female presented with recurrent episodes of gum bleeding, easy bruisibility and recurrent soft tissue haematoma following trivial trauma since childhood. Subsequently the patient developed features of extrahepatic portal vein obstruction due to formation of thrombus. Defective fibrinogen structure due to underlying inherited dysfibrinogenaemia led to the manifestations of both bleeding due to coagulation failure and thrombosis due to failure of abnormal fibrin to get lysed.

Synchronous multicentric giant cell tumor.

Multicentric giant cell tumors represent less than 1% of all giant cell tumors of bones. We report a case of multicentric giant cell tumors around both the knee joints in a mentally and physically challenged adult male that resulted in rapidly progressive painful swelling, restricted mobility and, ultimately, fixed deformity. These tumors had typical radiological appearance and the diagnosis was confirmed on histopathology.