Transcatheter closure of ventricular septal defects: preliminary results in children weighing 10 kg or less.

INTRODUCTION: Ventricular septal defect is one of the commonest heart defect in children and closure of this defect with devices has seen a rapid progression over a period of time. The availability of new and safer devices has made the transcatheter closure of ventricular septal defect a suitable option even in young children. AIM: The study was done to evaluate the feasibility and complications of device closure of ventricular septal defect in children weighing 10 kg or less with different types of devices. METHODS: The present study was undertaken in a newly established dedicated Paediatric Cardiac Unit at a Tertiary Care Hospital. Relevant data were obtained retrospectively from the case files and the catheterisation records and data were analysed for first 50 patients with ventricular septal defect weighing 10 kg or less between March 2018 and March 2021. RESULTS: Among these 50 patients selected, device closure was successfully done in 45 (90%) cases while 5 (10%) attempts were unsuccessful for various reasons. The mean weight in this study was 7.46 ± 1.89 kg (2.3-10 kg), 21 (42%) cases were females while 29 (58%) were males; mean age was 19.4 ± 11.88 months (4-48 months). Right heart catheterisation study showed 21 (42%) patients with normal pulmonary artery pressures (no pulmonary artery hypertension). Among 29 patients with pulmonary arterial hypertension, 13 patients (22%) were having mild pulmonary arterial hypertension, 4 (8%) were with moderate pulmonary arterial hypertension, and 12 (24%) were with severe pulmonary arterial hypertension. Mean Qp/Qs was 2.73 ± 0.72 (2.5-4.5) and mean pulmonary vascular resistance was 1.5 ± 1.04 (0.6-4.6 WU). Amplatzer Duct Occluder (ADOI) was used in 15 (30%) cases, 27 (52%) cases were closed with Amplatzer Duct Occluder (ADOII), and the 3 (6%) cases closure was done with Amplatzer muscular ventricular septal defect occluder. CONCLUSIONS: Transcatheter closure of ventricular septal defect in children 10 kg or less is feasible and safe alternative to surgical ventricular septal defect closure. The immediate and short-term outcomes have proven this method to be safe and valid.

Membranous nephropathy transplanted in the donor kidney: observations of resolving glomerulopathy in serial allograft biopsies.

We report a case of idiopathic, PLA2R-negative membranous nephropathy (MN) transplanted via a deceased donor kidney. Changes in glomerular immune deposits were followed in serial biopsies. The allograft recipient had end-stage disease without significant proteinuria from ischemic nephropathy due to chronic heart failure, hypertension, atherosclerosis and presumed diabetic nephropathy. Combined cardiac and renal transplants were performed. Maintenance immunosuppression consisted of prednisone, a calcineurin inhibitor and mycophenolate mofetil. MN was identified in the pre-implantation biopsy of the donor kidney. The recipient never developed significant proteinuria and there was no identifiable impact on graft function. Serial biopsies performed at Days 0, 18, 150, 234 and 812 revealed mild effacement of podocyte foot processes, progressive change from Ehrenreich-Churg Stage III-IV lesions of MN to segmental resolution by electron microscopy, and progressive decrease of IgG staining by immunofluorescence. The findings provide a novel observation of the protracted process of glomerular immune deposit resolution in healing MN transplanted in a neutral host environment.

Genomic aberrations in myeloid sarcoma without blood or bone marrow involvement: characterization of formalin-fixed paraffin-embedded samples by chromosomal microarrays.

Myeloid sarcoma (MS) is a presentation of acute myeloid leukemia (AML) as a tumor mass outside of the bone marrow. Viable cells from MS are frequently unavailable for cytogenetic studies. We therefore investigated whether chromosomal microarray analysis (CMA) using formalin-fixed paraffin-embedded (FFPE) tissues can detect clinically important genetic abnormalities in MS. CMA successfully identified genomic aberrations in six cases of MS, and in two cases it revealed multiple abnormalities equivalent to a complex karyotype, thus predicting a poor outcome. CMA using FFPE material is therefore a feasible and clinically applicable approach for detection of prognostically significant genomic abnormalities in MS.

Current status of prognostication in classical Hodgkin lymphoma.

Classical Hodgkin lymphoma (cHL) is characterized by a paucity of neoplastic Hodgkin/Reed Sternberg (HRS) cells within a complex cellular milieu that is rendered immunologically incapable of reacting against CD30(+) HRS cells due to a plethora of immune escape mechanisms initiated by the neoplastic cells. Accounting for 25% of all lymphomas and nearly 95% of all Hodgkin lymphomas, patients with cHL are typically young adults. Besides traditional prognostic factors, such as the International Prognostic Index (IPI), newer imaging and ancillary biomarkers (CD68, Galectin-1 and plasma microRNA) have shown promise. Furthermore, the evolution of gene expression profiling (GEP) in recent years has enabled the development of several practically feasible GEP-based predictors with prognostic relevance. This review discusses the current status of clinical prognostication in cHL, the critical role of histological evaluation in light of several mimicking entities, and the relevance of tissue as well as serum biomarkers pertaining to immune escape mechanisms and recent GEP studies.

How useful is GLUT-1 in differentiating mesothelial hyperplasia and fibrosing pleuritis from epithelioid and sarcomatoid mesotheliomas? An international collaborative study.

OBJECTIVE: Mesothelial hyperplasia (MH) and fibrosing pleuritis (FP) can be difficult to distinguish from epithelioid (MM-E) and sarcomatoid (MM-S) malignant pleural mesotheliomas. GLUT-1 has shown variable results regarding its sensitivity and specificity when used to evaluate mesothelial proliferations. We evaluated the utility of GLUT-1 immunostaining in differentiating MH and FP from MM-E and MM-S. MATERIALS AND METHODS: In this retrospective study, diagnostically well-characterized cases (MH=31, FP=29, MM-E=41, MM-S=29) were collected and manually stained for GLUT-1. All slides were visually scored by 2 pathologists; using the following system: 0%, 1+ 1-25%, 2+ 26-50% and 3+ >51% cells staining. RESULTS: All benign cases (n=60) were negative for GLUT-1 while 45 of 78 (58%) MM [21 of 41 (50%) MM-E, 21 of 29 (72%) MM-S and 3 of 3 biphasic mesothelioma (100%)] had 1+ to 3+ staining. Of the MM-E, 10 had 1+, and 11 had 2+ staining; of the MM-S 3 had 1+, 15 had 2+ and 3 had 3+ staining. Both sarcomatoid and epithelioid components of the 3 biphasic mesotheliomas revealed 1+ staining. All 5 desmoplastic MM were negative. CONCLUSIONS: Positive staining with GLUT-1 is helpful since it is present in half of MM-E and three-quarter of MM-S. Although all reactive mesothelial lesions were negative, the absence of immunoreactivity does not exclude the diagnosis of MM. As with all IHC stains used for diagnostic purposes, GLUT-1 has to be a part of a panel, and the results interpreted in the context of clinical, radiological and histological findings.

Is GATA3 expression maintained in regional metastases?: a study of paired primary and metastatic urothelial carcinomas.

GATA3 has been recognized as a promising marker for primary urothelial carcinoma (UC), consistently showing higher expression levels than urothelial markers thrombomodulin and uroplakin III. However, expression of GATA3 in comparison with UC-associated markers CK7 and p63 has not been systematically studied. Moreover, no studies have been conducted to establish GATA3 sensitivity in regional metastases. In this study, high-density tissue microarrays were constructed from 69 matched paired primary and metastatic bladder tumors including pure urothelial UCs with papillary (n=48) or flat phenotype (n=9), mixed tumors with micropapillary, glandular, small cell, squamous, giant cell, and plasmacytoid features (n=9), and 3 adenocarcinomas. GATA3 was expressed in 62/69 (90%) primary UC and 64/69 (93%) metastases, with significantly higher staining intensity in nodal metastases (P=0.03). In primary tumors, GATA3 was positive in 44/48 (92%) papillary UCs, 9/9 (100%) flat UCs, 8/9 (89%) mixed UCs, and 1/3 (33%) adenocarcinomas, whereas in metastases these numbers were 45/48 (94%), 9/9 (100%), 8/9 (89%), and 2/3 (67%), respectively. The majority of positive cases showed strong diffuse nuclear reactivity: 75% of primary UCs and 79% of metastases. GATA3 sensitivity in primary and metastatic UCs was comparable to that of CK7 and superior to that of p63 (P<0.05). GATA3 specificity was computed in comparison with its morphologic mimics expressing CK7 and p63, including 208 primary and 24 metastatic tumors from the lung, cervix, and head and neck regions. Strong GATA3 expression was present in 2/51 (4%) cervical carcinomas, whereas weak GATA3 expression was present in 7/51 (14%) cervical, 6/74 (8%) head and neck cancers, and 2/83 (3%) lung carcinomas. Remaining 191 primary and 24 metastatic tumors were GATA3 negative. Therefore, specificity of GATA3 calculated on the basis of morphologic and immunophenotypic UC mimics from lung, cervix, head and neck was 92%. Our findings demonstrate high sensitivity and specificity of the GATA3 diagnostic marker, with not only maintained but increased expression in regional metastases.

Adjunct therapeutic plasma exchange for anti-N-methyl-D-aspartate receptor antibody encephalitis: a case report and review of literature.

Encephalitis associated with autoantibodies directed against the N-methyl-D-aspartate receptor (NMDAR) is usually a paraneoplastic syndrome that presents in young females with ovarian teratomas. We report a case of a previously healthy 14-year-old girl with sudden-onset paranoia, hallucinations, hyperactivity, increased speech, decreased sleep, seizures, and violent behavior deteriorating to catatonia. Her cerebrospinal fluid tested positive for anti-NMDAR antibodies. She was treated with five sessions of therapeutic plasma exchange (TPE) after having failed therapy with antibiotics, intravenous steroids, intravenous immunoglobulin (IVIG), one dose of rituximab, and seven sessions of electroconvulsive therapy (ECT). The American Society for Apheresis assigns a Category III (Grade 2C) recommendation for TPE in paraneoplastic neurologic syndromes; however, apheresis specifically for anti-NMDAR encephalitis has not been well studied. Literature review revealed two case reports describing outstanding improvement in patients with anti-NMDAR encephalitis following TPE. We report no improvement in our patient's symptoms after plasma exchange and discuss possible reasons for why it failed along with review of the literature.

Kruppel-like factor-4 transcriptionally regulates VE-cadherin expression and endothelial barrier function.

RATIONALE: Vascular endothelial (VE)-cadherin localized at adherens junctions (AJs) regulates endothelial barrier function. Because WNT (wingless) signaling-induced activation of the transcription factor Krüppel-like factor (KLF)4 may have an important role in mediating the expression of VE-cadherin and AJ integrity, we studied the function of KLF4 in regulating VE-cadherin expression and the control of endothelial barrier function. OBJECTIVE: The goal of this study was to determine the transcriptional role of KLF4 in regulating VE-cadherin expression and endothelial barrier function. METHODS AND RESULTS: Expression analysis, microscopy, chromatin immunoprecipitation, electrophoretic mobility shift assays, and VE-cadherin-luciferase reporter experiments demonstrated that KLF4 interacted with specific domains of VE-cadherin promoter and regulated the expression of VE-cadherin at AJs. KLF4 knockdown disrupted the endothelial barrier, indicating that KLF4 is required for normal barrier function. In vivo studies in mice showed augmented lipopolysaccharide-induced lung injury and pulmonary edema following Klf4 depletion. CONCLUSION: Our data show the key role of KLF4 in the regulation of VE-cadherin expression at the level of the AJs and in the acquisition of VE-cadherin-mediated endothelial barrier function. Thus, KLF4 maintains the integrity of AJs and prevents vascular leakage in response to inflammatory stimuli.