Impact of immunological aging on T cell-mediated therapies in older adults with multiple myeloma and lymphoma.

The treatment landscape for lymphoma and multiple myeloma, which disproportionally affect older adults, has been transformed by the advent of T cell-mediated immunotherapies, including immune checkpoint inhibition, T cell-engaging bispecific antibodies, and chimeric antigen receptor (CAR) T cell therapy, during the last decade. These treatment modalities re-enable the patient's own immune system to combat malignant cells and offer the potential for sustained remissions and cure for various diseases.Age profoundly affects the physiological function of the immune system.

Inflammatory Back Pain and Psoriasis: Expecting Spondyloarthritis, Discovering Lymphoma.

Inflammatory back pain is a characteristic of spondyloarthritis. It is not, however, an exclusive symptom of inflammatory rheumatic diseases as it can also be associated with non-inflammatory entities. Infrequently, the etiology can be found in neoplastic conditions such as malignant lymphoma.

Cellular therapies in older adults with hematological malignancies: A case-based, state-of-the-art review.

Cellular therapies, including autologous stem cell transplant (ASCT), allogeneic hematopoietic cell transplantation (alloHCT), and chimeric antigen receptor- (CAR-) T cell therapies are essential treatment modalities for many hematological malignancies. Although their use in older adults has substantially increased within the past decades, cellular therapies represent intensive treatment approaches that exclude a large percentage of older adults due to comorbidities and frailty. Under- and overtreatment in older adults with hematologic malignancy is a challenge and many treatment decisions are influenced by chronologic age.

Chronic endoplasmic reticulum stress in myotonic dystrophy type 2 promotes autoimmunity via mitochondrial DNA release.

Myotonic dystrophy type 2 (DM2) is a tetranucleotide CCTG repeat expansion disease associated with an increased prevalence of autoimmunity. Here, we identified an elevated type I interferon (IFN) signature in peripheral blood mononuclear cells and primary fibroblasts of DM2 patients as a trigger of chronic immune stimulation. Although RNA-repeat accumulation was prevalent in the cytosol of DM2-patient fibroblasts, type-I IFN release did not depend on innate RNA immune sensors but rather the DNA sensor cGAS and the prevalence of mitochondrial DNA (mtDNA) in the cytoplasm.

Nursing home closures and access to post-acute care and long-term care services in rural areas.

Purpose: Nursing home closures have raised concerns about access to post-acute care (PAC) and long-term care (LTC) services. We estimate the additional distance rural residents had to travel to access PAC and LTC services because of nursing home closures.

Methods: We identify nursing home closures and the availability of PAC and LTC services in nursing homes, home health agencies, and hospitals with swing beds using the Medicare Provider of Services file (2008-2018).

Provider-to-provider telehealth for sepsis patients in a cohort of rural emergency departments.

Background: Telehealth has been proposed as one strategy to improve the quality of time-sensitive sepsis care in rural emergency departments (EDs). The purpose of this study was to measure the association between telehealth-supplemented ED (tele-ED) care, health care costs, and clinical outcomes among patients with sepsis in rural EDs.

Methods: Cohort study using Medicare fee-for-service claims data for beneficiaries treated for sepsis in rural EDs between February 1, 2017, and September 30, 2019.

An inducible Cd79b mutation confers ibrutinib sensitivity in mouse models of Myd88-driven diffuse large B-cell lymphoma.

Diffuse large B-cell lymphoma (DLBCL) is the most common aggressive lymphoma and constitutes a highly heterogenous disease. Recent comprehensive genomic profiling revealed the identity of numerous molecularly defined DLBCL subtypes, including a cluster which is characterized by recurrent aberrations in MYD88, CD79B, and BCL2, as well as various lesions promoting a block in plasma cell differentiation, including PRDM1, TBL1XR1, and SPIB. Here, we generated a series of autochthonous mouse models to mimic this DLBCL cluster and specifically focused on the impact of Cd79b mutations in this setting.

Entirely noninvasive outcome prediction in central nervous system lymphomas using circulating tumor DNA.

State-of-the-art response assessment of central nervous system lymphoma (CNSL) by magnetic resonance imaging is challenging and an insufficient predictor of treatment outcomes. Accordingly, the development of novel risk stratification strategies in CNSL is a high unmet medical need. We applied ultrasensitive circulating tumor DNA (ctDNA) sequencing to 146 plasma and cerebrospinal fluid (CSF) samples from 67 patients, aiming to develop an entirely noninvasive dynamic risk model considering clinical and molecular features of CNSL.

Telehealth and In-Person Behavioral Health Services in Rural Communities Before and During the COVID-19 Pandemic: Multisite Prospective Cohort Study.

Background: The COVID-19 pandemic triggered widespread adjustments across the US health care system. Telehealth use showed a substantial increase in mental health conditions and services due to acute public health emergency (PHE) behavioral health needs on top of long-standing gaps in access to behavioral health services. How health systems that were already providing behavioral telehealth services adjusted services and staffing during this period has not been well documented, particularly in rural areas with chronic shortages of behavioral health providers and services.

Spontaneous abortion as differential diagnosis of intermittent glomerular proteinuria in inactive systemic lupus erythematosus.

In women of childbearing age, severe proteinuria in systemic lupus erythematosus raises concern for renal involvement and pregnancy complications. While persisting renal loss of protein is known to culminate in extensive interventions, intermittent proteinuria in inactive disease requires an adjusted approach. Contextual awareness of this urinary finding is thus essential.

E-64c-Hydrazide Based Cathepsin C Inhibitors: Optimizing the Interactions with the S1'-S2' Area.

The zymogens of the neutrophil serine proteases elastase, proteinase 3, and cathepsin G are converted proteolytically into their pro-inflammatory active forms by the action of cathepsin C. The inhibition of this cysteine protease therefore is an interesting therapeutic approach for the treatment of inflammatory disorders with a high neutrophil burden such as COPD. Based on E-64c-hydrazide as lead structure, we have recently developed a covalently acting cathepsin C inhibitor using a n-butyl residue attached at the amine nitrogen of the hydrazide moiety to efficiently address the deep hydrophobic S2 pocket.

Change in Drug Use Disorders Identification Test - Consumption (DUDIT-C) with Telehealth Treatment Compared to in-Person Treatment.

: There is little published evidence for the effectiveness of telehealth in the treatment of substance use disorders. We analyzed Drug Use Disorders Identification Test - Consumption (DUDIT-C) scores from 360 patients who completed the measure as part of outpatient behavioral health treatment at rural clinic sites. Some patients received in-person care, while others received telehealth.

Two Teledentistry Models for the Provision of Essential Oral Health Care Services in Rural School Settings.

Access to adequate dental services is limited for children in rural communities in the United States.The purpose of this paper was to describe how two school-based teledentistry programs increased access to oral health services for children and adolescents living in rural areas. The School-Based Telehealth Network Grant Program (SB TNGP) was designed to expand access to, and improve the quality of health care services in schools through telehealth.

Comparison of in-person vs. telebehavioral health outcomes from rural populations across America.

Background: This study investigates outcomes from two federal grant programs: the Evidence-Based Tele-Behavioral Health Network Program (EB THNP) funded from September 2018 to August 2021 and the Substance Abuse Treatment Telehealth Network Grant Program (SAT TNGP) funded from September 2017 to August 2020. As part of the health services implementation program, the aims of this study were to evaluate outcomes in patient symptoms of depression and anxiety across the programs' 17 grantees and 95 associated sites, with each grantee having data from telehealth patients and from an in-person comparison group.

Methods: The research design is a prospective multi-site observational study.

Overview of School-Based Telehealth Network Grant Program Services Delivered to Students in Rural Schools.

Telehealth can expand and enhance access to school-based health care, but its use has been relatively limited. Recognizing that school-based health care is still not reaching many students, the Health Resources and Services Administration (HRSA) funded the School Based Telehealth Network Grant Program to expand telehealth in rural school-based settings to help to increase the availability and use of these services. The 19 grantees delivered telehealth to over 200 schools across 17 states, choosing which services they would deliver and how.

Risk factors for worsening of somatic symptom burden in a prospective cohort during the COVID-19 pandemic.

Introduction: Little is known about risk factors for both Long COVID and somatic symptoms that develop in individuals without a history of COVID-19 in response to the pandemic. There is reason to assume an interplay between pathophysiological mechanisms and psychosocial factors in the etiology of symptom persistence.

Objective: Therefore, this study investigates specific risk factors for somatic symptom deterioration in a cohort of German adults with and without prior SARS-CoV-2 infection.

The impact of Medicare shared savings program participation on hospital financial performance: An event-study analysis.

Objective: To evaluate the impact of hospitals' participation in the Medicare Shared Savings Program (MSSP) on their financial performance.

Data Sources: Centers for Medicare & Medicaid Services Hospital Cost Reports and MSSP Accountable Care Organizations (ACO) Provider-Level Research Identifiable File from 2011 to 2018.

Study Design: We used an event-study design to estimate the temporal effects of MSSP participation on hospital financial outcomes and compared within-hospital changes over time between MSSP and non-MSSP hospitals while controlling for hospital and year fixed effects and organizational and service-area characteristics.

Three Separate Spike Antigen Exposures by COVID-19 Vaccination or SARS-CoV-2 Infection Elicit Strong Humoral Immune Responses in Healthcare Workers.

Background: The immunogenicity of different COVID-19 vaccine regimens and combinations in naïve and convalescent individuals has not been formally tested in controlled studies, and real-life observational studies are scarce.

Methods: We assessed the SARS-CoV-2 infection and COVID-19 vaccination-induced immunity of 697 hospital workers at the University Medical Center Hamburg-Eppendorf between 17 and 31 January 2022.

Results: The overall prevalence of anti-NC-SARS-CoV-2 antibodies indicating prior infection was 9.

Early report on the severity of COVID-19 in hematologic patients infected with the SARS-CoV2 omicron variant.

Introduction: Patients with hematologic disease are at high risk of morbidity and mortality from COVID-19 due to disease-inherent and therapy-related immunodeficiency. Whether infection with the SARS-CoV2 omicron variant leads to attenuated disease severity in these patients is currently unknown.

Methods: We assessed clinical and laboratory parameters in 61 patients with underlying hematologic conditions with a SARS-CoV2 omicron variant infection confirmed by nucleic acid amplification testing.

An economic and health outcome evaluation of telehealth in rural sepsis care: a comparative effectiveness study.

Sepsis is a top contributor to in-hospital mortality and, healthcare expenditures and telehealth have been shown to improve short-term sepsis care in rural hospitals. This study will evaluate the effect of provider-to-provider video telehealth in rural emergency departments (EDs) on healthcare costs and long-term outcomes for sepsis patients. We will use Medicare administrative claims to compare total healthcare expenditures, mortality, length-of-stay, readmissions, and category-specific costs between telehealth-subscribing and control hospitals.