Role of interferon-gamma release assay for screening and monitoring of latent tuberculosis infection in kidney transplant recipients.

BACKGROUND: The reactivation of tuberculosis (TB) among kidney transplant (KT) recipients in an endemic area is of general concern. However, the epidemiology of latent TB infection (LTBI) status and its dynamic change responses have not been explored. METHODS: Between September 2020 and August 2021, a prospective study was conducted to investigate the status of LTBI in KT recipients who received a 9-month isoniazid universal prophylaxis. This status was measured using the interferon-gamma release assay (IGRA) with T-SPOT.TB before transplant, as well as at one month and nine months post-transplant. RESULTS: Ninety-one KT recipients had a mean (SD) age of 45 (11) years, and 41% were female. Sixty-eight (75%) patients received a deceased donor allograft, and eighty-six (91%) patients received induction immunosuppressive therapy. The IGRA results were positive, borderline, negative, and indeterminate in 14 (15.4%), 6 (6.6%), 64 (70.3%), and 7 (7.8%) patients, respectively. Among 84 evaluable patients, 20 (23.8%) KT recipients were defined as having LTBI. Older age was significantly associated with LTBI (OR 1.06 [95% CI 1.01-1.12], p = 0.03). Among the 77 KT recipients who completed monitoring, 55 had negative IGRA results. Three (5.4%) KT recipients had conversion post-transplant. One of them developed pulmonary TB at 1 week after the transplant. Among the 13 patients with positive results, 8 (61.5%) remained positive, 1 (7.7%) had an indeterminate result at 1-month post-transplant and subsequently tested positive at 9 months post-transplant, and 4 (30.8%) experienced reversion to negative results throughout the study. CONCLUSIONS: In a high TB-endemic area, one-quarter of KT recipients were reported to have LTBI, and the dynamic change of IGRA response in KT recipients is plausible post-transplant.

Optimizing the Yield of Abnormal Preoperative Chest Radiographs in Elective Non-cardiothoracic Surgery: Development of a Risk Prediction Score and External Validation.

BACKGROUND: Guideline recommendations for preoperative chest radiographs vary to the extent that individual patient benefit is unclear. We developed and validated a prediction score for abnormal preoperative chest radiographs in adult patients undergoing elective non-cardiothoracic surgery. METHODS: Our prospective observational study recruited 703 adult patients who underwent elective non-cardiothoracic surgery at Ramathibodi Hospital. We developed a risk prediction score for abnormal preoperative chest radiographs with external validation using data from 411 patients recruited from Thammasat University Hospital. The discriminative performance was assessed by receiver operating curve analysis. In addition, we assessed the contribution of abnormal chest radiographs to perioperative management. RESULTS: Abnormal preoperative chest radiographs were found in 19.5% of the 703 patients. Age, pulmonary disease, cardiac disease, and diabetes were significant factors. The model showed good performance with a C-statistics of 0.739 (95% CI, 0.691-0.786). We classified patients into four groups based on risk scores. The posttest probabilities in the intermediate-, intermediate-high-, and high-risk groups were 33.2%, 59.8%, and 75.7%, respectively. The model fitted well with the external validation data with a C statistic of 0.731 (95% CI, 0.674-0.789). One (0.4%) abnormal chest radiograph from the low-risk group and three (2.4%) abnormal chest radiographs from the intermediate-to-high-risk group had a major impact on perioperative management. CONCLUSIONS: Four predictors including age, pulmonary disease, cardiac disease, and diabetes were associated with abnormal preoperative chest radiographs. Our risk score demonstrated good performance and may help identify patients at higher risk of chest abnormalities.

Gastrointestinal microbiota profile and clinical correlations in advanced EGFR-WT and EGFR-mutant non-small cell lung cancer.

INTRODUCTION: Difference in clinical responses to cancer therapy in each patient is from several factors. Gastrointestinal microbiota is one of the reasons. However, this correlation remains unknown. This study aims to explore correlation between gastrointestinal microbiota profile and clinical outcomes in Thai advanced non-small cell lung cancer (NSCLC) according to epidermal growth factor receptor (EGFR) status. METHODS: We enrolled 13 patients with advanced EGFR-wild-type (WT) NSCLC who received chemotherapy and 15 patients with EGFR-mutant NSCLC who received EGFR tyrosine kinase inhibitors. We collected fecal samples at baseline and first disease evaluation and performed 16S rRNA gene sequencing by NGS to assess microbiota profile. The correlations between gastrointestinal microbiota and clinical variables were studied. RESULTS: The clinical characteristics were balanced between the cohorts, excluding significantly higher albumin levels in the EGFR-mutant group. Albumin was the only significant clinical factor affecting the treatment response in multivariate analysis (ORR 15.6%, P = 0.03). Proteobacteria counts were higher in the EGFR-WT group, whereas Bacteroidetes and Firmicutes counts were higher in the EGFR-mutant group. The alpha diversity of the gastrointestinal microbiome was significantly higher in the EGFR-mutant group (Shannon index: 3.82 vs. 3.25, P = 0.022). Following treatment, Proteobacteria counts were lower and Bacteroidetes and Firmicutes counts were higher in both cohorts; the changes were more prominent in the EGFR-WT cohort. No significant correlation between microbiota profile and treatment response were demonstrated in our study. However, beta diversity was significantly different according to severity of adverse events. Enrichment of Clostridia and Bacteroidia was associated with higher adverse event risk in the EGFR-WT cohort. CONCLUSIONS: Proteobacteria was dominant in Thai lung cancer patients both EGFR-WT and EGFR-mutant, and this phylum maybe associate with lung cancer carcinogenesis. Chemotherapy altered the gastrointestinal microbiota, whereas EGFR-TKIs had less effects. Our findings highlight the potential predictive utility of the gastrointestinal microbiota for lung cancer carcinogenesis. Studies with larger cohorts and comparison with the healthy Thai population are ongoing to validate this pilot study.

Rapidly progressive interstitial pneumonia associated with anti-NXP2 antibody secondary to malignancy.

The diagnosis of a diffuse lung disease is challenging for physicians and it requires a multidisciplinary team approach to solve this problem. Herein, we present a case of common bile duct obstruction from pancreatic ductal adenocarcinoma after biliary stent placement, which developed a rapidly progressive bilateral lung infiltration after oesophagogastroduodenoscopy. After a diagnostic evaluation based on clinical, radiographic, and pathological findings, a diagnosis of rapidly progressive interstitial pneumonia associated with anti-nuclear matrix protein (NXP) 2 antibody secondary to malignancy was made. In patients with interstitial lung disease with unclear aetiologies, autoantibodies, including antinuclear antibody and myositis-specific antibodies should be evaluated, even if there are no clinical signs of autoimmune disease. Although this is the first case report of an acute interstitial pneumonitis-associated anti-NXP2 antibody, physicians should recognise this condition as it can rapidly cause acute fulminant respiratory failure.

Myeloperoxidase-antineutrophil cytoplasmic antibody-associated diffuse alveolar hemorrhage caused by denosumab.

Denosumab is a bone anti-resorptive drug, commonly used for treating osteoporosis. Pulmonary involvement has rarely been reported as a possible serious adverse effect of this medication. Herein, we report the case of a 67-year-old woman who presented with non-massive hemoptysis, anemia, and extensive pulmonary opacities on a chest radiograph for 3 days after receiving denosumab. The patient was diagnosed with myeloperoxidase-antineutrophil cytoplasmic antibody-associated pulmonary hemorrhage secondary from denosumab. She was treated with high doses of intravenous methylprednisolone and cyclophosphamide combined with plasmapheresis. Subsequently, her clinical and radiological findings improved without residual abnormalities after treatment.

A Prospective Study of Plasma and Bronchoalveolar Lavage Fluid CMV DNA Load Quantification for the Diagnosis and Outcome of CMV Pneumonitis in Immunocompromised Hosts.

BACKGROUND: Molecular testing has been utilized for cytomegalovirus (CMV) pneumonitis (CMVP) diagnosis, although its validity and optimal cut-off values remain limited. METHODS: A prospective study of CMVP diagnosis among immunocompromised patients was conducted by measuring quantitative CMV DNA polymerase chain reaction in plasma and bronchoalveolar lavage fluid (BALF). RESULTS: Forty-five adult immunocompromised patients were investigated. Thirty-two patients (71%) received immunosuppressive therapy. Eleven patients (24%) were confirmed to have CMVP. Of those, three and eight patients were classified as proven and probable CMVP, respectively. Median (IQR) plasma CMV DNA loads in CMVP and non-CMVP were 41,939 (4,424-122,608) and 0 (0-44) IU/mL, respectively (p<0.001). Median (IQR) BALF CMV DNA loads in CMVP and non-CMVP were 379,652 (163,800-1,254,000) and 0 (0-1,348) IU/mL, respectively (p<0.001). A significant correlation was observed between plasma and BALF CMV DNA loads (r=0.887, p<0.001). Plasma CMV DNA load of 831 IU/mL was established as a cut-off value for diagnosing CMVP (AUC 0.9987, sensitivity 100%, specificity 94.1%, positive predictive value 84.5%, negative predictive value 100%). CONCLUSIONS: A strongly positive correlation was observed between CMV DNA loads measured in plasma and BALF. CMV DNA load quantification could potentially assist in diagnosing CMVP in immunocompromised patients, although bronchoscopy remains encouraged for a definitive diagnosis.

Crus Atrophy: Accuracy of Computed Tomography in Diagnosis of Diaphragmatic Paralysis.

PURPOSE: The aim of this study was to measure the association between crus atrophy as depicted by computed tomography (CT) and fluoroscopic diagnosis of hemidiaphragmatic paralysis in patients with suspected diaphragmatic dysfunction. MATERIALS AND METHODS: A retrospective review of patient data was approved by our institutional review board and was HIPPA-compliant. We reviewed 90 patients who had undergone diaphragmatic fluoroscopy; 72 had CT scans available for measurement of crus thickness at the levels of the celiac and superior mesenteric arteries and the L1 vertebral body. Receiver operating characteristic analysis was used to determine the threshold of crus thinning that best distinguished a paralyzed hemidiaphragm from a nonparalyzed one. RESULTS: Hemidiaphragmatic paralysis caused significant crus thinning at the celiac artery level (mean±SD, 1.7±0.6 vs. 3.6±1.3 mm, P=0.017, on the right; 1.1±0.4 vs. 3.0±1.4 mm, P=0.001, on the left) and the L1 vertebral level (mean±SD, 1.5±0.7 vs. 4.4±1.6 mm, P=0.018, on the right; 1.5±0.6 vs. 3.6+1.7 mm, P=0.017, on the left). On axial CT, thinning to ≤2.5 mm at the celiac artery level identified paralysis of the hemidiaphragm with a sensitivity of 100% and a specificity of 86% on the right and with a sensitivity of 100% and a specificity of 64% on the left. On coronal CT, thinning to ≤2.5 mm at the L1 vertebral level identified paralysis of the hemidiaphragm with a sensitivity of 100% and a specificity of 88% on the right and with a sensitivity of 100% and a specificity of 77% on the left. CONCLUSIONS: Atrophy of the crus assessed by CT is a good discriminator of paralyzed versus nonparalyzed hemidiaphragm in patients with suspected diaphragmatic dysfunction.

Visibility and variability of pleural fissures on normal digital chest radiographs of 1,000 healthy adults.

PURPOSE: To investigate the visibility and variability of pleural fissures on digital chest radiographs. METHODS: Posteroanterior digital chest radiographs of 566 males and 434 females were retrospectively reviewed for the frequencies and/or appearances of various pleural fissures. RESULTS: The right only, left only and bilateral minor fissures were visible in 722 (72.2 %), 1 (0.1 %) and 7 (0.7 %) subjects, respectively. The right minor fissures were visible as more than one line in 219 (30.0 %) subjects, i.e., 2, 3 and 4 lines in 214 (29.3 %), 4 (0.5 %) and 1 (0.1 %), respectively. The 955 visible right minor fissures exhibited variable length (<1/3 of right hemithorax, 17.8 %; 1/3-2/3, 60.1 %; >2/3, 22.1 %), alignment (medial higher 40.9 %; lateral higher 54.2 %; horizontal 4.8 %) and contour (convex upward 68.6 %; convex downward 2.7 %; flat 24.9 %; sigmoid 3.8 %). Superolateral major fissures were visualized in 14.8 % (right only 3.0 %; left only 9.0 %; bilateral 2.8 %), superomedial major fissures in 0.3 % (right 0.1 %; left 0.2 %), vertical fissures in 0.5 % (right 0.2 %; left 0.3 %), inferior accessory fissures in 5.4 % (right 4.8 %; left 0.6 %), right superior accessory fissures in 1.2 % and azygos fissures in 0.2 %. CONCLUSION: The right minor fissure was most frequently visible and exhibited variable appearances. Other pleural fissures were occasionally seen.