Myositis-specific Antibodies Identify A Distinct Interstitial Pneumonia with Autoimmune Features Phenotype.

Interstitial pneumonia with autoimmune features (IPAF) characterises individuals with interstitial lung disease (ILD) and features of connective tissue disease (CTD) who fail to satisfy CTD criteria. Inclusion of myositis-specific antibodies (MSAs) in the IPAF criteria has generated controversy, as these patients also meet proposed criteria for an anti-synthetase syndrome. Whether MSAs and myositis associated antibodies (MAA) identify phenotypically distinct IPAF subgroups remains unclear.A multi-center, retrospective investigation was conducted to assess clinical features and outcomes in patients meeting IPAF criteria stratified by the presence of MSAs and MAAs. IPAF subgroups were compared to cohorts of patients with idiopathic inflammatory myopathy-ILD (IIM-ILD), idiopathic pulmonary fibrosis (IPF) and non-IIM CTD-ILDs. The primary endpoint assessed was three-year transplant-free survival. Two hundred sixty-nine patients met IPAF criteria, including 35 (13%) with MSAs and 65 (24.2%) with MAAs. Survival was highest among patients with IPAF-MSA and closely approximated those with IIM-ILD. Survival did not differ between IPAF-MAA and IPAF without MSA/MAA cohorts. Usual interstitial pneumonia (UIP) morphology was associated with differential outcome risk, with IPAF patients with non-UIP morphology approximating survival observed in non-IIM CTD-ILDs. MSAs, but not MAAs identified a unique IPAF phenotype characterised by clinical features and outcomes similar to IIM-ILD. UIP morphology was a strong predictor of outcome in others meeting IPAF criteria. Because IPAF is a research classification without clear treatment approach, these findings suggest MSAs should be removed from the IPAF criteria and such patients should be managed as an IIM-ILD.

Diagnostic test interpretation and referral delay in patients with interstitial lung disease.

BACKGROUND: Diagnostic delays are common in patients with interstitial lung disease (ILD). A substantial percentage of patients experience a diagnostic delay in the primary care setting, but the factors underpinning this observation remain unclear. In this multi-center investigation, we assessed ILD reporting on diagnostic test interpretation and its association with subsequent pulmonology referral by a primary care physician (PCP). METHODS: A retrospective cohort analysis of patients referred to the ILD programs at UC-Davis and University of Chicago by a PCP within each institution was performed. Computed tomography (CT) of the chest and abdomen and pulmonary function test (PFT) were reviewed to identify the date ILD features were first present and determine the time from diagnostic test to pulmonology referral. The association between ILD reporting on diagnostic test interpretation and pulmonology referral was assessed, as was the association between years of diagnostic delay and changes in fibrotic features on longitudinal chest CT. RESULTS: One hundred and forty-six patients were included in the final analysis. Prior to pulmonology referral, 66% (n = 97) of patients underwent chest CT, 15% (n = 21) underwent PFT and 15% (n = 21) underwent abdominal CT. ILD features were reported on 84, 62 and 33% of chest CT, PFT and abdominal CT interpretations, respectively. ILD reporting was associated with shorter time to pulmonology referral when undergoing chest CT (1.3 vs 15.1 months, respectively; p = 0.02), but not PFT or abdominal CT. ILD reporting was associated with increased likelihood of pulmonology referral within 6 months of diagnostic test when undergoing chest CT (rate ratio 2.17, 95% CI 1.03-4.56; p = 0.04), but not PFT or abdominal CT. Each year of diagnostic delay was associated with a 1.8% increase in percent fibrosis on chest CT. Patients with documented dyspnea had shorter time to chest CT acquisition and pulmonology referral than patients with documented cough and lung crackles. CONCLUSIONS: Determinants of ILD diagnostic delays in the primary care setting include underreporting of ILD features on diagnostic testing and prolonged time to pulmonology referral even when ILD is reported. Interventions to modulate these factors may reduce ILD diagnostic delays in the primary care setting.

Nocardia brain abscess in a patient with diabetes: a case report.

BACKGROUND: Nocardia are aerobic Gram-positive bacilli that can invade multiple organ systems, including the brain and lungs. It is most frequently found in patients who are immunocompromised. Invasive nocardial disease is a potentially life-threatening infection that can pose a diagnostic challenge. CASE PRESENTATION: Our case details a 76-year-old Indian woman with poorly-controlled diabetes mellitus admitted for confusion and falls. Imaging revealed intracranial abscesses and necrotic masses in the mediastinum and lungs. The suspected diagnosis was tuberculosis; however, she underwent extensive workup without a final diagnosis. Ultimately, a craniotomy with partial brain abscess resection was performed. Dura matter samples revealed Nocardia farcinica. CONCLUSIONS: This case illustrates the importance of considering Nocardia in patients with brain abscesses, particularly in those with immunocompromised states and demonstrates the diagnostic challenges that may arise in definitively making this diagnosis. Invasive procedures may be needed for diagnostic confirmation.

Derivation and Validation of a Diagnostic Prediction Tool for Interstitial Lung Disease.

BACKGROUND: Interstitial lung disease (ILD) results in high morbidity and health-care utilization. Diagnostic delays remain common and often occur in nonpulmonology settings. Screening for ILD in these settings has the potential to reduce diagnostic delays and improve patient outcomes. RESEARCH QUESTION: This study sought to determine whether a pulmonary function test (PFT)-derived diagnostic prediction tool (ILD-Screen) could accurately identify incident ILD cases in patients undergoing PFT in nonpulmonology settings. STUDY DESIGN AND METHODS: Clinical and physiologic PFT variables predictive of ILD were identified by using iterative multivariable logistic regression models. ILD status was determined by using a multi-reader approach. An ILD-Screen score was generated by using final regression model coefficients, with a score ≥ 8 considered positive. ILD-Screen test performance was validated in an independent external cohort and applied prospectively to PFTs over 1 year to identify incident ILD cases at our institution. RESULTS: Variables comprising the ILD-Screen were age, height, total lung capacity, FEV1, diffusion capacity, and PFT indication. The ILD-Screen showed consistent test performance across cohorts, with a sensitivity of 0.79 and a specificity of 0.83 when applied prospectively. A positive ILD-Screen strongly predicted ILD (OR, 18.6; 95% CI, 9.4-36.9) and outperformed common ILD clinical features, including cough, dyspnea, lung crackles, and restrictive lung physiology. Prospective ILD-Screen application resulted in a higher proportion of patients undergoing chest CT imaging compared with a historical control cohort (74% vs 56%, respectively; P = .003), with a significantly shorter median time to chest CT imaging (5.6 vs 21.1 months; P < .001). INTERPRETATION: The ILD-Screen showed good test performance in predicting ILD across diverse geographic settings and when applied prospectively. Systematic ILD-Screen application has the potential to reduce diagnostic delays and facilitate earlier intervention in patients with ILD.

Therapeutic hypothermia and mortality in the intensive care unit: systematic review and meta-analysis.

OBJECTIVE: Therapeutic hypothermia (TH) is defined as the designed reduction of the human body's core temperature to 32°C-35°C for a period of 24-48 hours. TH has been studied extensively in many diseases related to critical care illness. This meta-analysis assesses the effect of TH on mortality across different indications in medical, neurological and cardiothoracic care. DATA SOURCES: The online databases Embase, Ovid MEDLINE, TRIP and CINAHL were searched for eligible studies published between 1940 and October 2018. STUDY SELECTION: Randomised clinical trials of induced TH in adults for any indication. DATA EXTRACTION: Information about baseline characteristics of patients, mortality outcomes, cooling strategy and target temperature achieved in hypothermia and normothermia groups was collected. DATA SYNTHESIS: Eighty studies, with a total of 13 418 patients, were included in this meta-analysis: 22 studies for traumatic brain injury, six studies for stroke, five studies for out-of-hospital cardiac arrest (OHCA), 34 studies for intraoperative cardiopulmonary bypass, and 13 studies for other diseases. A total of 6901 patients (51.4%) were randomly allocated to the TH group and 6517 patients (48.6%) were randomised to the normothermia control group. The unadjusted analysis showed no significant difference in mortality across different critical care illnesses. However, after adjusting for population, gender, age and temperature, only the OHCA group showed a small statistically significant difference favouring TH, but this had a questionable clinical significance. CONCLUSIONS: This meta-analysis suggests that after decades of extensive research, TH has yet to show a beneficial effect on mortality across different critical care diseases.