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Rationale & Objective: It is unclear whether the effect of canagliflozin on adverse kidney and cardiovascular events in those with diabetic kidney disease varies by age and sex. We assessed the effects of canagliflozin among age group categories and between sexes in the Canagliflozin and Renal Endpoints in Diabetes with Established Nephropathy Clinical Evaluation (CREDENCE) study.Study Design: Secondary analysis of a randomized controlled trial.Setting & Participants: Participants in the CREDENCE trial.Intervention: Participants were randomly assigned to receive canagliflozin 100 mg/d or placebo.Outcomes: Primary composite outcome of kidney failure, doubling of serum creatinine concentration, or death due to kidney or cardiovascular disease. Prespecified secondary and safety outcomes were also analyzed. Outcomes were evaluated by age at baseline (Results: The mean age of the cohort was 63.0 ± 9.2 years, and 34% were female. Older age and female sex were independently associated with a lower risk of the composite of adverse kidney outcomes. There was no evidence that the effect of canagliflozin on the primary outcome (a composite of kidney failure, a doubling of serum creatinine concentration, or death from kidney or cardiovascular causes) differed between age groups (HRs, 0.67 [95% CI, 0.52-0.87], 0.63 [0.48-0.82], and 0.89 [0.61-1.29] for ages Limitations: This was a post hoc analysis with multiple comparisons.Conclusions: Canagliflozin consistently reduced the relative risk of kidney events in people with diabetic kidney disease in both sexes and across age subgroups. As a result of greater background risk, the absolute reduction in adverse kidney outcomes was greater in younger participants.Funding: This post hoc analysis of the CREDENCE trial was not funded. The CREDENCE study was sponsored by Janssen Research and Development and was conducted collaboratively by the sponsor, an academic-led steering committee, and an academic research organization, George Clinical.Trial Registration: The original CREDENCE trial was registered at ClinicalTrials.gov with study number NCT02065791.

Supported by the National Health and Medical Research Council Centre of Research Excellence in Pulmonary Fibrosis (GNT1116371), and by foundation partner, Boehringer Ingelheim, and program partners, Roche and Galapagos. Rationale : The interstitial lung disease (ILD) multidisciplinary meetings (MDM), composed of pulmonologists, radiologists, and pathologists, is integral to the rendering of an accurate ILD diagnosis. However, there is significant heterogeneity in the conduct of ILD MDMs, and questions regarding their best practices remain unanswered. Objectives : To achieve consensus among ILD experts on essential components of an ILD MDM. Methods : Using a Delphi methodology, semi-structured interviews with ILD experts were used to identify key themes and features of ILD MDMs. These items informed two subsequent rounds of online questionnaires that were used to achieve consensus among a broader, international panel of ILD experts. Experts were asked to rate their level of agreement on a five-point Likert scale. An a priori threshold for consensus was set at a median score 4 or 5 with an interquartile range of 0. Results : We interviewed 15 ILD experts, and 102 ILD experts participated in the online questionnaires. Five items and two exploratory statements achieved consensus on being essential for an ILD MDM following two questionnaire rounds. There was consensus that the presence of at least one radiologist, a quiet setting with a visual projection system, a high-quality chest high-resolution computed tomography, and a standardized template summarizing collated patient data are essential components of an ILD MDM. Experts also agreed that it would be useful for ILD MDMs to undergo an annual benchmarking process and a validation process by fulfilling a minimum number of cases annually. Twenty-seven additional features were considered to be either highly desirable or desirable features based on the degree of consensus. Although our findings on desirable features are similar to the current literature, several of these remain controversial and warrant further research. The study also showed an agreement among participants on several future concepts to improve the ILD MDM, such as performing regular self-assessments and conducting research into shared practices to develop an international expert guideline statement on ILD MDMs. Conclusions : This Delphi study showed consensus among international ILD experts on essential and desirable features of an ILD MDM. Our data represent an important step toward potential collaborative research into future standardization of ILD MDMs. Postprint

Background To evaluate the chest CT appearance of patients with a clinicopathologic diagnosis of hypersensitivity pneumonia. Methods IRB approval was obtained for a retrospective review of patients with a preoperative CT scan, a surgical pathology report from a transbronchial biopsy or wedge resection consistent with hypersensitivity pneumonitis, and a pulmonary consultation, which also supported the diagnosis. The pathology report was evaluated for granulomas, airway-centered fibrosis, microscopic honeycombing, and fibroblast foci. The medical records were reviewed for any known antigen exposure. Patients were separated into two groups; those with and without a known antigen exposure. The CT scans were assessed for distribution of fibrosis: upper lobe or lower lobe predominance, airway-centered versus peripheral distribution, three-density pattern, and honeycombing. Results 264 pathology reports included the term chronic hypersensitivity pneumonitis (CHP). Thirty-eight of the patients had a pulmonologist who gave the patient a working diagnosis of CHP. The average age of these patients was 64 years, and 21/38 were women. Seventeen of the 38 patients had at least one antigen exposure described in the medical records. All the patients had fibrosis along the airways on chest CT. Both known antigen exposure and no known antigen patients had upper and lower lung-predominant fibrosis. There were more patients with hiatal hernias in the unknown antigen group. Honeycombing was an uncommon finding. Conclusion Airway-centered fibrosis was present on chest CT in all 38 patients with CHP (100%), with or without known antigen exposure.

Background Patients with COVID-19 and underlying malignancies, particularly those receiving immunosuppressive therapy, are at higher risk of severe COVID-19 disease. Our retrospective cohort study examines the outcomes of COVID-19 infection in patients with different underlying malignancies admitted to a 710- beds comprehensive cancer center during the first 2 years of the pandemic. Methods All patients with cancer admitted to MD Anderson Cancer Center with a positive PCR test for SARS-CoV-2 were included in a clinical case registry from 3/22/20 (first hospitalized COVID-19 patient) to 3/31/22. This clinical registry was approved at the beginning of the COVID-19 pandemic by the Quality Improvement Assessment Board at MDACC. Clinical information including type of malignancy, date of admission, length of stay, need for invasive mechanical ventilation (IMV), and in-hospital mortality was obtained from their electronic medical records. Statistical analysis was performed using a two-proportion z-test where p< 0.05 was considered significant. Results A total of 1748 patients with cancer and COVID-19 infection were admitted over a 2-year period (3.2% of total hospital admissions during the same period), 49% had hematological malignancies (HM) (see table). Patients with HM had significantly higher readmission rates (17.3% vs 9.1%, p< 0.0001), IMV rates (7.8% vs 4.4%, p=0.0029), and inpatient mortality rates (13.6% vs 7.1%, p< 0.0001). compared to patients with solid tumors (ST). Total mortality rate was 8.8% (154 patients), even higher in patients with different types of HM, such as lymphoma 18.1%, AML 14.2%, MM 8.4%, CML 7.1% while the mortality for ST was 7.1%. COVID-19 Hospitalized Patients at UT-MDACC (3/22/20-3/31/22) UT-MDACC: The University of Texas MD Anderson Cancer Center *p-value Conclusion HM patients hospitalized with COVID-19 infection had more severe disease and worse outcomes based on readmissions, IMV, and mortality rates. Preventive measures, prompt diagnosis and early treatments should be considered on this patient population. Disclosures Roy F. Chemaly, MD/MPH, Karius: Advisor/Consultant|Karius: Grant/Research Support.

BACKGROUND Chest CT scans are routinely obtained to monitor disease progression in pulmonary fibrosis. However, radiologists do not employ a standardized system for quantitative description of the severity of the disease. Development and validation of a grading system offers potential for enhancing the information that radiologists provide clinicians. STUDY DESIGN AND METHODS Our retrospective review analyzed 100 sequential patients with usual interstitial pneumonitis (UIP) on HRCT scans from 2018 and 2019. A radiologic scoring system evaluated the percent of normal lung on the basis of a 0-5 point scale per lobe (findings for the right middle lobe were included in the right upper lobe score), yielding an overall additive numerical score on a scale of 20 (completely normal lung) to 0 (no normal lung). Two radiologists quantified the percentage of normal lung by consensus agreement. Percent DLCO as well as demographic data were obtained from the medical record. Statistical analysis was performed using Spearman correlation to assess correlation between grade and percent DLCO. RESULTS 96 patients met the inclusion criteria; average age was 71, 68% were male. Score on CT scan ranged from 18 to 4; average 10.9, SD 3.58. The single-breath diffusing capacity (percent DLCO) ranged from 88% to 17%; mean 44.5%, SD 14.3%. Spearman's correlation for CT score and percent DLCO was 0.622, P

Systemic sclerosis (SSc) is a progressive and often devastating disease characterized by autoimmune dysfunction, vasculopathy, and fibrosis. Interstitial lung disease (ILD) is identified in the majority of patients with SSc and is the leading cause of SSc-related mortality. Although clinical manifestations and ILD severity vary among patients, lung function typically declines to the greatest extent during the first 3-4 years after disease onset. We aim to provide an overview of SSc-associated ILD (SSc-ILD) with a focus on current and emerging tools for early diagnosis of ILD and current and novel treatments under investigation. Early detection of ILD provides the opportunity for early therapeutic intervention, which could improve patient outcomes. Thoracic high-resolution computed tomography is the most effective method of identifying ILD in patients with SSc; it enables detection of mild lung abnormalities and plays an important role in monitoring disease progression. Cyclophosphamide and mycophenolate mofetil are the most commonly prescribed treatments for SSc-ILD. Recently, nintedanib (an antifibrotic) was approved by the Food and Drug Administration for patients with SSc-ILD; it is indicated for slowing the rate of decline in pulmonary function. However, there is a need for additional effective and well-tolerated disease-modifying therapy. Ongoing studies are evaluating other antifibrotics and novel agents. We envision that early detection of lung involvement, combined with the emergence and integration of novel therapies, will lead to improved outcomes in patients with SSc-ILD.

Interstitial lung disease (ILD) results in profound symptom burden and carries high mortality. Palliative care (PC) is dedicated to improving quality of life in patients with serious illness. Early PC provision improves rates of advance care planning and symptom management in patients with ILD.What are the current perspectives on PC among ILD providers, and what are the barriers to PC in ILD specialty centers?A 24-question electronic survey was disseminated to providers at the 68 Pulmonary Fibrosis Foundation Care Centers across the United States from October 2020 to December 2020.The survey was completed by 128 participants representing all 68 Pulmonary Fibrosis Foundation Care Center Network sites. Most respondents were physicians. Most providers exhibit good knowledge of, feel comfortable assessing a patient's readiness for, and agree with the need for PC for patients with ILD. Providers are most likely to refer to PC at objective disease and/or symptomatic progression rather than at initial diagnosis. In comparison with providers who report referring their patients to PC, providers who report rare referral are more likely to cite lack local PC availability (P .01) and less likely to feel comfortable discussing prognosis/disease trajectory (P = .03) or feel it is important to address advance directives in ILD clinic (P = .02). There is a lack of standardized measures used to assess specific symptoms, overall symptom burden, or health-related quality of life across institutions. Discordance exists between self-reported and actual access to local inpatient and outpatient PC services.Most ILD providers use PC and are comfortable discussing PC. Barriers to PC identified in this survey include the following: perceived lack of local access to PC, lack of systematic tools to assess symptom burden, lack of established optimal timing of PC referral, and unclear need for specialized PC delivery.

Escherichia coli plays an important role in biofilm formation across a wide array of disease and ecological settings. Insulin can function as an adjuvant in the regulation of biofilm levels. The modulation of insulin-regulated biofilm formation by environmental conditions has not been previously described. In the present study, the effects that various environmental growth conditions and nutrients have on insulin-modulated levels of biofilm production were measured. Micropipette tips were incubated with E. coli ATCC® 25922™ in a Mueller Hinton broth (MH), or a yeast nitrogen base with 1% peptone (YNBP), which was supplemented with glucose, lactose, galactose and/or insulin (Humulin®-R). The incubation conditions included a shaking or static culture, at 23 °C or 37 °C. After incubation, the biofilm production was calculated per CFU. At 23 °C, the presence of insulin increased biofilm formation. The amount of biofilm formation was highest in glucose &gt, galactose &gt, &gt, lactose, while the biofilm levels decreased in shaking cultures, except for galactose (3-fold increase, 0.1% galactose and 20 μU insulin). At 37 °C, regardless of condition, there was more biofilm formation/CFU under static conditions in YNBP than in MH, except for the MH containing galactose. E. coli biofilm formation is influenced by aeration, temperature, and insulin concentration in combination with the available sugars.

Background: 15.6% of adults in Arizona report smoking and approximately 40% of children show evidence of tobacco smoke exposure (TSE). Pediatric TSE causes a wide variety of disease and is associated with increased emergency room and hospital utilization. The American Academy of Pediatrics (AAP) recommends that pediatricians ask families about smoking, discuss the risks of TSE, and assist with cessation. Interventions aimed at increasing TSE screening and QUITline referral in inpatient and outpatient practices have demonstrated improvements in quit rates and sustained cessation. Objective: The purpose of this project is to evaluate the process of screening for TSE during …

Background Hospitalizations are common among patients with idiopathic pulmonary fibrosis (IPF). We investigated the impact of hospitalizations on outcomes in patients with IPF. Methods The IPF-PRO Registry is an observational US registry that enrolled patients with IPF that was diagnosed or confirmed at the enrolling center in the previous 6 months. Associations between patient characteristics and hospitalization, and between hospitalization and mortality, were analyzed using Cox regression models. Results A total of 1002 patients with IPF were enrolled into the IPF-PRO Registry. Over a median follow-up time of 23.7 months (maximum: 67.0 months), 568 patients (56.7%) had at least one hospitalization. Of these patients, 319 (56.2%) had at least one respiratory-related hospitalization and 120 (21.1%) had at least one hospitalization with ventilatory support. Younger age (HR 0.68 [95% CI 0.55, 0.84] per 5-year increase for patients Conclusions Data from the IPF-PRO Registry demonstrate that hospitalizations are common among patients with IPF. The risk of mortality during hospitalization or within 90 days of discharge was high, particularly among patients who were hospitalized for a respiratory cause or received ventilatory support. Trial registration ClinicalTrials.gov, NCT01915511. Registered 5 August 2013, https://clinicaltrials.gov/ct2/show/NCT01915511

Despite spending more on health care than any other country, the United States has the worst maternal mortality rate among all developed nations. African American and American Indian/Alaskan Native women have the worst outcomes by race, representing a stark health disparity within the country. Contributing factors disproportionately experienced by these minority populations include challenges of access to consistent and high-quality prenatal care, prevalence of underlying conditions, toxic stress due to systemic racism, and unconscious bias in health care. While many of these factors lie upstream in the lives of women, and seemingly beyond the scope of the clinical walls, the downstream health care delivery system can serve as a vital part of the solution via innovative practices, community-based collaborations, and by serving as advocates for the communities served. Such alignments between clinicians, community leaders, policymakers, and patients that extend beyond the health system can serve as the missing piece needed within the clinic to reverse the trajectory of maternal mortality for American women, especially those from traditionally underserved populations.

Rationale: Usual interstitial pneumonia (UIP) is the defining morphology of idiopathic pulmonary fibrosis (IPF). Guidelines for IPF diagnosis conditionally recommend surgical lung biopsy for histopathology diagnosis of UIP when radiology and clinical context are not definitive. A "molecular diagnosis of UIP" in transbronchial lung biopsy, the Envisia Genomic Classifier, accurately predicted histopathologic UIP.Objectives: We evaluated the combined accuracy of the Envisia Genomic Classifier and local radiology in the detection of UIP pattern.Methods: Ninety-six patients who had diagnostic lung pathology as well as a transbronchial lung biopsy for molecular testing with Envisia Genomic Classifier were included in this analysis. The classifier results were scored against reference pathology. UIP identified on high-resolution computed tomography (HRCT) as documented by features in local radiologists' reports was compared with histopathology.Measurements and Main Results: In 96 patients, the Envisia Classifier achieved a specificity of 92.1% (confidence interval [CI],78.6-98.3%) and a sensitivity of 60.3% (CI, 46.6-73.0%) for histology-proven UIP pattern. Local radiologists identified UIP in 18 of 53 patients with UIP histopathology, with a sensitivity of 34.0% (CI, 21.5-48.3%) and a specificity of 96.9% (CI, 83.8-100%). In conjunction with HRCT patterns of UIP, the Envisia Classifier results identified 24 additional patients with UIP (sensitivity 79.2%; specificity 90.6%).Conclusions: In 96 patients with suspected interstitial lung disease, the Envisia Genomic Classifier identified UIP regardless of HRCT pattern. These results suggest that recognition of a UIP pattern by the Envisia Genomic Classifier combined with HRCT and clinical factors in a multidisciplinary discussion may assist clinicians in making an interstitial lung disease (especially IPF) diagnosis without the need for a surgical lung biopsy.

* Abbreviation: CHIP — : Children’s Health Insurance Program Major policy changes have gone into effect that impact the health of some of the most vulnerable children in our nation, those of low-income immigrant families. This policy, better known as the public charge rule, is part of a compendium of highly controversial and litigated health-related federal immigration policies enacted by the Administration on the basis of financial criteria.1 The public charge rule has been traditionally used to determine ineligibility for immigration or residency status on the basis of health, education, and financial factors under the Immigration Act of 1882 and Immigration and Nationality Act of 1996. Recent changes reflect a redefinition and expansion of the term “public charge” for those applying for permanent residency.1 Under this new rule, US residency applicants who use any number of public benefits, including Medicaid, government housing, and the Supplemental Nutrition Assistance Program, are now also deemed a public charge, meaning that they are likely to become dependent on the government for subsistence.1 This label, along with other factors, can be used negatively in determinations for permanent residency applications. By tying the use of vital public health programs to immigration and residency status, the Administration is forcing a choice between seeking critical services or securing status in the United Status. Current antiimmigrant sentiment, rhetoric, and policy changes, such as the public charge rule, have resulted in a culture of fear, misinformation, distrust, and isolation, all of which have health implications for these … Address correspondence to Nina Patel, MS, College of Health Solutions, Arizona State University, 411 N Central Ave, Phoenix, AZ 85004. E-mail: ninapatel107{at}gmail.com

Background: In the INBUILD trial, nintedanib slowed the rate of decline in FVC over 52 weeks vs placebo in subjects with non-IPF progressive fibrosing ILDs. Subjects were required to have an FVC ≥45% predicted at baseline. Aim: To assess the effect of nintedanib on FVC decline in subjects with differing FVC at baseline in the INBUILD trial. Methods: The rate of decline in FVC (mL/year) over 52 weeks was assessed in subgroups by FVC % predicted at baseline (≤50%, >50%–≤70%, >70% predicted). Results: At baseline, in subjects with FVC ≤50% predicted (n=75), >50%–≤70% predicted (n=314) and >70% predicted (n=274), mean (SD) FVC was 1673 (374) mL, 2073 (511) mL and 2806 (739) mL, respectively. In the placebo group, the mean (SE) rate of decline in FVC over 52 weeks was numerically greater in subjects with FVC ≤50% predicted at baseline than in the other subgroups (Figure). The effect of nintedanib vs placebo on reducing the rate of decline in FVC was numerically more pronounced in subjects with FVC >70% predicted at baseline, but the treatment-by-subgroup-by-time interaction p-value did not indicate a differential treatment effect of nintedanib across the subgroups by FVC % predicted (p=0.75). Conclusion: Nintedanib slows the rate of FVC decline in subjects with progressive fibrosing ILDs, irrespective of their degree of FVC impairment at baseline.

Background The efficacy and safety of methylprednisolone in mechanically ventilated patients with acute respiratory distress syndrome resulting from coronavirus disease 2019 (COVID-19) are unclear. In this study, we evaluated the association between use of methylprednisolone and key clinical outcomes. Methods Clinical outcomes associated with the use of methylprednisolone were assessed in an unmatched, case-control study; a subset of patients also underwent propensity-score matching. Patients were admitted between 1 March and 12 April, 2020. The primary outcome was ventilator-free days by 28 days after admission. Secondary outcomes included extubation, mortality, discharge, positive cultures, and hyperglycemia. Results A total of 117 patients met inclusion criteria. Propensity matching yielded a cohort of 42 well-matched pairs. Groups were similar except for hydroxychloroquine and azithromycin use, which were more common in patients who did not receive methylprednisolone. Mean ventilator-free days were significantly higher in patients treated with methylprednisolone (6.21 ± 7.45 vs 3.14 ± 6.22; P = .044). The probability of extubation was also increased in patients receiving methylprednisolone (45% vs 21%; P = .021), and there were no significant differences in mortality (19% vs 36%; P = .087). In a multivariable linear regression analysis, only methylprednisolone use was associated with a higher number of ventilator-free days (P = .045). The incidence of positive cultures and hyperglycemia were similar between groups. Conclusions Methylprednisolone was associated with increased ventilator-free days and higher probability of extubation in a propensity-score matched cohort. Randomized, controlled studies are needed to further define methylprednisolone use in patients with COVID-19.

The INBUILD trial investigated the efficacy and safety of nintedanib versus placebo in patients with progressive fibrosing interstitial lung diseases (ILDs) other than idiopathic pulmonary fibrosis (IPF). We aimed to establish the effects of nintedanib in subgroups based on ILD diagnosis., info:eu-repo/semantics/published

Background We aimed to examine short- and long-term mortality in a mixed population of patients with interstitial lung disease (ILD) with acute respiratory failure, and to identify those at lower vs higher risk of in-hospital death. Methods We conducted a single-center retrospective cohort study of 126 consecutive adults with ILD admitted to an ICU for respiratory failure at a tertiary care hospital between 2010 and 2014 and who did not undergo lung transplantation during their hospitalization. We examined associations of ICU-day 1 characteristics with in-hospital and 1-year mortality, using Poisson regression, and examined survival using Kaplan-Meier curves. We created a risk score for in-hospital mortality, using a model developed with penalized regression. Results In-hospital mortality was 66%, and 1-year mortality was 80%. Those with connective tissue disease-related ILD had better short-term and long-term mortality compared with unclassifiable ILD (adjusted relative risk, 0.6; 95% CI, 0.3-0.9; and relative risk, 0.6; 95% CI, 0.4-0.9, respectively). Our prediction model includes male sex, interstitial pulmonary fibrosis diagnosis, use of invasive mechanical ventilation and/or extracorporeal life support, no ambulation within 24 h of ICU admission, BMI, and Simplified Acute Physiology Score-II. The optimism-corrected C -statistic was 0.73, and model calibration was excellent ( P = .99). In-hospital mortality rates for the low-, moderate-, and high-risk groups were 33%, 65%, and 96%, respectively. Conclusions We created a risk score that classifies patients with ILD with acute respiratory failure from low to high risk for in-hospital mortality. The score could aid providers in counseling these patients and their families.

Classic late infantile neuronal ceroid lipofuscinosis (CLN2 disease) is caused by a deficiency of tripeptidyl-peptidase-1. In 2017, the first CLN2 enzyme replacement therapy (ERT) cerliponase alfa (Brineura) was approved by the FDA and EMA. The CLN2 disease clinical rating scale (CLN2 CRS) was developed to monitor loss of motor function, language and vision as well as frequency of generalised tonic clonic seizures. Using CLN2 CRS in an open label clinical trial it was shown that Brineura slowed down the progression of CLN2 symptoms. Neurofilament light chain (NfL) is a protein highly expressed in myelinated axons. An increase of cerebrospinal fluid (CSF) and blood NfL is found in a variety of neuroinflammatory, neurodegenerative, traumatic, and cerebrovascular diseases. We analysed CSF NfL in CLN2 patients treated with Brineura to establish whether it can be used as a possible biomarker of response to therapy. Newly diagnosed patients had CSF samples collected and analysed at first treatment dose and up to 12 weeks post-treatment to look at acute changes. Patients on a compassionate use programme who were already receiving ERT for approximately 1yr had CSF samples collected and NfL analysed over the following 1.3 years (2.3 years post-initiation of ERT) to look at long-term changes. All newly diagnosed patients we investigated with classical late infantile phenotype had high NfL levels >2000 pg/ml at start of treatment. No significant change was observed in NfL up to 12 weeks post-treatment. After one year of ERT, two out of six patients still had high NfL levels, but all patients showed a continued decrease, and all had low NfL levels after two years on ERT. NfL levels appear to correspond and predict improved clinical status of patients on ERT and could be useful as a biomarker to monitor neurodegeneration and verify disease modification in CLN2 patients on ERT.

Interprofessional, student-run free clinics oversee many volunteers of different disciplines who may participate in multiple outreach programs. Effective organizational volunteer management is crucial to achievement of mission goals and volunteer retention. Students from different organizational and educational backgrounds may be required to complete a number of unique certifications and trainings in order to volunteer in a clinical role. Clear and concise dissemination of requirements to both new and returning volunteers must be performed in a structured and replicable way to ensure organizational consistency and accuracy. The Student Health Outreach for Wellness (SHOW) Community Initiative serves vulnerable populations in a variety of clinical settings, including outreaches to people experiencing homelessness and those in treatment for substance abuse disorders. Implementation of the cloud-based clinical checklist and volunteer roster has enabled our student-run free clinic to more effectively communicate both within our volunteer management team and with clinical volunteers we oversee. This article describes how a novel volunteer management workflow strategy was employed to improve volunteer compliance and communication between clinical staff and volunteers and volunteer onboarding efficiency, as well as how other student-run free clinics can implement similar strategic workflow practices to optimize their volunteer management efficiency and efficacy.

Summary: The pathogenesis of idiopathic pulmonary fibrosis (IPF), an intractable interstitial lung disease, is unclear. Recessive mutations in some genes implicated in Hermansky-Pudlak syndrome (HPS) cause HPS-associated interstitial pneumonia (HPSIP), a clinical entity that is similar to IPF. We previously reported that HPS1−/− embryonic stem cell-derived 3D lung organoids showed fibrotic changes. Here, we show that the introduction of all HPS mutations associated with HPSIP promotes fibrotic changes in lung organoids, while the deletion of HPS8, which is not associated with HPSIP, does not. Genome-wide expression analysis revealed the upregulation of interleukin-11 (IL-11) in epithelial cells from HPS mutant fibrotic organoids. IL-11 was detected predominantly in type 2 alveolar epithelial cells in end-stage IPF, but was expressed more broadly in HPSIP. Finally, IL-11 induced fibrosis in WT organoids, while its deletion prevented fibrosis in HPS4−/− organoids, suggesting IL-11 as a therapeutic target. hPSC-derived 3D lung organoids are, therefore, a valuable resource to model fibrotic lung disease. : Pulmonary fibrosis is an intractable disease that can be familial or idiopathic. Strikoudis et al. modeled pulmonary fibrosis in lung organoids generated from embryonic stem cells with mutations in Hermansky-Pudlak syndrome genes that strongly predispose to this disease and demonstrate an essential role for interleukin-11 in the fibrotic process. Keywords: organoids, lung, human pluripotent stem cells, Hermansky-Pudlak syndrome, pulmonary fibrosis, interleukin-11, disease modeling

Hypertrophic cardiomyopathy (HCM) is defined by pathological left ventricular hypertrophy (LVH). It is the commonest inherited cardiac condition and a significant number of high risk cases still go undetected until a sudden cardiac death (SCD) event. Plasma biomarkers do not currently feature in the assessment of HCM disease progression, which is tracked by serial imaging, or in SCD risk stratification, which is based on imaging parameters and patient/family history. There is a need for new HCM plasma biomarkers to refine disease monitoring and improve patient risk stratification. To identify new plasma biomarkers for patients with HCM, we performed exploratory myocardial and plasma proteomics screens and subsequently developed a multiplexed targeted liquid chromatography-tandem/mass spectrometry-based assay to validate the 26 peptide biomarkers that were identified. The association of discovered biomarkers with clinical phenotypes was prospectively tested in plasma from 110 HCM patients with LVH (LVH+ HCM), 97 controls, and 16 HCM sarcomere gene mutation carriers before the development of LVH (subclinical HCM). Six peptides (aldolase fructose-bisphosphate A, complement C3, glutathione S-transferase omega 1, Ras suppressor protein 1, talin 1, and thrombospondin 1) were increased significantly in the plasma of LVH+ HCM compared with controls and correlated with imaging markers of phenotype severity: LV wall thickness, mass, and percentage myocardial scar on cardiovascular magnetic resonance imaging. Using supervised machine learning (ML), this six-biomarker panel differentiated between LVH+ HCM and controls, with an area under the curve of ≥ 0.87. Five of these peptides were also significantly increased in subclinical HCM compared with controls. In LVH+ HCM, the six-marker panel correlated with the presence of nonsustained ventricular tachycardia and the estimated five-year risk of sudden cardiac death. Using quantitative proteomic approaches, we have discovered six potentially useful circulating plasma biomarkers related to myocardial substrate changes in HCM, which correlate with the estimated sudden cardiac death risk.

Objective The aim of this study was to determine the risk of developing a systemic autoimmune rheumatic disease (ARD) after an initial diagnosis of interstitial pneumonia with autoimmune features (IPAF). Methods We performed a retrospective cohort study of patients with interstitial lung disease (ILD) who were evaluated at Columbia University Irving Medical Center from 2009 to 2017. We divided patients with idiopathic ILD into two groups: those who met IPAF criteria and those who did not meet IPAF criteria at initial ILD diagnosis. We examined the association between IPAF and diagnosis of ARD during the follow-up period using a multivariable-adjusted logistic regression model. Results Of the 697 patients with ILD who were screened, 174 met inclusion criteria (50 met IPAF criteria and 124 did not). During a median follow-up period of 5.2 years, 16% (8/50) of subjects with IPAF were diagnosed with an ARD compared with 1.6% (2/124) of subjects without IPAF (P = 0.001). Adjusting for age, sex, smoking status and use of immunosuppressive therapy, the odds of progressing to an ARD were 14 times higher in subjects with IPAF than in those without IPAF (odds ratio 14.18, 95% CI 1.44–138.95, P = 0.02). Conclusion The presence of IPAF confers an increased risk of developing an ARD. Patients with IPAF should therefore be followed closely for the development of an ARD.

Extracellular matrix (ECM) disruption is known to be an early pathological feature of the Mucopolysaccharidoses (MPS). Collagen is the main component of the ECM and its metabolism could act as a useful indicator of ECM disruption. We have measured the specific collagen breakdown products; urinary free hydroxylated (Lys-OH) and glycosylated hydroxylysines (Lys-O-Gal and Lys-O-GalGlc) in MPS patients using a tandem liquid chromatography tandem mass spectrometry assay. A pilot study cohort analysis indicated that concentrations of lysine and Lys-OH were raised significantly in MPS I (Hurler) disease patients. Lys-O-GalGlc was raised in MPS II and MPS VI patients and demonstrated a significant difference between MPS I Hurler and an MPS I Hurler-Scheie group. Further analysis determined an age association for glycosylated hydroxylysine in control samples similar to that observed for the glycosaminoglycans. Using defined age ranges and treatment naive patient samples we confirmed an increase in glycosylated hydroxylysines in MPS I and in adult MPS IVA. We also looked at the ratio of Lys-O-Gal to Lys-O-GalGlc, an indicator of the source of collagen degradation, and noticed a significant change in the ratio for all pediatric MPS I, II, and IV patients, and a small significant increase in adult MPS IV. This indicated that the collagen degradation products were coming from a source other than bone such as cartilage or connective tissue. To see how specific the changes in glycosylated hydroxylysine were to MPS patients we also looked at levels in patients with other inherited metabolic disorders. MPS patients showed a trend towards increased glycosylated hydroxylysines and an elevated ratio compared to other metabolic disorders that included Battens disease, Fabry disease, Pyridoxine-dependent epilepsy (due to mutations in ALDH7A1), and Niemann Pick C disease.

Introduction: Mepolizumab targets eosinophils in the treatment of asthma. The dose used for asthma is considerably lower than that used for treating eosinophilic granulomatosis with polyangiitis, a...

The mucopolysaccharidoses (MPS) are lysosomal storage disorders that result from defects in the catabolism of glycosaminoglycans. Impaired muscle, bone, and connective tissue are typical clinical features of MPS due to disruption of the extracellular matrix Markers of MPS disease pathology are needed to determine disease severity and monitor effects of existing and emerging new treatments on disease mechanisms. Urine samples from a small cohort of MPS-I, -II, and -VI patients (n = 12) were analyzed using label-free quantative proteomics. Fifty-three proteins including many associated with extracellular matrix organization were differently expressed. A targeted multiplexed peptide MRM LC-MS/MS assay was used on a larger validation cohort of patient samples (MPS-I n = 18, MPS-II n = 12, MPS-VI n = 6, control n = 20). MPS-I and -II groups were further subdivided according to disease severity. None of the markers assessed were altered significantly in the mild disease groups compared to controls. beta-galactosidase, a lysosomal protein, was elevated 3.6-5.7-fold significantly (p

Imaging techniques are an essential component of the diagnostic process for interstitial lung diseases (ILDs). Chest radiography is frequently the initial indicator of an ILD, and comparison of radiographs taken at different time points can show the rate of disease progression. However, radiography provides only limited specificity and sensitivity and is primarily used to rule out other diseases, such as left heart failure. High-resolution computed tomography (HRCT) is a more sensitive method and is considered central in the diagnosis of ILDs. Abnormalities observed on HRCT can help identify specific ILDs. HRCT also can be used to evaluate the patient's prognosis, while disease progression can be assessed through serial imaging. Other imaging techniques such as positron emission tomography-computed tomography and magnetic resonance imaging have been investigated, but they are not commonly used to assess patients with ILDs. Disease severity may potentially be estimated using quantitative methods, as well as visual analysis of images. For example, comprehensive assessment of disease staging and progression in patients with ILDs requires visual analysis of pulmonary features that can be performed in parallel with quantitative analysis of the extent of fibrosis. New approaches to image analysis, including the application of machine learning, are being developed.

Christmas is a time for celebrations, feasting and rejoicing. It's a time when over indulgence in rich food is accepted as the norm. My thoughts at this time turn towards the Asian diabetic patient for whom religious festivities are common and where sweet and rich foods form an important part of what is eaten.