CD19-directed CART Therapy for T cell/Histiocyte Rich Large B-cell Lymphoma.

T-cell/histiocyte-rich large B-cell lymphoma (THRLBCL) is a rare histologic variant of LBCL. Limited data regarding CD19-directed chimeric antigen receptor T-cell (CART) therapy in relapsed/refractory (R/R) THRLBCL suggest poor efficacy. We investigated CART outcomes for R/R THRLBCL through the CIBMTR registry. A total of 58 adult patients with R/R THRLBCL who received commercial CD19-CART between 2018-2022 were identified. Most patients (67%) had early relapse of disease (45% primary refractory) with a median of 3 (range: 1-7) prior therapies and were treated with Axicabtagene ciloleucel (69%). At median follow-up of 23 months post-CART, 2-year overall and progression-free survival were 42% (95% CI: 27-57) and 29% (95% CI: 17-43), respectively. In univariable analysis, poor performance status pre-CART was associated with higher mortality (HR 2.35, 95%CI 1.02-5.5). The 2-year cumulative incidences of relapse/progression and non-relapse mortality were 69% and 2%, respectively. Grade ≥3 CRS and ICANS occurred in 7% and 15% of patients, respectively. In this largest analysis of CD19-CART for R/R THRLBCL, approximately 30% of patients were alive and progression-free 2 years post-CART. Despite a high incidence of progression (69% at 2 years), these results suggest a subset of patients with R/R THRLBCL may have durable responses with CART.

Anti-CD19 chimeric antigen receptor T-cell therapy in older patients with relapsed or refractory large B-cell lymphoma: A multicenter study.

Chimeric antigen receptor T-cell (CAR-T) therapy, despite being a potentially curative therapy in relapsed or refractory (RR) large B-cell lymphoma (LBCL), remains underutilized in older patients due to limited clinical data. We therefore studied the safety and efficacy of CAR-T therapy in older patients with RR LBCL in the real-world setting. Patients aged ≥65 years with RR LBCL, treated with anti-CD19 CAR-T therapy at 7 US institutions were included in this multicenter, retrospective, observational study. In total, 226 patients were included. Median age at infusion was 71 years (range 65-89). Best objective and complete response rates were 86% and 62%, respectively. Median follow-up after infusion was 18.3 months. The median progression-free survival (PFS) was 6.9 months, with 6- and 12-month PFS estimates of 54% and 44%, respectively. The nonrelapse mortality (NRM) rate was 10.9% at day 180, primarily due to infections, and not impacted by the age groups. Grade ≥3 cytokine release syndrome and neurotoxicity occurred in 7% and 26%, respectively. In univariate analysis, no significant difference in PFS was seen regardless of the age groups or CAR-T type, whereas ECOG PS ≥2, elevated LDH, bulky disease, advanced stage, extranodal involvement, the need for bridging therapy, and prior bendamustine exposure were associated with shorter PFS. These findings support the use of CAR-T in older patients, including those aged ≥80 years. The age at CAR-T therapy did not influence safety, survival, and NRM outcomes. Older patients should not be excluded from receiving CAR-T therapy solely based on their chronological age.

Optimization of Formaldehyde Fixative Concentration for Individual Blood Cells to Develop a Stabilized Blood Control for Automated Hematology Analyzers.

In a modern haematology laboratory, the complete and differential counts of blood are performed using complex haematology auto analyzers. In order to ensure the accuracy and reliability of test results, various regulatory authorities have prescribed the use of stabilized blood controls. The major pitfalls of these blood controls are their short shelf life. This could be due to the fact that they are prepared by a common cocktail of fixatives which acts on the discrete cells in various ways and would result in either under-fixation or over-fixation of various cells. Thus, in the present study, we have explored and optimized fixative and buffering for individual cells to achieve stable blood control. Blood cells were isolated using the centrifugation technique and were fixed individually with different concentrations of formaldehyde. After fixation, cells were pooled. Analysis of cell count was done till six months. Cells were also analysed morphologically to see the effect of fixation and storage on cell morphology. In the present study we compared the effect of the concentration of formaldehyde fixative for individual cells in the blood and their role in enhancing the shelf life and maintaining the morphology of the cells when suspended in plasma or suitable buffers post-fixation. It was observed that WBCs can be better fixed with 3 and 3.5% formaldehyde in a buffered solution, whereas RBCs and Platelets can be optimally fixed with 2.5% formaldehyde in a buffered solution.

Comparison of Adenosine Deaminase, C-reactive Protein, Uric Acid, and Rheumatoid Arthritis Levels in Patients With Rheumatoid Arthritis and Those Without Arthritis: A Review.

One of the hallmarks of rheumatoid arthritis (RA) is inflammation of the synovial membrane, and oxidative stress is a mediator of tissue damage. RA is characterized by persistent joint inflammation, which leads to pain, edema, and finally joint destruction. Numerous biochemical markers can cause RA because of their impact on systemic and local inflammation. Numerous biomarkers have been investigated for their potential application in the diagnosis and prognosis of RA. In this review article, we evaluate the role of RA factor or rheumatoid factor (RF), uric acid, C-reactive protein (CRP), and adenosine deaminases (ADAs) as biomarkers in patients with and without arthritis. Studies that analyze and compare the levels of uric acid, ADAs, CRP, and RF in patients with and without arthritis. Although recent research has shown higher levels of uric acid, ADA, CRP, and RA in patients with RF compared to healthy controls, these findings may indicate a role for these markers in reflecting inflammation and disease activity. In the metabolism of purines, the enzyme ADA is involved. The liver produces CRP, which is then released into the bloodstream. In inflammatory situations, there is a rise in CRP levels. This biomarker is frequently used for systemic inflammatory assessment in RA. The pathophysiology and severity of RA have both been connected to uric acid, which has historically been linked to gout. One particular biomarker for RA is RF. When compared to a healthy control group of individuals with arthritis, this review provides valuable insights into the diagnostic and prognostic use of uric acid, CRP, ADAs, and RF.

Serum Raman spectroscopy: Evaluation of tumour load variations in experimental carcinogenesis.

Several serum Raman spectroscopy (RS) studies have demonstrated its potential as an oral cancer screening tool. This study investigates influence of low tumour load (LTL) and high tumour load (HTL) on serum RS using hamster buccal pouch model of experimental oral carcinogenesis. Sera of untreated control, LTL, and HTL groups at week intervals during malignant transformation were employed. Serum Raman spectra were subjected to multivariate analyses-principal component analysis, principal component-based linear discriminant analysis (for stratification of study groups), and multivariate curve resolution-alternating least squares (MCR-ALS) (to comprehend biomolecular differences). Multivariate analysis revealed misclassifications between LTL and HTL at all week intervals. MCR-ALS components showed statistically significant abundances between control versus LTL and control versus HTL, but could not discern LTL and HTL. MCR-ALS components exhibited spectral mixtures of proteins, lipids, heme and nucleic acids. Thus, these findings support use of serum RS as a screening tool as varying tumour load is not a confounding factor influencing the technique.

Perceptions of antibiotic stewardship programmes and determinants of antibiotic prescribing patterns among physicians in tertiary hospitals in Bangladesh: implications for future policy and practice.

BACKGROUND: The concerning growth of antimicrobial resistance (AMR) renders common infections life-threatening due to irrational antibiotic use and a lack of effective antimicrobial stewardship programmes (ASPs). AIM: To investigate the awareness, perceptions and practices of physicians regarding ASPs, AMR and antibiotic prescribing in tertiary care hospitals in Bangladesh. METHODS: This hospital-based cross-sectional survey was conducted in 11 tertiary care hospitals across Bangladesh between September 2020 and January 2021. A semi-structured questionnaire was administered through face-to-face interviews for data collection. Descriptive and multi-variate analyses were performed using STATA Version 13. RESULTS: In total, 559 physicians were enrolled in this survey. Overall, 40.6% [95% confidence interval (CI) 36.5-44.8] of physicians reported being aware of ASPs, and this figure was higher in public hospitals compared with private hospitals (43.8% vs 27.1%). None of the study hospitals had any ASP initiatives. More than half (55.1%) of the participants were willing to receive feedback from an ASP on their antibiotic selection. Only 30.9% of respondents stated that they wait for the findings of microbiological tests before prescribing antibiotics, although challenges included empiric use of broad-spectrum antibiotics, delayed laboratory results and the existence of drug-resistant patients. In contrast, physicians aware of ASPs were 33% (adjusted odds ratio 0.67, 95% CI 0.45-0.98; P=0.033) less likely to wait for laboratory results before prescribing antibiotics. However, 42.5% of physicians considered patient affordability of purchasing antibiotics when prescribing. CONCLUSIONS: Physicians' fundamental knowledge of ASPs and rational antibiotic prescription were found to fall short of the standard. Context-specific and integrated ASP activities, availability and use of guidelines, and improved laboratory facilities are required to battle AMR in Bangladesh.

Management of an inadvertent late filtering bleb and hypotony in a scleral fixated intraocular lens implantation.

PURPOSE: To report a case of inadvertent cystic filtering bleb in a patient with scleral fixated intraocular lens (SFIOL) implantation 7 years after initial procedure. CASE PRESENTATION: A 14-year-old boy underwent lensectomy, vitrectomy and a sutured rigid SFIOL for microspherophakia in the right eye. Seven years later, the patient presented with hypotony related ocular changes. Examination revealed an inadvertent cystic filtering bleb at the scleral section. Anterior segment optical coherence tomography (ASOCT) revealed gap in inner lips of the scleral wound, bridged by a thin strip of scleral tissue. A conservative management with bandage contact lens (BCL) failed after an initial improvement. Injection of trypan blue dye in the anterior chamber confirmed the presence and site of wound filtration. Surgical closure of the fistula was done and patient showed both structural and visual improvement. CONCLUSION: Meticulous wound construction and water tight closure at the end of the surgery can avoid such complications. ASOCT can be helpful in diagnosing the area of fistula. A conservative management with BCL can help by tamponading the filtering bleb. However, in unresponsive cases, surgical closure of the fistula is recommended to improve the hypotony-related changes.

Across race, ethnicity, and language: An intervention to improve advance care planning documentation unmasks health disparities.

BACKGROUND: Racial and ethnic minority groups are less likely to have advance directives and living wills, despite the importance of advanced care planning (ACP) in end-of-life care. We aimed to understand the impact of an intervention to improve ACP documentation across race, ethnicity, and language on hospitalized patients at our institution. METHODS: We launched an intervention to improve the rates of ACP documentation for hospitalized patients aged >75 or with advanced illness defined by the International Classification of Diseases 10th Revision codes. We analyzed ACP completion rates, preintervention, and intervention, and used interrupted time-series analyses to measure the differential impact of the intervention across race, ethnicity, and language. KEY RESULTS: A total of 10,220 patients met the inclusion criteria. Overall rates of ACP documentation improved from 13.9% to 43.7% in the intervention period, with a 2.47% monthly increase in ACP documentation compared to baseline (p < .001). During the intervention period, the rate of ACP documentation increased by 2.72% per month for non-Hispanic White patients (p < .001), by 1.84% per month for Latinx patients (p < .001), and by 1.9% per month for Black patients (p < .001). Differences in the intervention trends between non-Hispanic White and Latinx patients (p = .04) and Black patients (p = .04) were significant. CONCLUSIONS: An intervention designed to improve ACP documentation in hospitalized patients widened a disparity across race and ethnicity with Latinx and Black patients having lower rates of improvement. Our findings reinforce the need to measure the impact of quality improvement interventions on existing health disparities and to implement specific strategies to prevent worsening disparities.

Effect of Integrated Yoga Program Along With Pilates in Abdominal Hysterectomy Patients: A Case Report.

Abdominal hysterectomy is a surgical procedure that involves the removal of the uterus through an incision in the abdominal wall. Hysterectomy is associated with a number of complications; hence, early mobilization and physiotherapy are necessary following surgery. This is a case report of a 45-year-old female who presented with complaints of abdominal pain associated with white discharge. Investigations showed an anterior submucosal fibroid measuring 3.2x2.7 cm and the patient underwent an abdominal hysterectomy. Early mobilization and physiotherapy were started on Day 6, which included breathing exercises, upper limb mobility, lower limb mobility, and positioning and postural advice. Yoga and pilates therapy were integrated into the protocol starting from the second week. The patient attended 30 days of therapy in two phases and was advised to continue even after discharge. We concluded that this unique approach of including pilates and yoga showed a positive impact on the patient's condition in terms of her quality of life, strength, endurance, and power, even decreasing her difficulty in performing activities of daily living.

Morphological control for high proton conduction in robust Co3O4-diethylmethylamine (metal-organic framework) membrane.

Metal-organic framework (MOF) based proton conductors are synthesized by the Avrami model (time-temperature modalities). Our objective here is to obtain a material with high proton conductivity in anhydrous conditions, improved catalytic behaviour and morphology control of conductivity, band gap and catalysis. For this purpose, we try to understand the role of morphology on mass transportation using computational fluid dynamics and the experimental realisation using the synthesis of MOF membranes with high protonic conductivity. In order to alter the morphology, the membranes are synthesized from protic ionic liquid (dimethyl ethyl amine H2PO4) and metal ion (Co3O4) at different temperatures and duration. A high protonic conductivity of 0.0286 S cm-1 with a high transference number >0.99 is observed in anhydrous conditions with the change in morphology. Furthermore, catalyst properties along with high activity (Tafel slope = 39 mV decade-1) with the alteration in morphology are also investigated in detail and observed adsorption governed conduction. This adsorption governed conduction is verified using computational fluid dynamics simulations with the alteration in morphology. This study suggests that morphology not only plays a pivotal role in obtaining a robust proton exchange membrane, it also improves the catalytic functionality and stability of the membrane.

Change in alcohol consumption during the Covid-19 pandemic and associations with mental health and financial hardship: results from a survey of Wisconsin patients with cancer.

PURPOSE: Alcohol consumption increases health risks for patients with cancer. The Covid-19 pandemic may have affected drinking habits for these individuals. We surveyed patients with cancer to examine whether changes in drinking habits were related to mental health or financial effects of the pandemic. METHODS: From October 2020 to April 2021, adult patients (age 18-80 years at diagnosis) treated for cancer in southcentral Wisconsin were invited to complete a survey. Age-adjusted percentages for history of anxiety or depression, emotional distress, and financial impacts of Covid-19 overall and by change in alcohol consumption (non-drinker, stable, decreased, or increased) were obtained via logistic regression. RESULTS: In total, 1,875 patients were included in the analysis (median age 64, range 19-87 years), including 9% who increased and 23% who decreased drinking. Compared to stable drinkers (32% of sample), a higher proportion of participants who increased drinking alcohol also reported anxiety or depression (45% vs. 26%), moderate to severe emotional distress (61% vs. 37%) and viewing Covid-19 as a threat to their community (67% vs. 55%). Decreased (vs. stable) drinking was associated with higher prevalence of depression or anxiety diagnosis, emotional distress, and negative financial impacts of the pandemic. Compared to non-drinkers (36% of sample), participants who increased drinking were more likely to report emotional distress (61% vs. 48%). CONCLUSIONS: Patients with cancer from Wisconsin who changed their alcohol consumption during the Covid-19 pandemic were more likely to report poor mental health including anxiety, depression, and emotional distress than persons whose alcohol consumption was stable. IMPLICATIONS FOR CANCER SURVIVORS: Clinicians working with cancer survivors should be aware of the link between poor mental health and increased alcohol consumption and be prepared to offer guidance or referrals to counseling, as needed.

Critical gaps in understanding treatment outcomes in adolescents and young adults with lymphoma: A review of current data.

Adolescents and young adults (AYA) with lymphoma experience treatment-related effects in the short and long term that impact their quality of life and survivorship experience. The effort to improve outcomes for AYA lymphoma survivors requires understanding the available literature, identifying current knowledge deficits, designing better clinical trials incorporating the patient perspective, using novel tools to bridge data gaps and building survivorship guidelines that translate research to clinical practice. This review article summarizes the current state of lymphoma treatment-related outcomes in AYAs and provides future direction.

Green synthesis of silver nanoparticles using Adhatoda vasica leaf extract and its application in photocatalytic degradation of dyes.

The paper describes biogenic synthesis of silver nanoparticles (AgNPs) using Adhatoda vasica leaf extracts at room temperature. The prepared AgNPs were characterized by UV-visible spectroscopy, Fourier-transform infrared spectroscopy, powder X-ray diffraction, Energy dispersive X-ray (EDX), High Resolution Transmission Electron Microscope, Scanning Electron Microscopy and Thermogravimetric analyser. The bio reduction method is devoid of any toxic chemicals, organic solvents, and external reducing, capping and stabilizing agent. The synthesized AgNPs had spherical shape with particle size ranging between 3.88 and 23.97 nm and had face centered cubic structure. UV-visible spectral analysis confirmed the formation of AgNPs with a characteristic surface plasmon resonance band at 419 nm. The EDX pattern revealed the presence of elemental Ag in AgNPs. The prepared AgNPs were used for degradation of Amaranth, Allura red and Fast green in aqueous medium, with ≥ 92.6% efficiency within 15 min using 5 mg of AgNPs. The optical bandgap, Eg value of 2.26 eV for AgNPs was found to be effective for rapid photocatalytic degradation of all the three dyes. The degradation process was observed to follow pseudo first order kinetics.

A rare case of renal squamous cell carcinoma presenting with psoas sign.

INTRODUCTION: Renal cancer is a relatively common form of cancer; however, squamous cell carcinoma of the kidney is extremely rare and it carries poor prognosis. CLINICAL PRESENTATION: We present a rare case of renal squamous cell carcinoma that was manifested with the psoas sign in a patient with a history of chronic staghorn calculus. DISCUSSION: Squamous cell carcinoma of kidney is rare and more invasive. Even though many risk factors have been identified, staghorn renal calculi with chronic infection have a higher incidence of renal squamous cell carcinoma (SCC). Squamous cell carcinoma (SCC) has a wider range of atypical presentations; the psoas sign is not commonly reported in other literature. Due to the lack of reporting and sufficient knowledge, there are currently no established management guidelines. Despite advancements in contemporary medicine, the survival rate of renal SCC remains remarkably low, necessitating further research to develop a standardized treatment protocol. CONCLUSION: Primary renal SCCs are rare tumors and exhibit a strong association with renal stones, requiring prompt assessment and treatment of renal stones in affected patients. Despite their aggressiveness and poor prognosis, timely intervention is crucial.

Retinal Displacement after Scleral Buckle versus Combined Buckle and Vitrectomy for Rhegmatogenous Retinal Detachment: ALIGN Scleral Buckle versus Pars Plana Vitrectomy with Scleral Buckle.

PURPOSE: To assess the risk of retinal displacement after scleral buckle (SB) versus pars plana vitrectomy with SB (PPV-SB). DESIGN: Multicenter prospective nonrandomized clinical trial. METHODS: The study took place at VitreoRetinal Surgery in Minneapolis, Minnesota, Sankara Nethralaya in Chennai, India, and St. Michael's Hospital in Toronto, Canada from July 2019 to February 2022. Patients who underwent successful SB or PPV-SB for fovea-involving rhegmatogenous retinal detachment with gradable postoperative fundus autofluorescence (FAF) imaging were included in the final analysis. Two masked graders assessed FAF images 3 months postoperatively. Metamorphopsia and aniseikonia were assessed with M-CHARTs and the New Aniseikonia Test, respectively. The primary outcome was the proportion of patients with retinal displacement detected with retinal vessel printings on FAF in SB versus PPV-SB. RESULTS: Ninety-one eyes were included in this study, of which 46.2% (42 of 91) had SB and 53.8% (49 of 91) underwent PPV-SB. Three months postoperatively, 16.7% (7 of 42) in the SB group and 38.8% (19 of 49) in the PPV-SB group had evidence of retinal displacement (difference = 22.1%; odds ratio = 3.2; 95% confidence interval [CI], 1.2-8.6; P = 0.02) on FAF. The statistical significance of this association increased after adjustment for extent of retinal detachment, baseline logarithm of the minimum angle of resolution, lens status, and sex in a multivariate regression analysis (P = 0.01). Retinal displacement was detected in 22.5% (6 of 27) of patients in the SB group with external subretinal fluid drainage and 6.7% (1 of 15) of patients without external drainage (difference = 15.8%; odds ratio = 4.0; 95% CI, 0.4-36.9; P = 0.19). Mean vertical metamorphopsia, horizontal metamorphopsia (MH), and aniseikonia were similar between patients in the SB and PPV-SB groups. There was a trend to worse MH in patients with retinal displacement versus those without retinal displacement (P = 0.067). CONCLUSIONS: Scleral buckle is associated with less retinal displacement compared with PPV-SB, indicating that traditional PPV techniques cause retinal displacement. There is a trend toward increased risk of retinal displacement in SB eyes that underwent external drainage compared with SB eyes without drainage, which is consistent with our understanding that the iatrogenic movement of subretinal fluid, such as that which occurs intraoperatively during external drainage with SB, may induce retinal stretch and displacement if the retina is then fixed in the stretched position. There was a trend to worse MH at 3 months in patients with retinal displacement. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

The Effectiveness of Ergonomic Training and Therapeutic Exercise in Chronic Neck Pain in Accountants in the Healthcare System: A Review.

Musculoskeletal illnesses or ailments that are linked to work-related risk factors are known as work-related musculoskeletal conditions. For this study, chronic neck pain is defined as the discomfort experienced between the C1 and C7 anatomic areas of the cervical spine as well as the adjacent muscles, excluding the shoulders. In the workplace, the term "ergonomics" refers to the interactions between workers and other workplace components. Clinically, deep cervical flexor training and retraining are used for treating neck pain and enhancing the capacity to maintain an upright posture. Ergonomic training and therapeutic exercises are significantly effective in reducing pain and disability and enhancing posture in the cervical region.

Efficacy of checkpoint inhibition after CAR-T failure in aggressive B-cell lymphomas: outcomes from 15 US institutions.

Checkpoint inhibitor (CPI) therapy with anti-PD-1 antibodies has been associated with mixed outcomes in small cohorts of patients with relapsed aggressive B-cell lymphomas after CAR-T failure. To define CPI therapy efficacy more definitively in this population, we retrospectively evaluated clinical outcomes in a large cohort of 96 patients with aggressive B-cell lymphomas receiving CPI therapy after CAR-T failure across 15 US academic centers. Most patients (53%) had diffuse large B-cell lymphoma, were treated with axicabtagene ciloleucel (53%), relapsed early (≤180 days) after CAR-T (83%), and received pembrolizumab (49%) or nivolumab (43%). CPI therapy was associated with an overall response rate of 19% and a complete response rate of 10%. Median duration of response was 221 days. Median progression-free survival (PFS) and overall survival (OS) were 54 and 159 days, respectively. Outcomes to CPI therapy were significantly improved in patients with primary mediastinal B-cell lymphoma. PFS (128 vs 51 days) and OS (387 vs 131 days) were significantly longer in patients with late (>180 days) vs early (≤180 days) relapse after CAR-T. Grade ≥3 adverse events occurred in 19% of patients treated with CPI. Most patients (83%) died, commonly because of progressive disease. Only 5% had durable responses to CPI therapy. In the largest cohort of patients with aggressive B-cell lymphoma treated with CPI therapy after CAR-T relapse, our results reveal poor outcomes, particularly among those relapsing early after CAR-T. In conclusion, CPI therapy is not an effective salvage strategy for most patients after CAR-T, where alternative approaches are needed to improve post-CAR-T outcomes.

Comprehensive analysis of physiological and metabolomic responses to drought reveals specific modulation of acquired tolerance mechanisms in rice.

Mild stresses induce "acquired tolerance traits" (ATTs) that provide tolerance when stress becomes severe. Here, we identified the genetic variability in ATTs among a panel of rice germplasm accessions and demonstrated their relevance in protecting growth and productivity under water-limited conditions. Diverse approaches, including physiological screens, association mapping and metabolomics, were adopted and revealed 43 significant marker-trait associations. Nontargeted metabolomic profiling of contrasting genotypes revealed 26 "tolerance-related-induced" primary and secondary metabolites in the tolerant genotypes (AC-39000 and AC-39020) compared to the susceptible one (BPT-5204) under water-limited condition. Metabolites that help maintain cellular functions, especially Calvin cycle processes, significantly accumulated more in tolerant genotypes, which resulted in superior photosynthetic capacity and hence water use efficiency. Upregulation of the glutathione cycle intermediates explains the ROS homeostasis among the tolerant genotypes, maintaining spikelet fertility, and grain yield under stress. Bioinformatic dissection of a major effect quantitative trait locus on chromosome 8 revealed genes controlling metabolic pathways leading to the production of osmolites and antioxidants, such as GABA and raffinose. The study also led to the identification of specific trait donor genotypes that can be effectively used in translational crop improvement activities.