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Clinical Practice Recommendations on the Role Of Allogeneic Hematopoietic Cell Transplantation and Chimeric Antigen Receptor T-Cell Therapy in Patients With Chronic Lymphocytic Leukemia on Behalf of the American Society for Transplantation and Cellular Therapy.
No full textChimeric antigen receptor T-cell therapy (CAR T-cell) is a new treatment option for relapsed and/or refractory (R/R) chronic lymphocytic leukemia (CLL). Novel therapies including Bruton\u27s tyrosine kinase inhibitors (BTK), covalent or noncovalent, and an inhibitor of the B-cell leukemia/lymphoma 2 protein (BCL-2), venetoclax, have replaced chemoimmunotherapy (CIT) regimens in the front-line and the R/R setting, and have relegated allogeneic hematopoietic cell transplantation (allo-HCT) to later treatment stages. Updating the 2016 clinical practice recommendations on allo-HCT in CLL is necessary to help guide contemporary clinical practice. A panel of 18 physicians with diverse expertise across different CLL treatment modalities and one methodologist participated in this effort. Any recommendation receiving ≥ 70% votes was considered a consensus. CAR T-cell therapy is recommended for patients not responding or relapsing after at least 2 lines of therapy consisting of a covalent BTK inhibitor and a BCL-2 inhibitor. In addition, CAR T-cell therapy is recommended for patients who subsequently received a noncovalent BTK inhibitor in the third-line or later setting, regardless of response. CAR T-cell therapy is also recommended in CLL relapsing after an allo-HCT, assuming that patients are fit for the procedure. In those CLL patients who are candidates, allo-HCT is recommended if disease is R/R to CAR T-cell therapy provided that an objective response is demonstrated prior to the allograft. Allo-HCT is also recommended in patients with clonally-related Richter transformation (RT) after demonstrating an objective response to front-line CIT or other treatments. CAR T-cell therapy is recommended in R/R RT. We emphasize the importance of enrolling patients in clinical trials whenever available to continue to advance the field and improve prognosis of R/R CLL. We acknowledge that there are unique clinical scenarios not covered herein which may require a case-by-case approach
Analyses of Lung Parenchyma Infiltrates Using Ultrasonography in Neurocritically ill Patients.
No full textPurposeTo evaluate the presence of pulmonary infiltrates on admission among patients with intracranial hemorrhages, further refining on etiology and the agreement between ultrasonography and chest radiography.Materials and MethodsProspective analysis of patients with aneurysmal subarachnoid hemorrhage (SAH) and intracerebral hemorrhage (ICH), during a 3-month period in a single center, utilizing a standardized protocol of lung ultrasonography. Clinical and ancillary testing data were also collected.Results44 patients were studied, 30 (68.18%) with ICH, and 14 (31.81%) with SAH. Among patients with ICH, 73.3% had B-lines detected in the assessment, and in the SAH group, 57.14% had presence of lung B-lines. Etiologically, 43% of patients with ICH and 7.1% with SAH had findings suggestive of neurogenic pulmonary edema. 13% of ICH patients and 28.5% in the SAH group had assessments consistent with cardiogenic pulmonary edema. Findings between chest radiography and lung ultrasonography showed poor agreement.ConclusionSonographic lung infiltrates in patients with severe brain injuries are common, reaching up to two-thirds of ICH admissions and the majority of SAH cases. The etiology varied, with presumed neurogenic pulmonary edema leading the incidence in the ICH cohort, and with cardiogenic pulmonary edema being the most common culprit within SAH patients
Efficacy and safety of izokibep in patients with active psoriatic arthritis: a randomised, double-blind, placebo-controlled, phase 2 study.
No full textOBJECTIVES: To evaluate the efficacy and safety of izokibep, a small protein therapeutic designed to inhibit interleukin-17A, in patients with active psoriatic arthritis (PsA) over 46 weeks.
METHODS: This phase 2, multicentre, placebo-controlled study randomised adult patients with active PsA 1:1:1 to izokibep 40 mg, izokibep 80 mg, or placebo every 2 weeks for 16 weeks; subsequently, placebo-treated patients switched to izokibep 80 mg. The primary end point was American College of Rheumatology criteria 50 (ACR50) at week 16 for izokibep 80 mg vs placebo. Additional efficacy end points and treatment-emergent adverse events were evaluated through week 16 (placebo-controlled) and week 46.
RESULTS: Of 172 patients screened, 135 were randomised to izokibep 40 mg (n = 44), izokibep 80 mg (n = 47), or placebo (n = 44). ACR50 response rates were significantly higher for izokibep 80 mg vs placebo at week 16 (52% vs 13%; 2-sided P = .0006) and week 12 (50% vs 6%; P \u3c .0001); lower rates were observed for izokibep 40 mg (48% and 43% for weeks 16 and 12, respectively). Additional analyses of arthritis, psoriasis, enthesitis, dactylitis, and quality of life outcomes supported the efficacy of izokibep at both doses. Response rates generally continued to increase through week 46 with izokibep 80 mg. Treatment-emergent adverse event rates were generally similar across treatment groups except for injection site reactions.
CONCLUSIONS: Izokibep resulted in significant and clinically meaningful improvements over placebo across multiple disease domains, and the originally randomised 80-mg dose showed continued improvements to week 46. There were no unexpected safety risks identified. Izokibep\u27s small size and high potency have the potential for further improved disease control, justifying additional investigation of higher doses
APOE genotype and biological age impact inter-omic associations related to bioenergetics
No full textApolipoprotein E (APOE) modifies human aging; specifically, the ε2 and ε4 alleles are among the strongest genetic predictors of longevity and Alzheimer\u27s disease (AD) risk, respectively. However, detailed mechanisms for their influence on aging remain unclear. In the present study, we analyzed multi-omic association patterns across APOE genotypes, sex, and biological age (BA) axes in 2,229 community dwelling individuals. Our analysis, supported by validation in an independent cohort, identified diacylglycerols as the top APOE-associated plasma metabolites. However, despite the known opposing aging effects of the allele variants, both ε2- and ε4-carriers showed higher diacylglycerols compared to ε3-homozygotes. \u27Omics association patterns of ε2-carriers and increased biological age were also counter-intuitively similar, displaying significantly increased associations between insulin resistance markers and energy-generating pathway metabolites. These results demonstrate the context-dependence of the influence of APOE, with ε2 potentially strengthening insulin resistance-like pathways in the decades prior to imparting its longevity benefits. Additionally, they provide an atlas of APOE-related \u27omic associations and support the involvement of bioenergetic pathways in mediating the impact of APOE on aging
Stakeholder perspectives on a hypothetical rapid test for antibiotic resistant bacteria: an exploratory study.
No full textAntibiotic resistance remains a significant public health concern. One possible solution is to develop a new type of highly accessible test for antibiotic resistance that can be rapidly and easily utilized. As new diagnostics for measuring antibiotic resistance continue to be developed, several key practical, ethical, and social factors must be considered, including the types of tests that might be useful, their potential beneficiaries, and the contexts in which they should be utilized. This study aims to gather insights from key stakeholders regarding the ethical implications, benefits, and potential risks associated with a hypothetical rapid antibiotic resistance test that may also be designed for home use. A total of 32 semi-structured interviews were conducted with three stakeholder groups: potential users, medical providers, and ethicists. While prospective users of the test were generally positive about the proposed test, this might reflect public acceptance of point of care/home tests in general, rather than one specifically measuring ABR. Medical providers and experts knowledgeable about the problems of antibiotic overuse quickly pointed out some drawbacks and areas of concern for home testing for ABR, offering helpful guidance on where further research and consideration are needed
Exploring decisional control preferences in older patients with cancer and their caregivers.
No full textINTRODUCTION: Exploring informational and decisional control preferences as well as examining concordance and patient-caregiver-physician factors associated with preferences in older adults with cancer and their caregivers may help to better understand the role of caregivers in supporting decision-making.
MATERIALS AND METHODS: We utilized data from a national geriatric assessment (GA) cluster-randomized trial (NCT02054741; PI: Mohile) that recruited patients aged ≥70 with incurable cancer, their caregivers, and oncologists. Dyadic decision-making control preferences were measured by the Control Preferences Scale (CPS). Patients and caregivers were asked to describe patient\u27s role in treatment decision-making (patient-role CPS); patients and caregivers were also asked to describe the caregiver\u27s role in treatment decision-making (caregiver-role CPS). Matching patient-caregiver responses were considered concordant. Patients and caregivers were also asked about their information preferences regarding the amount of detail about the patients\u27 illness using a scale from 1 (fewest detail) to 5 (the most detail). We used descriptive statistics to summarize CPS, informational preferences, and concordance in responses. We utilized logistic regression to assess dyads\u27 sociodemographic information, patients\u27 GA domain impairments, and physicians\u27 practice characteristics associated with patient-caregiver CPS concordance.
RESULTS: A total of 332 dyads participated; mean age (SD) of patients and caregivers was 76.6 (5.3) and 66.6 (12.2), respectively. Preferences for treatment decision-making varied, with some preferring shared decision-making and others preferring the doctor to make decisions. Concordance between patients and caregivers was observed in 46 % for patient-role CPS and 54 % for caregiver-role CPS. Baseline factors were not associated with dyad concordance. The majority of patients and caregivers preferred the most detailed information about the patient\u27s illness.
DISCUSSION: Clinicians should assess patients\u27 and caregivers\u27 informational and decisional control preferences for optimal support in decision-making
