Wang, Xiaofeng

Abstract RATIONALE The best described endotype of COPD is alpha-1 antitrypsin (AAT) deficiency, which is due to a genetic abnormality in the SERPINA1 gene. Homozygotes for the Z allele (PI[asterisk]ZZ individuals) carry the genotype most commonly associated with severe AAT deficiency, but a highly prevalent endotype is the heterozygous state (PI[asterisk]MZ individuals). Here we test the hypothesis that individuals with PI[asterisk]MZ genotype are at higher risk for COPD exacerbation and healthcare utilization compared to those with no pathogenic variants in the SERPINA1 gene (PI[asterisk]MM individuals). METHODS Real-world data on 4,456 individuals with available AAT genotyping were extracted from the Cleveland Clinic Health System (CCHS) electronic health records (EHR) and analyzed to compare the risk of moderate COPD exacerbation (defined as a short-term steroid prescription), all-cause emergent care (defined as an express care visit, urgent care visit, or emergency department visit), and all-cause hospitalization between individuals with PI[asterisk]MZ vs. PI[asterisk]MM genotypes. Cox proportional hazards models were used to adjust for age, sex, race, BMI, smoking status, comorbidity count, liver disease diagnosis, and median income by zip code.To assess the effect of AAT levels on outcomes, we categorized participants into three groups based on AAT level and used 90 mg/dL as a threshold given it is the lower limit of the normal reference range and genotype: MM individuals with an AAT level >90 mg/dL, MZ >90 mg/dL and MZ <90 mg/dL. To assess the effect of PI[asterisk]MZ genotype among individuals with pre-existing lung disease, we performed a subgroup analysis of individuals with at least a six-month inhaler prescription. RESULTS In this cohort, 308 individuals had a PI[asterisk]MZ genotype. PI[asterisk]MZ was associated with increased risk for moderate COPD exacerbations (adjusted HR [95% CI]: 1.66 [1.27, 2.17]) and hospitalizations (adjusted HR [95% CI]: 1.44 [1.19, 1.75]) compared to PI[asterisk]MM. The risk of hospitalization was higher among PI[asterisk]MZ individuals with AAT levels <90 mg/dL (adjusted HR [95% CI]: 1.59 [1.14, 2.23]) but not in those with AAT levels >90 mg/dL, as compared to PI[asterisk]MM. Sensitivity analysis in those treated with inhaler therapy showed overall similar results. CONCLUSIONS Increased hospitalizations and moderate COPD exacerbations among PI[asterisk]MZ individuals compared to PI[asterisk]MM individuals merit future prospective studies to better characterize the longitudinal course and healthcare utilization among those with an PI[asterisk]MZ genotype. Given the high prevalence of these carriers globally, PI[asterisk]MZ represents a COPD phenotype that invites additional investigation to identify biomarkers of worse disease and treatable traits.

Background Over half of ICU survivors experience post intensive care syndrome (PICS). Few PICS clinics were operational in the United States at the onset of the COVID-19 pandemic. Here we describe early experience of such a clinic at a large academic medical center. Our objective was to describe the (a) model of care (b) clinic interventions (c) short-term cognitive, psychiatric, and functional outcomes (d) one-year outcomes of COVID-19 ICU survivors at the Cleveland Clinic post-ICU recovery clinic (PIRC). Methods We conducted a retrospective cohort study through a chart review of all patients seen in PIRC from April 2020 – December 2020. A total of 59 patients completed the visit with 49% being virtual, and 51% being in-person. The cohort was predominantly white (50.8%), and male (57.6%) with a median age of 58.2 years. We screened for cognitive and psychiatric impairments using several different validated questionnaires. Functional impairments were self-reported and detected after assessment by a physical therapist. Quantifiable clinic interventions were referrals, pharmacy medication reconciliation, and vaccine administration. One-year outcomes were health care utilization, and death. Results In our cohort, 36%, 39.6%, and 17% of patients screened positive for cognitive impairment, anxiety and/or depression, and PTSD respectively. 42.3% of patients had lower extremity mobility impairment. 57.6% of patients required at least one referral after clinic. Of the 67.9% of patients who were working and 93.9% driving prior to hospitalization, only 24.6% and 73.2% had returned to those activities, respectively. The most common pharmacy intervention was discontinuation of a medication no longer in use. By one year, 34% of patients had hospital re-admissions with 5% requiring the ICU. There were no deaths. Conclusions Adult survivors of COVID-19 critical illness have impairments in all PICS domains as well as high health care utilization in the first year after hospital discharge. MeSH Terms Post intensive care syndrome, COVID-19 Key Points/Summary Adult survivors of COVID-19 critical illness have impairments in all PICS domains as well as high health care utilization in the first year after hospital discharge. Post-ICU recovery clinics can help survivors with recovery.

Abstract Rationale Current guidelines recognize the utility of provocative maneuvers during right heart catheterization to aid the diagnosis of pulmonary hypertension. Few studies have compared the performance of different provocation maneuvers. Objectives To assess the hemodynamic correlation among three provocative maneuvers, including their effect on pulmonary hypertension classification. Methods This prospective trial was conducted between October 2016 and May 2018. Adult patients underwent three provocative maneuvers during right heart catheterization: passive leg raise (PLR), load-targeted supine bicycle exercise, and rapid crystalloid fluid infusion. Patients were classified as follows: no pulmonary hypertension, precapillary pulmonary hypertension, isolated postcapillary pulmonary hypertension, combined pre- and postcapillary pulmonary hypertension, and uncategorized pulmonary hypertension. We assessed the hemodynamic changes associated with each maneuver. We also assessed whether provocative maneuvers led to hemodynamic reclassification of the patient to either postcapillary pulmonary hypertension with provocation or exercise pulmonary hypertension. Results Eighty-five patients (mean age 62 ± 12 years, 53% women) were included. Correlation between exercise and fluid challenge was moderate to strong (0.49–0.82; P < 0.001) for changes in right atrial pressure, mean pulmonary arterial pressure, pulmonary arterial wedge pressure, and cardiac index from baseline. Correlation between PLR and exercise (0.4–0.65; P < 0.001) and between PLR and fluid challenge (0.45–0.6; P < 0.001) was moderate for changes in right atrial pressure, mean pulmonary arterial pressure, pulmonary arterial wedge pressure, pulmonary vascular resistance, and cardiac index. Hemodynamic correlation between other provocative maneuvers was poor. Depending on provocative maneuver and classification criteria, there was significant variation in the number of patients reclassified as having exercise pulmonary hypertension (3–50%) or postcapillary pulmonary hypertension with provocation (11–48%). Conclusions Hemodynamic determinations during exercise and fluid challenge showed moderate to strong hemodynamic correlation. Moderate hemodynamic correlation was seen between PLR and exercise or fluid challenge. Although some provocative maneuvers demonstrate good hemodynamic correlation, there is inconsistency when using these maneuvers to identify patients with postcapillary or exercise pulmonary hypertension.

Abstract Quantitative volumetric brain MRI measurement is important in research applications, but translating it into patient care is challenging. We explore the incorporation of clinical automated quantitative MRI measurements in statistical models predicting outcomes of surgery for temporal lobe epilepsy. Four hundred and thirty-five patients with drug-resistant epilepsy who underwent temporal lobe surgery at Cleveland Clinic, Mayo Clinic and University of Campinas were studied. We obtained volumetric measurements from the pre-operative T1-weighted MRI using NeuroQuant, a Food and Drug Administration approved software package. We created sets of statistical models to predict the probability of complete seizure-freedom or an Engel score of I at the last follow-up. The cohort was randomly split into training and testing sets, with a ratio of 7:3. Model discrimination was assessed using the concordance statistic (C-statistic). We compared four sets of models and selected the one with the highest concordance index. Volumetric differences in pre-surgical MRI located predominantly in the frontocentral and temporal regions were associated with poorer outcomes. The addition of volumetric measurements to the model with clinical variables alone increased the model’s C-statistic from 0.58 to 0.70 (right-sided surgery) and from 0.61 to 0.66 (left-sided surgery) for complete seizure freedom and from 0.62 to 0.67 (right-sided surgery) and from 0.68 to 0.73 (left-sided surgery) for an Engel I outcome score. 57% of patients with extra-temporal abnormalities were seizure-free at last follow-up, compared to 68% of those with no such abnormalities (P-value = 0.02). Adding quantitative MRI data increases the performance of a model developed to predict post-operative seizure outcomes. The distribution of the regions of interest included in the final model supports the notion that focal epilepsies are network disorders and that subtle cortical volume loss outside the surgical site influences seizure outcome.