Coexisting Pulmonary Tuberculosis and Mucormycosis in a Patient with Aplastic Anemia Post Allogenic Stem Cell Transplantation

Infections are the most common cause of morbidity and mortality in allogenic stem cell transplant recipients. Survival of the patient depends on the accurate diagnosis of the infectious agents and prompt and effective management of the infection alongwith maintenance of adequate immunosuppression post transplantation. We here reported a case of aplastic anemia who developed left upper lobe consolidation post allogenic stem cell transplantation and was found to have combined infection with tuberculosis and mucormycosis. This is the first case of combined infection with tuberculosis and mucormycosis reported in such a host, with a favourable outcom

Clinical Profile of Dengue Infection in Patients with Hematological Diseases

Managing hematological disorders in a tropical country presents several unique diagnostic and management problems. Apart from the disease process, we need to be aware of infections that can exacerbate or mimic serious hematological problems. We present here a series of five patients with pre-existing hematological diseases who were infected by dengue virus. These cases highlight the need to keep a strong suspicion of common endemic diseases in tropical countries before considering extensive workup for the basic hematological disease. There was no mortality and all patients recovered without any significant impact on their pre-existing hematological condition inspite of their low baseline blood counts. There was no excessive bleeding, prolonged stay in the hospital or relapse of underlying hematological disease in these patients and the only major concern was the increased anxiety among both the patient and treating physician regarding the relapse/progression of pre-existing hematological disease

A randomized, prospective open labeled study of oral amoxicillin-clavulanate and levofloxacin with intravenous ceftriaxone and amikacin in chemotherapy induced low risk febrile neutropenia

Background : We compared the efficacy of oral antibiotics with intravenous antibiotics in low risk febrile neutropenia. Design : A prospective, randomized study Methods: Between April 2004 - December 2005, 55 patients with low risk febrile neutropenia (expected neutropenia duration < 7 days with no co-morbid features) between 15 and 75 years of age, were randomized to receive either oral amoxicillin-clavulanate 625mg twice daily and levofloxacin -500mg once daily OR intravenous (i.v.) ceftriaxone 2g and amikacin 15mg/kg once daily. Most patients were treated on out patient basis. The primary end point was response to therapy, defervescence of fever within 72 hours with improvement in any clinical manifestation of infection and no recurrence of fever for 48 hours without use of antipyretics. Use of growth factors was not permitted except in treatment failure. Results: A total of 64 febrile episodes were recorded (mean 1.20 ); 33 in the IV group and 31 in the oral antibiotics group. Both groups were equally matched for age (median 25 years in the IV group and 19 years in the oral group), gender, type of cancer, baseline absolute neutrophil count (median 200/cmm in both arms) and duration of neutropenia (5 days and 4 days in the IV and oral groups, respectively). A focus of infection was identified clinically in 15% of episodes and microbiologically in 11% of episodes; 57% of which were Gram positive organisms and the rest Gram negative. 72% in the IV arm and 77% in the oral arm responded to therapy (p=ns). One patient in IV group had one episode of seizure. Non-responding patients received second line IV antibiotics. There was no mortality in either group. Age > 60 years, neutropenia lasting > 7 days after the onset of fever and positive blood culture were predictors for lack of response to antibiotics on multivariate analysis. Conclusion: Oral antibiotics have comparable efficacy as IV antibiotics in the management of low risk febrile neutropenia

Pulseless Right Upper Limb: An Unusual Manifestation of Invasive Pulmonary Aspergillosis in Acute Myeloid Leukemia

Abstract Aspergillus is the most common cause of fungal pneumonia in acute leukemia patients receiving chemotherapy or undergoing hematopoietic stem cell transplantation. Despite a high index of suspicion and prompt institution of specific antifungal therapy, it causes significant morbidity and mortality in patients with hematological malignancies. It has to be differentiated from mucormycosis because the treatment differs. Histological confirmation obtained by lung biopsy is ideal, but is difficult to obtain in those patients who often have thrombocytopenia. We report a case of acute megakaryoblastic leukemia with typical manifestations of invasive pulmonary aspergillosis who developed pulseless right arm due to invasion of the right subclavian artery. When total leucocyte counts recovered, patient also developed immune reconstitution inflammatory syndrome and massive pulmonary hemorrhage, which was managed by bronchial artery embolization

Cancer Stem Cell Chemotherapeutics Assay for Prospective Treatment of Recurrent Glioblastoma and Progressive Anaplastic Glioma: A Single-Institution Case Series

© 2020 BACKGROUND: Chemotherapy-resistant cancer stem cells (CSC) may lead to tumor recurrence in glioblastoma (GBM). The poor prognosis of this disease emphasizes the critical need for developing a treatment stratification system to improve outcomes through personalized medicine. METHODS: We present a case series of 12 GBM and 2 progressive anaplastic glioma cases from a single Institution prospectively treated utilizing a CSC chemotherapeutics assay (ChemoID) guided report. All patients were eligible to receive a stereotactic biopsy and thus undergo ChemoID testing. We selected one of the most effective treatments based on the ChemoID assay report from a panel of FDA approved chemotherapy as monotherapy or their combinations for our patients. Patients were evaluated by MRI scans and response was assessed according to RANO 1.1 criteria. RESULTS: Of the 14 cases reviewed, the median age of our patient cohort was 49 years (21–63). We observed 6 complete responses (CR) 43%, 6 partial responses (PR) 43%, and 2 progressive diseases (PD) 14%. Patients treated with ChemoID assay-directed therapy, in combination with other modality of treatment (RT, LITT), had a longer median overall survival (OS) of 13.3 months (5.4-NA), compared to the historical median OS of 9.0 months (8.0–10.8 months) previously reported. Notably, patients with recurrent GBM or progressive high-grade glioma treated with assay-guided therapy had a 57% probability to survive at 12 months, compared to the 27% historical probability of survival observed in previous studies. CONCLUSIONS: The results presented here suggest that the ChemoID Assay has the potential to stratify individualized chemotherapy choices to improve recurrent and progressive high-grade glioma patient survival. Importance of the Study: Glioblastoma (GBM) and progressive anaplastic glioma are the most aggressive brain tumor in adults and their prognosis is very poor even if treated with the standard of care chemoradiation Stupp\u27s protocol. Recent knowledge pointed out that current treatments often fail to successfully target cancer stem cells (CSCs) that are responsible for therapy resistance and recurrence of these malignant tumors. ChemoID is the first and only CLIA (clinical laboratory improvements amendment) -certified and CAP (College of American Pathologists) -accredited chemotherapeutic assay currently available in oncology clinics that examines patient\u27s derived CSCs susceptibility to conventional FDA (Food and Drugs Administration) -approved drugs. In this study we observed that although the majority of our patients (71.5%) presented with unfavorable prognostic predictors (wild type IDH-1/2 and unmethylated MGMT promoter), patients treated with ChemoID assay-directed therapy had an overall response rate of 86% and increased median OS of 13.3 months compared to the historical median OS of 9.1 months (8.1–10.1 months) previously reported [1] suggesting that the ChemoID assay may be beneficial in personalizing treatment strategies

Regulatory T Cells Suppress T Cell Activation at the Pathologic Site of Human Visceral Leishmaniasis

Suppression of T cell response is thought to be involved in the pathogenesis of visceral leishmaniasis (VL). Regulatory T cell (Treg) mediated immune-suppression is reported in animal models of Leishmania infection. However, their precise role among human patients still requires pathologic validation. The present study is aimed at understanding the frequency dynamics and function of Treg cells in the blood and bone marrow (BM) of VL patients. The study included 42 parasitologically confirmed patients, 17 healthy contact and 9 normal bone marrow specimens (NBM). We show i) the selective accumulation of Treg cells at one of the disease inflicted site(s), the BM, ii) their in vitro expansion in response to LD antigen and iii) persistence after successful chemotherapy. Results indicate that the Treg cells isolated from BM produces IL-10 and may inhibit T cell activation in IL-10 dependent manner. Moreover, we observed significantly higher levels of IL-10 among drug unresponsive patients, suggesting their critical role in suppression of immunity among VL patients. Our results suggest that IL-10 plays an important role in suppression of host immunity in human VL and possibly determines the efficacy of chemotherapy

Cancer Stem Cell Assay-Guided Chemotherapy Improves Survival of Patients With Recurrent Glioblastoma in a Randomized Trial

Therapy-resistant cancer stem cells (CSCs) contribute to the poor clinical outcomes of patients with recurrent glioblastoma (rGBM) who fail standard of care (SOC) therapy. ChemoID is a clinically validated assay for identifying CSC-targeted cytotoxic therapies in solid tumors. In a randomized clinical trial (NCT03632135), the ChemoID assay, a personalized approach for selecting the most effective treatment from FDA-approved chemotherapies, improves the survival of patients with rGBM (2016 WHO classification) over physician-chosen chemotherapy. In the ChemoID assay-guided group, median survival is 12.5 months (95% confidence interval [CI], 10.2-14.7) compared with 9 months (95% CI, 4.2-13.8) in the physician-choice group (p = 0.010) as per interim efficacy analysis. The ChemoID assay-guided group has a significantly lower risk of death (hazard ratio [HR] = 0.44; 95% CI, 0.24-0.81; p = 0.008). Results of this study offer a promising way to provide more affordable treatment for patients with rGBM in lower socioeconomic groups in the US and around the world

Developing Standard Treatment Workflows—way to universal healthcare in India

Primary healthcare caters to nearly 70% of the population in India and provides treatment for approximately 80–90% of common conditions. To achieve universal health coverage (UHC), the Indian healthcare system is gearing up by initiating several schemes such as National Health Protection Scheme, Ayushman Bharat, Nutrition Supplementation Schemes, and Inderdhanush Schemes. The healthcare delivery system is facing challenges such as irrational use of medicines, over- and under-diagnosis, high out-of-pocket expenditure, lack of targeted attention to preventive and promotive health services, and poor referral mechanisms. Healthcare providers are unable to keep pace with the volume of growing new scientific evidence and rising healthcare costs as the literature is not published at the same pace. In addition, there is a lack of common standard treatment guidelines, workflows, and reference manuals from the Government of India. Indian Council of Medical Research in collaboration with the National Health Authority, Govt. of India, and the WHO India country office has developed Standard Treatment Workflows (STWs) with the objective to be utilized at various levels of healthcare starting from primary to tertiary level care. A systematic approach was adopted to formulate the STWs. An advisory committee was constituted for planning and oversight of the process. Specialty experts' group for each specialty comprised of clinicians working at government and private medical colleges and hospitals. The expert groups prioritized the topics through extensive literature searches and meeting with different stakeholders. Then, the contents of each STW were finalized in the form of single-pager infographics. These STWs were further reviewed by an editorial committee before publication. Presently, 125 STWs pertaining to 23 specialties have been developed. It needs to be ensured that STWs are implemented effectively at all levels and ensure quality healthcare at an affordable cost as part of UHC

Optimasi Portofolio Resiko Menggunakan Model Markowitz MVO Dikaitkan dengan Keterbatasan Manusia dalam Memprediksi Masa Depan dalam Perspektif Al-Qur`an

Risk portfolio on modern finance has become increasingly technical, requiring the use of sophisticated mathematical tools in both research and practice. Since companies cannot insure themselves completely against risk, as human incompetence in predicting the future precisely that written in Al-Quran surah Luqman verse 34, they have to manage it to yield an optimal portfolio. The objective here is to minimize the variance among all portfolios, or alternatively, to maximize expected return among all portfolios that has at least a certain expected return. Furthermore, this study focuses on optimizing risk portfolio so called Markowitz MVO (Mean-Variance Optimization). Some theoretical frameworks for analysis are arithmetic mean, geometric mean, variance, covariance, linear programming, and quadratic programming. Moreover, finding a minimum variance portfolio produces a convex quadratic programming, that is minimizing the objective function ðð¥with constraintsð ð 𥠥 ðandð´ð¥ = ð. The outcome of this research is the solution of optimal risk portofolio in some investments that could be finished smoothly using MATLAB R2007b software together with its graphic analysis

Differential cross section measurements for the production of a W boson in association with jets in proton–proton collisions at √s = 7 TeV

Measurements are reported of differential cross sections for the production of a W boson, which decays into a muon and a neutrino, in association with jets, as a function of several variables, including the transverse momenta (pT) and pseudorapidities of the four leading jets, the scalar sum of jet transverse momenta (HT), and the difference in azimuthal angle between the directions of each jet and the muon. The data sample of pp collisions at a centre-of-mass energy of 7 TeV was collected with the CMS detector at the LHC and corresponds to an integrated luminosity of 5.0 fb[superscript −1]. The measured cross sections are compared to predictions from Monte Carlo generators, MadGraph + pythia and sherpa, and to next-to-leading-order calculations from BlackHat + sherpa. The differential cross sections are found to be in agreement with the predictions, apart from the pT distributions of the leading jets at high pT values, the distributions of the HT at high-HT and low jet multiplicity, and the distribution of the difference in azimuthal angle between the leading jet and the muon at low values.United States. Dept. of EnergyNational Science Foundation (U.S.)Alfred P. Sloan Foundatio