Efficacy and safety of Nivolumab in patients with advanced esophageal, gastroesophageal, and gastric cancers: a meta-analysis of randomized controlled trials.

BACKGROUND: Immune checkpoint inhibitors (ICI) have revolutionized care in oncology with improved overall survival in several cancer populations. Nivolumab has recently been approved for use in patients with upper gastrointestinal cancers. We quantitatively summarized the efficacy and safety of Nivolumab use in patients with advanced esophageal, gastroesophageal, and gastric carcinoma compared to standard chemotherapy. METHODS: Systemic search of electronic databases was performed to analyze phase III randomized controlled trials (RCTs) comparing Nivolumab versus standard chemotherapy in patients with advanced upper gastrointestinal cancers. Primary endpoints were overall survival (OS) and progression-free survival (PFS). Data were pooled using random effects model via RevMan 5.4 software. RESULTS: Four RCTs with a total of 3369 patients and a median follow-up of 13 months were included. The patients' mean age was 61 ± 20 years, 74.6% were males, and 26% had ≥1% PD-L1 expression. Compared to the chemotherapy group, Nivolumab group had a significantly favorable OS and PFS [HR 0.81;95% CI (0.74, 0.89), p < .001], [HR 0.82;95% CI (0.69, 0.98), p = .03], respectively. Nivolumab significant effect was only in patients with ≥1% PD L1 expression [HR 0.72; 95% CI (0.58, 0.89), p < .001]. No statistical difference was detected between groups regarding serious adverse effects (AE) [OR 1.47; 95%CI (0.94,2.31), p = 0.09]. CONCLUSIONS: Compared to standard chemotherapy, the use of Nivolumab in patients with advanced esophageal, gastroesophageal, and gastric cancers is associated with improved overall and progression-free survival, with similar rates of AE and AE leading to death. The improvement in survival was significant in patients with ≥1% PD L1 expression.

Primary Repair of Pediatric Posttraumatic Complete Bladder Neck Horizontal Transection: Our Experience.

Complete transverse transection just below the bladder neck is extremely rare. We present two such cases with associated pelvic fracture following trauma. Both underwent early primary vesicourethral anastomosis with no postoperative complications and are continent in the follow-up.

Outcome of Patients with Antenatally Diagnosed hydronephrosis with Respect to Postnatal Diagnosis and Need for Surgical Intervention.

Aims: This study aims to determine the etiology of antenatal hydronephrosis (ANH) and predict need for surgical intervention based on antenatal renal pelvis anteroposterior diameter (APD). Materials and Methods: Combined prospective and retrospective study (2012-2018) of ANH cases with postnatal follow-up. Surgical intervention was correlated with the degree of hydronephrosis (HDN) and pelvis APD measured at the 2nd trimester, 3rd trimester, and postnatal 6-week follow-up. Results: One hundred and sixty-five patients were studied with a total of 219 ANH units. Transient HDN was seen in 116 units. Surgical intervention included pyeloplasty (n = 76), sub ureteric dextranomer injection (n = 8) and nephrectomy (n = 1). Chances of requiring surgery based on the degree of HDN in 2nd and 3rd trimester respectively were mild: 11.32% and 9.52%, moderate: 34.21% and 37.03% and severe: 85.71% and 86.27%. The mean increase in APD between the 2nd and 3rd trimester (n = 50) was lesser in conservatively managed (3.548 ± 4.219 mm) than surgically managed (8.261 ± 5.857 mm) patients (P = 0.002). In another subset (n = 37), the mean increase in APD between the 2nd trimester and postnatal period was less in conservatively managed (1.432 ± 0.612 mm) (P = 0.088) than surgically managed patients (12.91 ± 3.247 mm) (P = 0.004). The area under the receiver operating characteristic (ROC) curve showed that an APD of 8.2 mm in the 2nd trimester and 12.85 mm in the 3rd trimester correlated with the requirement of postnatal surgery. Conclusion: Apart from the degree of HDN, significant changes in APD between 2nd and 3rd trimester and cut off value suggested by the ROC curve will help during antenatal counseling with regard to requirement of postnatal surgery.

Origin and evolution of the genus Piper in Peninsular India.

The evolution of Peninsular Indian biodiversity has been a fascinating topic of research due to historical connections of this region to the ancient Gondwanaland. We investigated the phylogeny and historical biogeography of nearly all extant species of the genus Piper reported from the region to assess the biogeographical origins and test mechanisms of lineage diversification (dispersal, vicariance and in situ radiation) of this highly diverse genus of angiosperms commonly found in the understory of evergreen forests. The phylogeny of 21 species of Piper reported from Peninsular India was reconstructed for the first time, which included three new putative species from the Western Ghats. We used BEAST for the divergence time estimations (using three constraints), and ancestral range estimations were performed with the dated phylogenetic tree using BIOGEOBEARS. Divergence dating analysis revealed that the genus Piper originated during lower Cretaceous around 110 Ma [95% highest posterior density (HPD): 116-105 Ma] and colonized Peninsular India five times independently, from Southeast Asia starting from the Oligocene. The two major dispersals into India occurred during the periods of 27.3 Ma (95% HPD: 35.8-19.9.) and 15.5 Ma (95% HPD: 24.9-7.11). This was followed by rapid radiations in some lineages with subsequent back dispersals to Southeast Asia. Our study indicates that dispersals from Southeast Asia led to the arrival of Piper to Indian subcontinent following the Indo-Eurasian collision. Members of Piper have colonized and diversified within the climatically stable habitats of Peninsular India. Furthermore, the present study provides evidence for the Miocene overland dispersal of Piper species to Africa from South Asia.

Modeling the impact of climate change on wild Piper nigrum (Black Pepper) in Western Ghats, India using ecological niche models.

The center of diversity of Piper nigrum L. (Black Pepper), one of the highly valued spice crops is reported to be from India. Black pepper is naturally distributed in India in the Western Ghats biodiversity hotspot and is the only known existing source of its wild germplasm in the world. We used ecological niche models to predict the potential distribution of wild P. nigrum in the present and two future climate change scenarios viz (A1B) and (A2A) for the year 2080. Three topographic and nine uncorrelated bioclim variables were used to develop the niche models. The environmental variables influencing the distribution of wild P. nigrum across different climate change scenarios were identified. We also assessed the direction and magnitude of the niche centroid shift and the change in niche breadth to estimate the impact of projected climate change on the distribution of P. nigrum. The study shows a niche centroid shift in the future climate scenarios. Both the projected future climate scenarios predicted a reduction in the habitat of P. nigrum in Southern Western Ghats, which harbors many wild accessions of P. nigrum. Our results highlight the impact of future climate change on P. nigrum and provide useful information for designing sound germplasm conservation strategies for P. nigrum.

Isolated Duodenal Injury in Blunt Abdominal Trauma in Children: A Series of Five Cases.

ABSTRACT: Blunt abdominal trauma is one of the leading causes of trauma-related deaths in children. The commonly affected organs include the spleen, liver and kidneys, followed by uncommon ones such as the pancreas and intestine. Isolated duodenal injury is very rare and, at times, poses a diagnostic challenge due to the paucity of clinical symptoms and signs. Hence, delayed presentation is not uncommon. In this write-up, five such cases are presented with emphasis on their clinical presentation, diagnosis, management and outcome.

Integrative taxonomy of the genus Coridius Illiger, 1807 (Hemiptera: Heteroptera: Dinidoridae) reveals hidden diversity and three new species from North-East India.

The genus Coridius Illiger, 1807 (Heteroptera: Dinidoridae) comprises a group of phytophagous terrestrial bugs consisting of 36 species distributed in the Afrotropical and Indo-Malayan regions. In several communities in northeastern India, insects are recognised as a delicacy, medicine, and a nutritional supplement, with Coridius being a popular delicacy. However, Coridius has received little taxonomic attention to date due to large intraspecific variations, inadequate taxonomic treatments, and the rarity of many species. To address this gap, an integrative taxonomy of the genus was performed. Two mitochondrial genes, viz., cytochrome oxidase subunit 1 (COI) and 16S rRNA, were sequenced to reconstruct the phylogenetic relationships within Coridius. We performed both maximum likelihood (ML) and Bayesian inference (BI) to develop a species tree, followed by the Bayesian implementation of the Poisson tree process (bPTP) and Assemble Species by Automatic Partitioning (ASAP) as an additional test to assess species boundaries and delimit operational taxonomic units. A linear discriminant analysis (LDA) of four key morphological characters was then performed to identify species groups. Overall, our analysis supported the establishment of three new species: Coridius adii sp. nov., Coridius esculentus sp. nov., and Coridius insperatus sp. nov., and revealed six distinct lineages within Coridius chinensis (Dallas, 1851). Linear discriminant analysis of morphological characters indicated the clustering of eight species. The species status of Coridius nigriventris (Westwood, 1837) stat. rev, formerly synonymized under Coridius nepalensis (Westwood, 1837), is reinstated in this study. Further, we revised the genus Coridius from India and rediscovered Coridius assamensis (Distant, 1902) and Coridius fuscus (Westwood, 1837) after 100 years.

POEMS Syndrome - A Diagnostic Dilemma with Challenging Presentation.

Polyneuropathy, Organomegaly, Endocrinopathy, M-protein, Skin changes (POEMS) syndrome is a rare disorder with multiple presentations and a constellation of symptoms. We present a 62 year-old female who presented to the Emergency Department for acute dyspnea. Chest Xray showed sclerotic lesions in the ribs and thoracic spine. Further imaging studies with computed tomography (CT) and positron emission tomography (PET) scans were suggestive of a benign process. Improvement was seen with supportive management. A few months later, patient developed neurological symptoms with reduced exercise tolerance. Mixed demyelinating and axonal polyneuropathy was diagnosed by electromyography. Further work up with bone marrow biopsy and immunochemistry testing revealed lambda and kappa plasma cell disorder, with elevated vascular endothelial growth factor (VEGF). Patient was diagnosed with POEMS and initiated on chemotherapy. POEMS syndrome is commonly missed due to its rarity and varied clinical presentations. VEGF plays a crucial role in the diagnosis. Management requires a multidisciplinary approach.

Cardiac Sarcoma Presenting as Tamponade.

Sarcomas are a broad group of neoplasm that originate from the mesenchymal layer and represent about 1% of malignancy in the adult population. We describe a 46-year-old woman with no prior medical history who presented with worsening dyspnea. Physical examination was significant for jugular venous distension and bilateral lower extremity edema. Chest Xray showed cardiomegaly. Echocardiography showed a normal ejection fraction of 65%, pericardial effusion with tamponade physiology and three epicardial masses. Patient had pericardiocentesis performed followed by pericardial window. Biopsy of pericardial mass showed morphologic and immunophenotypic findings supportive of diagnosis of malignant soft tissue sarcoma. Though this type of cancer is rare, malignancy should be included as one of the differential diagnoses of new-onset pericardial effusion in a young patient. Early diagnosis and referral to a specialized sarcoma center for treatment is recommended.

Mammals, wildlife trade, and the next global pandemic.

Most new infectious diseases emerge when pathogens transfer from animals to humans.1,2 The suspected origin of the COVID pandemic in a wildlife wet market has resurfaced debates on the role of wildlife trade as a potential source of emerging zoonotic diseases.3-5 Yet there are no studies quantitatively assessing zoonotic disease risk associated with wildlife trade. Combining data on mammal species hosting zoonotic viruses and mammals known to be in current and future wildlife trade,6 we found that one-quarter (26.5%) of the mammals in wildlife trade harbor 75% of known zoonotic viruses, a level much higher than domesticated and non-traded mammals. The traded mammals also harbor distinct compositions of zoonotic viruses and different host reservoirs from non-traded and domesticated mammals. Furthermore, we highlight that primates, ungulates, carnivores, and bats represent significant zoonotic disease risks as they host 132 (58%) of 226 known zoonotic viruses in present wildlife trade, whereas species of bats, rodents, and marsupials represent significant zoonotic disease risks in future wildlife trade. Thus, the risk of carrying zoonotic diseases is not equal for all mammal species in wildlife trade. Overall, our findings strengthen the evidence that wildlife trade and zoonotic disease risks are strongly associated, and that mitigation measures should prioritize species with the highest risk of carrying zoonotic viruses. Curbing the sales of wildlife products and developing principles that support the sustainable and healthy trade of wildlife could be cost-effective investments given the potential risk and consequences of zoonotic outbreaks.

Grapefruit juice and verapamil: a toxic cocktail.

The US public consumes grapefruit juice in large quantities, with 14% of the population drinking the juice at least weekly. Grapefruit juice is a well-documented inhibitor of the CYP3A4 isoenzyme, which is involved in the metabolism of over 50% of commonly prescribed drugs. Here we report an unusual case of verapamil toxicity in a 42-year-old female, which resulted from accidental ingestion of only three tablets of the sustained release preparation (120 mg each) over 24 hours which resulted in severe toxicity.

Hemoperitoneum after Ovulation in Systemic Lupus Erythematosus and Autoimmune Thrombocytopenia.

BACKGROUND: Three prior cases of hemoperitoneum associated with immune thrombocytopenia (ITP) have been reported in adolescents. This reports a case of hemoperitoneum after ovulation in an adult. CASE: A 34-year-old nulligravida presented with abdominal pain after a heavy period and rebound tenderness. Urine beta-hCG was negative, hemoglobin was 5.4, and platelet count was zero. CT revealed hemoperitoneum and contrast blush surrounding the left ovary. She was treated for newly diagnosed systemic lupus erythematosus and steroid-refractory ITP. Her platelet count and symptoms improved. CONCLUSION: Hemoperitoneum after ovulation in ITP is rare; this represents the first adult case in the literature and reviews differential diagnosis of thrombocytopenia. The obstetrician/gynecologist is part of a multidisciplinary team caring for patients with bleeding of gynecological origin and should withhold surgical intervention for hemoperitoneum when medical therapy is warranted.

Acute pancreatitis with Cullen's sign presentation in a case of mixed type I and II choledochal cyst.

A 3 year old girl presented initially with acute severe hemorrhagic pancreatitis diagnosed by clinical features including a positive Cullen's sign and raised serum amylase. A contrast enhanced computed tomography (CECT) scan corroborated the same and also reported a type I choledochal cyst. Magnetic resonance cholangiopancreatography (MRCP) 2 months later reported a type II choledochal cyst and a persistent pseudo pancreatic cyst. Intraoperative features and close perusal of the CECT and MRCP films showed the presence of mixed type I and II choledochal cyst. The case is reported for the presence of Cullen's sign, CECT and MRCP features of a mixed type I and II choledochal cyst and successful surgical outcome. It appears to be only the fifth case of mixed type I and II choledochal cyst in world literature in the pediatric age group, following the 4 previous cases in children reported from Japan.

Philadelphia Translocation in MDS: A Case Report and a Brief Review of the Literature Looking at Its Prevalence, Disease Progression, and Treatment Options.

Myelodysplastic syndrome (MDS) is a group of clonal disorders characterized by ineffective and dysplastic hematopoiesis in the bone marrow with variable risk of progression to leukemia. MDS is characterized by specific karyotypic and molecular abnormalities. The t(9 : 22) Philadelphia translocation is not a common abnormality found in MDS, and it is not included in the prognostic indices for germline mutations. There are no definitive treatment guidelines for these patients either. Here, we reviewed previously reported cases of MDS with the Philadelphia translocation with a goal to determine their prognosis and treatment options, specifically the tyrosine kinase inhibitors (TKIs).

Ecological niche modeling for conservation planning of an endemic snail in the verge of becoming a pest in cardamom plantations in the Western Ghats biodiversity hotspot.

Conservation managers and policy makers are often confronted with a challenging dilemma of devising suitable strategies to maintain agricultural productivity while conserving endemic species that at the early stages of becoming pests of agricultural crops. Identification of environmental factors conducive to species range expansion for forecasting species distribution patterns will play a central role in devising management strategies to minimize the conflict between the agricultural productivity and biodiversity conservation. Here, we present results of a study that predicts the distribution of Indrella ampulla, a snail endemic to the Western Ghats biodiversity hotspot, which is becoming a pest in cardamom (Ellettaria cardamomum) plantations. We determined the distribution patterns and niche overlap between I. ampulla and Ellettaria cardamomum using maximum entropy (MaxEnt) niche modeling techniques under current and future (2020-2080) climatic scenarios. The results showed that climatic (precipitation of coldest quarter and isothermality) and soil (cation exchange capacity of soil [CEC]) parameters are major factors that determine the distribution of I. ampulla in Western Ghats. The model predicted cardamom cultivation areas in southern Western Ghats are highly sensitive to invasion of I. ampulla under both present and future climatic conditions. While the land area in the central Western Ghats is predicted to become unsuitable for I. ampulla and Ellettaria cardamomum in future, we found 71% of the Western Ghats land area is suitable for Ellettaria cardamomum cultivation and 45% suitable for I. ampulla, with an overlap of 35% between two species. The resulting distribution maps are invaluable for policy makers and conservation managers to design and implement management strategies minimizing the conflicts to sustain agricultural productivity while maintaining biodiversity in the region.

Endophytes: A Treasure House of Bioactive Compounds of Medicinal Importance.

Endophytes are an endosymbiotic group of microorganisms that colonize in plants and microbes that can be readily isolated from any microbial or plant growth medium. They act as reservoirs of novel bioactive secondary metabolites, such as alkaloids, phenolic acids, quinones, steroids, saponins, tannins, and terpenoids that serve as a potential candidate for antimicrobial, anti-insect, anticancer and many more properties. While plant sources are being extensively explored for new chemical entities for therapeutic purposes, endophytic microbes also constitute an important source for drug discovery. This review aims to comprehend the contribution and uses of endophytes as an impending source of drugs against various forms of diseases and other possible medicinal use.

An MPL W515L mutation in refractory anemia with ringed sideroblasts associated with marked thrombocytosis: A case report.

The current study presents the case of a 63-year-old patient exhibiting refractory anemia with ringed sideroblasts associated with marked thrombocytosis (RARS-T), who was positive for the MPL W515L mutation, but negative for the JAK2 V617F mutation. Following diagnosis, the patient remained asymptomatic for over three years, however, in August 2012, the patient relapsed and was administered with supportive treatment in the form of subcutaneous darbepoetin α at a dose of 300 µg/week, which resulted in an increased hemoglobin concentration, allowing the patient to remain transfusion-independent. The MPL W515L mutation has been reported in two previous cases of myelodysplastic/myeloproliferative neoplasms (MDS/MPN) with ringed sideroblasts, however, to the best of our knowledge, the current report is the first to present a case of RARS-T with an MPL W515L mutation. A clinical trial designed to evaluate the efficacy of a targeted agent against the JAK2 V617F mutation is currently ongoing, with the aim of providing a novel therapeutic strategy for treating MDS/MPN patients. As MPL is located upstream of the JAK-STAT signaling pathway, it is a possible therapeutic target in MDS/MPN patients positive for an MPL W515L mutation, but negative for a JAK2 V617F mutation.

Visceral leishmaniasis in India: promises and pitfalls of a PCR-based blood test.

Traditional methods of diagnosing visceral leishmaniasis (kala-azar) in India suffer from a number of disadvantages. Amplification of multicopy nuclear genes and messenger ribonucleic acid of Leishmania by the polymerase chain reaction (PCR) was evaluated as an alternative assay under various clinical conditions. PCR of peripheral blood has the highest absolute sensitivity among all the available procedures, and is particularly useful for detecting parasites in early infections, post kala-azar dermal leishmaniasis, concurrent infections and immunocompromised cases, but is not so reliable for late infections. PCR of immunopurified blood mononuclear cells indicated the association of parasites with monocytes as well as non-monocyte cell types.

Genetic diversity analysis in Piper species (Piperaceae) using RAPD markers.

The genetic diversity of eight species of Piper (Piperaceae) viz., P. nigrum, P. longum, P. betle, P. chaba, P. argyrophyllum, P. trichostachyon, P. galeatum, and P. hymenophyllum from Kerala state, India were analyzed by Random amplified polymorphic DNA (RAPD). Out of 22 10-mer RAPD primers screened, 11 were selected for comparative analysis of different species of Piper. High genetic variations were found among different Piper species studied. Among the total of 149 RAPD fragments amplified, 12 bands (8.05%) were found monomorphic in eight species. The remaining 137 fragments were found polymorphic (91.95%). Species-specific bands were found in all eight species studied. The average gene diversity or heterozygosity (H) was 0.33 across all the species, genetic distances ranged from 0.21 to 0.69. The results of this study will facilitate germplasm identification, management, and conservation.