Utility of shaking chills as a diagnostic sign for bacteremia in adults: a systematic review and meta-analysis.

BACKGROUND: Accurate prediction of bacteremia is essential for guiding blood culture collection and optimal antibiotic treatment. Shaking chills, defined as a subjective chill sensation with objective body shivering, have been suggested as a potential predictor of bacteremia; however, conflicting findings exist. To address the evidence gap, we conducted a systematic review and meta-analysis of studies to assess the diagnostic accuracy of shaking chills for predicting bacteremia among adult patients. METHODS: We included studies reporting the diagnostic accuracy of shaking chills or chills for bacteremia. Adult patients with suspected bacteremia who underwent at least one set of blood cultures were included. Our main analysis focused on studies that assessed shaking chills. We searched these studies through CENTRAL, MEDLINE, Embase, the World Health Organization ICTRP Search Portal, and ClinicalTrials.gov. Study selection, data extraction, evaluation for risk of bias, and applicability using the QUADAS-2 tool were conducted by two independent investigators. We estimated a summary receiver operating characteristic curve and a summary point of sensitivity and specificity of the index tests, using a hierarchical model and the bivariate model, respectively. RESULTS: We identified 19 studies with a total of 14,641 patients in which the accuracy of shaking chills was evaluated. The pooled sensitivity and specificity of shaking chills were 0.37 (95% confidence interval [CI], 0.29 to 0.45) and 0.87 (95% CI, 0.83 to 0.90), respectively. Most studies had a low risk of bias in the index test domain and a high risk of bias and a high applicability concern in the patient-selection domain. CONCLUSIONS: Shaking chills are a highly specific but less sensitive predictor of bacteremia. Blood cultures and early initiation of antibiotics should be considered for patients with an episode of shaking chills; however, the absence of shaking chills must not lead to exclusion of bacteremia and early antibiotic treatment.

Predictors of longitudinal changes in body weight, muscle and fat in patients with and ever-smokers at risk of COPD.

BACKGROUND AND OBJECTIVE: Weight and muscle loss are predictors of poor outcomes in chronic obstructive pulmonary disease. However, to our knowledge, no study has investigated the predictors of longitudinal weight loss or its composition from functional and morphological perspectives. METHODS: This longitudinal observational study with a median follow-up period of 5 years (range: 3.0-5.8 years) included patients with COPD and ever-smokers at risk of COPD. Using chest computed tomography (CT) images, airway and emphysematous lesions were assessed as the square root of the wall area of a hypothetical airway with an internal perimeter of 10 mm (√Aaw at Pi10) and the percentage of low attenuation volume (LAV%). Muscle mass was estimated using cross-sectional areas (CSAs) of the pectoralis and erector spinae muscles, and fat mass was estimated using the subcutaneous fat thickness at the level of the 8th rib measured using chest CT images. Statistical analyses were performed using the linear mixed-effects models. RESULTS: In total, 114 patients were enrolled. Their body mass index remained stable during the study period while body weight and muscle CSA decreased over time and the subcutaneous fat thickness increased. Reduced forced expiratory volume in 1 s and peak expiratory flow (PEF) at baseline predicted the future decline in muscle CSA. CONCLUSION: Severe airflow limitation predicted future muscle wasting in patients with COPD and ever-smokers at risk of COPD. Airflow limitation with a PEF slightly below 90% of the predicted value may require intervention to prevent future muscle loss.

Concordance between transbronchial lung cryobiopsy and surgical lung biopsy for interstitial lung disease in the same patients.

BACKGROUND: The diagnostic accuracy and safety of transbronchial lung cryobiopsy (TBLC) via a flexible bronchoscope under sedation compared with that of surgical lung biopsy (SLB) in the same patients is unknown. METHODS: Retrospectively the data of fifty-two patients with interstitial lung diseases (median age: 63.5 years; 21 auto-antibody positive) who underwent TBLC followed by SLB (median time from TBLC to SLB: 57 days) was collected. The samples from TBLC and SLB were randomly labelled to mask the relationship between the two samples. Diagnosis was made independently by pathologists, radiologists, and pulmonary physicians in a stepwise manner, and a final diagnosis was made at multidisciplinary discussion (MDD). In each diagnostic step the specific diagnosis, the diagnostic confidence level, idiopathic pulmonary fibrosis (IPF) diagnostic guideline criteria, and treatment strategy were recorded. RESULTS: Without clinical and radiological information, the agreement between the histological diagnoses by TBLC and SLB was 42.3% (kappa [κ] = 0.23, 95% confidence interval [CI]: 0.08-0.39). However, the agreement between the TBLC-MDD and SLB-MDD diagnoses and IPF/non-IPF diagnosis using the two biopsy methods was 65.4% (κ = 0.57, 95% CI: 0.42-0.73) and 90.4% (47/52), respectively. Out of 38 (73.1%) cases diagnosed with high or definite confidence at TBLC-MDD, 29 had concordant SLB-MDD diagnoses (agreement: 76.3%, κ = 0.71, 95% CI: 0.55-0.87), and the agreement for IPF/non-IPF diagnoses was 97.4% (37/38). By adding the pathological diagnosis, the inter-observer agreement of clinical diagnosis improved from κ = 0.22 to κ = 0.42 for TBLC and from κ = 0.27 to κ = 0.38 for SLB, and the prevalence of high or definite diagnostic confidence improved from 23.0% to 73.0% and from 17.3% to 73.0%, respectively. Of all 383 TBLC performed during the same period, pneumothorax occurred in 5.0% of cases, and no severe bleeding, acute exacerbation of interstitial lung disease, or fatal event was observed. CONCLUSIONS: TBLC via a flexible bronchoscope under deep sedation is safely performed, and the TBLC-MDD diagnosis with a high or definite confidence level is concordant with the SLB-MDD diagnosis in the same patients.

Risk factors for pneumonitis in advanced extrapulmonary cancer patients treated with immune checkpoint inhibitors.

BACKGROUND: Immune-mediated pneumonitis has a high mortality rate; however, information regarding the related risk factors remains limited. This study aimed to analyze risk factors for pneumonitis, including smoking and lung metastasis (LM), in patients with extrapulmonary primary tumors. METHODS: Data of 110 patients treated with immune checkpoint inhibitors (ICIs) (nivolumab/pembrolizumab) for treating extrapulmonary primary tumors at the Shiga University of Medical Science Hospital between January 2015 and December 2019 were retrospectively collected. The association between the onset of pneumonitis and treatment-related factors was analyzed by logistic regression. The severity of pneumonitis was graded according to the Common Terminology Criteria for Adverse Events version 5.0. Risk factors, such as the absence or presence of interstitial lung disease (ILD) and LM, or other clinical factors, including smoking status before ICI administration, were analyzed. RESULTS: Multivariate analyses indicated that the amount of smoking was significantly associated with an increase in the development of all-grade pneumonitis types (odds ratio (OR) = 20.33, 95% confidence interval (CI) = 20.03-20.66; p = 0.029). LM and ILD were significantly related to an increase in the development of symptomatic pneumonitis (≥ Grade 2) (OR = 10.08, 95% CI = 1.69-199.81; p = 0.076, and OR = 6.76, 95% CI = 1.13-40.63; p = 0.037, respectively). CONCLUSIONS: Pre-screening for ILD and LM and recognizing patients' smoking history is important for determining the risk of ICI-induced pneumonitis and allowing safe ICI administration.

Clinical Utility of Surgical Lung Biopsy for Patients with Acute Respiratory Distress Syndrome: A Systematic Review and Meta-Analysis.

BACKGROUND: Surgical lung biopsy (SLB) is performed in patients with acute respiratory distress syndrome (ARDS); however, its clinical utility remains unclear. OBJECTIVES: We categorized the pathological diagnoses and investigated the predictive value for short-term mortality. METHOD: Three electronic databases (MEDLINE, the Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov) were searched for the included studies. The QUADAS-2 was used to evaluate the risk of bias and its applicability. The types and populations of pathological diagnoses were investigated. The pooled sensitivity, positive likelihood ratio (LR+), negative likelihood ratio (LR-), and diagnostic odds ratio (DOR) were estimated at a fixed specificity. Hierarchical summary receiver operating characteristic curves were drawn. RESULTS: A total of 16 studies that enrolled 758 patients were included. The pathological diagnoses were as follows: diffuse alveolar damage (DAD) 29.9%; infection 24.7%; interstitial lung disease 17.2%; malignancy 3.6%; cardiovascular disease 3.6%; drug toxicity 2.3%; connective tissue disease 2.2%; allergic disease 1.1%; and nonspecific diagnosis 15.4%. To predict short-term mortality, 13 studies that enrolled 613 patients used DAD as an index test and recorded a mortality rate of 56.9% (349 of 613 patients). A total of 3 studies that used index tests other than DAD were excluded. The pooled sensitivity, fixed specificity, LR+, LR-, and DOR were 0.46 (95% confidence interval [CI]: 0.29-0.56), 0.69, 1.48 (95% CI: 0.92-1.81), 0.78 (95% CI: 0.63-1.03), and 1.90 (95% CI: 0.89-2.86), respectively. CONCLUSIONS: SLB is unlikely to provide a specific diagnosis and should not be recommended for confirming DAD or predicting ARDS prognosis.

Effectiveness and Safety of Bronchial Thermoplasty in the Treatment of Severe Asthma with Smoking History: A Single-Center Experience.

INTRODUCTION: Bronchial thermoplasty (BT) improves asthma-related quality of life and decreases the number of asthma exacerbations. However, the effectiveness of BT in the treatment of severe asthma with smoking history is unclear because previous studies have excluded patients with smoking history of more than 10 pack-years. OBJECTIVE: The aim of the study was to clarify the effectiveness and safety of BT for severe asthma with smoking history. METHODS: We retrospectively reviewed patients who received BT and compared its effectiveness and safety with and without smoking history. RESULTS: Seven patients were assigned to the smoking group and 9 to the nonsmoking group. Before BT, despite Global Initiative for Asthma step 4 or 5 treatment including oral corticosteroids (OCS) or monoclonal antibody drugs, most patients in both groups had asthma-related symptoms every day (85.7 vs. 77.8%; p = 0.475) and frequent asthma exacerbations. After BT, in the smoking group, 3 patients could discontinue or reduce OCS and all 3 patients treated with monoclonal antibody drugs could discontinue them. In the smoking group, 6 patients (85.7%) experienced a reduction in the rate of symptoms, of which 3 patients (42.9%) had a disappearance of symptoms, similar to the nonsmoking group. BT was effective in 5 patients (83.3%) in the smoking group and 6 patients (75.0%) in the nonsmoking group. There were no severe complications. CONCLUSIONS: BT was found to be effective and safe for treatment of severe asthma with smoking history. Our results suggest that BT may be a therapeutic option for asthma-chronic obstructive pulmonary disease overlap.

Relationship of flow-volume curve pattern on pulmonary function test with clinical and radiological features in idiopathic pulmonary fibrosis.

BACKGROUND: The flow-volume (FV) curve pattern in the pulmonary function test (PFT) for obstructive lung diseases is widely recognized. However, there are few reports on FV curve pattern in idiopathic pulmonary fibrosis (IPF). In this study, we investigated the relationship between FV curve pattern and clinical or radiological features in IPF. METHODS: The FV curves on PFTs and chest high-resolution computed tomography (HRCT) images of 130 patients with IPF were retrospectively evaluated. The FV curves were divided into four groups based on the presence or absence of the convex and concave patterns: convex/concave, non-convex/concave, convex/non-concave, and non-convex/non-concave. Using a computer-aided system, CT honeycombing area (%HA) and subtracted low attenuation area (%sLAA) were quantitatively measured. To assess the distribution of CT findings, the lung area was divided into upper, lower, central, and peripheral areas. The relationships of FV curve patterns with patient characteristics, spirometry results, and quantitative CT findings were evaluated. RESULTS: The patients with convex pattern was identified in 93 (71.5%) and concave pattern in 72 (55.4%). Among the four groups, patients with the convex/non-concave pattern had significantly lower forced vital capacity (FVC) and higher %HA of the upper/peripheral lung area (p = 0.018, and p = 0.005, respectively). The convex/non-concave pattern was a significant predictor of mortality for IPF (hazard ratio, 2.19; p = 0.032). CONCLUSIONS: Patients with convex/non-concave pattern in FV curve have lower FVC and poorer prognosis with distinct distribution of fibrosis. Hence, FV curve pattern might be a useful predictor of mortality in IPF.

Oral Litholysis in Patients with Chronic Calcific Pancreatitis Unresponsive to or Ineligible for Extracorporeal Shock Wave Lithotripsy and Endoscopic Therapy.

BACKGROUND/AIMS: Our study aimed to evaluate the effect of oral litholysis in patients with chronic calcific pancreatitis (CCP) unresponsive to or ineligible for extracorporeal shock wave lithotripsy (ESWL) and endoscopic therapy. METHODS: Trimethadione, an antiepileptic agent, was administered orally at a dose of 0.6-0.9 g/day to 15 patients with this condition. Treatment outcome was evaluated by assessment of dissolution of the pancreatic stones on plain X-ray films and computed tomography scans of the upper abdomen. Plasma glucose, hemoglobin A1c, and body mass index (BMI) were also monitored throughout the therapy. RESULTS: Litholysis was observed in 13 out of 15 patients (86.7%) and was definite in 10 and partial in 3. Six patients had pancreatitis attacks during the therapy; 5 of whom showed definite litholysis and had only 1 mild attack. Of the 11 patients with normal or impaired glucose tolerance at baseline, none developed diabetes mellitus and all showed litholysis. BMI significantly increased in patients whose pancreatic stones dissolved. There was no vital organ impairment by trimethadione. CONCLUSION: Oral litholysis using trimethadione may represent a noninvasive and effective complementary treatment in patients with CCP unresponsive to or ineligible for ESWL and endoscopic therapy.

An unsaturated aliphatic alcohol as a natural ligand for a mouse odorant receptor.

We report the identification of a physiological receptor-volatile pair in the mouse olfactory system. By activity-guided fractionation of exocrine gland extracts and subsequent chemical analysis, (Z)-5-tetradecen-1-ol was identified as a natural ligand for a mouse odorant receptor. (Z)-5-tetradecen-1-ol is excreted into male mouse urine under androgen control and enhances urine attractiveness to female mice. This report is to our knowledge the first to describe natural product-based deorphanization of an odorant receptor.

Association of gut microbiome with COPD in Japanese male residents: the SESSA study.

Background: Altered gut microbiota may contribute to COPD development or progression. Herein, we investigated the association of gut microorganisms with COPD, taking into account the impact of smoking status. Methods: This cross-sectional observational study was a part of the Shiga Epidemiological Study of Subclinical Atherosclerosis, a population-based cohort study of Japanese men aged 46-76 years, conducted from 2010 to 2016. The gut microbiome, determined using 16S rRNA gene sequencing, was compared among 99 never-smokers, 306 non-COPD ever-smokers and 76 patients with COPD while adjusting for age, body mass index, ethanol consumption and treatment for type 2 diabetes mellitus. Results: The abundance of phylum Firmicutes was comparable between patients with COPD and non-COPD ever-smokers but tended to be higher in never-smokers. Similarly, the α- and ß-diversity analysis showed similarity between patients with COPD and non-COPD ever-smokers, which tended to differ from never-smokers. Discriminant analysis identified the genus [Prevotella] to be more prevalent in patients with COPD than in never-smokers or non-COPD ever-smokers. Post hoc analysis confirmed similarity of gut microbiome between COPD Global Initiative for Chronic Obstructive Lung Disease (GOLD) I and non-COPD ever-smokers, which was different from GOLD II. Conclusion: Smoking may alter the overall gut microbial composition, but gut microbial composition itself may not play a role in the development of COPD. Rather, specific gut bacteria, such as [Prevotella], could be a risk factor for the development of COPD; this may be a potential therapeutic target.