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A multisite, randomized, controlled, double-blinded phase I/II clinical trial.The purpose of this clinical trial is to evaluate the safety, feasibility and efficacy of pairing noninvasive transcranial direct current stimulation (tDCS) with rehabilitation to promote paretic upper extremity recovery and functional independence in persons living with chronic cervical spinal cord injury (SCI).Four-site trial conducted across Cleveland Clinic, Louis Stokes Veterans Affairs Medical Center of Cleveland and MetroHealth Rehabilitation Rehabilitation Institute of Ohio, and Kessler Foundation of New Jersey.Forty-four adults (age ≥18 years) with tetraplegia following cervical SCI that occurred ≥1-year ago will participate. Participants will be randomly assigned to receive anodal tDCS or sham tDCS given in combination with upper extremity rehabilitation for 15 sessions each over 3-5 weeks. Assessments will be made twice at baseline separated by at least a 3-week interval, once at end-of-intervention, and once at 3-month follow-up.Primary outcome measure is upper extremity motor impairment assessed using the Graded Redefined Assessment of Strength, Sensibility and Prehension (GRASSP) scale. Functional abilities will be assessed using Capabilities of Upper Extremity-Test (CUE-T), while functional independence and participation restrictions will be evaluated using the self-care domain of Spinal Cord Independent Measure (SCIM), and Canadian Occupational Performance Measure (COPM).Treatment-associated change in corticospinal excitability and output will also be studied using transcranial magnetic stimulation (TMS) and safety (reports of adverse events) and feasibility (attrition, adherence etc.) will also be evaluated.ClincalTrials.gov identifier NCT03892746. This clinical trial is being performed at four sites within the United States: Cleveland Clinic (lead site), Louis Stokes Cleveland Veterans Affairs Medical Center (VAMC) and MetroHealth Rehabilitation Institute in Ohio, and Kessler Foundation in New Jersey. The U.S. Army Medical Research Acquisition Activity, 820 Chandler Street, Fort Detrick MD 21702-5014 is the awarding and administering acquisition office.

Background: The use of stress dose corticosteroids, specifically, hydrocortisone, in septic shock is heterogeneous, and current clinical trials yield conflicting results. Regardless, they are still recommended by guidelines for vasopressor-dependent septic shock. Objectives: This study sought to characterize current practice of hydrocortisone use in patients with septic shock and secondarily to compare clinical outcomes of those who received hydrocortisone to those who did not. Methods: This single center, retrospective cohort study evaluated patients with septic shock admitted to a tertiary care center between 2012 and 2017. Patients receiving hydrocortisone for at least two doses were compared to those without. Results: 3411 septic shock patients were included; 1593 (47%) received hydrocortisone and 1818 (53%) did not. Patients who received hydrocortisone had higher lactate (4.0 vs 3.4 mmol/L; P < .01) and Acute Physiology and Chronic Health Evaluation (APACHE) III scores (104.1 vs 91.0; P < .01). Vasopressor duration was 1.7 days longer in the hydrocortisone group ( P < .01), and the hydrocortisone group had higher hospital mortality (52% vs 38%; P < .01). A propensity score–matched population was conducted in patients with APACHE scores >100: vasopressor duration was longer in those who received hydrocortisone (3.9 vs 2.0 days; P < .01), and hospital mortality was higher (59.3% vs 53.1%; P = .036); however, after multivariable adjustment, no association between receipt of hydrocortisone and hospital mortality was detected (OR 1.2 [95% CI .9–1.6]). Conclusions: Patients who received hydrocortisone were more severely ill than those that did not, making retrospective evaluation of this question challenging. These results highlight the wide variability and heterogeneity in hydrocortisone use in clinical practice.

Background A mean pulmonary artery pressure >20 mm Hg now defines pulmonary hypertension. We hypothesize that echocardiographic thresholds must be adjusted. Research Question Should tricuspid regurgitation velocity thresholds to screen for pulmonary hypertension be revised, given the new hemodynamic definition? Study Design and Methods This multicenter retrospective study included 1,608 patients who underwent both echocardiography and right heart catherization within 4 weeks. The discovery cohort consisted of 1,081 individuals; the validation cohort included 527. Screening criteria for pulmonary hypertension were derived with the use of receiver operating characteristic analysis and the Youden index, assuming equal cost for false-positive and -negative classification. A lower threshold was calculated with the use of a predefined sensitivity: 95%. Results In the discovery cohort, echocardiographic tricuspid regurgitation velocity had a good discrimination for pulmonary hypertension: area under the curve, 88.4 (95% CI, 85.3-91.5). A 3.4-m/s threshold provided a 78% sensitivity, 87% specificity, and 6.13 positive likelihood ratio to detect pulmonary hypertension; 2.7 m/s had a 95% sensitivity and 0.12 negative likelihood ratio to exclude pulmonary hypertension. In the validation cohort, the discovery threshold of 2.7 m/s provided sensitivity and negative likelihood ratios of 80% and 0.31, respectively. Right cardiac size improved detection of pulmonary hypertension in the lower tricuspid regurgitation velocity groups. Interpretation Our data support a lower tricuspid regurgitation velocity of approximately 2.7 m/s for screening pulmonary hypertension, with a high sensitivity in tertiary referral centers. Right heart chamber measurements improve the diagnostic yield of echocardiography.

Background: Atrial fibrillation of new onset during acute illness (AFNOAI) has a variable incidence of 1%–44% in hospitalized patients. This study assesses the risk factors for persistence of AFNOAI in the 5 years post hospital discharge for critically ill patients.Methods: This was a retrospective cohort study. All patients ≥18 years old admitted to the medical intensive care unit (MICU) of a tertiary care hospital from January 1st, 2012, to October 31st, 2015, were screened. Those designated with atrial fibrillation (AF) for the first time during the hospital admission were included. Risk factors for persistent AFNOAI were assessed using a Cox’s proportional hazards model. Results: Two-hundred and fifty-one (1.8%) of 13,983 unique MICU admissions had AFNOAI. After exclusions, 108 patients remained. Forty-one patients (38%) had persistence of AFNOAI. Age (hazard ratio [HR], 1.05; 95% confidence interval [CI], 1.01–1.08), hyperlipidemia (HR, 2.27; 95% CI, 1.02–5.05) and immunosuppression (HR, 2.29; 95% CI, 1.02–5.16) were associated with AFNOAI persistence. Diastolic dysfunction (HR, 1.46; 95% CI, 0.71–3.00) and mitral regurgitation (HR, 2.00; 95% CI, 0.91–4.37) also showed a trend towards association with AFNOAI persistence. Conclusions: Our study showed that AFNOAI has a high rate of persistence after discharge and that certain comorbid and cardiac factors may increase the risk of persistence. Anticoagulation should be considered, based on a patient’s individual AFNOAI persistence risk.

Transcranial magnetic stimulation (TMS) is used to investigate corticomotor neurophysiology associated with functional recovery in individuals with spinal cord injury (SCI). There is insufficient evidence about test–retest measurement properties of TMS in SCI. Therefore, we investigated test–retest agreement and reliability of TMS metrics representing corticomotor excitability, output, gain, map (representation), and inhibition in individuals with cervical SCI. We collected TMS metrics from biceps and triceps muscles because of the relevance of this proximal muscle pair to the cervical SCI population. Twelve individuals with chronic C3–C6 SCI participated in two TMS sessions separated by ≥ 2 weeks. Measurement agreement was evaluated using t tests, Bland–Altman limits of agreement and relative standard error of measurement (SEM%), while reliability was investigated using intra-class correlation coefficient (ICC) and concordance correlation coefficient (CCC). We calculated the smallest detectable change for all TMS metrics. All TMS metrics except antero-posterior map coordinates and corticomotor inhibition were in agreement upon repeated measurement though limits of agreement were generally large. Measures of corticomotor excitability, output and medio-lateral map coordinates had superior agreement (SEM% 0.75). The smallest detectable change for TMS metrics was generally high for a single individual, but this value reduced substantially with increase in sample size. We recommend use of corticomotor excitability and recruitment curve area owing to their superior measurement properties. A modest group size (20 or above) yields more stable measurements, which may favor use of TMS metrics in group level modulation after SCI.

BACKGROUND: In contrast to pulmonary vascular resistance (PVR), PVR index (PVRI) accounts for variations in body habitus. We tested the association of PVRI compared to PVR with clinical outcomes in lean and obese (BMI ≥30 kg/m(2)) patients with pulmonary arterial hypertension (PAH). METHODS: This retrospective study included adult patients with PAH who underwent right heart catheterization at Cleveland Clinic between February 1992 and November 2019. RESULTS: We included 644 patients (mean age, 53 ± 16 years, and 74 % females). PAH was idiopathic or heritable in 44% of patients. Cardiac output increased (p

Objective Patients undergoing frontal lobectomy demonstrate lower seizure-freedom rates than patients undergoing temporal lobectomy and several other resective interventions. We attempted to utilize automated preoperative quantitative analysis of focal and global cortical volume loss to develop predictive volumetric indicators of seizure outcome after frontal lobectomy. Methods Ninety patients who underwent frontal lobectomy were stratified based on seizure freedom at a mean follow-up time of 3.5 (standard deviation [SD] 2.5) years. Automated quantitative analysis of cortical volume loss organized by distinct brain region and laterality was performed on preoperative T1-weighted magnetic resonance imaging (MRI) studies. Univariate statistical analysis was used to select potential predictors of seizure freedom. Backward variable selection and multivariate logistical regression were used to develop models to predict seizure freedom. Results Forty-eight of 90 (53.3%) patients were seizure-free at the last follow-up. Several frontal and extrafrontal brain regions demonstrated statistically significant differences in both volumetric cortical volume loss and volumetric asymmetry between the left and right sides in the seizure-free and non-seizure-free cohorts. A final multivariate logistic model utilizing only preoperative quantitative MRI data to predict seizure outcome was developed with a c-statistic of 0.846. Using both preoperative quantitative MRI data and previously validated clinical predictors of seizure outcomes, we developed a model with a c-statistic of 0.897. Significance This study demonstrates that preoperative cortical volume loss in both frontal and extrafrontal regions can be predictive of seizure outcome after frontal lobectomy, and models can be developed with excellent predictive capabilities using preoperative MRI data. Automated quantitative MRI analysis can be quickly and reliably performed in patients with frontal lobe epilepsy, and further studies may be developed for integration into preoperative risk stratification.

Background Penicillin allergy is frequently reported. In pregnant women, reported penicillin allergy is associated with negative health outcomes and suboptimal group B streptococcal prophylaxis. For individuals having penicillin allergy, skin testing followed by an observed oral challenge is recommended. Previous data indicate a low risk of adverse reaction with skin testing in pregnant women, but the subsequent oral challenge was not routinely pursued. Objective To determine whether skin testing followed by the outpatient oral challenge is tolerated by pregnant women. Methods We conducted a retrospective review of all pregnant women who underwent penicillin allergy evaluation at an outpatient allergy and clinical immunology clinic. The patients underwent oral amoxicillin challenges based on the discretion of the allergy provider. We evaluated the index reaction history, skin test results, oral challenge results, and subsequent antibiotic exposure. Results A total of 46 pregnant women underwent skin testing without adverse reactions, of whom 44 patients (95.6%) received negative results. A total of 18 women (39%) completed an oral challenge without adverse reactions. Patients challenged vs not challenged did not differ in patient age, gestational age, latency since index reaction, or reaction history risk level. Notably, 28 women received intrapartum antibiotics. There was no difference in intrapartum antibiotic administration between those who did or who did not complete an in-office oral challenge (P = .90). Conclusion Penicillin skin testing and oral challenge in pregnant women can safely be performed in the outpatient setting. There was no difference in the intrapartum antibiotic use between women who were and those who were not challenged. Further research is needed to determine the utility of oral challenge in pregnant patients.

Objective A recent “bimodal-balance recovery” model suggests that contralesional influence varies based on the amount of ipsilesional reserve: inhibitory when there is a large reserve, but supportive when there is a low reserve. Here, we investigated the relationships between contralesional influence (inter-hemispheric inhibition, IHI) and ipsilesional reserve (corticospinal damage/impairment), and also defined a criterion separating subgroups based on the relationships. Methods Twenty-four patients underwent assessment of IHI using Transcranial Magnetic Stimulation (ipsilateral silent period method), motor impairment using Upper Extremity Fugl-Meyer (UEFM), and corticospinal damage using Diffusion Tensor Imaging and active motor threshold. Assessments of UEFM and IHI were repeated after 5-week rehabilitation (n = 21). Results Relationship between IHI and baseline UEFM was quadratic with criterion at UEFM 43 (95%conference interval: 40–46). Patients less impaired than UEFM = 43 showed stronger IHI with more impairment, whereas patients more impaired than UEFM = 43 showed lower IHI with more impairment. Of those made clinically-meaningful functional gains in rehabilitation (n = 14), more-impaired patients showed further IHI reduction. Conclusions A criterion impairment-level can be derived to stratify patient-subgroups based on the bimodal influence of contralesional cortex. Contralesional influence also evolves differently across subgroups following rehabilitation. Significance The criterion may be used to stratify patients to design targeted, precision treatments.

Study Objectives:Sleep-disordered breathing and nocturnal hypoxia are prevalent among patients with precapillary pulmonary hypertension (PAH). The rationale for these associations remains unclear a...

Background Urinary tract infection (UTI) caused by various pathogenic microorganisms is ubiquitous in the parts of the urinary system such as kidney, ureter, bladder, and urethra. Currently, clinical detection of UTI is mainly focused on urine culture; however, the diagnostic value of urine culture remains limited due to the time-consuming procedure and low detection rate, especially in patients who have used antibiotics. Generally, treatment for UTI relies on empirical medication rather than pathogen diagnosis, which leads to the inappropriate use of antimicrobial agents and a significant increase in resistant strains. Comparatively, metagenomic next-generation sequencing (mNGS) is capable of overcoming the disadvantages of clinical culture, and identifying pathogens for further treatment. Case presentation A 33-year-old male patient was admitted to hospital with a high fever and chills. None of his autoimmune disease or thyroid function related indicators were positive, and he had no risk of endocarditis. His white blood cell count, C-reactive protein, procalcitonin, interleukin 6, and neutrophil proportion were markedly elevated. He was initially diagnosed as having an infection of unknown etiology. Since empirical treatment of Sulperazon and Metronidazole did not relieve his symptoms, both the blood and urine specimens were examined using traditional culture, serological testing, and mNGS assay. Traditional culture and serological testing produced negative results, while the mNGS assay revealed the presence of a potential pathogen, Enterococcus faecalis, in the urine specimen, which was further confirmed by both Sanger sequencing and qPCR analysis. A CT scan of the patient’s whole abdomen showed stones in the right kidney. Once targeted antibiotic therapy was administered, the patient recovered quickly. Conclusions Our case illustrated that mNGS, as a novel culture-independent approach, demonstrated the capability of rapid, sensitive, and accurate pathogen identification. Furthermore, this technology provides strong support for guiding clinicians to determine appropriate treatment.

Background β-Adrenergic blockers (BBs) have been associated with increased risk for severe anaphylactic reaction (AR) from contrast media; however, this was shown with intravenous contrast media, before widespread use of low osmolar contrast media, angiotensin-converting enzyme-inhibitors (ACE-Is), and cardioselective BBs. Objective To assess the risk for AR during cardiac catheterization (CC) associated with BB or ACE-I exposure. Methods Patients who experienced adverse reactions during CC from January 2004 to December 2013 were identified; 1 to 2 matched controls were assigned for each case. We analyzed AR rates in association with demographic variables, medication exposures (BBs, ACE-Is, angiotensin-receptor blockers, aspirin), and comorbidities: cardiovascular disorders, asthma, and atopy. Results We analyzed 71,782 CCs. Of these, severe 70 reactors were identified—46 (0.06%) fulfilled AR criteria. There were 35 cases of mild to moderate AR and 11 cases of severe AR (0.015%). There were no significant differences in age (61.3% vs 61.5%), sex (63% vs 64% males), cardiovascular disorder rate (78% vs 93%), and exposure to BBs (46% vs 51%; cardioselective: 77% vs 80%) and ACE-Is (37.0% vs 37.2%) in cases versus controls. Via multivariate logistic regression, BB exposure was not associated with greater AR frequency (P = .35) or severity (P = .40). Neither cardioselective BBs (P = 0.2) nor noncardioselective BBs (P = .5) influenced AR severity. ACE-Is had no effect on AR frequency (P = .35) or severity (P = .14). Lower AR frequency was associated with cardiovascular disorder (P = .01). Conclusions In this case-control study, severe AR was rarely observed. Exposure to BBs or ACE-Is did not significantly influence AR frequency or severity; however, most BBs were cardioselective. Our findings imply that cardioselective BB or ACE-I suspension is not warranted in association with CC.

Initial fluid resuscitation volume for sepsis is controversial, particularly in patients at high baseline risk for complications. This study was designed to assess the association between 30 mL/kg crystalloids and intubation in patients with sepsis or septic shock and heart failure, end-stage renal disease, or cirrhosis.This propensity score-matched retrospective cohort study included patients with sepsis or septic shock admitted to a large medical ICU. Primary exposure was IV fluid volume in the first 6 h following sepsis diagnosis, divided into two cohorts: ≥ 30 mL/kg (standard group) and 30 mL/kg (restricted group). The primary outcome was need for mechanical ventilation within 72 h following initiation of fluid resuscitation. Secondary outcomes were length of stay, ventilator days, and time to intubation.A total of 208 patients were included, with 104 (50%) in the restricted group ( 30 mL/kg) and 104 in the standard group (≥ 30 mL/kg). No difference in intubation incidence was detected between the two groups, with 36 patients (35%) in the restricted group and 33 (32%) in the standard group (adjusted OR, 0.75; 95% CI, 0.41-1.36; P = .34) intubated. There was no difference between standard and restricted groups in alive ICU-free days (17 ± 11 days vs 17 ± 10 days; P = .64), duration of mechanical ventilation (10 ± 12 days vs 11 ± 16 days; P = .96), or hours to intubation (16 ± 19 h vs 14 ± 15; P = .55).No differences were detected in the incidence of intubation in patients with sepsis and cirrhosis, end-stage renal disease, or heart failure who received guideline-recommended fluid resuscitation with 30 mL/kg compared with patients initially resuscitated with a lower fluid volume.

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., Abbreviated summary Morita-Sherman et al. demonstrate how sophisticated research imaging can cross the divide to clinical practice. They show how quantitative MRI can enhance epilepsy surgery outcome prediction. Volume changes in the structures highlighted were identified as outcome predictors, supporting the hypothesis that subtle cortical atrophy outside the resection influences seizure outcome., Graphical Abstract Graphical Abstract

Background: No previous studies exist examining 2 inhaled epoprostenol formulations in an acute respiratory distress syndrome (ARDS) patient population. Objective: The study aim was to evaluate a formulary conversion from inhaled Flolan to Veletri to determine the impact on effectiveness, safety, and cost in patients with ARDS. Methods: This was a single-center, retrospective, matched cohort observational study at a tertiary care academic medical center. Patients included were mechanically ventilated, adult patients with ARDS receiving inhaled Flolan or Veletri for ≥1 hour in the intensive care unit. Results: A total of 132 patients were included in the matched cohort. There was no difference detected in change in partial pressure of arterial O2/fraction of inspired O2(PaO2/FiO2) ratio after 1 hour of therapy between the inhaled Flolan and Veletri groups (27.2 ± 46.2 vs 30 ± 68 mm Hg, P = 0.78). Significant differences in secondary outcomes included incidence of hypotension (83% vs 95.5%, P = 0.04) and thrombocytopenia (9.1% vs 29.5%, P < 0.01) in the inhaled Flolan and Veletri groups, respectively, with no difference in cost per duration of therapy ( P = 0.29). Conclusions and Relevance: There was no difference in the change in PaO2/FiO2ratio after 1 hour of therapy between inhaled Flolan and Veletri in an ARDS patient population. The formulary conversion from inhaled Flolan to Veletri was likely justified.

Disparities in the frequency of publications by gender have been reported in various medical subspecialties.Review author gender in the Journal of Allergy and Clinical Immunology and Annals of Allergy, Asthma and Immunology from 1997 to 2017.Data on frequency and patterns of authorship by gender were collected in 5-year intervals and analyzed by journal, article type, and year of publication. Logistic regression was used to analyze factors associated with a greater likelihood of first authors being women. We compared these patterns with the frequency of women AAAAI (American Academy of Allergy, AsthmaImmunology) members and AAAAI fellows-in-training.Women were first authors in 36.5% of publications, increasing from 26.6% in 1997 to 48.1% in 2017 (P.001). Their share as first author was highest (42.5%) for original articles and lowest (17.1%) for editorials. Share of women as last authors increased from 18.1% in 1997 to 30.9% in 2017 (P = .001). Women were less likely to be sole authors: 17.7% (P .001). Articles with women as first authors were observed more frequently when women were last authors (odds ratio [OR], 3.14; P.0001). This association was more likely in original investigations (OR, 2.1; P.001) and articles published more recently (2007, 2012, 2017) (OR, 1.75; P.001). The increasing rate of women first authors correlated with rising proportions of women AAAAI members (Pearson correlation = 0.96; P = .01) and fellows-in-training (Pearson correlation = 0.96; P.01).Women authorship has become more frequent in the Journal of Allergy and Clinical Immunology and Annals of Allergy, Asthma and Immunology. The probability of women being first authors is more likely in articles with women as last authors, implying that mentorship of women by women may encourage women to become more active in scholarship.

Objective: The diagnostic criteria for secondary hemophagocytic lymphohistiocytosis (HLH) have not been validated in the critically ill adult population. We set out to evaluate the performance of diagnostic criteria and determine the ferritin cutoff in critically ill adults. Design: A retrospective single-center study. Setting and Patients: Patients admitted to intensive care unit between 2008 and March 2010. Data were collected on consecutive patients who had ferritin measured. Charts were reviewed for the diagnostic criteria of HLH and components of Hscore. Measurements and Main Results: A total of 445 patients had a ferritin level measured during the study period. A diagnosis of HLH was made for 10 patients. Having 5 of 6 criteria had a specificity of 97% and a sensitivity of 70%. Hemophagocytosis was found in 41 (47.1%) of 87 bone marrow biopsies. Two hundred thirty-one patients had a ferritin level above 500 ng/dL. When determining the odds of HLH being clinically diagnosed, the optimal cut point for ferritin was 1197 ng/dL. When determining the odds of HLH based on the Hscore, the best cutoff was 143.5 (sensitivity of 90% and specificity of 90%) and patients who had HLH in our study population had an Hscore of 203.8 ± 64.9. Conclusion: In this cohort of critically ill patients, the HLH criteria are specific for HLH but not sensitive. Critically ill patients can have a higher incidence of hemophagocytosis without HLH. A higher ferritin cutoff in combination with 5 other clinical criteria is comparable to the Hscore for the recognition of HLH in the critically ill population.

This study, for the first time, compared illness and antidepressant response characteristics of young subjects with major depression (MDD) at low (LRMDD) or high-risk (HRMDD) for developing bipolar disorder with characteristics of young bipolar (BPD) subjects and healthy controls (HC).One hundred and six young (15-30 yr), medication-free subjects MDD subjects (HRMDD, N = 51; LRMDD, N = 55) were compared with 32 BPD (Type I: 14; Type II: 18) as well as 49 HC subjects. Baseline illness characteristics and frequency of comorbid conditions were examined using Analysis of Variance and Cochran-Armitage trend test. Additionally, in MDD subjects, the effect of open-label antidepressant treatment for up to 24 months with periodic assessments was compared between HRMDD and LRMDD groups for treatment response, remission and (hypo)mania switch while controlling for attrition.Significant gradation from LRMDD to HRMDD to BPD groups was found for increasing occurrence of alcohol dependence (p = 0.006), comorbid PTSD (p = 0.006), borderline personality traits (p = 0.001), and occurrence of melancholic features (p 0.005). Antidepressant treatment response was similar between the two groups except that for the 12-month period HRMDD showed a trend for a lower response. Switch to (hypo)mania was infrequent in both groups though the HRMDD showed a higher occurrence of spikes in (hypo)mania symptoms (25% increase in YMRS scores)(p = 0.04).Findings of the study indicate that a substantial proportion of young MDD subjects share BPD illness characteristics. These HRMDD subjects, if treated with antidepressants, need to be monitored for development of BPD.NCT01811147.

Objective: To describe treatment trends and outcomes of liver metastasis from uveal melanoma. Methods: Retrospective case series of 73 patients with uveal melanoma liver metastasis. Patients were treated first-line with systemic therapy (not including checkpoint inhibitors), checkpoint inhibitors, local therapy or no treatment. Time to metastasis, detection method, and survival data were collected. Time periods were divided between 2004–2011 and 2012–2016. Cox proportional hazards models were used to compare progression-free survival (PFS) and overall survival (OS). Results: Median PFS and OS for the entire cohort was 4 months (95% CI 3–5) and 15 months (95% CI 11–18), respectively. There was no statistically significant difference in PFS and OS across the two time periods. Patients who received no treatment had the shortest OS (median 4.9 months), whereas those treated with local therapy had the longest PFS (median 4.6 months) and OS (median 18.7 months). Having liver metastasis diagnosed by symptoms was associated with a greater risk of mortality (p < 0.001). Conclusion: Patients who received first-line local treatment had the longest PFS and OS, while patients who received no treatment had the shortest OS. Survival outcomes did not improve for patients including those receiving check point inhibitors.

Transcranial magnetic stimulation (TMS) is used to investigate corticomotor neurophysiology associated with functional recovery in individuals with spinal cord injury (SCI). There is insufficient evidence about test-retest measurement properties of TMS in SCI. Therefore, we investigated test-retest agreement and reliability of TMS metrics representing corticomotor excitability, output, gain, map (representation), and inhibition in individuals with cervical SCI. We collected TMS metrics from biceps and triceps muscles because of the relevance of this proximal muscle pair to the cervical SCI population. Twelve individuals with chronic C3-C6 SCI participated in two TMS sessions separated by ≥ 2 weeks. Measurement agreement was evaluated using t tests, Bland-Altman limits of agreement and relative standard error of measurement (SEM%), while reliability was investigated using intra-class correlation coefficient (ICC) and concordance correlation coefficient (CCC). We calculated the smallest detectable change for all TMS metrics. All TMS metrics except antero-posterior map coordinates and corticomotor inhibition were in agreement upon repeated measurement though limits of agreement were generally large. Measures of corticomotor excitability, output and medio-lateral map coordinates had superior agreement (SEM% 10). Metrics representing corticomotor excitability, output, and inhibition had good-to-excellent reliability (ICC/CCC 0.75). The smallest detectable change for TMS metrics was generally high for a single individual, but this value reduced substantially with increase in sample size. We recommend use of corticomotor excitability and recruitment curve area owing to their superior measurement properties. A modest group size (20 or above) yields more stable measurements, which may favor use of TMS metrics in group level modulation after SCI.

IntroductionInsulin pumps are increasingly being used as a method of insulin delivery in patients with type 1 diabetes mellitus (T1DM). Diabetic ketoacidosis (DKA) is a serious complication of T1DM. This study aims to identify the causes of DKA in patients with T1DM on continuous subcutaneous insulin infusion (CSII) and to compare these with patients with T1DM on multiple daily insulin injections (MDIIs).Research design and methodsThis is a prospective observational study between January and June 2019 at the Cleveland Clinic Fairview Hospital. Demographic, clinical, and biochemical data were obtained from chart review. A questionnaire to explore additional clinical data relating to DKA was administered, with additional items for patients on the insulin pump.ResultsSeventy-four patients were admitted with a diagnosis of DKA between the period of January and June 2019. Of these, 45 met the inclusion criteria and 43 consented. These were divided into two groups: group 1 included patients on MDII and group 2 included CSII. Overall, the most common precipitating factor for developing DKA was insulin non-adherence, seen in 51.2% of the cases. The most common cause of DKA in group 2 was pump/tubing related to 55% of the cases.ConclusionDespite non-adherence being common in both CSII and MDII, a combination of social factors, education and insulin pump malfunction, such as pump/tubing problems, might be playing a pivotal role in DKA etiology in young adults with T1DM, especially in CSII users. Continued education on pump use may reduce the rate of DKA in pump users.

Background IV pushes of phenylephrine may be used for patients with septic shock with the intent of rapidly achieving mean arterial pressure (MAP) goals. However, the clinical effectiveness and safety of this approach are unclear. Research Question In patients with septic shock, is administration of a phenylephrine push before norepinephrine initiation associated with a higher incidence of hemodynamic stability? Methods This retrospective, multicenter cohort study included adult patients with septic shock initiated on norepinephrine. Propensity scores for initial phenylephrine push receipt were generated, and patients receiving an initial phenylephrine push were propensity score-matched 1:2 to those not receiving an initial phenylephrine push. The primary outcome was achievement of hemodynamic stability (defined as maintaining MAP of ≥ 65 mm Hg for at least 6 h without an increase in continuous infusion vasoactive agent dosage) within 3 and 12 h of norepinephrine initiation. Results Of 1,317 included patients, 181 received an initial phenylephrine push; 141 phenylephrine push patients were matched to 282 patients not receiving a phenylephrine push. More patients who received a phenylephrine push achieved hemodynamic stability at hour 3 than those who did not receive a phenylephrine push (28.4% vs 18.8%; risk difference, 10%; 95% CI, 0.9%-18%). Phenylephrine push receipt was associated independently with hemodynamic stability within 3 h (adjusted OR, 1.8; 95% CI, 1.09-2.97), but not at 12 h (adjusted OR, 1.42; 95% CI, 0.93-2.16). Phenylephrine push receipt was associated independently with higher ICU mortality (adjusted OR, 1.88; 95% CI, 1.1-3.21). Interpretation Phenylephrine pushes were associated with a higher incidence of early, but not sustained, hemodynamic stability and were associated independently with higher ICU mortality. Caution is warranted when clinicians are considering the use of phenylephrine pushes in patients with septic shock.

Prednisone has been shown to reverse lung function declines in hypersensitivity pneumonitis patients without established fibrosis. Second line immunosuppressants like azathioprine and mycophenolate mofetil have a steroid sparing effect and improve DLCO. There is no published literature on the use of leflunomide in such patients. We reviewed our experience with leflunomide for treatment of hypersensitivity pneumonitis in 40 patients. We stratified patients according to the presence or absence of significant (>20%) fibrosis. We studied the effect of leflunomide on FVC and DLCO trajectory and reported the changes at 12 months.Treatment with leflunomide tended to improve the estimated FVC slope from 0.18±1.90% (SEM) of predicted per year to 4.62±1.65% of predicted (NS, p=0.118). It significantly improved the FVC at 12 months of treatment by 4.4% of predicted (p=0.02). DLCO continued to increase at 1.45±1.44% (SEM) of predicted per year. Non-fibrotic HP patients had the largest gain in pulmonary function. Their FVC increased by 8.3% (p=0.001) and DLCO by 4.8% (p=0.011). Patients with fibrotic HP did not improve. Leflunomide treatment was associated with significant gastrointestinal and other adverse effects leading 40% of patients to discontinue therapy. It had a significant steroid sparing effect with half the patients weaned off prednisone entirely.Leflunomide appears to be a fairly well tolerated steroid sparing immunosuppressant that improves pulmonary function in HP patients. It is most effective in patients without significant fibrosis.

Additional file 1: Table S1. Primers used in polymerase chain reaction. Figure S1. Electrophoretogram of PCR identified Enterococcus faecalis. On the right side of the figure, two sets of primers are used for PCR amplification. Urine represents the patient’s first urine sample. PTC represents positive template control. NTC represents negative template control. L100 represents DNA ladder.

Purpose Noninfectious uveitis has been treated historically with corticosteroid therapy in varying doses and routes. Triesence, a preservative-free sterile formulation of triamcinolone acetonide, has been used in a wide spectrum of ocular pathologies, but there have been few large studies validating its dosing or detailing long-term side effects in uveitic disease. The primary aim of this study was to describe the relative duration of action and side effects of 2 doses of preservative-free intravitreal triamcinolone acetonide (PF-IVTA) in uveitis. Design Retrospective, comparative consecutive case series. Methods Charts of all patients receiving PF-IVTA (2 mg or 4 mg) in a defined time period (2012–2014) at the Cole Eye Institute were examined for patient demographics, time to treatment failure (TTF), use of systemic immunosuppression, use of intraocular pressure–lowering therapies, date of cataract surgery and glaucoma filtration surgery, and adverse events. Results The final data set examined 514 injections in 214 eyes. Mean duration of follow-up was 1.5 years. There was similar demographic distribution between eyes that received 2 mg PF-IVTA only and eyes that received a combination of 4 + 2 mg PF-IVTA. No statistically significant difference in TTF between injection dosages was observed. There was a higher incidence of glaucoma filtering surgery and cataract surgery in eyes that received 4 + 2 mg PF-IVTA as well as a shorter time to glaucoma surgery, when compared to eyes that received 2 mg PF-IVTA alone. Conclusions This retrospective study supports that 2 mg PF-IVTA displayed noninferior treatment duration to 4 mg PF-IVTA, and may carry a significantly lower side-effect profile of cataract development and glaucoma filtering surgery.

Purpose Although safety and tolerability of approved antifibrotics has been reported extensively, little is known about their effects on weight. We analyzed predictors of weight change after one year of uninterrupted antifibrotic therapy in patients followed at our institution's interstitial lung disease clinic. Methods/Results We identified 80 patients on antifibrotic therapy (44 pirfenidone/36 nintedanib) with at least one year of follow-up and no therapy interruptions. Thirty-five patients (44%) lost more than 5% of their baseline body weight, and 11 (19%) lost more than 10%. A higher proportion of patients on nintedanib experienced a clinically significant weight loss (>5%) versus pirfenidone (61% vs 30%, p = 0.005). Univariate and multivariate analyses identified nintedanib therapy and a higher composite physiologic index (CPI) as predictors of weight loss. Conclusions Weight loss is common among IPF patients on antifibrotic therapy. Nintedanib therapy and more advanced disease were identified as predictors of weight loss in this population.