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1.
Cancers (Basel) ; 15(13)2023 Jun 29.
Article in English | MEDLINE | ID: mdl-37444527

ABSTRACT

The clinical management of patients with indeterminate pulmonary nodules is associated with unintended harm to patients and better methods are required to more precisely quantify lung cancer risk in this group. Here, we combine multiple noninvasive approaches to more accurately identify lung cancer in indeterminate pulmonary nodules. We analyzed 94 quantitative radiomic imaging features and 41 qualitative semantic imaging variables with molecular biomarkers from blood derived from an antibody-based microarray platform that determines protein, cancer-specific glycan, and autoantibody-antigen complex content with high sensitivity. From these datasets, we created a PSR (plasma, semantic, radiomic) risk prediction model comprising nine blood-based and imaging biomarkers with an area under the receiver operating curve (AUROC) of 0.964 that when tested in a second, independent cohort yielded an AUROC of 0.846. Incorporating known clinical risk factors (age, gender, and smoking pack years) for lung cancer into the PSR model improved the AUROC to 0.897 in the second cohort and was more accurate than a well-characterized clinical risk prediction model (AUROC = 0.802). Our findings support the use of a multi-omics approach to guide the clinical management of indeterminate pulmonary nodules.

2.
Indian J Ophthalmol ; 71(3): 920-926, 2023 03.
Article in English | MEDLINE | ID: mdl-36872710

ABSTRACT

Purpose: This study aimed to assess and compare the changes in peripapillary retinal nerve fiber layer (RNFL) thickness in nondiabetics and diabetics with various stages of diabetic retinopathy (DR). Methods: The study subjects were divided into four groups based on their diabetic status and findings, namely, controls (normal subjects without diabetes [NDM]), diabetics without retinopathy (NDR), nonproliferative DR (NPDR), and proliferative DR (PDR). Peripapillary RNFL thickness was assessed using optical coherence tomography. One-way analysis of variance (ANOVA) with the post-Tukey HSD test was done to compare RNFL thickness in different groups. The Pearson coefficient was used to determine the correlation. Results: There was statistically significant difference in measured average RNFL (F = 14.8000, P < 0.05), superior RNFL (F = 11.7768, P < 0.05), inferior RNFL (F = 12.9639, P < 0.05), nasal RNFL (F = 12.2134, P < 0.05), and temporal RNFL (F = 4.2668, P < 0.05) across the different study groups. Pairwise comparison showed that there was a statistically significant difference in RNFL measured (average and all quadrants) in patients with DR (NPDR and PDR) and the NDM control group (P < 0.05). In diabetics without retinopathy, the RNFL measured was reduced compared to controls, but it was statistically significant only in the superior quadrant (P < 0.05). Average RNFL and RNFL in all quadrants showed a small negative correlation with the severity of DR and it was statistically significant (P < 0.001). Conclusion: In our study, peripapillary RNFL thickness was reduced in diabetic retinopathy compared to normal controls and the thinning increased with the severity of DR. This was evident in the superior quadrant even before the fundus signs of DR set in.


Subject(s)
Diabetes Mellitus , Diabetic Retinopathy , Retinal Diseases , Humans , Tomography, Optical Coherence , Retina , Nerve Fibers
3.
Eur Radiol ; 33(7): 4746-4757, 2023 Jul.
Article in English | MEDLINE | ID: mdl-36786906

ABSTRACT

OBJECTIVES: Interstitial lung disease (ILD) impacts mortality in antisynthetase syndrome (ASyS). Computed tomographic (CT) patterns and evolution in ASyS ILD are not well described. We report longitudinal CT patterns in ASyS-ILD and their impact on survival. METHODS: This is a monocentric retrospective study of 47 patients with ASyS-ILD. Longitudinal CT patterns and fibrosis severity (severity of radiographic features indicating fibrosis) were analyzed by two radiologists in consensus. The association between imaging features and survival was examined using univariate Cox regression analysis. RESULTS: In total, 211 CT scans were analyzed with an average of 4 ± 2 CT scans/patient with a median follow-up of 79 months in 47 patients. Non-fibrotic patterns were present initially in 63.8% (n = 30) of patients, while fibrotic patterns occurred in 36.2% (n = 17). The initial non-fibrotic patterns/abnormalities resolved in 23.3% (n = 7), evolved in 6.7% (n = 2), persisted in 13.3% (n = 4), and progressed in 56.7% (n = 17), while initial fibrotic patterns persisted in 82.4% (n = 14) and progressed in 17.6% (n = 3). Radiographic progression of ILD (progression in CT pattern or increased fibrosis severity) occurred in 53.2% (n = 25) of patients. Advanced age and radiographic progression were associated with decreased survival (all p < 0.05). The presence of ground-glass opacities (GGO) and predominant lower lung distribution of abnormalities on initial CTs were associated with increased survival (all p < 0.05). CONCLUSION: Progression occurred in 56.7% of ASyS-ILD patients presenting with non-fibrotic patterns. Fibrotic patterns tended to persist. Age and radiographic progression were associated with reduced survival while the initial presence of GGO and predominant lower lobe distribution were associated with increased survival. KEY POINTS: • In ASyS-ILD, initial non-fibrotic patterns such as OP, cNSIP, or OP-cNSIP tended to progress to fNSIP. • Fibrotic patterns such as fNSIP or UIP in ASyS-ILD tended to persist without pattern changes. • GGO and lower lung predominance on initial CT were associated with better survival while advanced baseline age and radiographic ILD progression during follow-up were associated with decreased survival.


Subject(s)
Lung Diseases, Interstitial , Humans , Retrospective Studies , Lung Diseases, Interstitial/complications , Lung Diseases, Interstitial/diagnostic imaging , Lung/diagnostic imaging , Fibrosis , Disease Progression
4.
J Curr Ophthalmol ; 35(3): 281-286, 2023.
Article in English | MEDLINE | ID: mdl-38681688

ABSTRACT

Purpose: To study the prevalence of musculoskeletal disorder (MSD) and the associated occupational risk factors among Indian ophthalmologists, including residents and fellows. Methods: A cross-sectional survey was conducted among ophthalmologists in India using a semi-structured questionnaire in a web-based survey. The questionnaire was prepared in English after extensive literature research and consulting with subject experts. It was pretested on ten ophthalmologists and after confirming that there were no ambiguities, the questionnaire was circulated. After providing informed consent online and ensuring the confidentiality of information, respondents could fill out the questionnaire containing questions to assess demographic details, risk factors, and musculoskeletal symptoms. Results: We received 551 valid responses, out of which 74.77% reported musculoskeletal symptoms since starting practice in ophthalmology. We found a statistically significant association of work-related MSD with greater hours of practice, a higher number of hours of surgery, and a larger patient load. The self-reported symptoms were maximum in lower back (56.55%), followed by neck (49.03%), upper back (38.59%), and shoulder (23.79%). As a remedial measure, 58.98% resorted to rest while only 8.98% consulted orthopedist. Only 46% were aware of good ergonomic practices. Surgery (74.5%), indirect ophthalmoscopy (51.69%), and slit-lamp examination (50.73%) were reported as the major culprits. Respondents declared an interference with personal life (39.56%), with work (33.74%) as well as having caused psychological stress (43.2%) due to work-related MSD. Conclusion: A vast majority of our respondents reported work-related MSD. Major risk factors were hours of practice, hours of surgery, higher body mass index, sedentary lifestyle, and higher patient load. The awareness of ergonomic practices was low.

5.
Taiwan J Ophthalmol ; 12(2): 155-163, 2022.
Article in English | MEDLINE | ID: mdl-35813797

ABSTRACT

PURPOSE: The aim of this study was to compare the visual acuity (VA) by smartphone-based applications - EyeChart and the Peek Acuity to the standard Snellen chart to explore the possibility of using them as an alternative in tele-ophthalmology in the current COVID-19 pandemic. MATERIALS AND METHODS: An analytical type of observational study was done on 360 eyes of 184 patients above 18 years of age. Patients with VA <6/60 and gross ocular pathology were excluded from the study. VA measured by these three methods was converted to logMAR scale for ease of statistical analysis. One-way analysis of variance with post Tukey HSD was used to compare the VA measured by these three methods. RESULTS: There was no statistically significant difference between VA measured using the smartphone-based apps (EyeChart and Peek Acuity) and the Snellen chart (F = 2.5411, P = 0.7925) in 360 eyes assessed. VA measured by Peek Acuity (P = 0.5225) was more comparable to Snellen chart than EyeChart (P = 0.4730). Intraclass correlation coefficient (ICC) demonstrated a strong positive correlation for EyeChart (ICC: 0.982, P < 0.001) and Peek Acuity (ICC: 0.980, P < 0.001) with Snellen chart. A Bland-Altman difference plot showed good limits of agreement for both EyeChart and Peek Acuity with Snellen chart. In subgroup analysis, VA measured by Peek Acuity was not statistically different from Snellen in any subgroups, but in EyeChart, it was statistically different in emmetropes. CONCLUSION: VA measured by smartphone apps (EyeChart and Peek Acuity) was comparable with traditional Snellen chart and can be used as an effective, reliable, and feasible alternative to assess VA in tele-ophthalmology.

6.
Oman J Ophthalmol ; 15(3): 284-289, 2022.
Article in English | MEDLINE | ID: mdl-36760942

ABSTRACT

OBJECTIVE: The objective of the study was to assess the perception, knowledge, attitude, and practices of eye donation among fresh medical graduates in India. MATERIALS AND METHODS: Responses to a semi-structured questionnaire were collected from 410 respondents using an online Google Form which were analyzed using IBM SPSS software version 21. RESULTS: First information source about eye donation was textbooks (31%), while ophthalmologists accounted for 10.7%. Forty-two respondents had pledged their eyes, 116 were willing to pledge their eyes. Majority had "adequate" knowledge (74.1%). The knowledge levels were directly related to the practice of motivation for eye donation (P = 0.032). Around 62% had "poor" eye donation practices. Significant relationship between practice and knowledge levels (P = 0.004) was noted. Participants who graduated from institutions with eye banks were more likely to have good practice (P = 0.005). CONCLUSIONS: A curriculum focusing on practical exposure to eye donation and eye banking services would address the current deficits in eye donation. Reinforcing knowledge of eye banking among non-ophthalmologist doctors can enhance the eye donation trend. Timely counseling of patients and bystanders by well-informed sensitized doctors is hence of utmost importance.

7.
Am J Case Rep ; 22: e933458, 2021 Dec 01.
Article in English | MEDLINE | ID: mdl-34848676

ABSTRACT

BACKGROUND The COVID-19 global pandemic is ongoing, and despite vaccination efforts, SARS-CoV-2 continues to circulate worldwide. The spectrum of COVID-19 illness is broad, from asymptomatic infection to respiratory failure and acute respiratory distress syndrome (ARDS), and the long-term sequelae of infection are unclear. COVID-19-related pulmonary fibrosis has been previously described in the setting of critical illness and ARDS but has not been well described in cases requiring minimal supplemental oxygen. CASE REPORT We present the case of a 42-year-old man hospitalized with coronavirus disease 2019 (COVID-19) who initially required minimal supplemental oxygen but weeks later developed progressive pulmonary fibrosis requiring high-flow nasal cannula and ICU admission. Using novel computed tomography (CT) imaging processing techniques, we demonstrate progression from initial ground-glass opacities to pulmonary fibrosis and traction bronchiectasis over several months. Additionally, we describe clinical responsiveness to an extended course of corticosteroids. CONCLUSIONS Although pulmonary fibrosis is a known complication of severe COVID-19-related ARDS requiring mechanical ventilation, our report suggests that patients with milder forms of COVID-19 infection may develop post-acute pulmonary fibrosis.


Subject(s)
COVID-19 , Pulmonary Fibrosis , Respiratory Distress Syndrome , Adult , Humans , Male , Pandemics , Pulmonary Fibrosis/etiology , Respiratory Distress Syndrome/etiology , SARS-CoV-2
8.
Transplant Cell Ther ; 27(8): 684.e1-684.e9, 2021 08.
Article in English | MEDLINE | ID: mdl-33964516

ABSTRACT

Patients with hematologic malignancy or bone marrow failure are typically required to achieve radiographic improvement or stabilization of invasive fungal infection (IFI) before hematopoietic cell transplantation (HCT) owing to a concern for progression before engraftment. Refractory IFI with a mixture of improvement and progression on serial imaging (ie, mixed response) poses a clinical dilemma, because a delay in HCT may allow for a hematologic relapse or other complications. Furthermore, HCT itself may yield the immune reconstitution necessary for clearance of infection. We sought to describe the characteristics and outcomes of patients who underwent HCT with mixed response IFI. We performed a chart review of all patients who underwent HCT between 2014 and 2020 in whom imaging within 6 weeks before HCT indicated a mixed response to treatment of a diagnosed IFI. Fourteen patients had evidence of a mixed response in low-to-moderate burden of diagnosed IFI by imaging before HCT, including 9 with pulmonary aspergillosis, 2 with hepatosplenic candidiasis (1 also with aspergillosis), and 4 with pulmonary nodules of presumed fungal etiology. Five had refractory severe neutropenia at evaluation for HCT (median, 95 days). All 14 patients showed radiographic stability or improvement in imaging following engraftment; no IFI-related surgeries were required, and no IFI-related deaths occurred. For patients without relapse who underwent HCT more than 1 year earlier, 7 of 8 (88%) were alive at 1 year. Our findings suggest that low-to-moderate burden IFI with mixed response is unlikely to progress on appropriate therapy before engraftment during allogeneic HCT.


Subject(s)
Aspergillosis , Hematologic Neoplasms , Hematopoietic Stem Cell Transplantation , Invasive Fungal Infections , Aspergillosis/therapy , Hematopoietic Stem Cell Transplantation/adverse effects , Humans , Invasive Fungal Infections/diagnosis , Neoplasm Recurrence, Local
9.
J Med Virol ; 92(10): 2205-2208, 2020 10.
Article in English | MEDLINE | ID: mdl-32470156

ABSTRACT

Acute respiratory distress syndrome and coagulopathy played an important role in morbidity and mortality of severe COVID-19 patients. A higher frequency of pulmonary embolism (PE) than expected in COVID-19 patients was recently reported. The presenting symptoms for PE were untypical including dyspnea, which is one of the major symptoms in severe COVID-19, especially in those patients with acute respiratory distress syndrome (ARDS). We reported two COVID-19 cases with coexisting complications of PE and ARDS, aiming to consolidate the emerging knowledge of this global health emergency and raise the awareness that the hypoxemia or severe dyspnea in COVID-19 may be related to PE and not necessarily always due to the parenchymal disease.


Subject(s)
COVID-19/complications , Pulmonary Embolism/complications , Respiratory Distress Syndrome/complications , SARS-CoV-2/pathogenicity , Acute Disease , Aged , Biomarkers/blood , Blood Platelets/drug effects , Blood Platelets/pathology , Blood Platelets/virology , COVID-19/diagnostic imaging , COVID-19/virology , Ceftazidime/therapeutic use , Dyspnea/physiopathology , Fibrin Fibrinogen Degradation Products/metabolism , Heparin/therapeutic use , Humans , Hypoxia/physiopathology , Lung/blood supply , Lung/drug effects , Lung/pathology , Lung/virology , Male , Methylprednisolone/therapeutic use , Middle Aged , Pulmonary Embolism/diagnostic imaging , Pulmonary Embolism/drug therapy , Pulmonary Embolism/virology , Respiratory Distress Syndrome/diagnostic imaging , Respiratory Distress Syndrome/drug therapy , Respiratory Distress Syndrome/virology , Ribavirin/therapeutic use , Tomography, X-Ray Computed , Treatment Outcome , COVID-19 Drug Treatment
10.
Clin Infect Dis ; 71(11): 2777-2786, 2020 12 31.
Article in English | MEDLINE | ID: mdl-31793991

ABSTRACT

BACKGROUND: Hematopoietic-cell transplant (HCT) recipients are at risk for severe respiratory syncytial virus (RSV) infection. We evaluated the RSV fusion inhibitor presatovir in a randomized, double-blind, Phase II trial in HCT recipients with RSV upper respiratory tract infections. METHODS: Patients were stratified by lymphopenia (<200/µL) and ribavirin use; were randomized, stratified by lymphopenia (<200/µL) and ribavirin use, to receive oral presatovir at 200 mg or a placebo on Days 1, 5, 9, 13, and 17, and were followed through Day 28. The coprimary efficacy endpoints were the time-weighted average change in the nasal RSV viral load between Days 1 and 9 and the proportion of patients developing lower respiratory tract complications (LRTCs) through Day 28. RESULTS: From 23 January 2015 to 16 June 2017, 189 patients were randomly assigned to treatment (96 to presatovir and 93 to the placebo). Presatovir treatment, compared with the placebo treatment, did not significantly affect (prespecified α = 0.01) a time-weighted average decline in the RSV viral load from Day 1 to 9 (treatment difference, -0.33 log10 copies/mL; 95% confidence interval [CI] -.64 to -.02 log10 copies/mL; P = .040) or the progression to LRTC (11.2% vs 19.5%, respectively; odds ratio, 0.50; 95% CI, .22-1.18; P = .11). In a post hoc analysis among patients with lymphopenia, presatovir decreased LRTC development by Day 28 (2/15 [13.3%] vs 9/14 [64.3%], respectively; P = .008), compared with the placebo. Adverse events were similar for patients receiving presatovir and the placebo. CONCLUSIONS: Presatovir had a favorable safety profile in adult HCT recipients with RSV but did not achieve the coprimary endpoints. Exploratory analyses suggest an antiviral effect among patients with lymphopenia. CLINICAL TRIALS REGISTRATION: NCT02254408; EUDRA-CT#2014-002474-36.


Subject(s)
Hematopoietic Stem Cell Transplantation , Respiratory Syncytial Virus Infections , Respiratory Tract Infections , Adult , Antiviral Agents/therapeutic use , Double-Blind Method , Hematopoietic Stem Cell Transplantation/adverse effects , Humans , Respiratory Syncytial Virus Infections/drug therapy , Respiratory Tract Infections/drug therapy , Transplant Recipients
11.
Eur Radiol ; 29(11): 6100-6108, 2019 Nov.
Article in English | MEDLINE | ID: mdl-31115618

ABSTRACT

PURPOSE: To compare the ability of radiological semantic and quantitative texture features in lung cancer diagnosis of pulmonary nodules. MATERIALS AND METHODS: A total of N = 121 subjects with confirmed non-small-cell lung cancer were matched with 117 controls based on age and gender. Radiological semantic and quantitative texture features were extracted from CT images with or without contrast enhancement. Three different models were compared using LASSO logistic regression: "CS" using clinical and semantic variables, "T" using texture features, and "CST" using clinical, semantic, and texture variables. For each model, we performed 100 trials of fivefold cross-validation and the average receiver operating curve was accessed. The AUC of the cross-validation study (AUCCV) was calculated together with its 95% confidence interval. RESULTS: The AUCCV (and 95% confidence interval) for models T, CS, and CST was 0.85 (0.71-0.96), 0.88 (0.77-0.96), and 0.88 (0.77-0.97), respectively. After separating the data into two groups with or without contrast enhancement, the AUC (without cross-validation) of the model T was 0.86 both for images with and without contrast enhancement, suggesting that contrast enhancement did not impact the utility of texture analysis. CONCLUSIONS: The models with semantic and texture features provided cross-validated AUCs of 0.85-0.88 for classification of benign versus cancerous nodules, showing potential in aiding the management of patients. KEY POINTS: • Pretest probability of cancer can aid and direct the physician in the diagnosis and management of pulmonary nodules in a cost-effective way. • Semantic features (qualitative features reported by radiologists to characterize lung lesions) and radiomic (e.g., texture) features can be extracted from CT images. • Input of these variables into a model can generate a pretest likelihood of cancer to aid clinical decision and management of pulmonary nodules.


Subject(s)
Algorithms , Carcinoma, Non-Small-Cell Lung/diagnosis , Lung Neoplasms/diagnosis , Lung/diagnostic imaging , Multiple Pulmonary Nodules/diagnosis , Semantics , Tomography, X-Ray Computed/methods , Case-Control Studies , Female , Humans , Male , Middle Aged , Predictive Value of Tests
12.
J Am Coll Radiol ; 16(4 Pt A): 446-450, 2019 Apr.
Article in English | MEDLINE | ID: mdl-30777648

ABSTRACT

Lung cancer screening with low-dose chest CT has been demonstrated to reduce lung cancer mortality among a subset of high-risk current and former smokers. Despite randomized trial evidence and widespread guideline recommendations, uptake of lung cancer screening among currently eligible individuals remains poor. Recent studies estimate that less than 5% of all eligible individuals have undergone screening. Moreover, inappropriate screening of ineligible individuals seems to be common, and among those who have been screened, follow-up may also be poor. In this review, the authors examine recent studies demonstrating the current state of suboptimal implementation of lung cancer screening. The authors also introduce both patient- and provider-facing evidence-based interventions that may improve implementation of screening. These include tailored navigation interventions to overcome patient barriers throughout the screening care continuum and interventions to improve the identification of eligible individuals for providers. Further evidence on best practices around the implementation of lung cancer screening is essential to ensure that recent evidence can be translated into practice to improve the early detection of lung cancer for high-risk individuals.


Subject(s)
Lung Neoplasms/diagnostic imaging , Mass Screening/statistics & numerical data , Patient Acceptance of Health Care , Tomography, X-Ray Computed , Early Detection of Cancer , Humans
13.
J Comput Assist Tomogr ; 43(1): 109-114, 2019.
Article in English | MEDLINE | ID: mdl-30119061

ABSTRACT

PURPOSE: The aim of the study was to assess the ability of chest digital tomosynthesis (DTS) for detection of interstitial lung disease (ILD) compared with conventional chest radiography. MATERIALS AND METHODS: We retrospectively reviewed 78 patients (60 males, 18 females, mean age = 53.05 years, range, 19-83 years) who underwent chest DTS for a 5-year interval (January 1, 2009-December 31, 2014). Of the 78 patients, 33 (42.3%) carried a diagnosis of ILD and 45 (57.7%) were not ILD. All computed tomography reports and medical records were reviewed. The conventional chest radiography and DTS were separately reviewed by 2 radiologists for the presence of ILD and the confidence in diagnosis. RESULTS: The diagnostic accuracy of DTS for the detection of ILD was better than conventional chest radiography (P < 0.05). Digital tomosynthesis had a sensitivity of 83.3% and negative predictive value of 89.0% that were statistically significantly better than conventional chest radiography (43.9% and 70.9%, respectively). Confidence in diagnosing ILD at DTS was higher than conventional chest radiography (P < 0.001) and had higher interobserver agreement than conventional chest radiography (P < 0.01). CONCLUSIONS: Digital tomosynthesis improves diagnostic performance and confidence in diagnosing ILD compared with conventional chest radiography. Digital tomosynthesis can be suggested as the initial diagnostic technique for patients with suspected ILD.


Subject(s)
Lung Diseases, Interstitial/diagnostic imaging , Radiography, Thoracic/methods , Tomography, X-Ray Computed/methods , Adult , Aged , Aged, 80 and over , Female , Humans , Lung/diagnostic imaging , Male , Middle Aged , Reproducibility of Results , Retrospective Studies , Sensitivity and Specificity , Young Adult
14.
Am J Respir Crit Care Med ; 199(10): 1257-1266, 2019 05 15.
Article in English | MEDLINE | ID: mdl-30422669

ABSTRACT

Rationale: Screening for non-small cell lung cancer is associated with earlier diagnosis and reduced mortality but also increased harm caused by invasive follow-up of benign pulmonary nodules. Lung tumorigenesis activates the immune system, components of which could serve as tumor-specific biomarkers. Objectives: To profile tumor-derived autoantibodies as peripheral biomarkers of malignant pulmonary nodules. Methods: High-density protein arrays were used to define the specificity of autoantibodies isolated from B cells of 10 resected lung tumors. These tumor-derived autoantibodies were also examined as free or complexed to antigen in the plasma of the same 10 patients and matched benign nodule control subjects. Promising autoantibodies were further analyzed in an independent cohort of 250 nodule-positive patients. Measurements and Main Results: Thirteen tumor B-cell-derived autoantibodies isolated ex vivo showed greater than or equal to 50% sensitivity and greater than or equal to 70% specificity for lung cancer. In plasma, 11 of 13 autoantibodies were present both complexed to and free from antigen. In the larger validation cohort, 5 of 13 tumor-derived autoantibodies remained significantly elevated in cancers. A combination of four of these autoantibodies could detect malignant nodules with an area under the curve of 0.74 and had an area under the curve of 0.78 in a subcohort of indeterminate (8-20 mm in the longest diameter) pulmonary nodules. Conclusions: Our novel pipeline identifies tumor-derived autoantibodies that could effectively serve as blood biomarkers for malignant pulmonary nodule diagnosis. This approach has future implications for both a cost-effective and noninvasive approach to determine nodule malignancy for widespread low-dose computed tomography screening.


Subject(s)
Autoantibodies/immunology , Carcinoma, Non-Small-Cell Lung/diagnosis , Carcinoma, Non-Small-Cell Lung/immunology , Early Detection of Cancer/methods , Lung Neoplasms/diagnosis , Lung Neoplasms/immunology , Multiple Pulmonary Nodules/immunology , Aged , Biomarkers, Tumor/immunology , Carcinoma, Non-Small-Cell Lung/physiopathology , Diagnosis, Differential , Female , Humans , Lung Neoplasms/physiopathology , Male , Middle Aged , Sensitivity and Specificity , Tomography, X-Ray Computed
15.
Am J Respir Crit Care Med ; 198(5): e44-e68, 2018 09 01.
Article in English | MEDLINE | ID: mdl-30168753

ABSTRACT

BACKGROUND: This document provides clinical recommendations for the diagnosis of idiopathic pulmonary fibrosis (IPF). It represents a collaborative effort between the American Thoracic Society, European Respiratory Society, Japanese Respiratory Society, and Latin American Thoracic Society. METHODS: The evidence syntheses were discussed and recommendations formulated by a multidisciplinary committee of IPF experts. The evidence was appraised and recommendations were formulated, written, and graded using the Grading of Recommendations, Assessment, Development, and Evaluation approach. RESULTS: The guideline panel updated the diagnostic criteria for IPF. Previously defined patterns of usual interstitial pneumonia (UIP) were refined to patterns of UIP, probable UIP, indeterminate, and alternate diagnosis. For patients with newly detected interstitial lung disease (ILD) who have a high-resolution computed tomography scan pattern of probable UIP, indeterminate, or an alternative diagnosis, conditional recommendations were made for performing BAL and surgical lung biopsy; because of lack of evidence, no recommendation was made for or against performing transbronchial lung biopsy or lung cryobiopsy. In contrast, for patients with newly detected ILD who have a high-resolution computed tomography scan pattern of UIP, strong recommendations were made against performing surgical lung biopsy, transbronchial lung biopsy, and lung cryobiopsy, and a conditional recommendation was made against performing BAL. Additional recommendations included a conditional recommendation for multidisciplinary discussion and a strong recommendation against measurement of serum biomarkers for the sole purpose of distinguishing IPF from other ILDs. CONCLUSIONS: The guideline panel provided recommendations related to the diagnosis of IPF.


Subject(s)
Idiopathic Pulmonary Fibrosis/diagnosis , Idiopathic Pulmonary Fibrosis/pathology , Biopsy , Europe , Humans , Idiopathic Pulmonary Fibrosis/diagnostic imaging , Japan , Latin America , Lung/diagnostic imaging , Lung/pathology , Societies, Medical , Tomography, X-Ray Computed/methods , United States
16.
Am J Respir Crit Care Med ; 197(3): 325-336, 2018 02 01.
Article in English | MEDLINE | ID: mdl-28934595

ABSTRACT

RATIONALE: Chronic obstructive pulmonary disease (COPD) and non-small cell lung cancer (NSCLC) are interrelated diseases with substantial mortality, and the pathogenesis of both involves aberrant immune functioning. OBJECTIVES: To profile immune cell composition and function in patients with NSCLC and describe the effects of COPD on lung and tumor microenvironments. METHODS: We profiled resected lung and tumor tissue using flow cytometry and T-cell receptor sequencing in patients with and without COPD from a prospective cohort of patients undergoing resection of NSCLC. A murine cigarette smoke exposure model was used to evaluate the effect on pulmonary immune populations. A separate retrospective cohort of patients who received immune checkpoint inhibitors (ICIs) was analyzed, and their survival was quantified. MEASUREMENTS AND MAIN RESULTS: We observed an increased number of IFN-γ-producing CD8+ and CD4+ (T-helper cell type 1 [Th1]) lymphocytes in the lungs of patients with COPD. In both humans and mice, increased Th17 content was seen with smoke exposure, but was not associated with the development or severity of COPD. COPD-affected lung tissue displayed increased Th1 differentiation that was recapitulated in the matching tumor sample. PD-1 (programmed cell death protein 1) expression was increased in tumors of patients with COPD, and the presence of COPD was associated with progression-free survival in patients treated with ICIs. CONCLUSIONS: In patients with COPD, Th1 cell populations were expanded in both lung and tumor microenvironments, and the presence of COPD was associated with longer progression-free intervals in patients treated with ICIs. This has implications for understanding the immune mediators of COPD and developing novel therapies for NSCLC.


Subject(s)
CD8-Positive T-Lymphocytes/immunology , Carcinoma, Non-Small-Cell Lung/immunology , Lung Neoplasms/immunology , Pulmonary Disease, Chronic Obstructive/immunology , Tumor Microenvironment/immunology , Aged , Carcinoma, Non-Small-Cell Lung/physiopathology , Carcinoma, Non-Small-Cell Lung/surgery , Cohort Studies , Female , Flow Cytometry , Humans , Immunosuppressive Agents/therapeutic use , Lung Neoplasms/physiopathology , Lung Neoplasms/surgery , Male , Middle Aged , Pneumonectomy/methods , Prospective Studies , Pulmonary Disease, Chronic Obstructive/drug therapy , Pulmonary Disease, Chronic Obstructive/physiopathology , Sensitivity and Specificity , Signal Transduction/immunology , T-Lymphocytes, Helper-Inducer/drug effects , T-Lymphocytes, Helper-Inducer/immunology
17.
Clin Respir J ; 12(2): 459-466, 2018 Feb.
Article in English | MEDLINE | ID: mdl-27460837

ABSTRACT

INTRODUCTION: Mycobacterium abscessus infection in cystic fibrosis (CF) patients can lead to poor outcomes. Early diagnosis is important, but there are no studies outlining specific imaging features of M. abscessus in CF. OBJECTIVES: To describe the computed tomography (CT) findings of early M. abscessus infection in our CF population. METHODS: Thirteen CF patients with sputum cultures positive for M. abscessus from 2006 to 2013 were identified at our institution. Clinical characteristics including culture dates and lung function were reviewed. Positive cultures were classified as "disease" versus "colonization" based on published criteria. Chest CT scans were reviewed at times closest to initial infection, and features including bronchiectasis, mucous plugging, consolidation, ground glass opacities, nodules, and cavitation were evaluated. Brody scores were calculated to evaluate extent of CF lung disease. RESULTS: All patients had bronchiectasis and mucous plugging, with 10 of 13 (76.9%) in an upper lobe distribution. Consolidation was seen in 12 of 13 (92.3%) patients, 8 (61.5%) patients had nodules, and 5 (38.5%) with cavitation. The average Brody score was 59.5, which was no different than previously described CF cohorts without M. abscessus. There were no significant differences between subjects with disease versus colonization. CONCLUSION: The most common CT features of early M. abscessus in our CF population include bronchiectasis, mucus plugging, and consolidation, but the findings did not reveal a unique radiologic signature. CT at this initial time point may not distinguish early M. abscessus infection from background lung disease or mycobacterial colonization in CF patients.


Subject(s)
Cystic Fibrosis/microbiology , Lung/microbiology , Mycobacterium Infections, Nontuberculous/microbiology , Mycobacterium abscessus/isolation & purification , Adolescent , Adult , Bronchiectasis/complications , Bronchiectasis/diagnostic imaging , Cystic Fibrosis/diagnostic imaging , Cystic Fibrosis/epidemiology , Cystic Fibrosis/physiopathology , Female , Forced Expiratory Volume , Genotype , Humans , Lung/diagnostic imaging , Lung/pathology , Male , Mycobacterium Infections, Nontuberculous/diagnostic imaging , Mycobacterium Infections, Nontuberculous/epidemiology , Retrospective Studies , Sputum/microbiology , Tomography, X-Ray Computed/methods , Young Adult
18.
Vet Parasitol Reg Stud Reports ; 12: 61-68, 2018 05.
Article in English | MEDLINE | ID: mdl-31014811

ABSTRACT

Toxoplasmosis, caused by Toxoplasma gondii, is an important food borne zoonosis worldwide. Although goat meat constitutes an important dietary protein source, improperly cooked meat is a potential source of infection to humans. Data on prevalence of toxoplasma in goat is scanty from India. Serological detection is the practical option for prevalence studies on T. gondii, as no biological stage of the parasite is present in the clinical materials from the intermediate hosts. The present study was undertaken in the Jharkhand state of India which is largely inhabited by economically weaker aborigine population, who depend largely on animal husbandry for livelihood. A total of 445 serum samples were collected for testing, which represented goats under intensive and free range system of rearing. T. gondii specific IgG antibodies were detected in 42.47% (n = 189) samples by rSAG1 based indirect ELISA. The seroprevalence data were analyzed in respect of age, sex, breed of the goats and altitude of the study area as well as rearing conditions of the animals to establish correlation, if any. Though age and sex of the animals had a direct correlation with infection, the same could not be established with the other factors. The sensitivity and specificity of the diagnostic ELISA were compared with IFAT, as well as with a commercially available ELISA kit. The rSAG1-ELISA had 92.66% sensitivity and 90.67% specificity with a positive predictive value of 86.77% and negative predictive value 94.92% when compared with IFAT, whereas when compared with the commercial ELISA kit, 87.50% sensitivity and 90.91% specificity with a positive predictive value of 91.30% and negative predictive value 86.96% were observed. Inter rater agreement (kappa) was calculated. rSAG1-ELISA showed good agreement with IFAT (kappa = 0.824) and commercially available ELISA Kit (kappa = 0.783). Receiver Operating Characteristics (ROC) curve analysis, revealed a larger area under curve (AUC) of 0.99 (95%CI, 0.97-1.0) when compared with IFAT as gold standard and a highest relative sensitivity 91.30 (95% CI 72-98.3) and specificity 1.0 (95% CI 85.2-100) for the cut off value of 0.6005. The present study revealed high seroprevalence of T. gondii in goats from Jharkhand, which has public health significance.


Subject(s)
Antibodies, Protozoan/blood , Goat Diseases/diagnosis , Goat Diseases/epidemiology , Toxoplasmosis, Animal/epidemiology , Animals , Antigens, Protozoan/immunology , Area Under Curve , Enzyme-Linked Immunosorbent Assay/veterinary , Female , Fluorescent Antibody Technique, Indirect/veterinary , Goat Diseases/parasitology , Goats/parasitology , India/epidemiology , Male , ROC Curve , Reagent Kits, Diagnostic/veterinary , Sensitivity and Specificity , Seroepidemiologic Studies , Toxoplasma/isolation & purification , Toxoplasmosis, Animal/diagnosis
19.
J Cyst Fibros ; 16(6): 735-743, 2017 Nov.
Article in English | MEDLINE | ID: mdl-28757079

ABSTRACT

BACKGROUND: Tracheal diverticula (TD) are rare anomalies that may harbor infected secretions, posing potential risk to patients with lung disease. In an end-stage cystic fibrosis (CF) cohort, we describe the characteristics and associated post-lung transplant (LTx) outcomes of TD. METHODS: Pre-transplant computed tomography (CT)'s were reviewed in CF patients undergoing LTx. TD were characterized radiographically and on autopsy when available. Pre-transplant clinical variables and post-transplant outcomes were compared by TD status. RESULTS: Of 93 patients, 35 (37.6%) had TD. 58% of TD had fat-stranding, and post-mortem TD examinations revealed histology carrying intense submucosal inflammation, and purulent contents that cultured identical species to sputum. There was no difference in post-LTx survival [HR 1.77 (0.82-3.82), p=0.147], bacterial re-colonization, or rejection in patients with TD compared to those without. Patients with TD were more likely to die from infection, but the result was not statistically significant [HR 2.02 (0.62-6.63), p=0.245]. CONCLUSIONS: We found a high prevalence of TD in end-stage CF, where diverticula may represent a large-airway bacterial reservoir. TD were not associated with differences in post-LTx outcomes, but given the infectious concerns further investigation is necessary.


Subject(s)
Cystic Fibrosis , Diverticulum , Tracheal Diseases , Adult , Autopsy/methods , Autopsy/statistics & numerical data , Bacteria/isolation & purification , Cystic Fibrosis/complications , Cystic Fibrosis/mortality , Cystic Fibrosis/physiopathology , Cystic Fibrosis/surgery , Disease Progression , Diverticulum/diagnosis , Diverticulum/epidemiology , Diverticulum/etiology , Diverticulum/microbiology , Female , Humans , Male , Preoperative Care/methods , Prevalence , Sputum/microbiology , Statistics as Topic , Tomography, X-Ray Computed/methods , Tracheal Diseases/diagnosis , Tracheal Diseases/epidemiology , Tracheal Diseases/etiology , Tracheal Diseases/microbiology , United States/epidemiology
20.
J Parasit Dis ; 40(4): 1174-1178, 2016 Dec.
Article in English | MEDLINE | ID: mdl-27876909

ABSTRACT

Coprological examination of 416 bovine faecal samples revealed the presence of parasitic stages of Toxocara vitulorum, strongyles, Strongyloides spp., Fasciola spp., amphistomes, coccidia (Eimeria spp. and Cryptosporidium spp.) and Buxtonella sulcata. About 42 % (n = 302) faecal samples from cattle and 36 % (n = 114) samples from buffaloes were positive for gastrointestinal (GI) parasitic infections. Both cattle (14.57 %) and buffalo (15.79 %) had the highest incidence of Buxtonella sulcata, respectively. The overall incidence of GI parasitic infections in young animals (below 1 year) was higher followed by older (more than 5 years) and adult animals (1-5 years) and the difference was statistically significant (p < 0.05). Non descriptive breeds of bovines showed more parasitic infections than pure breeds, the difference being statistically non-significant (p > 0.05). Season wise GI parasitic infections were recorded to be non-significantly (p > 0.05) higher in monsoon (48.38 %) followed by summer (39 %) and winter (34.61 %) in cattle. There was no significant variation of GI infections in buffaloes in relation to season though highest prevalence was documented in monsoon (44.89 %) followed by winter (35.71 %) and summer (24.32 %). Similarly, sex wise females recorded higher infection rates than males in bovines and the difference being statistically non-significant (p > 0.05).

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