Molecular detection of Orientia tsutsugamushi strains circulating in Nagaland

The antigenic heterogeneity of Orientia in India is still unknown in many disease endemic areas. The present study aims to characterize the strains of O. tsutsugamushi circulating in Nagaland, Northeast India. Two patients clinically diagnosed with ST and hospitalized in Mon district hospital, Nagaland were identified from whom eschar tissues were collected. Both patients demonstrated antibodies against O. tsutsugamushi along with positive PCR amplification for 56 ?kDa gene. The prototype strain TA763 shared 90.4% homology with the sequences. Both the sequences formed a distinctive cluster demonstrating 100% similarity with strains identified from Thailand, Vietnam, China and southern parts of India.     

MicroRNAs as Potential Diagnostic,Prognostic, and Predictive Biomarkers for Acute Graft-versus-Host Disease

Successful treatment of various hematologic diseases with allogeneic hematopoietic stem cell transplantation is often limited due to the occurrence of acute graft-versus-host disease (aGVHD). So far, there are no approved molecular biomarkers for the diagnosis and prediction of aGVHD at the clinical level due to our incomplete understanding of the molecular biology of the disease. Various studies have been conducted on animal models and humans to investigate the role of microRNAs in aGVHD pathogenesis to implicate them as biomarkers and therapeutic targets. Because of their high stability, tissue specificity, ease of measurement, low cost, and simplicity, they are excellent targets for biomarkers. In this review, we focused on microRNA expression profiling studies that were performed recently in both animal models and human cases of aGVHD to identify diagnostic and predictive biomarkers for this disease. The expression pattern of microRNAs can be specific to cells and tissues. Because aGVHD affects several organs, microRNA signatures in target tissues may help to understand the molecular pathology of the disease. Identification of organ-specific microRNAs in aGVHD can be promising to categorize patients for organ-specific therapies. Thus, microRNAs can be used as noninvasive diagnostic tests in clinic to improve prophylaxis, predict incidence and severity, and reduce morbidity.     

Development and Internal Validation of a Risk Prediction Model for Acute Cardiovascular Morbidity in Preeclampsia

BackgroundWomen with preeclampsia are at increased short-term risk of adverse cardiovascular outcomes during pregnancy and the early postpartum period. We aimed to develop and internally validate a risk assessment tool to predict acute cardiovascular morbidity in preeclampsia.MethodsThe study was conducted at an academic obstetrics hospital. Participants with preeclampsia at delivery from 2007 to 2017 were included. A model to predict acute cardiovascular morbidity at delivery and within 6 weeks after delivery was developed and evaluated. The primary composite outcome included pulmonary edema/acute heart failure, myocardial infarction, aneurysm, cardiac arrest/ventricular fibrillation, heart failure/arrest during surgery or procedure, cerebrovascular disorders, cardiogenic shock, conversion of cardiac rhythm, and difficult-to-control severe hypertension. We assessed model discrimination and calibration. We used bootstrapping for internal validation.ResultsA total of 4171 participants with preeclampsia were included. The final model comprised 8 variables. Predictors positively associated with acute cardiovascular morbidity (presented as odds ratio with 95% confidence interval) were: gestational age at delivery (20-36 weeks: 5.36 [3.67-7.82]; 37-38 weeks: 1.75 [1.16-2.64]), maternal age (≥ 40 years: 1.65 [1.00-2.72]; 35-39 years: 1.49 [1.07-2.09]), and previous caesarean delivery (1.47 [1.01-2.13]). The model had an area under the receiver operating characteristic curve of 0.72 (95% CI 0.69-0.74). Moreover, it was adequately calibrated and performed well on internal validation.ConclusionsThis risk prediction tool identified women with preeclampsia at highest risk of acute cardiovascular morbidity. If externally validated, this tool may facilitate early interventions aimed at preventing adverse cardiovascular outcomes in pregnancy and postpartum.     

Surgical Management and Outcomes of Patients with Multifocal Hepatoblastoma

ObjectiveTo compare the outcomes of patients with multifocal hepatoblastoma (HB) treated at our institution with either orthotopic liver transplant (OLTx) or hepatic resection to determine outcomes and risk factors for recurrence.BackgroundMultifocality in HB has been shown to be a significant prognostic factor for recurrence and worse outcome. The surgical management of this type of disease is complex and primarily involves OLTx to avoid leaving behind microscopic foci of disease in the remnant liver.MethodsWe performed a retrospective chart review on all patients <18 years of age with multifocal HB treated at our institution between 2000 and 2021. Patient demographics, operative procedure, post-operative course, pathological data, laboratory values, short- and long-term outcomes were analyzed.ResultsA total of 41 patients were identified as having complete radiologic and pathologic inclusion criteria. Twenty-three (56.1%) underwent OLTx and 18 (43.9%) underwent partial hepatectomy. Median length of follow-up across all patients was 3.1 years (IQR 1.1–6.6 years). Cohorts were similar in rates of PRETEXT designation status identified on standardized imaging re-review (p = .22). Three-year overall survival (OS) estimate was 76.8% (95% CI: 60.0%–87.3%). There was no difference in rates of recurrence or overall survival in patients who underwent either resection or OLTx (p = .54 and p = .92 respectively). Older patients (>72 months), patients with a positive porta hepatis margin, and patients with associated tumor thrombus experienced worse recurrence rates and survival. Histopathology demonstrating pleomorphic features independently associated with worse rates of recurrence.ConclusionsThrough proper patient selection, multifocal HB was adequately treated with either partial hepatectomy or OLTx with comparable outcome results. HB with pleomorphic features, increased patient age at diagnosis, involved porta hepatis margin on pathology, and the presence of associated tumor thrombus may be associated with worse outcomes regardless of the local control surgery offered.Level of EvidenceIII.     

Association of multidimensional comorbidities with survival,toxicity, and unplanned hospitalizations in older adults with metastatic colorectal cancer treated with chemotherapy

BackgroundStudies of older patients with colorectal cancer(CRC) have found inconsistent results about the correlation of various comorbidities with overall survival(OS) and treatment tolerance. To refine our understanding, we evaluated this correlation using the Cumulative Illness Rating Scale-Geriatric(CIRS-G) and heat maps to identify subgroups with the highest impact.MethodsWe retrospectively reviewed 153 patients aged 65 years and older with stage IV CRC undergoing chemotherapy. We calculated CIRS-G scores, and a Total Risk Score(TRS) derived from a previous heat map study. The association between CIRS-G scores/TRS and OS, unplanned hospitalizations, and chemotoxicity was examined by the Cox proportional hazards model.ResultsMedian age was 71 years. Median MAX2 score of chemotherapies was 0.134(0.025–0.231). The most common comorbidities were vascular(79.8%), eye/ear/nose/throat(68%), and respiratory disease(52.4%). Median OS was 25.1 months(95% confidence interval: 21.2–27.6). In univariate analysis, ECOG PS ≥ 2(HR 1.86(1.1–3.17), p = 0.019), poorly differentiated histology(HR 2.03(1.27–3.25), p = 0.003), primary site(rectum vs colon)(HR 0.58 (0.34–0.98), p = 0.04), age at diagnosis(HR per 5y 1.20 (1.04–1.39), p = 0.012), and number of CIRS-G grade 4 comorbidities(HR 1.86 (1.1–3.17), p = 0.019) were associated with OS. In multivariate analysis, the number of CIRS-G grade 4 comorbidities lost significance, although it retained it in the subgroup of patients with colon cancer. Conversely, the TRS was associated with OS in patients with rectal cancer. No association of comorbidity with unplanned hospitalization or chemotoxicity was observed.ConclusionsIn older adults with metastatic CRC, the number of CIRS-G grade 4 comorbidities was associated with worse OS but no specific CIRS-G category was independently associated with OS, unplanned hospitalization, or toxicities.     

Clinicopathological Profile of Myelomatous Pleural Effusion: Single-center Real-world Experience and Review of Literature

Background

Multiple myeloma (MM) is a hematologic malignancy of plasma cell origin. MM primarily affects bone marrow, but extramedullary sites can also be involved. Myelomatous pleural effusion (MPE) is an atypical and rare complication of MM. We aimed to systematically study the incidence and clinicopathologic profile of patients with MPE in a real-world setting.

Mechanisms and clinical course of cardiovascular toxicity of cancer treatment I. Oncology

The opening session of Second International Colloquium on Cardio-Oncology addressed two areas of vital interest. The first reviewed new thoughts related to established agents. While anthracycline cardiotoxicity has been studied and reviewed extensively, ongoing research attempting to understand why it appears the mechanism(s) of toxicity differs from that of oncologic efficacy continue to evoke comment and intriguing speculation. Better understanding of the role of β-topoisomerase II in toxicity has advanced our understanding of the cascade of events that lead to heart failure. Additionally, the cardioprotective role of dexrazoxane fits well with our new understanding of how β-topoisomerase II works. Beyond the anthracyclines, new insight is providing us insight to better understand the impact on cardiac function seen with other agents including those targeting HER2 and several tyrosine-kinase inhibitors. Unlike the anthracyclines, these agents affect cardiac function in ways that are less direct, and therefore have different characteristics and should be thought of in alternate ways. This new knowledge regarding established agents furthers our understanding of the spectrum of cardiotoxicity and cardiac dysfunction in the cancer patient. The session also addressed cardiovascular toxicities of newer and established agents beyond myocardial dysfunction including effects on the vasculature. These agents cause changes that may be temporary or permanent, and that range from subclinical to life-threatening. The session ended with a discussion of the cardiac effects of immune checkpoint inhibitors. These agents can cause rare and sometimes fatal cardiac inflammation, for which long-term follow up may be required.