Citations

Abstract Introduction Interstitial lung disease (ILD) is a heterogenous group of parenchymal lung disorders with multiple etiologies. ILD often affects the quality of life and survival of patients. OSA is commonly diagnosed among ILD patients with reported prevalences of 50-90%, and a prevalence of moderate to severe OSA as high as 65%. There is also concern that patients with ILD may be less tolerant of PAP therapies. We aim to identify differences in PAP treatment response and adherence in patients with ILD and OSA compared with a group of matched OSA controls. Methods A retrospective cohort analysis was conducted on patients ≥ 18 years-old that were evaluated at Mayo Clinic Center for Sleep Medicine between July 2012 to June 2022. Inclusion criteria were patients with a diagnosis of ILD per ATS criteria also diagnosed with OSA by HSAT or PSG. Control OSA patients were matched to ILD/OSA patients by age, BMI, and AHI ranges. Exclusion criteria included comorbid conditions of asthma or COPD. Patients with early non-adherence to CPAP or those who didn't have sleep follow up were also excluded. Follow-up sleep visits were assessed to determine CPAP adherence, change in PAP pressure, addition of oxygen, and change in Epworth sleepiness scale. Results We compared 51 patients with ILD/OSA and 51 OSA matched-controls. Twenty-five ILD/OSA patients were diagnosed by PSG and 26 by HSAT. Median treatment follow-up for the ILD group was 7 months (IQR of 3 to 18 months). Baseline characteristics, including oxygen desaturation index (ODI), oxygen saturation, time spent below 89% during overnight oximetry, and baseline Epworth scale, were similar between ILD/OSA and non-ILD OSA patients. Importantly, there was no statistically significant difference in PAP adherence, median PAP levels, PAP pressure change, residual AHI, or change in Epworth after treatment Conclusion There was no significant difference in baseline OSA characteristics, treatment response, and PAP adherence in ILD patients with OSA compared with matched non-ILD OSA controls. Outcome assessment may be limited by sample size and the shorter follow-up period. Future studies should include longer-term follow-up with a larger ILD cohort to assess the impact of ILD progression on PAP adherence over time. Support (if any)

PittUDT, a recursive partitioning decision tree algorithm for predicting urine culture (UC) positivity based on macroscopic and microscopic urinalysis (UA) parameters, was developed in support of a broader system-wide diagnostic stewardship initiative to increase appropriateness of UC testing. Reflex algorithm training utilized results from 19,511 paired UA and UC cases (26.8% UC positive); the average patient age was 57.4 years, and 70% of samples were from female patients.

Pharmacogenetics can improve clinical outcomes by reducing adverse drug effects and enhancing therapeutic efficacy for commonly used drugs that treat a wide range of cardiovascular diseases. One of the major barriers to the clinical implementation of cardiovascular pharmacogenetics is limited education on this field for current healthcare providers and students. The abundance of pharmacogenetic literature underscores its promise, but it can also be challenging to learn such a wealth of information. Moreover, current clinical recommendations for cardiovascular pharmacogenetics can be confusing because they are outdated, incomplete, or inconsistent. A myriad of misconceptions about the promise and feasibility of cardiovascular pharmacogenetics among healthcare providers also has halted clinical implementation. Therefore, the main goal of this tutorial is to provide introductory education on the use of cardiovascular pharmacogenetics in clinical practice. The target audience is any healthcare provider (or student) with patients that use or have indications for cardiovascular drugs. This tutorial is organized into the following 6 steps: (1) understand basic concepts in pharmacogenetics; (2) gain foundational knowledge of cardiovascular pharmacogenetics; (3) learn the different organizations that release cardiovascular pharmacogenetic guidelines and recommendations; (4) know the current cardiovascular drugs/drug classes to focus on clinically and the supporting evidence; (5) discuss an example patient case of cardiovascular pharmacogenetics; and (6) develop an appreciation for emerging areas in cardiovascular pharmacogenetics. Ultimately, improved education among healthcare providers on cardiovascular pharmacogenetics will lead to a greater understanding for its potential in improving outcomes for a leading cause of morbidity and mortality.

In the original publication [...]

Abstract The intrinsic and acquired resistance to PD-1/PD-L1 immune checkpoint blockade is an important challenge for patients and clinicians because no reliable tool has been developed to predict individualized response to immunotherapy. In this study, we demonstrate the translational relevance of an ex vivo functional assay that measures the tumor cell killing ability of patient-derived CD8 T and NK cells (referred to as “cytotoxic lymphocytes,” or CLs) isolated from the peripheral blood of patients with renal cell carcinoma. Patient-derived PBMCs were isolated before and after nephrectomy from patients with renal cell carcinoma. We compared the efficacy of U.S. Food and Drug Administration (FDA)-approved PD-1/PD-L1 inhibitors (pembrolizumab, nivolumab, atezolizumab) and a newly developed PD-L1 inhibitor (H1A Ab) in eliciting cytotoxic function. CL activity was improved at 3 mo after radical nephrectomy compared with baseline, and it was associated with higher circulating levels of tumor-reactive effector CD8 T cells (CD11ahighCX3CR1+GZMB+). Treatment of PBMCs with FDA-approved PD-1/PD-L1 inhibitors enhanced tumor cell killing activity of CLs, but a differential response was observed at the individual-patient level. H1A demonstrated superior efficacy in promoting CL activity compared with FDA-approved PD-1/PD-L1 inhibitors. PBMC immunophenotyping by mass cytometry revealed enrichment of effector CD8 T and NK cells in H1A-treated PBMCs and immunosuppressive regulatory T cells in atezolizumab-treated samples. Our study lays the ground for future investigation of the therapeutic value of H1A as a next-generation immune checkpoint inhibitor and the potential of measuring CTL activity in PBMCs as a tool to predict individual response to immune checkpoint inhibitors in patients with advanced renal cell carcinoma.

Multiple myeloma (MM) arises following malignant proliferation of plasma cells in the bone marrow, that secrete high amounts of specific monoclonal immunoglobulins or light chains, resulting in the massive production of unfolded or misfolded proteins. Autophagy can have a dual role in tumorigenesis, by eliminating these abnormal proteins to avoid cancer development, but also ensuring MM cell survival and promoting resistance to treatments. To date no studies have determined the impact of genetic variation in autophagy-related genes on MM risk. We performed meta-analysis of germline genetic data on 234 autophagy-related genes from three independent study populations including 13,387 subjects of European ancestry (6863 MM patients and 6524 controls) and examined correlations of statistically significant single nucleotide polymorphisms (SNPs; p < 1 × 10−9) with immune responses in whole blood, peripheral blood mononuclear cells (PBMCs), and monocyte-derived macrophages (MDM) from a large population of healthy donors from the Human Functional Genomic Project (HFGP). We identified SNPs in six loci, CD46, IKBKE, PARK2, ULK4, ATG5, and CDKN2A associated with MM risk (p = 4.47 × 10−4−5.79 × 10−14). Mechanistically, we found that the ULK4rs6599175 SNP correlated with circulating concentrations of vitamin D3 (p = 4.0 × 10−4), whereas the IKBKErs17433804 SNP correlated with the number of transitional CD24+CD38+ B cells (p = 4.8 × 10−4) and circulating serum concentrations of Monocyte Chemoattractant Protein (MCP)-2 (p = 3.6 × 10−4). We also found that the CD46rs1142469 SNP correlated with numbers of CD19+ B cells, CD19+CD3− B cells, CD5+IgD− cells, IgM− cells, IgD−IgM− cells, and CD4−CD8− PBMCs (p = 4.9 × 10−4−8.6 × 10−4) and circulating concentrations of interleukin (IL)-20 (p = 0.00082). Finally, we observed that the CDKN2Ars2811710 SNP correlated with levels of CD4+EMCD45RO+CD27− cells (p = 9.3 × 10−4). These results suggest that genetic variants within these six loci influence MM risk through the modulation of specific subsets of immune cells, as well as vitamin D3−, MCP-2−, and IL20-dependent pathways.

These NCCN Guidelines for Distress Management discuss the identification and treatment of psychosocial problems in patients with cancer. All patients experience some level of distress associated with a cancer diagnosis and the effects of the disease and its treatment regardless of the stage of disease. Clinically significant levels of distress occur in a subset of patients, and identification and treatment of distress are of utmost importance. The NCCN Distress Management Panel meets at least annually to review comments from reviewers within their institutions, examine relevant new data from publications and abstracts, and reevaluate and update their recommendations. These NCCN Guidelines Insights describe updates to the NCCN Distress Thermometer (DT) and Problem List, and to the treatment algorithms for patients with trauma- and stressor-related disorders.

Objective: The effects of demographic and socioeconomic characteristics on delay of minimally invasive gynecologic surgery (MIGS) before and during the COVID-19 pandemic were studied. The primary outcome was interval between first MIGS appointment and date of surgery. Materials and Methods: This retrospective cohort study used electronic medical record data of a historical cohort who had benign MIGS in 2014–2016 ( n = 370) and a cohort in 2020 during the COVID pandemic ( n = 249). Included procedures were laparoscopic hysterectomy, myomectomy, adnexal surgery, or endometriosis excision. Patient demographics (race, ethnicity, age, marital status, language, insurance, and socioeconomic factors) were evaluated for associations with surgery delay (> 90 days from initial consultation to operating room date). Results: Median time to surgery was 21 days faster during the pandemic. In the historical cohort, 61% patients waited >90 days, and in the pandemic cohort, 47% patients waited >90 days. In the pandemic cohort, race and primary language were new factors associated with surgery delays. During the pandemic, a greater proportion of patients having surgery delays were Black or other races, compared to White, and a greater proportion did not speak English. After adjusting for referral indications, in multivariable logistic regression, patients who reported Other race had 3 times the odds of surgery delay, compared to White patients. Black patients had higher odds of surgery delay, although this estimate was less precise. Patients with a non-English primary language had >4 times the odds of surgery delay. Ethnicity, insurance and employment status, median household income, neighborhood segregation, and distance to hospital were not associated with surgery delay. Telemedicine accounted for 71% of visits in the pandemic cohort and was associated with a significant decrease in surgery delays with a median wait time of 87 days for patients seen via telemedicine, compared to 101 days for patients seen in-person. A higher proportion of patients using telemedicine were White and spoke English. Hispanic/Latino ethnicity, non-English primary language, and unemployment were associated with in-person versus telemedicine visits. Visit type was not correlated with insurance status, median household income, neighborhood segregation, and distance from the hospital. A risk score was calculated to summarize the estimated effect of intersectionality of multiple identities; multiple minority characteristics were correlated with surgery delays. Time to benign MIGS decreased from historical baselines during the pandemic, indicating improved access to surgical care. This benefit did not apply equally. Disproportionately, White patients who spoke English had no delays and used telemedicine; racial minority patients who did not speak English had greater odds of surgery delays and in-person appointments. Conclusions: Telemedicine can improve access to both MIGS care and surgical outcomes; additional strategies are needed to ensure that all patients receive care advances equitably. (J GYNECOL SURG 39:162)

Current validated hidradenitis suppurativa (HS) severity assessment tools are time-consuming and impractical in fast-paced, ambulatory clinic settings. This study evaluated the construct validity of the most severe or ‘worst’ area local Hidradenitis suppurativa Activity and Severity Index-Revised (W-HASI-R) as a novel target area assessment tool for clinical setting use. W-HASI-R had strong association with the International Hidradenitis Suppurativa Severity Score System and abscess and nodule count, moderate association with Hurley stage and HS physician global assessment and weak, negative association with reverse-scored Dermatology Quality Life Index. The resulting data suggest that W-HASI-R may be an option as an efficient target area assessment tool for fast-paced, ambulatory settings.