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Introduction: Whole-genome sequencing of diffuse large B-cell lymphoma (DLBCL) has identified recurrent mutations involved in pathogenesis and potentially affecting response to therapy. In this pilot study, a targeted gene panel was created to identify mutations associated with relapse/refractoriness. Material and Methods: A 14-gene targeted panel was designed to sequence thirteen patients who were in remission and 8 cases that had relapsed/refractory to treatment. A paired diagnostic biopsy and a relapse biopsy were sequenced to find genes repeatedly altered in relapse. Results: A total of 751 nonsynonymous and truncating mutations were identified. Truncated mutations in NOTCH1, TNFAIP3, and CD58 were associated with poor treatment outcomes. In cases that did not respond to treatment, a high number of mutations were found in the EZH2 gene, followed by the DNA-binding domain of TP53 and MYD88. Termination mutations in the intracellular domain of NOTCH were found in 75% of non-responsive cases. Co-occurrence of loss of function mutations of TNFAIP3 and missense mutations in MYD88 was associated with a non-responsive cohort. Discussion: The study highlights mutations associated with chemotherapeutic response in DLBCL with implications for initial diagnostic biopsy response prediction. [ABSTRACT FROM AUTHOR]

Metalloid pollution, including arsenic poisoning, is a serious environmental issue, plaguing plant productivity and quality of life worldwide. Biochar, a carbon-rich material, has been known to alleviate the negative effects of environmental pollutants on plants. However, the specific role of biochar in mitigating arsenic stress in maize remains relatively unexplored. Here, we elucidated the functions of biochar in improving maize growth under the elevated level of sodium arsenate (Na2AsO4, AsV). Maize plants were grown in pot-soils amended with two doses of biochar (2.5% (B1) and 5.0% (B2) biochar Kg−1 of soil) for 5 days, followed by exposure to Na2AsO4 ('B1 + AsV'and 'B2 + AsV') for 9 days. Maize plants exposed to AsV only accumulated substantial amount of arsenic in both roots and leaves, triggering severe phytotoxic effects, including stunted growth, leaf-yellowing, chlorosis, reduced photosynthesis, and nutritional imbalance, when compared with control plants. Contrariwise, biochar addition improved the phenotype and growth of AsV-stressed maize plants by reducing root-to-leaf AsV translocation (by 46.56 and 57.46% in 'B1 + AsV' and 'B2 + AsV' plants), improving gas-exchange attributes, and elevating chlorophylls and mineral levels beyond AsV-stressed plants. Biochar pretreatment also substantially counteracted AsV-induced oxidative stress by lowering reactive oxygen species accumulation, lipoxygenase activity, malondialdehyde level, and electrolyte leakage. Less oxidative stress in 'B1 + AsV' and 'B2 + AsV' plants likely supported by a strong antioxidant system powered by biochar-mediated increased activities of superoxide dismutase (by 25.12 and 46.55%), catalase (51.78 and 82.82%), and glutathione S-transferase (61.48 and 153.83%), and improved flavonoid levels (41.48 and 75.37%, respectively). Furthermore, increased levels of soluble sugars and free amino acids also correlated with improved leaf relative water content, suggesting a better osmotic acclimatization mechanism in biochar-pretreated AsV-exposed plants. Overall, our findings provided mechanistic insight into how biochar facilitates maize's active recovery from AsV-stress, implying that biochar application may be a viable technique for mitigating negative effects of arsenic in maize, and perhaps, in other important cereal crops. Highlights: Maize developed significant growth defects under excessive arsenate (AsV) stress. Biochar addition decreased root AsV uptake and root-to-leaf AsV translocation. Biochar protected photosynthetic rate and pigment levels from AsV -stress. Biochar reduced AsV-caused oxidative damage by strengthening antioxidant defense. Biochar boosted osmoprotectant levels and nutrient uptake in AsV-stressed maize. [ABSTRACT FROM AUTHOR]

Backgrounds and Aims: Progressive familial intrahepatic cholestasis type 2 (PFIC2) is caused by a defect or deficiency of bile salt export protein (BSEP) due to mutation in the ABCB11 gene. We intend to evaluate the phenotype–genotype correlation in 10 diagnosed cases of PFIC2 in a single tertiary care center in North India. Methods: The clinical, biochemical, histopathological, immunohistochemical, ultrastructural and genetic data of the 10 diagnosed cases of PFIC2 were recorded. Results: Icterus, pruritus and bleeding manifestations were the commonest clinical symptoms. Giant cell transformation was seen in 50% of the patients. Two predominant genetic variants were ABCB11 missense p.Val444Ala (c. 1331 T > C) and ABCB11 missense p.Asn591Ser (c. 1772 A > G) in their homozygous or compound heterozygous states and were associated with retained BSEP immunopositivity and reduced but retained BSEP immunopositivity respectively. Conclusion: Retention of BSEP is common in North Indian children of PFIC2 with no phenotype-genotype correlation. [ABSTRACT FROM AUTHOR]

The empowerment of women is one of the central issues in the process of development of countries in all over the world. India has a glorious tradition of recognizing the importance of empowering women over several centuries now. In recent decades, empowerment of women emerged as one of the significant strategies in the development process. The Government of India has made Empowerment of Women as one of the prime objectives of the 9th Five Year Plan (1997-2002) and also declared 2001 as the year of 'Womens empowerment'. Empowerment is a multi-dimensional, multi-faceted and multi-layered concept. It is a process to enable women to realize their identity and powers in all spheres of life. Further, empowerment provides better access to knowledge and resources, more independence in decision making, better ability to plan their lives, which influence their lives and freedom from belief, practice and custom. In this present study we have tried to analyze the empowerment of women through Self Help Groups (SHG) in a village of Junglemahal of Paschim Medinipur District of West Bengal and also to assess the socio-economic conditions of the beneficiaries of groups. The study also identifies the common problems faced by the members in this group. [ABSTRACT FROM AUTHOR]

Background and objectives Histopathological distinction of various nodular lesions in liver with sufficient sensitivity and specificity is a challenge even in an expert set up. The panel of immunohistochemical markers composed of glutamine synthetase (GS), Glypican3 (GPC3) and heat shock protein 70 (HSP70) was recommended by the International Consensus Group for Hepatocellular Neoplasia group for the differentiation of high grade dysplastic nodule and early hepatocellular carcinoma (HCC). The panel has been extensively validated in the western population. This study aims to test this panel on Indian population on resected, explanted and autopsy cirrhotic and non-cirrhotic liver specimens of HCC. Methodology This study was conducted on 39 such liver specimens (12 cirrhotic, 12 pre-cirrhotic and 11 non-cirrhotic, non-fibrotic livers), including 35 cases of HCC over a period of 12 years. Immunohistochemistry was performed with antibodies against GS, GPC3 and HSP70 on the sections containing both malignant and dysplastic nodules. Results The diagnostic yield depended upon the nature of background liver pathology and was found to be high for only those HCCs arising in cirrhotic background, when positivity of any two markers was taken to be in favor of HCC (sensitivity—58.33%; specificity—100%). GS had a sensitivity and Negative predictive value of 100% for HCCs arising in cirrhotic livers. Conclusions Strong positivity for GS is a highly sensitive marker for HCC in a cirrhotic background regardless of the differentiation of the tumor in Indian population. This may be due to preferential activation of Wnt pathway in Indian patients with cirrhosis. The sensitivity of the panel was too low for detecting HCCs arising in non-cirrhotic livers, even in the pre-cirrhotic chronically inflamed livers, even though the specificity was high. GPC3 and HSP70 appear to be useful as individual markers for HCCs arising in non-cirrhotic livers. [ABSTRACT FROM AUTHOR]

Skin appendage tumours can occasionally be diagnosed cytologically. The fine needle aspiration cytology of a eccrine spiradenoma in axillary skin is described. [ABSTRACT FROM AUTHOR]

The detection of the primary site in Carcinoma of Unknown Primary (CUP) is a challenging task which can significantly alter the course of management and also prognosis. Various modalities have been assessed with varying sensitivity and specificity. Imaging and cytological diagnosis have formed a key part of the diagnostic algorithm of CUP. Trans Oral Robotic Surgery offers the advantage of being both diagnostic as well as therapeutic with promising sensitivity and specificity and can form an integral part in the management of CUP. A prospective study was carried out at a tertiary care centre over a period of one year. Patients with unilateral neck swelling which was histopathologically proven squamous cell carcinoma neck metastasis were included in the study. They were evaluated with endoscopy and radiology according to the standard algorithm. When these failed to detect the primary, the patients underwent ipsilateral radical tonsillectomy and tongue base mucosal wedge biopsy via TORS. Post-operative histopathological examination was done on the resected specimens to detect the primary site. Transoral Robotic Surgery was able to localise primary in 50% of the patients enrolled in the study. Out of the primary site identified by TORS; 55.56% were located in the tonsil and 44.4% in the tongue base. TORS can offer promising detection rates of the occult primary in CUP and should form an integral part of the diagnostic algorithm. [ABSTRACT FROM AUTHOR]

BACKGROUND: Agents targeting the PI3K pathway in triple negative breast cancer did not show any significant efficacy so far mostly because of the complex nature of these targeted inhibitors. Targeting the cancer cells with the combination of inhibitors may help in decelerating the regulatory pathways further achieving optimum clinical benefit. In this study, we investigated the effect of PIK3CA and mTOR inhibition in-vitro in triple-negative breast cancer (TNBC) cell lines. OBJECTIVE AND METHODS: Three TNBC cell lines; MDA MB231, MDA MB468, and MDA MB453 were subtyped using immunohistochemistry and were screened for hotspot mutations in PIK3CA and AKT1. All cell lines were treated with different concentrations of inhibitors; PI3K inhibitor (BKM 120), mTOR inhibitor (AZD 8055), and dual PI3K/mTOR inhibitor (BEZ 235), and cell viability was assessed by MTT (3-(4, 5-Dimethylthiazol-2-yl)-2, 5-Diphenyltetrazolium Bromide), Trypan blue and Annexin-V/PI Assays. RESULTS: Using immunohistochemistry, TNBC cell lines were subtyped as; mesenchymal subtype-specific cell line (MDA MB231), basal subtype-specific cell line (MDA MD468), and Luminal androgen receptor (LAR) subtype-specific cell line (MDA MB453). PIK3CA hot spot mutation (p.H1047R) in exon 20 was identified in the Luminal androgen receptor subtype (MDA MB453 cells) cell line. Cell viability assays showed that the Mesenchymal subtype-specific cell line (MDA MB231) was the most resistant to all inhibitors and the Luminal Androgen subtype (MDA MB453 cells) cell line was more sensitive to BKM120 (PI3K inhibitor) inhibition compared to other subtypes. CONCLUSIONS: This study identified that the Luminal androgen receptor subtype of triple-negative breast cancer with PIK3CA mutation may be targeted with PIK3CA inhibitors with a favorable outcome. [ABSTRACT FROM AUTHOR]

Waterlogging (WL) is a major hindrance to the growth and development of leguminous crops, including mung bean. Here, we explored the effect of salicylic acid (SA) pretreatment on growth and yield output of two elite mung bean genotypes (BU Mung bean-4 and BU Mung bean-6) subjected to WL stress. SA pretreatment significantly improved shoot dry weight, individual leaf area, and photosynthetic pigment contents in both genotypes, while those improvements were higher in BU Mung bean-6 when compared with BU Mung bean-4. We also found that SA pretreatment significantly reduced the reactive oxygen species-induced oxidative burden in both BU Mung bean-6 and BU Mung bean-4 by enhancing peroxidase, glutathione S -transferase, catalase, and ascorbate peroxidase activities, as well as total flavonoid contents. SA pretreatment further improved the accumulation of proline and free amino acids in both genotypes, indicating that SA employed these osmoprotectants to enhance osmotic balance. These results were particularly corroborated with the elevated levels of leaf water status and leaf succulence in BU Mung bean-6. SA-mediated improvement in physiological and biochemical mechanisms led to a greater yield-associated feature in BU Mung bean-6 under WL conditions. Collectively, these findings shed light on the positive roles of SA in alleviating WL stress, contributing to yield improvement in mung bean crop. • Waterlogging (WL) stress resulted in significant growth defects in mung bean plants. • Salicylic acid (SA) treatment rescued growth features under WL stress. • SA strengthened antioxidant defense to reduce oxidative stress in mung bean. • Osmoprotectants were highly accumulated in WL-stressed mung bean. • Yield and yield-related traits were significantly improved in SA-treated plants. [ABSTRACT FROM AUTHOR]

BACKGROUND: Tumour microenvironment (TME) contributes to resistance to anti-cancer drugs through multiple mechanisms including secretion of pro-survival factors by cancer associated fibroblasts (CAFs). In this study, we determined the chemotherapy resistance producing potential of CAFs in molecular subtypes of breast cancer. METHODS: The CAFs were isolated from fresh lumpectomy/mastectomy specimens of different molecular subtypes of breast cancer. The CAFs were cultured and secretome was collected from each breast cancer subtype. Breast cancer cell lines MCF-7, SKBR3, MDA-MB-231, and MDA-MB-468 were treated with different doses of tamoxifen, trastuzumab, cisplatin, and doxorubicin alone respectively and in combination with secretome of CAFs from respective subtypes. MTT assay was done to check cell death after drug treatment. Liquid chromatography–mass spectrometry (LCMS) analysis of CAF secretome was also done. RESULTS: MTT assay showed that anti-cancer drugs alone had growth inhibitory effect on the cancer cells however, presence of CAF secretome reduced the anti-cancer effect of the drugs. Resistant to drugs in the presence of secretome, was determined by increased cell viability i.e., MCF-7, 51.02% to 63.02%; SK-BR-3, 34.22% to 44.88%; MDA-MB-231, 52.59% to 78.63%; and MDA-MB-468, 48.92% to 55.08%. LCMS analysis of the secretome showed the differential abundance of CAFs secreted proteins across breast cancer subtypes. CONCLUSIONS: The treatment of breast cancer cell lines with anti-cancer drugs in combination with secretome isolated from molecular subtype specific CAFs, reduced the cytotoxic effect of the drugs. In addition, LCMS data also highlighted different composition of secreted proteins from different breast cancer associated fibroblasts. Thus, TME has heterogenous population of CAFs across the breast cancer subtypes and in vitro experiments highlight their contribution to chemotherapy resistance which needs further validation. [ABSTRACT FROM AUTHOR]

Objective: The 2015 WHO classification classifies neuroendocrine tumours (NET) of the lung into typical carcinoid, atypical carcinoid, large cell neuroendocrine carcinoma and small cell carcinoma based on morphology alone. Mitosis is the major parameter for this classification, and thus several studies have focused on the role of Ki67 in these tumours but without conclusive results. The aim of the study was to categorize neuroendocrine tumours of the lung based on morphology and to assess the utility of Ki67 in diagnosis. Material and Method: The study included 42 cases (23 biopsies and 19 lobectomy specimens) of neuroendocrine tumours (excluding small cell carcinoma). Haematoxylin & eosin stained sections, immunohistochemistry for neuroendocrine markers and Ki67 were studied. Results: Based on WHO criteria, cases were classified as typical carcinoids (83.3%), atypical carcinoids (12%) and large cell neuroendocrine carcinomas (4.7%). The Ki67 index ranged between 1%-10% (mean 2.6%), 10%-30% (mean 19%), 35%-50% (mean 42.5%) in typical carcinoid, atypical carcinoid and large cell neuroendocrine carcinoma respectively. Using the ROC curve, the cut off value of Ki67 for typical and atypical carcinoids was 7.5% (P value<0.001), and for atypical carcinoid/large cell neuroendocrine carcinoma was 32.5% (P value=0.051). On comparing the size and infiltration pattern (both local and lymphovascular invasion) of tumours in resected specimens, there was no association with the proliferation index (P value >0.05). Conclusion: Morphological features are the gold standard for subtyping of neuroendocrine tumours. Ki-67 is a potentially meaningful marker for sub-categorization of lung NETs, especially in small biopsies. However, the size and infiltrative pattern of the tumours are independent of the proliferation index. [ABSTRACT FROM AUTHOR]

Villous adenoma and urothelial carcinoma with villoglandular differentiation (UCVGD) are rare urothelial tumours showing villous morphology, the former being a preneoplastic entity and the latter being a malignant one. The detailed immunohistochemistry of these entities is previously not described in the literature. Moreover, a limited biopsy sample of UCVGD or a villous adenoma with or without adenocarcinoma may be difficult to distinguish on the basis of the histomorphology alone. An immunohistochemical panel comprising of GATA3, p63, β‐catenin, CK7 and CK20 was performed on five cases of UCVGD and three cases of villous adenoma with the aim of studying the expression of the proteins thereby aiding in the diagnosis of these entities in a limited surgical pathology specimen. The mean age of UCVGD was 66.8 years and all the patients were male. All the cases of UCVGD were associated with high grade papillary urothelial carcinoma with lamina propria invasion. The immunohistochemical panel showed strong nuclear GATA3 expression in the urothelial component of UCVGD. Interestingly, the high grade and the low grade villoglandular components of UCVGD also expressed GATA3 (nuclear) with a progressive loss of expression from the high grade to the low grade component. The villous adenomas showed negativity or aberrant cytoplasmic positivity for GATA3. The β‐catenin showed a gradual loss of membranous expression from villous adenoma to low grade and high grade villoglandular components of UCVGD with a patchy membranous expression in the urothelial component of the UCVGD. p63 showed strong nuclear positivity in the urothelial component and uniform negativity in the villous adenoma and villoglandular component of UCVGD irrespective of its grade, thereby distinguishing the villoglandular component from the urothelial component. The urothelial component of UCVGD showed strong membranous CK7 expression and was higher than the CK20 expression in the urothelial component. In contrast, CK20 expression was higher in villous adenoma as compared to CK7. There was no difference in the expression of CK7 and CK20 in the villoglandular components and low grade and high grade villoglandular areas. The above‐mentioned immunohistochemical pattern may help to distinguish the UCVGD from the villous adenoma. [ABSTRACT FROM AUTHOR]

Malignant peripheral nerve sheath tumors (MPNSTs) are rare neuroectodermal tumors resulting from the malignant transformation of benign plexiform neurofibromas. The sporadic form of these tumors is rare than familial variants (seen in neurofibromatosis Type 1) and making the diagnosis difficult. We are presenting a case of 40--year-old female with the complaint of progressive swelling of lower limb with initial suspicion of lymphedema and underwent lymphoscintigraphy, magnetic resonance imaging, and finally fluorine-18-2-fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography scans were done to rule out mitotic etiology and extent of the disease. The patient underwent below-knee amputation, and histopathological examination confirmed the diagnosis of sporadic MPNST. [ABSTRACT FROM AUTHOR]

Nonalcoholic fatty liver disease (NAFLD) is a major cause of chronic liver disease globally and in India. The already high burden of NAFLD in India is expected to further increase in the future in parallel with the ongoing epidemics of obesity and type 2 diabetes mellitus. Given the high prevalence of NAFLD in the community, it is crucial to identify those at risk of progressive liver disease to streamline referral and guide proper management. Existing guidelines on NAFLD by various international societies fail to capture the entire landscape of NAFLD in India and are often difficult to incorporate in clinical practice due to fundamental differences in sociocultural aspects and health infrastructure available in India. A lot of progress has been made in the field of NAFLD in the 7 years since the initial position paper by the Indian National Association for the Study of Liver on NAFLD in 2015. Further, the ongoing debate on the nomenclature of NAFLD is creating undue confusion among clinical practitioners. The ensuing comprehensive review provides consensus-based, guidance statements on the nomenclature, diagnosis, and treatment of NAFLD that are practically implementable in the Indian setting. [ABSTRACT FROM AUTHOR]

Autoimmune liver disease (AILD) comprises of autoimmune hepatitis (AIH), primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC) with a spectrum of overlap amongst the three. We analyzed the spectrum and treatment outcomes of patients with AILD presenting to a tertiary care center in India. A retrospective analysis of AILD patients from June 2008 to April 2021 was performed. The diagnosis was based on clinical, biochemical, imaging, serological, and histological characteristics. Eligible patients received treatment depending on the disease stage. Biochemical response to treatment was defined as normalization of AST, ALT, bilirubin, and immunoglobulin G levels at 6 months in AIH, normalization of total bilirubin and/or albumin at 1 year in PBC and decrease in alkaline phosphatase (ALP) levels by 40% in PSC. Two hundred seventy-five patients were analyzed. AIH (58.54%) was most common, followed by an overlap of AIH-PBC (24%) and AIH-PSC (6.54%), PSC (6.18%), and PBC (4.72%). Most patients presented in 3rd or 4th decade, except PBC which occurred predominantly in 5th decade. The majority of patients were females (72.72%). Jaundice was the most common presentation seen in 60% of patients. Cirrhosis was present in 57.47% of patients. Patients with overlap had more pruritus (54.76 vs 6.83%), fatigue (63.1% vs 49.7%), hepatomegaly (52.4% vs 25.5%), and higher ALP (80.9% vs 37.7%) than patients with AIH alone. Acute presentation was seen in 33 patients (13.5%) with most having AIH flare. Five patients had acute liver failure (ALF) and 9 had acute-on-chronic liver failure (ACLF). ALF was associated with 80% mortality while 55.56% of patients with ACLF had a complete biochemical response to immunosuppression. Among patients with AIH and/or overlap who received immunosuppression, a complete biochemical response to immunosuppression was seen in 60.69% of patients. High ALT (OR 1.001 [1.000–1.003], P = 0.034), high albumin (OR 1.91 [1.05–3.48], P = 0.034) and low fibrosis on biopsy (OR 0.54 [0.33–0.91], P = 0.020) predicted complete response. AIH is the most common AILD followed by overlap syndromes, PSC and PBC in our cohort. Biochemical response to immunosuppression is seen in 60% of patients with AIH & low fibrosis score on histopathology predicts a complete response. [Display omitted] [ABSTRACT FROM AUTHOR]

To find if an association could be established between Human Papilloma Virus (HPV) infection and oropharyngeal cancers (OPCs) in a group of patients known to be regular users of tobacco, and to determine the impact of HPV status on clinical outcomes.Case records of 212 patients with AJCC-7 (The American Joint Committee on Cancer 7th edition) stages II–IVB non metastatic squamous cell carcinoma of the oropharynx treated using radical radiotherapy with or without chemotherapy during the years 2015–2018 were retrieved. Formalin-fixed, paraffin-embedded blocks from oropharyngeal biopsies were available for 177 patients and were evaluated for p16 expression by immunohistochemical (IHC) staining. More than 50% nuclear staining with or without cytoplasmic staining was considered HPV+. The association between tobacco use and HPV, as well as the influence of HPV status on survival outcomes were assessed. p16 expression was found to be positive in 23(13%) patients. Significant association was found between chewable tobacco usage and HPV positivity (p = 0.051). The median follow up was 20.5 months (range: 3–80). 5-year Overall Survival was 43.4% and 29.8% (p = 0.044) in HPV+ and HPV− patients, respectively. Local control was significantly better in HPV+ patients (38.6% vs. 25.3%, p = 0.049). There was also a trend towards improved Disease-free Survival in HPV+ patients (31 months vs. 15 months, p = 0.078). Though less in prevalence among the Indian population, improved outcomes in HPV+ OPC patients and widely available IHC HPV assays signifies the routine implementation of p16 testing in day-to-day clinical practice. [ABSTRACT FROM AUTHOR]

Autoimmune liver diseases ( AILDs) encompass a group of diseases with variable clinicopathological manifestations. Th17 and Treg cells have roles in the pathogenesis of AILDs with a balance shifted towards a relative increase in activity of the Th17 cells. In this study, the balance between the transcription factors of Treg and Th17 cells (FoXp3 and RORγt) was sought as a molecular marker of disease activity and to highlight the pathogenesis. The peripheral blood samples of 46 treatment-naive patients were collected and RNA was extracted. Real time PCR was performed and the ratio of gene expression was calculated. Histopathology of 18 patients was obtained and the activity score of these biopsies were also corroborated with their respective molecular (FoXp3/ RORγt) ( FRGT=FoXp3- ROR Gamma T) ratio. The FRGT ratio in healthy individuals was close to 1 and in disease the ratio changed significantly. This ratio ( FRGT) was not significantly different in different varieties of AILD or in adult or paediatric form of the disease. However, the ratio remained consistently below 1 (mean 0.3) in acute disease and high (mean 224.7) in chronic or asymptomatic form of the disease (p < 0.001). The histopathological activity score also significantly correlated with the ratio. This signified the relative excess of Th17 ( RORγt) in active disease as compared to Treg (FoXp3) and the reverse in chronic form. This ratio can be an important peripheral molecular marker to assess the disease activity without the necessity of performing a liver biopsy. [ABSTRACT FROM AUTHOR]

Liver transplant recipients are at an increased risk of opportunistic infections due to the use of immunosuppression. Coronavirus disease of 2019 (COVID-19) increases the risk of these infections further due to associated immune dysfunction and the use of high-dose steroids. We present a case of a liver transplant recipient who developed disseminated tuberculosis and invasive pulmonary aspergillosis complicated by acquired hemophagocytic lymphohistiocytosis after recovering from severe COVID-19. [ABSTRACT FROM AUTHOR]

Takayasu arteritis, a chronic inflammatory vasculitis affecting aorta and its major branches, is complicated by stenosis, occlusion, and aneurysm formation. The aneurysm formation and subsequent complications such as heart failure, aortic regurgitation, and aneurysm rupture can be fatal. The aortic aneurysm rupture is a rare and fatal complication with only a few cases reported in the English literature. The involvement of coronary artery in Takayasu occurs in about 10% patients, and the coronary artery aneurysm is the least common manifestation. Here, we describe a case of Takayasu arteritis with abdominal aortic aneurysm rupture and coronary artery aneurysm. This patient also had associated systemic inflammatory diseases like sarcoidosis and Hashimoto's thyroiditis. [ABSTRACT FROM AUTHOR]

The FibroScan-AST (FAST) score was recently described to detect patients with nonalcoholic steatohepatitis (NASH) having elevated nonalcoholic fatty liver disease (NAFLD) activity score (NAS ≥ 4) and significant fibrosis (≥ F2) on liver biopsy (NASH+ NAS ≥ 4 + F ≥ 2). The aim of this study was to validate the FAST score in Indian patients with NAFLD and to derive optimal cut-offs. Sixty patients with biopsy-proven NAFLD [men: 38 (63.3%), age 40 (32–52) years] with all parameters for assessing the FAST score within 3 months of liver histology were retrospectively analysed. Histological NASH was present in 17 patients (28.3%), while 11 (18.3%) patients had NASH + NAS ≥ 4 + F ≥ 2. The area under the curve (AUROC) of the FAST score for discriminating NASH + NAS ≥ 4 + F ≥ 2 was 0.81. Using cut-offs by Newsome et al , the rule-out cut-off (FAST: ≤ 0.35) had a negative predictive value (NPV) of 0.88 [sensitivity: 0.91, specificity: 0.14, negative likelihood ratio (LR): 0.64], while the rule-in cut-off (FAST: ≥ 0.67) had a positive predictive value (PPV) of 0.33 (sensitivity: 0.73, specificity: 0.67, positive LR: 2.22). Fifteen (25%) patients were correctly classified as per histology, while 28 (46.67%) patients fell in the grey zone. On recalculating the optimal cut-offs for our patients, the rule-out cut-off (FAST: ≤ 0.55) had an NPV of 0.95 (sensitivity: 0.90, specificity: 0.45, negative LR: 0.21), while the optimal rule-in cut-off (FAST: ≥ 0.78) had a PPV of 0.70 (sensitivity: 0.64, specificity 0.94, positive LR: 10.39). With these cut-offs, 27 (45%) patients fell in the grey zone and 29 (48.3%) were correctly classified as per histology, performing better than the cut-offs by Newsome et al (P < 0.001). The FAST score demonstrates good AUROC for detecting NASH with significant fibrosis and inflammation on histology. Cut-offs should be recalibrated based on prevalence of disease. India has a high burden of NAFLD with an estimated 25 million patients at potential risk for significant liver disease. Liver biopsy remains the gold standard for diagnosing NASH, although its application in routine clinical practice is limited. Noninvasive tests for the simultaneous detection of steatosis, inflammation and fibrosis are thus the need of the hour. The FAST score has been recently suggested for the noninvasive detection of NASH with significant fibrosis (≥ F2) and inflammation (NAS ≥ 4) on liver biopsy. We validated the utility of the FAST score for detecting NASH with significant fibrosis and inflammation on liver biopsy in Indian patients with NAFLD. This noninvasive, easy-to-use and nonproprietary FAST score can correctly classify disease severity in more than 50% patients. However, our results suggest that cut-offs should be recalibrated based on the anticipated prevalence of NASH + NAS ≥ 4 + F ≥ 2 in the given population. [ABSTRACT FROM AUTHOR]

Background & objectives: Standard donor lung preservation with cold flush and storage allows up to six hours between retrieval of lungs from the donor and transplantation in the recipient. Ex vivo lung perfusion (EVLP) systems mimic physiological ventilation and perfusion in the donor lungs with potential for prolonged lung preservation and donor lung reconditioning. In this study, it was aimed to perform EVLP on discarded donor lungs using a locally developed EVLP system. Methods: Equipment that are routinely used for cardiac surgeries were collected and a functional EVLP system was assembled. This system was used on five pairs of lungs retrieved from brain-dead organ donors. The lungs were ventilated and pulmonary circulation was continuously perfused with a solution containing oxygen and nutrients for four hours. The system was tested without red blood cells (RBCs) added to the solution (acellular group; n=3; A1, A2 and A3) and also with RBCs added to the solution (cellular group; n=2; C1 and C2). Results: The EVLP system was successfully used in four (A1, A2, A3 and C2) of the five lung pairs. Mechanical and gas exchange functions of the lungs were preserved in these lung pairs. One lung pair (C1) worsened and developed pulmonary oedema. Histopathological examination of all five lung pairs was satisfactory at the end of the procedure. Major challenges faced were leakage of solution from the system and obstruction to drainage of RBCs containing solution from the lungs. Interpretation & conclusions: The results of the present study suggest that, it is possible to maintain the lungs retrieved for transplantation in a physiological condition using a locally prepared EVLP system and a solution without RBCs. [ABSTRACT FROM AUTHOR]

BACKGROUND: Breast cancer heterogeneity is well documented and to some extent is attributed to the presence of cancer stem cells (CSCs). Breast cancer stem cells are identified by the presence of cell surface molecule CD44 and absence of CD24. METHODS: In the present study a flowcytometric analysis was done to study the expression distribution of CSC phenotype of CD44+/CD24-/low, among different molecular subtypes of breast cancer and to find a correlation with clinicopathological features. RESULTS: CSCs were observed in all the molecular subtypes of breast cancer. The highest population of CSCs was noted in luminal B (3.4%), followed by TNBC (1.7%), and Her-2 subtype (1.6%). The least number of CD44+/CD24- cells were seen in Luminal A subgroup (1.3%). CONCLUSION: Existence of cancer stem cells in all the subtypes may suggest the possibility of failure of current therapies in treatment of patients. [ABSTRACT FROM AUTHOR]

To assess the exact role of high-risk HPV testing in patients of carcinoma unknown primary with secondary metastasis to the neck who underwent TORS and neck dissection for identification of the primary site.A prospective study was carried out at a tertiary care centre over one year. Patients with unilateral neck swelling, which was cytologically proven squamous cell carcinoma neck metastasis, were included in the study. After clinicopathological evaluation, they underwent TORS-assisted ipsilateral radical tonsillectomy, tongue base mucosal wedge biopsy for primary site identification, and ipsilateral neck dissection. They underwent HPV RNA ISH from the tonsil, the base of the tongue and blood. They also underwent HPV DNA testing from the blood. P16 was done in the base of tongue, tonsil, and lymph node specimens.In the study cohort of 18 patients who underwent ipsilateral radical tonsillectomy, mucosal tongue base wedge biopsy and neck dissection, p16 positivity was isolated in 5.56%, 0% and 2.78% of patients, respectively. (n = 1/18, 0/18, 5/18). Interestingly, HPV E7 mRNA expression was absent in the tonsil /base of tongue specimens, but metastatic lymph nodes displayed expression in 11.11%. HPV DNA was undetected in all analysed tissues and patients’ blood.In the Indian subcontinent, it is not essential to do detailed high-risk HPV analysis in cases of carcinoma unknown primary with secondary metastasis to the neck. [ABSTRACT FROM AUTHOR]

Extraosseous primary spinal intradural Ewing's sarcoma (ES) is an unusual entity. Bleed within such tumors with acute neurological worsening is extremely rare, especially in the pediatric age. In this article, we present two children with intradural-extramedullary ES who had sudden decline in their neurological status consequent to an intratumoral hemorrhage. We discuss their clinical course and also briefly review the pertinent literature. Spinal intradural Ewing's sarcomas possibly have a tendency to bleed. A short clinical symptomatology along with an acute neurological deterioration and radiologic evidence of intratumoral hemorrhage in a spinal intradural tumor should raise the suspicion of an ES. [ABSTRACT FROM AUTHOR]

Context: Fine-needle aspiration cytology (FNAC) is a rapid and accurate first-line diagnostic modality in lymphadenopathy. Aims: To determine the utility of FNAC for the diagnosis of lymphoma and highlight the various pitfalls in morphological interpretation. Settings and Design: This was a retrospective study of 3 years duration in which cytology diagnosis was compared with the follow-up histopathology diagnosis wherever available. Results: A cytodiagnosis of lymphoma was made in a total of 868 cases (2.8%) out of nearly 33,000 FNAC performed during the study period; 556 (64.1%) cases were diagnosed as non-Hodgkin lymphoma (NHL), 198 (22.8%) as Hodgkin lymphoma (HL), and in 114 (13.1%) cases, a cytological diagnosis of lymphoma without further categorization was given. Histopathological reports were available in 348 cases, with an overall concordance rate of 93.1% (324), which was slightly higher in the HL cases (95.8%) as compared to NHL (91.7%). Twenty-four cases (6.9%) showed discordant cytological diagnosis with subsequent histopathology. The main reasons for the erroneous diagnosis were the over-interpretation of the germinal center cells as atypical lymphoid cells, over-interpretation of immunoblasts with prominent nucleoli as Hodgkin cells, and sheets of monomorphic lymphoid cells interpreted as low-grade lymphoma. Conclusion: Cytomorphology alone can make a correct basic diagnosis of lymphoma with a high degree of accuracy. The errors in interpretation can be further reduced by careful attention to the diagnostic pitfalls and common differential diagnoses. [ABSTRACT FROM AUTHOR]

Exposure to drought stress negatively affects plant productivity and consequently threatens global food security. As global climates change, identifying solutions to increase the resilience of plants to drought is increasingly important. Several chemical treatments have recently emerged as promising techniques for various individual and combined abiotic stresses. This study shows compelling evidence on how acetic acid application promotes drought acclimation responses in soybean by investigating several morphological, physiological and biochemical attributes. Foliar applications of acetic acid to drought-exposed soybean resulted in improvements in root biomass, leaf area, photosynthetic rate and water use efficiency; leading to improved growth performance. Drought-induced accumulation of reactive oxygen species, and the resultant increased levels of malondialdehyde and electrolyte leakage, were considerably reverted by acetic acid treatment. Acetic acid-sprayed plants suffered less oxidative stress due to the enhancement of antioxidant defense mechanisms, as evidenced by the increased activities of superoxide dismutase, ascorbate peroxidase, catalase, glutathione peroxidase and glutathione S-transferase. Improved shoot relative water content was also linked to the increased levels of soluble sugars and free amino acids, indicating a better osmotic adjustment following acetic acid treatment in drought-exposed plants. Acetic acid also increased stem/root, leaf/stem and leaf/root mineral ratios and improved overall mineral status in drought-stressed plants. Taken together, our results demonstrated that acetic acid treatment enabled soybean plants to positively regulate photosynthetic ability, water balance, mineral homeostasis and antioxidant responses; thereby suggesting acetic acid as a costeffective and easily accessible chemical for the management of soybean growth and productivity in drought-prone areas. [ABSTRACT FROM AUTHOR]

Hepatitis E is one of the leading causes of acute viral hepatitis worldwide. Chronic infection with hepatitis E is less common and limited to immunosuppressed patients and is usually due to genotype 3 of the virus. Genotype 1, the most prevalent strain in the South Asian region, is seldom known to be associated with chronic hepatitis. Here we describe a case of chronic hepatitis E with genotype 1 in a post-liver transplant setting. In the index case, previously compensated cryptogenic cirrhosis was decompensated by an acute hepatitis E infection, which necessitated liver transplantation because of acute chronic liver failure. This later progressed to chronicity. This case may have significant implications in management, especially in the post-liver transplant setting. [ABSTRACT FROM AUTHOR]

Introduction: Angiofibromas classically develop in the lateral wall of the nasopharynx from the sphenopalatine region. Extra-nasopharyngeal angiofibromas are rare entities, with the maxillary sinus being the most common site. Parapharyngeal angiofibroma is an extremely rare entity, being seldom reported in English literature. Case Report: We present a case of parapharyngeal angiofibroma, which came as a diagnostic surprise in a young adult 25-year-old male. The radiological picture showed a highly vascular lesion, which did draw our attention for not going for a direct or guided FNAC, and upfront excision was planned through the transcervical route. A firm 5*7 cm mass was excised and sent for histopathologic examination. The histopathology showed angiofibroma like features as a diagnostic surprise as angiofibroma of parapharyngeal space is a known but rare entity. Conclusion: The knowledge of angiofibroma as a differential in parapharyngeal space will help the clinicians to properly deal with these disorders during preoperative evaluation and definitive surgery and thus prevent the chances of vascular injuries and complications associated with an FNAC. A high level of suspicion regarding this differential as a possible lesion in the parapharynx is required for the entity's diagnosis. [ABSTRACT FROM AUTHOR]

• Submergence (Sub) reduced growth and biomass of rice cultivars BRRI dhan29 and 52. • Sub declined antioxidant enzyme activities, provoking H 2 O 2 and malondialdehyde levels. • Exogenous glutathione (GSH) protected photosynthetic pigments, proline and proteins. • GSH sustained enzymatic defense system to reduce oxidative damage in both cultivars. • dhan52 showed greater tolerance to Sub, and GSH effectively rescued both cultivars. Complete submergence (Sub) imposes detrimental effects on growth and survival of crop plants, including rice. Here, we investigated the beneficial effects of reduced glutathione (GSH) in mitigating Sub-induced adverse effects in two high-yielding rice cultivars BRRI dhan29 and dhan52. Both cultivars experienced growth defects, severe yellowing, necrosis and chlorosis, when they were completely immersed in water for 14 days. The poor growth performance of these cultivars was linked to biomass reduction, decreased levels of photosynthetic pigments and proline, increased levels of H 2 O 2 and malondialdehyde, and declined activities of enzymatic antioxidants like superoxide dismutase, ascorbate peroxidase, peroxidase, catalase, glutathione peroxidase and glutathione S -transferase. Pretreatment with exogenous GSH led to significant growth restoration in both cultivars exposed to Sub. The elevated Sub-tolerance promoted by GSH could partly be attributed to increased levels of chlorophylls, carotenoids, soluble proteins and proline. Exogenous GSH also mitigated Sub-induced oxidative damage, as evidenced from reduced levels of H 2 O 2 and malondialdehyde in accordance with the increased activities of antioxidant enzymes. Results revealed that dhan52 was more tolerant to Sub-stress than dhan29, and GSH successfully rescued both cultivars from the damage of Sub-stress. Collectively, our findings provided an insight into the GSH-mediated active recovery of rice from Sub-stress, thereby suggesting that external supply of GSH may be an effective strategy to mitigate the adverse effects of Sub in rice. [ABSTRACT FROM AUTHOR]

The objective of this study was to compare diagnostic accuracy of elastography point quantification (ElastPQ) with transient elastography (TE) and liver histology for measuring liver stiffness in patients with chronic viral hepatitis (CVH) and nonalcoholic fatty liver disease (NAFLD). Thirty-two patients with chronic liver disease (CVH and NAFLD) were evaluated by ElastPQ and TE within 7 days of liver biopsy. Within the CVH group, subgroup analysis was carried out in patients with end-stage renal disease (ESRD) and without ESRD. Area under the receiver operating characteristic (AUROC) curves were calculated for ElastPQ and TE. There were 15 patients with CVH and 17 patients with NAFLD. In the CVH group, there were 8 patients with ESRD and 7 patients without ESRD. Taking liver histopathology as the gold standard, liver stiffness measurement by ElastPQ (ρ = 0.826; P < 0.0001) and TE (ρ = 0.649; P < 0.0001) correlated significantly with the stage of fibrosis. AUROCs of ElastPQ and TE for the diagnosis of any fibrosis (F ≥ 1), significant fibrosis (F ≥ 2), and advanced fibrosis (F ≥ 3) were 0.907, 0.959, 0.926 and 0.870, 0.770, 0.881, respectively, in both CVH and NAFLD groups. However, the accuracy of both these techniques was poor in patients with CVH and ESRD (AUROCs for ElastPQ and TE of 0.667 and 0.167 for the diagnosis of significant fibrosis, respectively, and 0.429 and 0.143 for the diagnosis of advanced fibrosis, respectively). The diagnostic accuracy of both ElastPQ and TE for detecting significant fibrosis was excellent in patients with NAFLD (AUROC of 1.000 and 0.936, respectively). ElastPQ was superior to TE in the diagnosis of significant fibrosis in the combined analysis (P = 0.0149) and in the CVH group (P = 0.0391), while both modalities were comparable in patients of the NAFLD group (P = 0.2539). ElastPQ may be equally accurate as Fibroscan, and large prospective studies are required to validate the same. [ABSTRACT FROM AUTHOR]

The article offers information about the assessment of PD-L1 expression and tumor-infiltrating lymphocytes (TILs) across molecular subtypes of triplenegative breast cancer. It mentions that triple-negative breast cancers (TNBC) lack actionable targets and show varied responses to chemotherapy influenced by molecular heterogeneity or degree of immune cell (IC) infiltration.

Exposure to drought stress negatively affects plant productivity and consequently threatens global food security. As global climates change, identifying solutions to increase the resilience of plants to drought is increasingly important. Several chemical treatments have recently emerged as promising techniques for various individual and combined abiotic stresses. This study shows compelling evidence on how acetic acid application promotes drought acclimation responses in soybean by investigating several morphological, physiological and biochemical attributes. Foliar applications of acetic acid to drought‐exposed soybean resulted in improvements in root biomass, leaf area, photosynthetic rate and water use efficiency; leading to improved growth performance. Drought‐induced accumulation of reactive oxygen species, and the resultant increased levels of malondialdehyde and electrolyte leakage, were considerably reverted by acetic acid treatment. Acetic acid‐sprayed plants suffered less oxidative stress due to the enhancement of antioxidant defense mechanisms, as evidenced by the increased activities of superoxide dismutase, ascorbate peroxidase, catalase, glutathione peroxidase and glutathione S‐transferase. Improved shoot relative water content was also linked to the increased levels of soluble sugars and free amino acids, indicating a better osmotic adjustment following acetic acid treatment in drought‐exposed plants. Acetic acid also increased stem/root, leaf/stem and leaf/root mineral ratios and improved overall mineral status in drought‐stressed plants. Taken together, our results demonstrated that acetic acid treatment enabled soybean plants to positively regulate photosynthetic ability, water balance, mineral homeostasis and antioxidant responses; thereby suggesting acetic acid as a cost‐effective and easily accessible chemical for the management of soybean growth and productivity in drought‐prone areas. [ABSTRACT FROM AUTHOR]

Breast cancer is a heterogeneous disease with wide range of clinical behaviour. Tumour angiogenesis and metastasis have been considered as prognostic markers of the breast carcinoma, and c‐Met, a transmembrane receptor tyrosine kinase has been implicated in both these processes of tumour progression. This study was conducted to elucidate c‐Met and downstream signalling pathways in breast cancer and correlate with angiogenesis as assessed by microvessel density (MVD) and other prognostic parameters including lymph node metastases. Microvessel density (MVD) was assessed by endothelial cell (CD34) marker in breast cancers. c‐Met was evaluated by immunohistochemistry for protein expression and by copy number assay for amplification at gene level. PCR array for gene expression related to c‐Met, RAS‐MAPK, PI3K‐AKT and angiogenesis pathway was performed by real‐time PCR. c‐Met protein, copy number and mRNA expression did not differ significantly with the lymph node status or MVD. However, Her‐2 overexpressing group showed c‐Met protein overexpression and amplification. c‐Met protein overexpression was also noted in the Luminal B subtype though no amplification was noted. Thus, the c‐Met immunohistochemistry score and the c‐MET copy numbers did not correlate with each other. c‐Met downstream pathway genes (RAS‐MAPK, PI3K‐AKT and angiogenesis pathway) showed significant upregulation in Luminal B molecular subtype, lymph node‐positive cases and cases with high MVD. The downstream signalling pathways (angiogenesis, RAS‐MAPK and PI3K‐AKT) were associated high MVD, lymph node metastases, and Her‐2 and Luminal B subtype. Since inhibitors of these pathways are commercially available, these can be of therapeutic significance. [ABSTRACT FROM AUTHOR]

Background: Gallstone disease (GSD) and nonalcoholic fatty liver disease (NAFLD) are connected with a high prevalence in the general population and they share common risk factors for their occurrence. Limited literature with inconsistent results is available, suggesting a potential association between these lifestyle-induced diseases. Liver biopsy is the gold standard for diagnosing NAFLD. The aim of this study was (1) to identify the prevalence of asymptomatic NAFLD or NASH in liver biopsy; (2) to identify the association of hypercholesterolemia with NAFLD in patients undergoing laparoscopic cholecystectomy (LC). Methods: This is a prospective observational study conducted on patients who underwent LC for symptomatic gallstones in the Department of General Surgery, Post Graduate Institute of Medical Education and Research, Chandigarh, India, from 1st July 2013 to 31st December 2014. All included patients had ultrasonography (USG) and the following parameters tested: serum triglycerides (TG), cholesterol, low density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C). A wedge liver biopsy was obtained from free edge of the right liver lobe during LC and all biopsy specimens were analyzed by a single pathologist. Results: Among 101 patients included in the study, dyslipidemia was present in 49.50%. There was no association between NAFLD and serum cholesterol, TG or LDL-C (P, 0.428, 0.848, 0.371 respectively). NAFLD was confirmed in liver biopsy in 21.8% of patients but none had fibrosis or cirrhosis on biopsy. No complications were observed following liver biopsy. conclusions: Liver biopsy during LC gives an opportunity to diagnose the disease at an early and reversible stage. It is feasible, safe and cost effective. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the relationship of mucosa‐associated candida (MAC) and disease severity in patients with ulcerative colitis (UC). Methods: We prospectively investigated the presence, nature, and quantification of MAC in patients with UC and its relationship with disease severity. Consecutive patients with UC were assessed for clinical, endoscopic, histological features and serum markers of disease severity. All patients underwent mucosal brushing cytology, brushing culture, and biopsy culture for candida growth. MAC was considered present if mucosal biopsy culture grew candida. Candida spp. identification was performed by matrix‐assisted laser desorption/ionization. Serum β‐D‐glucan was measured with a Fungitell assay. Patients with irritable bowel syndrome who had undergone similar investigations were included as controls. Results: Ninety‐six patients with UC showed evidence of MAC more often than the controls (n = 20) based on biopsy culture (33.3% vs 5.0%, P = 0.011), brush cytology (30.2% vs 5.0%, P = 0.019), and brush culture (36.5% vs 10.0%, P = 0.021). Patients with UC had higher candida colony counts (≥103 CFU/mL) than controls (34.4% vs 5.0%, P = 0.007). Median β‐D‐glucan values were higher in patients with UC than in controls (103.26 pg/mL vs 66.51 pg/mL, P = 0.011). The UC group with MAC had a higher median total Mayo score, C‐reactive protein, fecal calprotectin, β‐D‐glucan, and histological activity than those without MAC. Conclusions: Patients with UC more often show evidence of MAC and a higher candida colony count than controls. The presence of MAC is associated with high disease severity in patients with UC. [ABSTRACT FROM AUTHOR]

Primary ovarian non-Hodgkin lymphoma (PONHL) is extremely rare, accounting for 0.5% of all NHLs and 1.5% of all ovarian tumors. Establishing an early and accurate clinical as well as histopathological diagnosis, although challenging, is essential for the appropriate management of these patients and to avoid unnecessary surgeries. Furthermore, it is important to exclude secondary involvement of the ovary by disseminated NHL in these patients, as the two entities carry significantly different prognosis. The diagnostic struggle is mainly due to its rarity, morphological similarities with other malignancies and the relative lack of awareness among the histopathologists. In this article, we present a case of primary ovarian diffuse large B cell lymphoma in a young nulliparous female, who was diagnosed based on histopathological and immunohistochemical findings. [ABSTRACT FROM AUTHOR]

Primary orbital chondromyxoid fibroma is a rarely reported entity. A 34-year-old lady presented with painless, non-axial proptosis of the left eye of 6 months duration. Orbital imaging showed a supero-temporal mass with calcific foci and bone erosion. The mass caused globe compression resulting in choroidal folds. Anterior orbitotomy with complete mass excision was performed. The histopathology revealed a chondromyxoid fibroma. At 12-months follow-up, the patient is doing fine with no clinical recurrence. Chondromyxoid fibroma is an important differential diagnosis for bony orbital tumors. [ABSTRACT FROM AUTHOR]

Objective: Retroperitoneal fibrosis (RPF) is a rare proliferative fibro-inflammatory disease involving the soft tissues of the retroperitoneum. IgG4 related retroperitoneal fibrosis is an emerging entity which needs to be distinguished from idiopathic RPF. We describe a clinical case of IgG4 related RPF highlighting the importance of clinching this diagnosis.Methods: A 70 year old female was referred to the outpatient department of our institute with complaints of fatigue, bilateral flank pain and loss of appetite for the past 1 month. The CT and PET scan demonstrated a uniformly enhancing bulky retroperitoneal mass causing bilateral hydroureteronephrosis. The biopsy from the mass lesion revealed IgG4 related disease. The patient was started on corticosteroids after percutaneous nephrostomy placement.Results: Three months post induction of therapy, repeat PET-CT shows resolution of the mass with no FDG avid lesion. Serum IgG4 levels were reduced to normal (27 mg/dL) suggestive of response to treatment. The percutaneous nephrostomies were removed and the patient is doing well on maintenance dose of corticosteroids for her disease.Conclusion: The availability of serum IgG4 levels for monitoring treatment response and follow-up can curtail the repeated radiological imaging and associated contrast exposure as compared to idiopathic RPF. Secondly, the diagnosis of IgG4-related RPF shall alert the clinician to look out for extra-retroperitoneal diseases on follow up of this multi-organ disease. [ABSTRACT FROM AUTHOR]

There is no consensus on the classification of the diagnostic certainty of hypersensitivity pneumonitis (HP) based on the histopathological findings. This retrospective study aimed to describe the clinical and histopathological spectrum of HP. Herein, we also propose different grades of diagnostic certainty. Based on the histology, the cases were classified as: 'definite HP', 'probable HP', and 'possible HP'. Of the 47 subjects screened, 30 cases of histologically diagnosed HP (mean age 48.4 years; 50% women) were included. The findings of cellular bronchiolitis, interstitial pneumonia, interstitial granuloma, isolated interstitial multinucleated giant cells (MNGCs), airspace granulomas, isolated airspace MNGCs, and organizing pneumonia were present in 96.7%, 80%, 46.7%, 50%, 10%, 63.3%, and 16.7% cases, respectively. Based on the various combinations of histopathological findings, the cases were classified as 'definite', 'probable', and 'possible' HP in 56.7%, 33.3%, and 10%, respectively. Chronic HP was diagnosed in 56.7% cases based on the presence of fibrosis on histopathology. The histopathological diagnosis of subacute or chronic HP did not corroborate with the disease duration, and 17.6% of the subjects with duration of symptoms of <6 months had evidence of fibrotic disease on histopathology. [ABSTRACT FROM AUTHOR]

Mesenchymal stem/stromal cell (MSC) spheroids generated in a three-dimensional (3D) culture system serve as a surrogate model that maintain stem cell characteristics since these mimic the in vivo behavior of cells and tissue more closely. Our study involved a detailed characterization of the spheroids generated in ultra-low attachment flasks. The spheroids were evaluated and compared for their morphology, structural integrity, viability, proliferation, biocomponents, stem cell phenotype and differentiation abilities with monolayer culture derived cells (2D culture). The in-vivo therapeutic efficacy of DPSCs derived from 2D and 3D culture was also assessed by transplanting them in an animal model of the critical-sized calvarial defect. DPSCs formed compact and well-organized multicellular spheroids when cultured in ultra-low attachment condition with superior stemness, differentiation, and regenerative abilities than monolayer cells. They maintained lower proliferative state and showed marked difference in the cellular biocomponents such as lipid, amide and nucleic acid between DPSCs from 2D and 3D cultures. The scaffold-free 3D culture efficiently preserves DPSCs intrinsic properties and functionality by maintaining them in the state close to the native tissues. The scaffold free 3D culture methods allow easy collection of a large number of multicellular spheroids of DPSCs and therefore, this can be adopted as a feasible and efficient method of generating robust spheroids for various in-vitro and in-vivo therapeutic applications. • Compact multi-cellular, viable spheroids were obtained from DPSCs in scaffold free 3D culture. • FTIR analysis showed difference in lipid, amide and nucleic acid content between cells in monolayer and spheroids. • DPSCs spheroids showed superior bone regeneration ability in in-vivo bone defect model. [ABSTRACT FROM AUTHOR]

Incidental intrahepatic cholangiocarcinoma (iCCA) is a rare neoplastic lesion in the explant liver specimens with an approximate incidence of 0.7%. The detection of iCCA is associated with poor prognosis in the posttransplant setting. The occurrence of a subcentimetric iCCA is very rare and poses a major diagnostic challenge to the pathologist. This article presents a rare case of subcentimetric iCCA in a young male in the background of advanced stage chronic liver disease resulting from autoimmune hepatitis possibly with chronic cholangiopathy along with the histomorphological differentials. [ABSTRACT FROM AUTHOR]

Primary hepatic leiomyosarcoma is a rare primary mesenchymal tumor of the liver requiring exclusion of any other primary site of origin and histological and immunohistochemical exclusion of other hepatic/extrahepatic tumors with spindle cell morphology. Only about 70 cases are reported in the English literature and many of these tumors have predisposing conditions in the form of immunosuppression or associated malignancies. The occurrence of this tumor in the immunocompetent individual is also known. Histomorphology of this tumor shows a spindle cell lesion which needs to be distinguished from other spindle cell lesions of this region. The main diagnostic challenge of this tumor lies in its rarity, lack of awareness and morphological mimickers in the given site. A complete range of immunohistochemical markers is required to distinguish the lesion from its close morphological mimickers. Here, we discuss a case of primary hepatic leiomyosarcoma in an adult female patient with detailed histomorphological differentials and respective immunoprofiles. [ABSTRACT FROM AUTHOR]

Pericarditis is a raremanifestation of tuberculosis in children. The usual clinical features include fever, cough, tachypnea, chest pain, and pedal edema. Very rarely, generalized edema may occur as a presenting feature. We describe a 10-year-old boy, who presented with anasarca and had received treatment with corticosteroids for a mistaken diagnosis of nephrotic syndrome and was subsequently diagnosed with tuberculous pericardial effusion. The rarity of manifestations and the difficulties encountered to diagnose tuberculous pericarditis prompted us to report this case. The reportmay serve to sensitize pediatricians to consider systematic investigations to reach the diagnosis in children presenting with anasarca and avoid the empiric use of steroids in anasarca. [ABSTRACT FROM AUTHOR]

The article describes a case of Myeloid Sarcoma (MS) in a 30 year old female patient presented with bilateral breast lumps. Clinical examination showed vague nodularity in bilateral breasts with tenderness and microscopic examination of the core biopsies from both breasts indicated a cellular tumor arranged in a single cell pattern and in sheets. A diagnosis of acute myeloid leukemia (AML) with monocytic differentiation was made following bone marrow examination.

Background Acute exacerbation of Autoimmune Hepatitis (AIH) poses a significant challenge for diagnosis as it can mimic acute viral hepatitis especially in absence of autoantibodies and hypergammaglobulinemia. Aim To determine the clinical, laboratory, histopathological characteristics and response to treatment in AIH patients with acute exacerbation. Methods A retrospective analysis of 16 patients with acute exacerbation of AIH diagnosed over a period of eight years (2008–2016). Results Out of the 111 patients diagnosed with AIH, acute exacerbation of AIH was diagnosed in 16 (14.4%) patients. All patients were females with median age of 35 years. Nine patients (56%) had Type 1 AIH and seven (44%) patients were diagnosed with seronegative AIH. All 16 (100%) patients had acute viral hepatitis like illness at presentation. The median bilirubin was 4.2 mg/dl (range, 2.2–20), aspartate transaminase was 568 IU/L (range, 390–908), alanine transaminase was 430 IU/L (range, 257–1026) and serum alkaline phosphatase was 395 IU/L (range, 112–890) during symptomatic period. The histopathological examination showed underlying chronic hepatitis in 10 (71.4%) patients, only fibrosis in 2 (14.2) patients and cirrhosis with activity in 2 (14.2%). All 16 (100%) patients were treated with a combination of steroids and azathioprine. Thirteen (81%) patients achieved complete biochemical remission and three (19%) patients achieved partial remission out of which one (6%) patient succumbed to illness because of the complications of cirrhosis. Conclusion A suspicion of acute exacerbation of AIH should be considered in patients with unexplained acute hepatitis mimicking acute viral hepatitis in the absence of positive viral markers. Through evaluation with immunoserological markers and liver biopsy can clinch the diagnosis of acute exacerbation of AIH in such cases. [ABSTRACT FROM AUTHOR]