Stem cell homing: From physiology to therapeutics.

Stem cell homing is a multistep endogenous physiologic process that is also used by exogenously administered hematopoietic stem and progenitor cells (HSPCs). This multistep process involves cell migration and is essential for hematopoietic stem cell transplantation. The process can be manipulated to enhance ultimate engraftment potential, and understanding stem cell homing is also important to the understanding of stem cell mobilization. Homing is also of potential importance in the recruitment of marrow mesenchymal stem and stromal cells (MSCs) to sites of injury and regeneration. This process is less understood but assumes importance when these cells are used for repair purposes. In this review, the process of HSPC and MSC homing is examined, as are methods to enhance this process.

Emerging biorefinery technologies for Indian forest industry to reduce GHG emissions.

The production of biofuels as alternative energy source over fossil fuels has gained immense interest over the years as it can contribute significantly to reduce the greenhouse gas (GHG) emissions from energy production and utilization. Also with rapidly increasing fuel price and fall in oil wells, the present scenario forces us to look for an alternative source of energy that will help us in the operation of industrial as well as the transportation sector. The pulp mills in India are one of the many options. The pulp mills in India can help us to produce bio-fuels by thermo-chemical/biochemical conversion of black liquor and wood residues. These technologies include extraction of hemi-cellulose from wooden chips and black liquor, lignin from black liquor, methanol from evaporator condensates, biogas production from waste sludge, syngas production from biomass using gasification and bio-oil production from biomass using pyrolysis. The objective of this paper is to overview these emerging bio-refinery technologies that can be implemented in Indian Forest Industry to get bio-fuels, bio-chemicals and bio-energy to reduce GHG emissions.

NPM 1 Mutations in AML-The Landscape in 2023.

Acute myeloid leukemia (AML) represents 80% of acute leukemia in adults and is characterized by clonal expansion of hematopoietic stem cells secondary to genomic mutations, rendering a selective growth advantage to the mutant clones. NPM1mut is found in around 30% of AML and clinically presents with leukocytosis, high blast percentage and extramedullary involvement. Considered as a "gate-keeper" mutation, NPM1mut appears to be a "first hit" in the process of leukemogenesis and development of overt leukemia. Commonly associated with other mutations (e.g., FLT 3, DNMT3A, TET2, SF3B1), NPM1 mutation in AML has an important role in diagnosis, prognosis, treatment and post-treatment monitoring. Several novel therapies targeting NPM1 are being developed in various clinical phases with demonstration of efficacy. In this review, we summarize the pathophysiology of the NPM1 gene mutation in AML, clinical implications and the novel targeted therapies to date.

Quality of content reporting on two major oncology media websites: OncLive and Targeted Oncology.

INTRODUCTION: Oncology media websites such as Oncology Live (OncLive) and Targeted Oncology (TargetedOnc) play an important role in the dissemination of oncology news to patients and clinicians; however, the quality of the content on these websites has not been assessed. Our study aimed to analyze content from these websites and assess financial conflicts of interest (FCOI) amongst speakers interviewed on these websites. METHODS: Articles published on OncLive and TargetedOnc during October 2021, were prospectively captured and analyzed. The primary outcome of our study was the quality of oncology news reporting in OncLive and TargetedOnc. We assessed the FCOI amongst speakers using data from Open Payments. RESULTS: We examined 196 articles (OncLive 108, TargetedOnc 88). Limitations of cited research were reported in 7% (7/105) of OncLive and zero TargetedOnc articles. Benefit and risks in absolute numbers were reported in 28% (28/99) of OncLive and 16% (7/45) of TargetedOnc articles. Independent experts were quoted in 47% (51/108) and 51% (44/86) of the OncLive and TargetedOnc articles, respectively (Table 3). Pharmaceutical executives were quoted in 18% (20/108) and 11% (10/88) of OncLive and TargetedOnc articles, respectively. No FCOI disclosures were listed or reported for any articles. The mean general payment received from industry by United States physicians was $63,861 in 2019 and $39,639 in 2020. CONCLUSION: Our study demonstrates low quality and potentially biased reporting of oncology news on OncLive and TargetedOnc. Careful safeguards, oversight and reporting of relevant FCOI are needed to maintain the quality and transparency of content being provided.

Cytopenia after CAR-T Cell Therapy-A Brief Review of a Complex Problem.

Chimeric Antigen Receptor T-cell (CAR-T) immunotherapy has emerged as an efficacious and life extending treatment modality with high response rates and durable remissions in patients with relapsed and refractory non-Hodgkin lymphoma (NHL), follicular lymphoma, and B-cell acute lymphoblastic leukemia (B-ALL) as well as in other diseases. Prolonged or recurrent cytopenias after CAR-T therapy have increasingly been reported at varying rates, and the pathogenesis of this complication is not yet well-understood but is likely contributed to by multiple factors. Current studies reported are primarily retrospective, heterogeneous in terms of CAR-Ts used and diseases treated, non-uniform in definitions of cytopenias and durations for end points, and vary in terms of recommended management. Prospective studies and correlative laboratory studies investigating the pathophysiology of prolonged cytopenias will enhance our understanding of this phenomenon. This review summarizes knowledge of these cytopenias to date.

Clinical characteristics and outcomes of critically ill patients with COVID-19 in a tertiary community hospital in upstate New York.

Background: There are limited reports describing critically ill COVID-19 patients in the state of New York. Methods: We conducted a retrospective analysis of 32 adult critically ill patients admitted to a community hospital in upstate New York, between 14 March and 12 April 2020. We collected demographic, laboratory, ventilator and treatment data, which were analyzed and clinical outcomes tabulated. Results: 32 patients admitted to the intensive care unit (ICU) were included, with mean (±SD) follow-up duration 21 ± 7 days. Mean (±SD) age was 62.2 ± 11.2 years, and 62.5% were men. 27 (84.4%) of patients had one or more medical co-morbidities. The mean (±SD) duration of symptoms was 6.6 (±4.4) days before presentation, with cough (81.3%), dyspnea (68.7%), and fever (65.6%) being the most common. 23 (71.9%) patients received invasive mechanical ventilation. 5 (15.6%) died, 11 (34.4%) were discharged home, and 16 (50%) remained hospitalized, 8 (25%) of which were still in ICU. Mean (±SD) length of ICU stay was 10.2 (±7.7) days, and mean (±SD) length of hospital stay was 14.8 (±7.7) days. Conclusion: Majority of patients were of older age and with medical comorbidities. With adequate resource utilization, mortality of critically ill COVID-19 patients may not be as high as previously suggested. Abbreviations: ACE-i: Angiotensin converting enzyme inhibitor; ARB: Angiotensin receptor blocker; ARDS: Acute Respiratory Distress Syndrome; BiPAP: Bilevel positive airway pressure; CABG: Coronary artery bypass graft; CFR: Case fatality rate; COVID-19: Coronavirus disease 19; CPAP: Continuous positive airway pressure; CRP: C - Reactive Protein; CT: Computed tomography; DVT: Deep vein thrombosis; ECMO: Extra Corporeal Membrane Oxygenation; ESICM: European Society of Intensive Care Medicine; FiO2: Fraction of inspired O2; HFNC: High Flow Nasal Cannula; HITF: Hypoxia-Inducible Transcription Factor; IBM: International Business Machines; ICU: Intensive Care Unit; IL: Interleukin; IMV: Invasive Mechanical Ventilation; IQR: Interquartile Range; ISTH: International Society of Thrombosis Hemostasis; NIV: Non Invasive Ventilation; NY: New York; PAI: Plasminogen activator inhibitor; PaO2: partial pressure of arterial oxygen; PCV: Pressure Control Ventilation; PEEP: Positive End Expiratory Pressure; RGH: Rochester General Hospital; RRH: Rochester Regional Health; RT-PCR: Reverse transcriptase polymerase chain reaction; RSV: Respiratory Syncytial virus; SARS-CoV-2: Severe Acute Respiratory Syndrome Coronavirus 2; SD: Standard Deviation; STEMI: ST segment elevation myocardial infarction; TNF: Tumor necrosis factor; USA: USA; VTE: Venous thromboembolism.

Tele-ophthalmology: Need of the hour.

Telemedicine and tele-ophthalmology have been in existence since many years, but have recently gained more importance in the present scenario of pandemic COVID-19. The attitude and perception of the doctors and patients has been changing gradually. Telemedicine has many advantages including providing care in inaccesible areas.In the present scenario, tele-ophthalmology gives an oppurtunity to patient for seeking consultation while also protecting against the contagion. There are many barriers faced by the patients and doctors that have restricted use of this technology in the past. However, with a systematic approach to designing the best suited technology, these barriers can be overcome and user friendly platforms can be created. Furthermore, the demand and use of teleconsulation had increased presently in this area of pandemic. Recent survey conducted by the All India Ophthalmological Society also reveals that many ophthalmologists who have not used tele-ophthalmology in the past are more keen to use it presently. In this article, we have reviewed telemedicine and tele-ophthalmology literature on Google and PubMed to get a holistic idea towards teleconsultation, its advantages, increased importance and prefrence during COVID-19 pandemic and various barriers faced so that the known challenges can be understood, which can pave way for better understanding and future incorporation into practice.

Cardiac ALL: Most Unusual Occurrence of Lenalidomide-associated Acute Lymphoblastic Leukemia with Subsequent Cardiac Involvement.

Leukemic infiltration of the myocardium is an extremely rare complication and requires high clinical suspicion, as <5% pf patients are symptomatic. Commonly encountered cardiovascular complications are secondary to anemia, infections, and chemotherapy. We present an unusual case of biopsy-proven myocardial B-cell acute lymphoblastic leukemia (ALL) in an elderly male on chronic maintenance therapy with lenalidomide, with a previous history of multiple myeloma (MM) and subsequent ALL. Lenalidomide is a Category 1 recommendation for primary and maintenance therapy of MM, but there is growing evidence of secondary primary malignancies (SPMs). Despite this increase in SPM, the overall survival (OS) benefit associated with the use of maintenance immunomodulatory (IMID) therapy in multiple myeloma outweighs the risk of SPMs. Only age-appropriate screening methods are recommended. This case report serves as an important reminder of a rare manifestation of leukemia and presents as anecdotal evidence of response to the monoclonal antibody inotuzumab for visceral involvement of ALL, which has not been reported to our knowledge and requires further exploration.

Emerging investigator series: oxidative potential of diesel exhaust particles: role of fuel, engine load, and emissions control.

Exposure to diesel exhaust particles (DEP) has been linked to adverse human health outcomes. DEPs are reactive and can directly or indirectly lead to oxidative stress, which promotes inflammation in the body. The oxidative potential (OP) of DEPs is not well understood, particularly for combustion with alternative fuels, under different engine loads, and in combination with modern emissions control devices. In this study, we measured the OP of DEPs using a dithiothreitol assay (OP-DTT) from a modern-day non-road diesel engine for two different fuels (conventional diesel and soy-based biodiesel), two different engine loads (idle and 50% load), and with and without an emissions control system. The OP-DTT of DEPs was sensitive to the fuel used and the presence of an emissions control system but not to the engine load. On average, the use of biodiesel resulted in factor of ∼6 reduction in OP-DTT normalized to the DEP mass and a factor of ∼12 reduction in OP-DTT normalized to the fuel consumed. The use of the emissions control, on average, resulted in a factor of ∼6 reduction in OP-DTT normalized to the DEP mass and a three order of magnitude decrease in OP-DTT normalized to the fuel consumed. When studied in conjunction with the DEP composition, the OP-DTT seemed to correlate most strongly with elemental carbon (EC), followed by semi-volatile organic vapors. Assays performed on DEPs where EC was deliberately filtered out suggested that the species responsible for the OP-DTT might be correlated with EC but would need to be water soluble (e.g., quinones). The semi-volatile organic vapors accounted for more than a quarter of the OP-DTT of DEPs collected on the quartz filters. Finally, sensitivity studies performed with a different filter membrane (i.e., Teflon®) and solvent (i.e., dichloromethane) tended to increase the OP-DTT value. OP-DTT is emerging as an important metric for studying the adverse effects of DEPs and PM2.5 on human health; results of this work help define the sources and components of diesel PM2.5 that contribute to OP-DTT.

A novel luciferase-based assay for the detection of Chimeric Antigen Receptors.

Chimeric Antigen Receptor-T (CAR-T) cell immunotherapy has produced dramatic responses in hematologic malignancies. One of the challenges in the field is the lack of a simple assay for the detection of CARs on the surface of immune effector cells. In this study, we describe a novel luciferase-based assay, termed Topanga Assay, for the detection of CAR expression. The assay utilizes a recombinant fusion protein, called Topanga reagent, generated by joining the extra-cellular domain of a CAR-target in frame with one of the marine luciferases or their engineered derivatives. The assay involves incubation of CAR expressing cells with the Topanga reagent, a few washes and measurement of luminescence. The assay can detect CARs comprising either immunoglobulin- or non-immunoglobulin-based antigen binding domains. We further demonstrate that addition of epitope tags to the Topanga reagent not only allows its convenient one step purification but also extends its use for detection of CAR cells using flow cytometry. However, crude supernatant containing the secreted Topanga reagent can be directly used in both luminescence and flow-cytometry based assays without prior protein purification. Our results demonstrate that the Topanga assay is a highly sensitive, specific, convenient, economical and versatile assay for the detection of CARs.