Clonal Monocytosis of Renal Significance.

Clonal monocytosis reflects a preneoplastic or neoplastic sustained increase in the absolute monocyte count in the absence of reactive causes. Causes of clonal monocytosis include clonal cytopenias with monocytosis and acute and chronic myeloid neoplasms. Chronic myelomonocytic leukemia (CMML) is a prototypical myelodysplastic/myeloproliferative overlap neoplasm in adults, characterized by sustained peripheral blood monocytosis. Renal abnormalities, including acute kidney injury (AKI) and chronic kidney disease (CKD), are frequent in patients with CMML and are predictors of worse outcomes. In addition, AKI/CKD often limits eligibility for allogeneic stem cell transplantation or enrollment in clinical trials. In this review, we highlight clonal monocytosis-related etiologies that give rise to AKI and CKD, with special emphasis on CMML and lysozyme-induced nephropathy (LyN). Monocytes produce lysozyme, which, in excess, can accumulate in and damage the proximal renal tubular epithelium. Early identification of this etiology and a timely reduction in monocyte counts can salvage renal function. Other etiologies of renal injury associated with clonal monocytosis include direct renal infiltration by monocytes, renal extramedullary hematopoiesis, myeloproliferative neoplasm-associated glomerulopathy, auto-immune (membranous nephropathy, minimal change disease) and paraneoplastic manifestations, thrombotic microangiopathy, obstructive nephropathy due to myeloproliferation, and urate nephropathy due to tumor lysis syndrome. We propose to group these mechanistic etiologies of renal injury as clonal monocytosis of renal significance and provide guidance on their diagnosis and management.

Malignant pleural effusion cell blocks are reliable resources for PD-L1 analysis in advanced lung adenocarcinomas: a concordance study with matched histologic samples.

INTRODUCTION: In lung cancer patients presenting with malignant pleural effusion (MPE), cytology might represent the only source of tumor tissue for diagnosis and predictive biomarker testing. Programmed death ligand 1 (PD-L1) expression in tumor cells is a predictive biomarker for immunotherapy in non-small cell lung carcinomas and is tested using immunohistochemistry. However, knowledge of the validity of PD-L1 testing on MPE samples is limited. We evaluated the feasibility of immunocytochemistry (ICC) for PD-L1 in MPE cell blocks (CBs) and assessed the concordance in expression with patient-matched histologic samples. MATERIALS AND METHODS: ICC for PD-L1 was performed on formalin-fixed paraffin-embedded CBs of MPE and patient-matched histologic samples, if available, using the automated Ventana PD-L1 SP263 assay. The tumor proportion score (TPS), based on partial or complete membranous tumor cell staining, was categorized as negative (<1%), low (≥1% to <50%), and high (≥50%). In CBs with any degree of PD-L1 expression, ICC for CD163 highlighting macrophages was performed to exclude nonspecific PD-L1 expression in macrophages. The CB PD-L1 TPS was compared with the TPS obtained from the patient-matched histologic samples. RESULTS: Of 43 MPE CBs available, 25 were positive for PD-L1 (25 of 42; 59%), and 1 sample was inadequate. Of the 11 patient-matched histologic samples tested, the PD-L1 TPS categories were concordant for 10 of the 11 (91% concordance) cases. CONCLUSIONS: PD-L1 expression in MPE CBs showed good concordance with expression in histologic samples and is feasible as a source for PD-L1 testing. The concurrent use of CD163 immunostains will aid in the manual assessment of PD-L1 TPS.

ALK-Negative Primary Cutaneous Anaplastic Large Cell Lymphoma With Systemic Involvement or Systemic ALCL With Cutaneous Lesion. A Diagnostic Dilemma.

ABSTRACT: Primary cutaneous anaplastic large-cell lymphoma (C-ALCL) is a cutaneous CD30-positive lymphoproliferative disorder. The patients usually present with single or multiple cutaneous nodules or papules and about 10% cases present with extracutaneous manifestations, which are predominantly in the form of regional lymph nodal involvement. Visceral involvement especially pulmonary or hepatic involvement in C-ALCL is only rarely described in the scientific literature. Approximately 20%-42% cases show spontaneous regression, about 50% cases may recur; however, C-ALCL generally carries a good prognosis. We present a rare case of primary C-ALCL in a 66-year-old man with regional lymph nodal and hepatic involvement. Differential diagnostic entities are discussed in this report with the review of the literature.

Molecular and genomic landscapes in secondary & therapy related acute myeloid leukemia.

Acute myeloid leukemia (AML) is a complex, aggressive myeloid neoplasm characterized by frequent somatic mutations that influence different functional categories' genes, resulting in maturational arrest and clonal expansion. AML can arise de novo (dn-AML) or can be secondary AML (s-AML) refers to a leukemic process which may arise from an antecedent hematologic disorder (AHD-AML), mostly from a myelodysplastic syndrome (MDS) or myeloproliferative neoplasm (MPN) or can be the result of an antecedent cytotoxic chemotherapy or radiation therapy (therapy-related AML, t-AML). Clinical and biological features in secondary and therapy-related AML are distinct from de novo AML. Secondary and therapy-related AML occurs mainly in the elderly population and responds worse to therapy with higher relapse rates due to resistance to cytotoxic chemotherapy. Over the last decade, advances in molecular genetics have disclosed the sub-clonal architecture of secondary and therapy-related AML. Recent investigations have revealed that cytogenetic abnormalities and underlying genetic aberrations (mutations) are likely to be significant factors dictating prognosis and critical impacts on treatment outcome. Secondary and therapy-related AML have a poorer outcome with adverse cytogenetic abnormalities and higher recurrences of unfavorable mutations compared to de novo AML. In this review, we present an overview of the clinical features of secondary and therapy-related AML and address the function of genetic mutations implicated in the pathogenesis of secondary leukemia. Detailed knowledge of the pathogenetic mechanisms gives an overview of new prognostic markers, including targetable mutations that will presumably lead to the designing and developing novel molecular targeted therapies for secondary and therapy-related AML. Despite significant advances in knowing the genetic aspect of secondary and therapy-related AML, its influence on the disease's pathophysiology, standard treatment prospects have not significantly evolved during the past three decades. Thus, we conclude this review by summarizing the modern and developing treatment strategies in secondary and therapy-related acute myeloid leukemia.

Mortality and Clinical Outcomes among Patients with COVID-19 and Diabetes.

Background Diabetes mellitus (DM) is a decisive risk factor for severe illness in coronavirus disease 2019 (COVID-19). India is home to a large number of people with DM, and many of them were infected with COVID-19. It is critical to understand the impact of DM on mortality and other clinical outcomes of COVID-19 infection from this region. Aims The primary objective of our study was to analyze the mortality rate in people with DM infected with COVID-19. The secondary objectives were to assess the effect of various comorbidities on mortality and study the impact of DM on other clinical outcomes. Methods This is a retrospective study of COVID-19 infected patients admitted to a tertiary care hospital in north India in the early phase of the pandemic. Results Of the 1211 cases admitted, 19 were excluded because of incomplete data, and 1192 cases were finally considered for analysis. DM constituted 26.8% of total patients. The overall mortality rate was 6.1%, and the rate was 10.7% in the presence of diabetes (p < 0.01, OR 2.55). In univariate analysis, increased age, chronic kidney disease (CKD), coronary artery disease (CAD), stroke, and cancer were associated with mortality. On multiple logistic regression, the independent predictors of mortality were CAD, CKD, and cancer. Breathlessness and low SpO2 at presentation, extensive involvement in CXR, and elevated ANC/ALC ratio were also significantly associated with mortality. Conclusions The presence of comorbidities such as DM, hypertension, CAD, CKD, and cancer strongly predict the risk of mortality in COVID-19 infection. Early triaging and aggressive therapy of patients with these comorbidities can optimize clinical outcomes.

Smartphone-enabled field monitoring tool for rapid hexavalent chromium detection in water.

Chromium contamination of soil and water is a serious environmental and public health concern as the hexavalent form of chromium [Cr(VI)] is readily soluble in water and is a confirmed carcinogen. There is an imminent need for a robust, low-cost, and simple analytical technique to facilitate in situ monitoring of Cr(VI) in water. Current quantitative methods of Cr(VI) detection are largely laboratory-based, time-consuming, expensive, and require training for implementation. In this contribution, a portable, easy-to-use, and compact measuring tool is presented that provides Cr(VI) concentration within 10 min of water sampling over a linear range of 0-3 mg L-1. This tool utilizes a relatively inexpensive camera-enabled smartphone with a custom-made test chamber attachment to seamlessly perform Cr(VI) measurements on water samples in the field. For analysis, an android-based software application was developed that directs the user to perform a simple series of steps following the diphenylcarbazide-based colorimetric method prescribed by the American Public Health Association. The tool was validated against a standard UV-visible spectrophotometer for a variety of synthetic and naturally contaminated water samples, with correlation factors greater than 0.993 (p < .001). The colorimetric method was also validated against a non-colorimetric Cr(VI) detection technique-ion chromatography-inductively coupled plasma mass spectrometry. Furthermore, Cr(VI) detection limits for the smartphone-enabled colorimetric method were found to be within 1.3-11.6 µg L-1, which were significantly better than reported for commercially available field test kits, and even surpassed the limits exhibited by a typical spectrophotometer (25-50 µg L-1). Finally, real-time mapping of source waters at a contaminated site was demonstrated by remote logging of Cr(VI) water quality data and corresponding GPS coordinates into a cloud server. This study highlights the potential role of smartphone-based monitoring tool in providing information to the affected community and enabling safe access to drinking water. An accurate, robust, simple-to-use, and economic method to measure hexavalent chromium in water within 10 min of sampling at site.

A systematic review of clinical and laboratory parameters of 3,000 COVID-19 cases.

The coronavirus disease 2019 (COVID-19) has spread worldwide. It is still a pandemic and poses major health problem across the globe. In our review, clinical characteristics and laboratory parameters of COVID-19 patients were compiled systematically, with special reference to pregnant women in order to understand the disease course. An extensive literature search on various scientific databases for relevant manuscripts was conducted, which yielded 7 manuscripts for final analysis. The most common symptoms were fever (85%), cough (70.63%), chest tightness (37.36%), expectoration (33.27%), fatigue (32%), dyspnea (31.95%), and shortness of breath (31.19%), while hemoptysis (1.0%) was the least common. The associated comorbidities were hypertension (21.6%) and diabetes (10.0%). In terms of hematological parameters, lower total leukocyte counts were observed in 65% of cases and biochemical parameters, patients demonstrated elevated levels of albumin (53.72%), lactate dehydrogenase (45.71%), and natriuretic peptide (34.84%); however, total bilirubin was elevated in only 8% of cases. In the acute inflammatory cytokine profile, C-reactive protein (59.0%), tumor necrosis factor (58.0%), erythrocyte sedimentation rate (57.0%), interleukin-2 (IL- 2, 54.0%), and IL-6 (52.0%) levels were increased, while prolactin levels (6.5%) were minimally elevated. The recovery rate was approximately 41%, and mortality was about 6.5%. The study also concluded that the clinical symptoms of COVID-19 were similar among pregnant and non-pregnant women. There was no evidence of vertical transmission of COVID-19 infection. This review critically analyzed COVID-19 as a public health hazard in order to help policy makers, health care givers, and primary physicians to promote early diagnosis and prevention.