BCMA-CD19 compound CAR T cells for systemic lupus erythematosus: a phase 1 open-label clinical trial.

OBJECTIVES: This study aims to evaluate the safety and efficacy of BCMA-CD19 compound chimeric antigen receptor T cells (cCAR) to dual reset the humoral and B cell immune system in patients with systemic lupus erythematosus (SLE) with lupus nephritis (LN). METHODS: This is a single-arm open-label multicentre phase 1 study of BCMA and CD19-directed cCAR in patients suffering from SLE/LN with autoantibodies produced by B cells and plasma/long-lived plasma cells. In this clinical trial, we sequentially assigned biopsy-confirmed (classes III-V) LN patients to receive 3×106 cCAR cells/kg postcessation of all SLE medications and conditioning. The primary endpoint of safety and toxicity was assessed. Complete immune reset was indicated by B cell receptor (BCR) deep sequencing and flow cytometry analysis. Patient 11 (P11) had insufficient lymphocyte counts and was underdosed as compassionate use. RESULTS: P1 and P2 achieved symptom and medication-free remission (MFR) from SLE and complete remission from lymphoma. P3-P13 (excluding P11) received an initial dose of 3×106 cCAR cells /kg and were negative for all autoantibodies, including those derived from long-lived plasma cells, 3 months post-cCAR and the complement returned to normal levels. These patients achieved symptom and MFR with post-cCAR follow-up to 46 months. Complete recovery of B cells was seen in 2-6 months post-cCAR. Mean SLE Disease Activity Index 2000 reduced from 10.6 (baseline) to 2.7 (3 months), and renal function significantly improved in 10 LN patients ≤90 days post-cCAR. cCAR T therapy was well tolerant with mild cytokine-release syndrome. CONCLUSIONS: Data suggest that cCAR therapy was safe and effective in inducing MFR and depleting disease-causing autoantibodies in patients with SLE.

Thromboprophylaxis in multiple myeloma: a case-based review with practical guidelines.

Venous thromboembolism (VTE) poses a significant challenge in the context of multiple myeloma, with an incidence of up to 10% in newly diagnosed patients and varying frequency in the relapsed/refractory setting. Accurate VTE risk assessment and personalized thromboprophylaxis strategies are important parts of supportive care in myeloma. There are three validated risk assessment models for prediction of VTE risk in newly diagnosed myeloma-SAVED, IMPEDE-VTE, and PRISM. In this review, we delve into the practical applications of VTE risk prediction models in the context of current therapies. By emphasizing the necessity of a tailored approach, we underscore the importance of considering patient-specific, disease-specific, and treatment-specific risk factors in each clinical scenario, and using that data to complement the output from risk assessment models. We also provide a summary of currently available data on VTE thromboprophylaxis in myeloma, and highlight specific situations where direct oral anticoagulants should be strongly considered. Our objective is to fill the critical gaps in VTE prophylaxis and management through the analysis of specific patient cases and provide a practical overview for clinicians.

Occupational-related exposure to diesel exhaust and risk of leukemia: systematic review and meta-analysis of cohort studies.

PURPOSE: Diesel exhaust (DE) is an established lung carcinogen. The association with leukemia is not well established. We conducted a systematic review and meta-analysis of cohort studies to determine the association between occupational DE exposure and risk of leukemia. METHODS: A systematic literature review was performed to identify all cohort studies on occupational exposure to DE and associated risk of leukemia. STROBE guidelines and PECOS criteria were followed. Meta-analyses with fixed effects (and random-effects model in cases of high heterogeneity) were performed to calculate summary relative risks (RR) and 95% confidence intervals (CI), including subgroup analyses by outcome (mortality or incidence), sex, geographic region, industry type, and study quality. Study quality was assessed using the the Joanna Briggs Institute (JBI) critical appraisal checklist for cohort studies. RESULTS: Of the 30 studies retained, 20 (8 from North America, 12 from Europe) reported a total of 33 estimates of the risk of leukemia. Overall, the relative risk (RR) of leukemia was 1.01 (95% CI = 0.97-1.05, I2 = 21.2%, n = 33); corresponding results for leukemia incidence and mortality were RR = 1.02 (95% CI = 0.98-1.06, I2 = 27.9%, n = 19) and RR = 0.91 (95% CI = 0.81-1.02, I2 = 0.0%, n = 15), respectively. The main results were confirmed in analyses by sex and geographic area. A statistically significant association was detected for miners (RR = 1.58, 95% CI = 1.15-2.15, I2 = 77.0%, n = 2) but not for other occupational groups. Publication bias was not detected (p = 0.7). CONCLUSION: Our results did not indicate an association between occupational DE exposure and leukemia, with the possible exception of miners. Residual confounding cannot be excluded.

Occupational Exposure to Benzene and Risk of Breast Cancer: Systematic Review and Meta-Analysis.

INTRODUCTION: Benzene is a recognized carcinogen; however, its association with breast cancer is not well established. Hence, a meta-analysis of cohort and case-control studies was performed to determine the association between occupational benzene exposure and the risk of breast cancer. METHODS: A systematic literature review identified 7573 publications from which 23 cohort and case-control studies were retained and evaluated using meta-analyses (fixed effects model). PRISMA guidelines were followed. Our protocol was registered in the PROSPERO database (Registration No. CRD42022379720). Study quality was assessed using a modified Newcastle-Ottawa scale (NOS). RESULTS: The summary relative risk (RR) for ever-benzene exposure was 1.08 (95% CI=1.03-1.14, I2=38.6%, n=23 risk estimates); corresponding RR for cancer incidence and mortality were 1.08 (95% CI=1.02-1.14, I2=56.1%, n=16) and 1.10 (95% CI=0.87-1.37, I2<0.001%, n=10). However, heterogeneity was detected for sex (p-het=0.002), publication year (p-het<0.001), study design (p-het<0.001), study quality (p-het<0.001), and industry of employment (p-het=0.03). The RR for high level of exposure showed positive association with breast cancer 1.35 (95% CI=1.06-1.72, I2 =<0.001%, n=3) and (P-het=0.64). Publication bias was detected (p=0.03). CONCLUSIONS: The results of our meta-analysis indicate a positive association between occupational benzene exposure and an increased risk of breast cancer, particularly when exposed to higher levels of benzene. However, bias and confounding could not be excluded.

Outcomes of Breast Cancer Patients Treated with Chemotherapy, Biologic Therapy, Endocrine Therapy, or Active Surveillance During the COVID-19 Pandemic.

PURPOSE: Provide real-world data regarding the risk for SARS-CoV-2 infection and mortality in breast cancer (BC) patients on active cancer treatment. METHODS: Clinical data were abstracted from the 3778 BC patients seen at a multisite cancer center in New York between February 1, 2020 and May 1, 2020, including patient demographics, tumor histology, cancer treatment, and SARS-CoV-2 testing results. Incidence of SARS-CoV-2 infection by treatment type (chemotherapy [CT] vs endocrine and/or HER2 directed therapy [E/H]) was compared by Inverse Probability of Treatment Weighting. In those diagnosed with SARS-CoV-2 infection, Mann-Whitney test was used to a assess risk factors for severe disease and mortality. RESULTS: Three thousand sixty-two patients met study inclusion criteria with 641 patients tested for SARS-COV-2 by RT-PCR or serology. Overall, 64 patients (2.1%) were diagnosed with SARS-CoV-2 infection by either serology, RT-PCR, or documented clinical diagnosis. Comparing matched patients who received chemotherapy (n = 379) with those who received non-cytotoxic therapies (n = 2343) the incidence of SARS-CoV-2 did not differ between treatment groups (weighted risk; 3.5% CT vs 2.7% E/H, P = .523). Twenty-seven patients (0.9%) expired over follow-up, with 10 deaths attributed to SARS-CoV-2 infection. Chemotherapy was not associated with increased risk for death following SARS-CoV-2 infection (weighted risk; 0.7% CT vs 0.1% E/H, P = .246). Advanced disease (stage IV), age, BMI, and Charlson's Comorbidity Index score were associated with increased mortality following SARS-CoV-2 infection (P ≤ .05). CONCLUSION: BC treatment, including chemotherapy, can be safely administered in the context of enhanced infectious precautions, and should not be withheld particularly when given for curative intent.

ONCOPEDS: A mobile application to improve early diagnosis and timely referral in childhood cancer in a low- and middle-income country-A pilot study.

BACKGROUND: Diagnosis delay in children and adolescents with cancer is a public health problem in Peru that leads to high rates of advanced disease and mortality. We aimed to assess the implementation feasibility and potential utility of ONCOpeds®, a mobile application that provides consultations with pediatric oncologists, in reducing the latency to diagnosis (LD) and referral time (RT) among children and adolescents in Peru diagnosed with cancer. MATERIAL AND METHODS: A prospective pilot study was conducted in the region of Callao between November 2017 and April 2018. Primary and secondary care providers were trained on the use of ONCOpeds in five educational sessions. Patients younger than 18 years who resided in Callao and were diagnosed with cancer at four pediatric cancer units in Lima were analyzed by referral type: ONCOpeds facilitated or conventional. RESULTS: ONCOpeds was successfully installed in the smartphones of 78 primary and secondary care providers of Callao. During the study period, 23 new cases of cancer in children and adolescents from the region were diagnosed. Ten patients received ONCOpeds-facilitated referrals and 13 received conventional referrals. The RT decreased among those who received ONCOpeds-facilitated referrals by 66% (P = 0.02); however, the LD did not significantly decrease with the use of ONCOpeds. CONCLUSIONS: The implementation of ONCOpeds was found to be feasible in this pilot study, having a potential utility in improving early diagnosis and referral in children and adolescents newly diagnosed with cancer. Directions for future research include multicenter studies with a larger population to further test the application's effectiveness.

Return of voiding function after greenlight photovaporisation of the prostate for a patient with giant bladder.

Giant bladder is a rare condition with varied definitions and causes. It can lead to complications such as urinary tract infections, retrograde urine reflux, pyelonephritis, renal damage and occasionally vascular obstruction. In this case report, we present a man in his 70s with massive urinary retention >7 L and severe bilateral hydronephrosis. The patient underwent a successful Greenlight photovaporisation of the prostate to address underlying bladder outlet obstruction. The surgical procedure resulted in significant improvement in urinary function, enabling the patient to live catheter and infection free, and without renal damage. This case demonstrates that bladder outlet surgery can be useful in selected cases of giant bladder to avoid complications of chronic catheterisation or ongoing retention.

Occupational benzene exposure and risk of kidney and bladder cancers: a systematic review and meta-analysis.

INTRODUCTION: Benzene is recognized as leukemogenic. However, the association between it and solid cancers has been the subject of less investigation. We aim to conduct a systematic review and meta-analysis to evaluate the association between occupational exposure to benzene and the risk of urinary tract cancer, including kidney and bladder. METHODS: We included 41 cohort and case-control studies listed in the most recent International Agency for Research on Cancer (IARC) Monograph on benzene exposure and the result of a literature review to identify more recent studies. Forest plots of relative risk (RR) were constructed for kidney, bladder, and urinary tract cancer overall. A random-effects model was used to address heterogeneity between studies. Stratified analyses were conducted to explore effect modification. RESULTS: Our findings revealed an association between exposure to occupational benzene and kidney and unspecified urinary tract cancers (RR = 1.20, 95% confidence interval = 1.03-1.39), and an association of borderline statistical significance with bladder cancer (RR = 1.07, 95% confidence interval = 0.97-1.18). Publication bias was excluded for both kidney (P = 0.809) and bladder cancer (P = 0.748). Stratification analysis according to the selected study characteristics showed no difference except regarding the industry for kidney cancer (P < 0.000), with a stronger association in the chemical industry. An analysis by exposure level did not reveal any trend for kidney cancer, whereas there was a trend (P = 0.01) for bladder cancer. CONCLUSION: Our study found an association between occupational benzene exposure and kidney cancer and a dose-effect association between benzene exposure and bladder cancer.

Systematic Approach to Address Early Pandemic's Diagnostic Unmet Needs.

During the first few months of the global Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) pandemic, the medical research community had to expeditiously develop, select, and deploy novel diagnostic methods and tools to address the numerous testing challenges presented by the novel virus. Integrating a systematic approach to diagnostic selection with a rapid validation protocol in a clinical setting can shorten the timeline to bring new technologies to practice. In response to the urgent need to provide tools for identifying SARS-CoV-2-positive individuals, we developed a framework for assessing technologies against a set of prioritized performance metrics to guide device selection. We also developed and proposed clinical validation frameworks for the rapid screening of new technologies. The rubric described here represents a versatile approach that can be extended to future technology assessments and can be implemented in preparation for future emerging pathogens.