Remdesivir versus Favipiravir in Hospitalized Patients with Moderate to Severe COVID-19 Pneumonia: A Propensity Score-Matched Retrospective Cohort Study.

Background: Remdesivir treatment was associated with a reduced 28-day mortality and recovery time among patients hospitalized with severe COVID-19. Favipiravir is broadly used to treat COVID-19. However, various studies have had conflicting results on the efficacy of favipiravir for COVID-19. We hypothesized that remdesivir is more effective in clinical outcomes regarding the 29-day mortality rates, length of stay, and recovery rate than favipiravir in patients with moderate to severe COVID-19 pneumonia. Methods: We performed a retrospective cohort study that included adult hospitalized COVID-19 pneumonia patients with hypoxemia. Patients were classified into two groups according to the antiviral drugs. Age, oxygen saturation, fraction of inspired oxygen, and Charlson comorbidity index were used for propensity score matching. The primary objective was to determine whether the type of antiviral agent is associated with 29-day mortality. Other outcomes were the 15-day recovery rate and the length of intensive care unit or hospital stay. Results: A total of 249 patients with moderate to severe COVID-19 pneumonia were included. With an adjustment for propensity score-matched, there were 204 patients for further analysis (102 patients in each antiviral drug group). Remdesivir patients had higher Radiographic Assessment of Lung Edema (RALE) scores on Chest X-ray (14.32±9.08 vs 11.34±8.46; standardized mean difference =33.9%). The Charlson Comorbidity Index Scores were comparable. The prevalences of diabetes, obesity, hypertension, and non-HIV immunocompromised state were higher in the remdesivir group. Regarding the primary outcomes, after adjusting by diabetes, obesity, and RALE score, there was no difference in the 29-day mortality rate between both groups [26 patients (25.5%) in the remdesivir group vs 28 patients (27.5%) in the favipiravir group]. The Kaplan-Meier curve analysis at 29 days indicated no significant difference in cumulative survival rate. The two groups' adjusted hazard ratio was 0.72; 95% CI, 0.41 to 1.25, p=0.24. A Kaplan-Meier analysis on the 15-day cumulative survival rate observed a trend towards a higher survival rate in the remdesivir group (adjusted hazard ratio 0.41; 95% CI, 0.20 to 0.84; p= 0.02) The proportion of patients who recovered on day 15, the length of intensive care unit(ICU) stays, and the hospital stay were not different between remdesivir and favipiravir groups (62 patients (60.8%) vs 56 patients (54.9%), p=0.39; 11.48 ± 11.88 days vs 10.87 ± 9.31 days, p=0.69; and 16.64±14.28 days vs 16.59 ±11.31 days, p=0.98, respectively). Conclusion: In patients with moderate to severe COVID-19 pneumonia, Remdesivir did not demonstrate superior benefits over Favipiravir regarding 29-day mortality, 15-day recovery rates, or hospital and ICU stay lengths. However, further investigation into the 15-day cumulative survival rate revealed a trend towards improved survival in the Remdesivir group.

Expiratory flow limitation during mechanical ventilation: real-time detection and physiological subtypes.

BACKGROUND: Tidal expiratory flow limitation (EFLT) complicates the delivery of mechanical ventilation but is only diagnosed by performing specific manoeuvres. Instantaneous analysis of expiratory resistance (Rex) can be an alternative way to detect EFLT without changing ventilatory settings. This study aimed to determine the agreement of EFLT detection by Rex analysis and the PEEP reduction manoeuvre using contingency table and agreement coefficient. The patterns of Rex were explored. METHODS: Medical patients ≥ 15-year-old receiving mechanical ventilation underwent a PEEP reduction manoeuvre from 5 cmH2O to zero for EFLT detection. Waveforms were recorded and analyzed off-line. The instantaneous Rex was calculated and was plotted against the volume axis, overlapped by the flow-volume loop for inspection. Lung mechanics, characteristics of the patients, and clinical outcomes were collected. The result of the Rex method was validated using a separate independent dataset. RESULTS: 339 patients initially enrolled and underwent a PEEP reduction. The prevalence of EFLT was 16.5%. EFLT patients had higher adjusted hospital mortality than non-EFLT cases. The Rex method showed 20% prevalence of EFLT and the result was 90.3% in agreement with PEEP reduction manoeuvre. In the validation dataset, the Rex method had resulted in 91.4% agreement. Three patterns of Rex were identified: no EFLT, early EFLT, associated with airway disease, and late EFLT, associated with non-airway diseases, including obesity. In early EFLT, external PEEP was less likely to eliminate EFLT. CONCLUSIONS: The Rex method shows an excellent agreement with the PEEP reduction manoeuvre and allows real-time detection of EFLT. Two subtypes of EFLT are identified by Rex analysis. TRIAL REGISTRATION: Clinical trial registered with www.thaiclinicaltrials.org (TCTR20190318003). The registration date was on 18 March 2019, and the first subject enrollment was performed on 26 March 2019.

Phenotypic subtypes of fibrotic hypersensitivity pneumonitis identified by machine learning consensus clustering analysis.

BACKGROUND: Patients with fibrotic hypersensitivity pneumonitis (f-HP) have varied clinical and radiologic presentations whose associated phenotypic outcomes have not been previously described. We conducted a study to evaluate mortality and lung transplant (LT) outcomes among clinical clusters of f-HP as characterized by an unsupervised machine learning approach. METHODS: Consensus cluster analysis was performed on a retrospective cohort of f-HP patients diagnosed according to recent international guideline. Demographics, antigen exposure, radiologic, histopathologic, and pulmonary function findings along with comorbidities were included in the cluster analysis. Cox proportional-hazards regression was used to assess mortality or LT risk as a combined outcome for each cluster. RESULTS: Three distinct clusters were identified among 336 f-HP patients. Cluster 1 (n = 158, 47%) was characterized by mild restriction on pulmonary function testing (PFT). Cluster 2 (n = 46, 14%) was characterized by younger age, lower BMI, and a higher proportion of identifiable causative antigens with baseline obstructive physiology. Cluster 3 (n = 132, 39%) was characterized by moderate to severe restriction. When compared to cluster 1, mortality or LT risk was lower in cluster 2 (hazard ratio (HR) of 0.42; 95% CI, 0.21-0.82; P = 0.01) and higher in cluster 3 (HR of 1.76; 95% CI, 1.24-2.48; P = 0.001). CONCLUSIONS: Three distinct phenotypes of f-HP with unique mortality or transplant outcomes were found using unsupervised cluster analysis, highlighting improved mortality in fibrotic patients with obstructive physiology and identifiable antigens.

Effect of the Ramathibodi Rapid Response System Triggered by the Ramathibodi Early Warning Score and Clinical Warning Signs on in-Hospital Mortality and the Incidence of Cardiopulmonary Resuscitation in Adult Hospitalized Patients.

Purpose: The Ramathibodi Rapid Response System (RRRS), implemented in March 2017, aims to identify and respond to patients with deteriorating conditions outside the ICU. It employs the Ramathibodi early warning score and clinical signs to monitor all admitted patients, providing expert physician monitoring and early treatment for stabilization and appropriate care triage. This study assesses the RRRS's effectiveness in reducing in-hospital mortality and CPR events outside the ICU. Patients and Methods: We conducted a retrospective observational study from March 2014 to February 2020 in a tertiary care hospital's general wards. We included adult patients experiencing unplanned ICU admission, sudden cardiac arrest, or unexpected death. The study compared in-hospital mortality and CPR incidence outside the ICU between pre- and post-RRRS implementation groups. The associations between RRRS implementation and in-hospital mortality and the incidence of CPR outside the ICU were assessed using multiple logistic regression analyses. Results: We evaluated 17,741 admissions, with 9168 before RRRS implementation (1 March 2014 to 28 February 2017) and 8573 after RRRS implementation (1 March 2017 to 29 February 2020). The implementation of RRRS was associated with a significant reduction in in-hospital mortality, which decreased from 30.0% to 20.8% (odds ratio, 0.62; 95% confidence interval [CI], 0.57 to 0.66; P<0.0001). Even after adjusting for age, sex, and comorbidities, the reduction in in-hospital mortality remained significant (adjusted odds ratio, 0.58; 95% CI, 0.54 to 0.63; P<0.0001). The incidence of CPR outside the ICU also decreased from 1.8% to 1.1% (adjusted odds ratio, 0.6; 95% CI, 0.46 to 0.77; P<0.0001). Additionally, the rate of ICU transfer increased from 85.4% to 92.1% (risk difference, 6.7; 95% CI, 7.6 to 5.8; P<0.0001) after implementing the RRRS. Conclusion: Implementing the RRRS is associated with a reduction in in-hospital mortality and the incidence of CPR outside the ICU.

Clinical Characteristics of Anti-Synthetase Syndrome and Variables Associated with Interstitial Lung Disease and Mortality: A Retrospective Cohort Study.

Anti-synthetase syndrome (ASS) is a rare autoimmune disease. Since the knowledge of ASS remains limited, we conducted the retrospective study aiming to describe clinical characteristics and identify variables associated with interstitial lung disease (ILD) and mortality among patients with ASS. Patients diagnosed with ASS from January 2013 to October 2022 were included. Patient demographics, clinical manifestations, myositis auto-antibody profiles, HRCT findings, and laboratory tests were collected. Variables associated with mortality risk and ILD were evaluated using the Cox proportional hazards model and the logistic regression model, respectively. A total of 82 patients with ASS were included. Clinical manifestations included arthritis (57%), Raynaud's phenomenon (32%), mechanic's hands (29%), fever (26%), and myositis (17%). The myositis auto-antibody profiles included anti-PL-7 (29%), anti-Jo-1 (27%), anti-EJ (17%), anti-PL-12 (16%), and anti-OJ (11%). ILD was observed in 64 patients (78%). Among patients with ILD, 21 initially presented with ILD before developing other ASS clinical manifestations, 29 simultaneously presented with ILD and other symptoms, and 14 had isolated ILD throughout follow-up. Overall, 6 patients presented with rapid-progressive ILD. With a median follow-up time of 2.5 years, mortality was observed in 10 patients (12.2%). Factors associated with mortality included increased lymphocyte counts (adjusted HR, 0.74; 95% CI, 0.61-0.91; p < 0.01), isolated ILD (adjusted HR, 9.59; 95% CI, 1.52-60.61; p = 0.02) and the presence of anti-Ro52 antibodies (adjusted HR, 0.14; 95% CI, 0.02-0.93; p = 0.04). Factors associated with ILD included age (adjusted OR, 1.10; 95% CI, 1.03-1.18; p = 0.01), presence of anti-Ro52 antibodies (adjusted OR, 17.92; 95% CI, 2.13-138.68; p = 0.01), and presence of arthritis (adjusted OR, 0.09; 95% CI, 0.01-0.75; p = 0.03). Our study demonstrated a favorable overall mortality rate among ASS patients.

Clinical and chest radiographic features of missed lung cancer and their association with patient outcomes.

PURPOSE: To examine clinical and chest radiographic features of missed lung cancer (MLC) and explore their association with patient outcomes. METHODS: We retrospectively reviewed chest radiographs obtained at least six months before lung cancer (LC) diagnosis in 95 patients to identify the first positive chest radiograph showing MLC. We assessed chest radiographic features of MLC and their association with patient outcomes. RESULTS: Seventy-five (78.9%) patients (39 men, 36 women; mean age, 64.5 ± 10.5 years) had MLC. The median diagnostic delay was 31.3 months (6.6-128.0 months). The median MLC size was 16 mm (5-57 mm), and 54.7%, 68.0%, and 74.7% of MLC were in the left lung, the middle/lower zones, and the outer two-thirds of the lung, respectively. MLC exhibited a round/oval shape, partly/poorly defined margin, irregular/spiculated border, a density less than the aortic knob, and anatomical superimposition in 57.3%, 77.3%, 61.3%, 85.3%, and 88.0% of cases, respectively. Thirty-five (46.7%) patients had stage III + IV LC at diagnosis. Thirty-one (41.3%) patients died. MLC in the inner one-third of the lung, exhibiting a density equal to/greater than the aortic knob, or superimposed by midline structures was significantly associated with stage III + IV LC at diagnosis. The 3-year all-cause mortality significantly increased when MLC was in the upper zone, superimposed by pulmonary vessels, superimposed by pulmonary vessels plus ribs, or superimposed by pulmonary vessels plus in the inner one-third of the lung. CONCLUSION: MLC with some radiographic features pertaining to their location, density, and superimposed structures was found to portend a worse outcome.

Impact of Antifibrotic Treatment on Postoperative Complications in Patients with Interstitial Lung Diseases Undergoing Lung Transplantation: A Systematic Review and Meta-Analysis.

Antifibrotic treatment has been approved for reducing disease progression in fibrotic interstitial lung disease (ILD). As a result of increased bleeding risk, some experts suggest cessation of antifibrotics prior to lung transplantation (LT). However, extensive knowledge regarding the impact of antifibrotic treatment on postoperative complications remains unclear. We performed a comprehensive search of several databases from their inception through to 30 September 2021. Original studies were included in the final analysis if they compared postoperative complications, including surgical wound dehiscence, anastomosis complication, bleeding complications, and primary graft dysfunction, between those with and without antifibrotic treatment undergoing LT. Of 563 retrieved studies, 6 studies were included in the final analysis. A total of 543 ILD patients completing LT were included, with 161 patients continuing antifibrotic treatment up to the time of LT and 382 without prior treatment. Antifibrotic treatment was not significantly associated with surgical wound dehiscence (RR 1.05; 95% CI, 0.31-3.60; I2 = 0%), anastomotic complications (RR 0.88; 95% CI, 0.37-2.12; I2 = 31%), bleeding complications (RR 0.76; 95% CI, 0.33-1.76; I2 = 0%), or primary graft dysfunction (RR 0.87; 95% CI, 0.59-1.29; I2 = 0%). Finally, continuing antifibrotic treatment prior to LT was not significantly associated with decreased 1-year mortality (RR 0.80; 95% CI, 0.41-1.58; I2 = 0%). Our study suggests a similar risk of postoperative complications in ILD patients undergoing LT who received antifibrotic treatment compared to those not on antifibrotic therapy.

Association of hypochloremia with mortality among patients requiring continuous renal replacement therapy.

BACKGROUND: Serum chloride derangement is common in critically ill patients requiring continuous renal replacement therapy (CRRT). We aimed to assess the association between serum chloride levels before and during CRRT with mortality. METHODS: This is a retrospective cohort study of critically ill patients receiving CRRT for acute kidney injury from December 2006 through November 2015 in a tertiary referral hospital in the United States. We used logistic regression to assess serum chloride before and mean serum chloride during CRRT as predictors for 90 days mortality after CRRT initiation. The normal reference range for serum chloride was 99-108 mmol/L. RESULTS: Of 1282 eligible patients, 25%, 50%, and 25% had hypochloremia, normochloremia, and hyperchloremia, respectively. The adjusted odds ratio for 90 days mortality in patients with hypochloremia before CRRT was 1.82 (95% CI 1.29-2.55). During CRRT, 4%, 70%, 26% of patients had mean serum chloride in the hypochloremia, normochloremia, and hyperchloremia range, respectively. The adjusted odds ratio for 90 days mortality in patients with mean serum chloride during CRRT in the hypochloremia range was 2.96 (95% CI 1.43-6.12). Hyperchloremia before and during CRRT was not associated with mortality. The greater serum chloride range during CRRT was associated with increased mortality (OR 1.29; 95% CI 1.13-1.47 per 5 mmol/L increase). CONCLUSION: Hypochloremia before and during CRRT is associated with higher mortality.

Association of Serum Phosphate Derangement With Mortality in Patients on Continuous Renal Replacement Therapy.

Background: There is limited evidence on the association of serum phosphate with mortality in patients receiving continuous renal replacement therapy (CRRT). Objective: To assess the association of serum phosphate with mortality in critically ill patients requiring CRRT for acute kidney injury (AKI). Design: A cohort study. Setting: A tertiary referral hospital in the United States. Patients: Acute kidney injury patients receiving CRRT from 2006 through 2015 in intensive care units. Measurements: (1) Serum phosphate before CRRT and (2) mean serum phosphate during CRRT were categorized into 3 groups; ≤2.4 (hypophosphatemia), 2.5 to 4.5 (normal serum phosphate group), and ≥4.6 (hyperphosphatemia) mg/dL. Methods: Multivariable logistic regression was used to assess the association between serum phosphate and 90-day mortality. Results: A total of 1108 patients were included in this study. Of these, 55% died within 90 days after CRRT initiation. Before CRRT, 3%, 30%, and 66% had hypophosphatemia, normophosphatemia, and hyperphosphatemia, respectively. Before CRRT, both hypophosphatemia and hyperphosphatemia were significantly associated with higher 90-day mortality with the adjusted odds ratio (OR) of 2.22 (95% confidence interval [CI]: [1.03, 4.78]) and 1.62 (95% CI: [1.21, 2.18]), respectively. During CRRT, 3%, 85%, and 12% had mean serum phosphate in hypophosphatemia, normophosphatemia, and hyperphosphatemia range. During CRRT, hyperphosphatemia was significantly associated with higher 90-day mortality with adjusted OR of 2.22 (95% CI: [1.45, 3.38]). Limitations: Single center, observational design, lack of information regarding causes of serum phosphate derangement. Conclusion: Most CRRT patients had hyperphosphatemia before CRRT initiation but maintain normal serum phosphate during CRRT. Before CRRT, hypo- and hyperphosphatemia, and during CRRT, hyperphosphatemia predicted higher mortality. Trial registration: Not registered.

Contexte: Il existe peu de données sur l'association entre la phosphatémie et la mortalité chez les patients recevant une thérapie de remplacement rénal continue (TRRC). Objectif: Examiner l'association entre la phosphatémie et la mortalité chez les patients gravement malades nécessitant une TRRC pour suppléer une insuffisance rénale aiguë (IRA). Type d'étude: Étude de cohorte. Cadre: Un hôpital central de soins tertiaires aux États-Unis. Patients: Des patients atteints d'IRA ayant reçu une TRRC entre 2006 et 2015 dans les unités de soins intensifs. Mesures: 1) la phosphatémie avant la TRRC et 2) la phosphatémie moyenne pendant la TRRC ont été classées en trois groupes: hypophosphatémie (≤ 2,4 mg/dl), normophosphatémie (2,5 à 4,5 mg/dl) et hyperphosphatémie (≥ 4,6 mg/dl). Méthodologie: La régression logistique multivariable a été utilisée pour évaluer l'association entre la phosphatémie et la mortalité à 90 jours. Résultats: L'étude a inclus un total de 1 108 patients dont 55 % sont décédés dans les 90 jours suivant le début de la TRRC. Avant d'amorcer la TRRC, 3 % des patients présentaient une hypophosphatémie, 30 % une normophosphatémie et 66 % une hyperphosphatémie. Avant l'amorce de la TRRC, avec leur rapport de cotes ajusté de 2,22 (IC 95 %: 1,03-4,78) et 1,62 (IC 95 %: 1,21-2,18) respectivement, l'hypophosphatémie et l'hyperphosphatémie étaient significativement associées à une mortalité plus élevée à 90 jours. Pendant la TRRC, 3 % des patients présentaient un taux de phosphate sérique moyen dans les gammes d'hypophosphatémie; ces proportions étaient de 85 % pour la normophosphatémie et de 12 % pour l'hyperphosphatémie. Cette dernière était également significativement associée à un taux de mortalité plus élevé à 90 jours, avec un taux ajusté de 2,22 (IC à 95 %: 1,45-3,38), pendant la TRRC. Limites: Étude dans un seul center, conception observationnelle, manque d'information sur les causes du dérèglement de la phosphatémie. Conclusion: La plupart des patients présentaient une hyperphosphatémie avant l'initiation de la TRRC, mais ont maintenu des valeurs normales pendant la TRRC. L'hypophosphatémie et l'hyperphosphatémie avant l'amorce de la TRRC, ainsi que l'hyperphosphatémie pendant la TRRC, se sont avérés des facteurs prédictifs d'un taux de mortalité plus élevé. Enregistrement de l'essai: Non enregistré.

Diagnostic accuracy of interferon-gamma release assays for diagnosis of smear-negative pulmonary tuberculosis: a systematic review and meta-analysis.

INTRODUCTION: The diagnosis of smear-negative pulmonary tuberculosis (SNPTB) is challenging. Interferon gamma-release assays (IGRAs) may be helpful in early diagnosis among these patients resulting in prompt treatment and favorable outcomes. METHODS: We performed a comprehensive search from each databases' inception to April 5, 2021. The studies that provided sufficient data regarding the sensitivity and specificity of IGRAs included QuantiFERON-TB Gold In-Tube (QFT-GIT), T-SPOT.TB, or QuantiFERON-TB Gold Plus for diagnosis of SNPTB were included. RESULTS: Of 1,312 studies screened, 16 studies were included; 11 QFT-GIT, 2 T-SPOT.TB, and 3 QFT-GIT and T-SPOT.TB. For diagnosis of SNPTB, QFT-GIT had sensitivity of 0.77 (95% CI 0.71-0.82), specificity of 0.70 (95% CI 0.58-0.80), diagnostic odds ratio (DOR) of 8.03 (95% CI 4.51-14.31), positive likelihood ratio (LR) of 2.61 (95% CI 1.80-3.80), negative LR of 0.33 (95% CI 0.25-0.42), and area under receiver operating characteristic (AUROC) of 0.81 (95% CI 0.77-0.84). T-SPOT.TB had sensitivity of 0.74 (95% CI 0.71-0.78), specificity of 0.71 (95% CI 0.49-0.86), DOR of 6.96 (95% CI 2.31-20.98), positive LR of 2.53 (95% CI 1.26-5.07), negative LR of 0.36 (95% CI 0.24-0.55), and AUROC of 0.77 (95% CI 0.73-0.80). The specificity seemed lower in the subgroup analyses of studies from high tuberculosis burden counties compared to the studies from low tuberculosis burden. CONCLUSION: IGRAs do have insufficient diagnostic performance for SNPTB. However, the tests are still helpful to exclude tuberculosis among patients with low pre-test probability. Registry: PROSPERO: CRD42021274653.

Effect size of rituximab on pulmonary function in the treatment of connective-tissue disease-related interstitial lung disease: a systematic review and meta-analysis.

BACKGROUND: Rituximab (RTX) has been previously reported as directed treatment in patients with connective-tissue disease-related interstitial lung diseases (CTD-ILD). A systematic assessment of treatment effect size on pulmonary function outcomes and related adverse effects in patients with CTD-ILD has not been previously reported. METHODS: We performed a systematic review and meta-analysis of published reports from PubMed, Embase, and Cochrane Libraries. Randomized and non-randomized controlled trials, case-control, cohort, and case series (with five or more cases) containing individual pulmonary function data and adverse effects were included. Study endpoints were pre- and post-treatment change in percent predicted forced vital capacity (FVC %) and diffusion capacity for carbon monoxide (DLCO%), along with reported drug-related adverse events. RESULTS: Twenty studies totaling 411 patients were identified with 14 included in the meta-analysis of pulmonary function and six in the descriptive review. Random effects meta-analysis of pre- and post-treatment pulmonary function findings demonstrated increases in FVC% (n = 296) (mean difference (MD) 4.57%, [95% CI 2.63-6.51]) and DLCO% (n = 246) (MD 5.0% [95% CI 2.71-7.29]) after RTX treatment. RTX treatment-related adverse effects were reported in 13.6% of the pooled cohort. CONCLUSIONS: A systematic assessment of post-treatment effect size suggests a potential role for RTX in stabilizing or improving lung function in patients with CTD-ILD, with a modest but not insignificant adverse effect profile.

Antigen identification and avoidance on outcomes in fibrotic hypersensitivity pneumonitis.

BACKGROUND: Suspected causative antigens may be unidentified in 30-50% of patients with fibrotic hypersensitivity pneumonitis (f-HP). It is unclear whether antigen identification and avoidance in this setting offer any additional clinical benefit. We hypothesised that antigen identification and avoidance may improve the clinical course of patients with fibrotic disease. METHODS: Patients meeting recent international practice guidance for f-HP diagnosis evaluated at Mayo Clinic Rochester from January 2005 to December 2018 were included. Causative antigen and antigen avoidance were specifically defined and ascertained through review of the medical records. Cox proportional-hazards regression was performed to assess antigen identification and avoidance as predictors of either all-cause mortality or lung transplantation. RESULTS: 377 patients were included. Of these, suspected causative antigen was identified in 225 (60%). Identification of a suspected antigen (adjusted hazard ratio (HR) 0.69, 95% CI 0.48-0.99; p=0.04) and subsequent antigen avoidance (adjusted HR 0.47, 95% CI 0.31-0.71; p<0.001) were associated with decreased all-cause mortality and transplantation. Both those with suspected antigen identification but nonavoidance and those with unidentifiable antigen had increased risk of all-cause mortality or transplantation (adjusted HR 2.22, 95% CI 1.34-3.69; p=0.002 versus adjusted HR 2.09, 95% CI 1.34-3.26; p=0.001, respectively). Exposure to avian antigen was associated with better outcome compared to other antigen subtypes (adjusted HR 0.63, 95% CI 0.43-0.93; p=0.02). CONCLUSION: Our findings suggest that antigen identification and antigen avoidance remain relevant even in patients with fibrotic disease, where both appear to be associated with improved outcomes.

Challenges in the Diagnosis and Management of Fibrotic Hypersensitivity Pneumonitis: A Practical Review of Current Approaches.

Recent advances in fibrotic hypersensitivity pneumonitis include improved diagnostic guidance, systematic assessments of immunosuppressive therapy, and the recent availability of antifibrotic therapy (nintedanib) for those with progressive disease. A standardized approach to diagnosis may lead to better inclusion criteria for future therapeutic protocols and delineation of disease or treatment response predictors for real-world management. This review will highlight current diagnostic and treatment challenges and remaining knowledge gaps or areas of uncertainty, with a practical overview of supporting evidence and its clinical implications. Exposure history, serologic testing for antigen sensitivity, bronchoalveolar lavage lymphocytosis, histopathology, and radiologic findings will be covered in the diagnosis section, with immunosuppression, antifibrotic therapy, lung transplantation, and disease prognosis in the treatment and management section.

Bronchoalveolar lavage lymphocytosis in hypersensitivity pneumonitis: a retrospective cohort analysis with elimination of incorporation bias.

BACKGROUND: Recent studies support the diagnostic role of bronchoalveolar lavage lymphocytosis (BALL) in patients with suspected hypersensitivity pneumonitis (HP). Our study aim was to determine the spectrum of BALL findings with elimination of incorporation bias in non-fibrotic and fibrotic patients and assess correlates of positive BALL cut-off and BALL association with long-term outcomes in those with fibrotic disease (f-HP). METHODS: A single-center retrospective cohort study was pursued of patients undergoing diagnostic bronchoscopy for interstitial lung disease. Strict study enrollment was based on recent ATS/JRS/ALAT diagnostic guidance meeting 'moderate' or higher diagnostic confidence. BALL findings were assessed in both fibrotic and non-fibrotic HP patients with regression and survival analysis pursued for correlates of positive BALL cut-off and long-term outcome. RESULTS: A total of 148 patients (88 fibrotic and 60 non-fibrotic) meeting moderate or higher diagnostic confidence were included. Median BALL in f-HP was 15% compared to 19% in non-fibrotic patients, with only 28% of f-HP meeting diagnostic cut-off (≥ 30%) compared to 41% of non-fibrotic. For f-HP, centrilobular nodules on computed tomography was positively correlated with a diagnostic BALL (OR 4.07; p = 0.018) while honeycombing was negatively correlated (OR 6.9 × e-8; p = 0.001). Higher BALL was also associated with lower all-cause mortality (HR 0.98; p = 0.015). CONCLUSION: With elimination of incorporation bias, most patients with well-described HP did not meet diagnostic BALL thresholds. Higher BALL was associated with better long-term survival in those with fibrosis, but its diagnostic role may be more additive than characteristic or distinguishing.

Association of serum potassium derangements with mortality among patients requiring continuous renal replacement therapy.

INTRODUCTION: We aimed to assess the association between serum potassium and mortality in patients receiving continuous renal replacement therapy (CRRT). METHODS: We studied 1279 acute kidney injury patients receiving CRRT in a tertiary referral hospital in the United States. We used logistic regression to assess the association of serum potassium before CRRT and mean serum potassium during CRRT with 90-day mortality after CRRT initiation, using serum potassium 4.0-4.4 mmol/L as reference group. RESULTS: Before CRRT, there was a U-shaped association between serum potassium and 90-day mortality. There was a significant increase in mortality when serum potassium before CRRT was ≤3.4 and ≥4.5 mmol/L. During CRRT, progressively increased mortality was noted when mean serum potassium was ≥4.5 mmol/L. The odds ratio of 90-day mortality was significantly higher when mean serum potassium was ≥4.5 mmol/L. CONCLUSION: Hypokalemia and hyperkalemia before CRRT and hyperkalemia during CRRT predicts 90-day mortality.

Prevalence of Diabetes Mellitus in Patients with Tuberculosis: A Prospective Cohort Study.

BACKGROUND: Diabetes mellitus (DM) and poor glycemic control significantly increase the risk of tuberculosis (TB) and adverse outcomes after TB treatment. However, DM screening is not universally performed. METHOD: Patients diagnosed with TB were enrolled and tested for fasting plasma glucose (FPG) and hemoglobin A1c (HbA1c) within 3 months after TB diagnosis. RESULTS: A total of 216 patients with TB were included. Median (IQR) age was 60 years (53-73), and 57% were male. The prevalence of DM was 42.6%. Patients with TB with DM were more likely to have other comorbidities (76% vs 52%, p<0.001), a higher proportion of positive sputum acid-fast bacilli (AFB) (27% vs 11%, p=0.001), and a positive culture for Mycobacterium tuberculosis in bronchoalveolar lavage (10% vs 3%, p=0.045) compared to those withour DM. Patients with TB with DM had a lower cure rate at 6 months (30% vs 57%, p=0.001), a higher death rate at 6 months (14% vs 3%, p=0.016), and a higher proportion of treatment complications (22% vs 10%, p=0.014) than those without DM. Having pre-existing underlying impaired fasting glucose (odds ratio [OR] 8.03, p<0.001) and positive sputum AFB (OR 7.41, p<0.001) were associated with newly diagnosed DM cases among patients with TB. CONCLUSIONS: The prevalence of DM in patients with TB in our study's setting was unexpectedly high. Patients with TB with DM had unfavorable outcomes compared with those without DM. We recommend routinely screening for DM in all patients with newly diagnosed TB.

Hospital-acquired serum phosphate derangements and their associated in-hospital mortality.

BACKGROUND: We aimed to report the incidence of hospital-acquired hypophosphataemia and hyperphosphataemia along with their associated in-hospital mortality. METHODS: We included 15 869 adult patients hospitalised at a tertiary medical referral centre from January 2009 to December 2013, who had normal serum phosphate levels at admission and at least two serum phosphate measurements during their hospitalisation. The normal range of serum phosphate was defined as 2.5-4.2 mg/dL. In-hospital serum phosphate levels were categorised based on the occurrence of hospital-acquired hypophosphataemia and hyperphosphataemia. We analysed the association of hospital-acquired hypophosphataemia and hyperphosphataemia with in-hospital mortality using multivariable logistic regression. RESULTS: Fifty-three per cent (n=8464) of the patients developed new serum phosphate derangements during their hospitalisation. The incidence of hospital-acquired hypophosphataemia and hyperphosphataemia was 35% and 27%, respectively. Hospital-acquired hypophosphataemia and hyperphosphataemia were associated with odds ratio (OR) of 1.56 and 2.60 for in-hospital mortality, respectively (p value<0.001 for both). Compared with patients with persistently normal in-hospital phosphate levels, patients with hospital-acquired hypophosphataemia only (OR 1.64), hospital-acquired hyperphosphataemia only (OR 2.74) and both hospital-acquired hypophosphataemia and hyperphosphataemia (ie, phosphate fluctuations; OR 4.00) were significantly associated with increased in-hospital mortality (all p values <0.001). CONCLUSION: Hospital-acquired serum phosphate derangements affect approximately half of the hospitalised patients and are associated with increased in-hospital mortality rate.

Impact of serum magnesium levels at hospital discharge and one-year mortality.

BACKGROUND: We aimed to determine the optimal range of discharge serum magnesium in hospitalized patients by evaluating one-year mortality risk according to discharge serum magnesium. METHODS: This was a single-center cohort study of hospitalized adult patients who survived until hospital discharge. We classified discharge serum magnesium, defined as the last serum magnesium within 48 hours of hospital discharge, into ≤1.6, 1.7-1.8, 1.9-2.0, 2.1-2.2, and ≥2.3 mg/dL. We assessed one-year mortality risk after hospital discharge based on discharge serum magnesium, using discharge magnesium of 2.1-2.2 mg/dL as the reference group. RESULTS: Of 39,193 eligible patients, 8%, 23%, 34%, 23%, and 12% had a serum magnesium of ≤1.6, 1.7-1.8, 1.9-2.0, 2.1-2.2, and ≥2.3 mg/dL, respectively, at hospital discharge. After the adjustment for several confounders, discharge serum magnesium of ≤1.6, 1.7-1.8, and ≥2.3 mg/dL were associated with higher one-year mortality with hazard ratio of 1.35 (95% CI 1.21-1.50), 1.14 (95% CI 1.06-1.24), and 1.17 (95% CI 1.07-1.28), respectively, compared to discharge serum magnesium of 2.1-2.2 mg/dL. There was no significant difference in one-year mortality between patients with discharge serum magnesium of 1.9-2.0 and 2.1-2.2 mg/dL. CONCLUSION: The optimal range of serum magnesium at discharge was 1.9-2.2 mg/dL. Both hypomagnesemia and hypermagnesemia at discharge were associated with higher one-year mortality.

The Prognostic Importance of Serum Sodium for Mortality among Critically Ill Patients Requiring Continuous Renal Replacement Therapy.

BACKGROUND: Serum sodium derangement is common in critically ill patients requiring continuous renal replacement therapy (CRRT). We aimed to assess the association between serum sodium before and during CRRT with mortality. METHODS: This is a historical cohort study of 1,520 critically ill patients receiving CRRT from December 2006 through November 2015 in a tertiary hospital in the United States. Using logistic regression analysis, we used serum sodium before CRRT, mean serum sodium, and serum sodium changes during CRRT to predict 90-day mortality after CRRT initiation. RESULTS: Compared with the normal serum sodium levels, the odds ratio (OR) of 90-day mortality in patients with serum sodium before CRRT of 143-147 and ≥148 mmol/L were 1.45 (95% CI 1.03-2.05) and 2.24 (95% CI 1.33-3.87), respectively. There was no significant increase in 90-day mortality in serum sodium of ≤137 mmol/L. During CRRT, the mean serum sodium levels of ≤137 (OR 1.41; 95% CI 1.01-1.98) and ≥143 mmol/L (OR 1.52; 95% CI 1.14-2.03) were associated with higher 90-day mortality. The greater serum sodium changes during CRRT were associated with higher 90-mortality (OR 1.35; 95% CI 1.21-1.51 per 5-mmol/L increase). CONCLUSION: Before CRRT initiation, hypernatremia and during CRRT, hypo- and hypernatremia were associated with increased mortality.