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Background Thrombolytic therapy is widely accepted for massive pulmonary embolism (PE) due to the high mortality risk associated with standard anticoagulation alone. Its role in submassive PE, however, has remained controversial. We aimed to evaluate whether the selective use of systemic thrombolytic therapy with intravenous tissue plasminogen activator (IV-tPA) improves the survival of patients with submassive PE at increased risk for clinical deterioration. Methods A total of 184 consecutive patients diagnosed with acute PE by chest thoracic angiography (CTA) were included in a retrospective study. Pulmonary artery obstruction and right/left ventricular dysfunction were evaluated by CTA and echocardiography. Medical history and simplified PE Severity Index (sPESI) were assessed at diagnosis. Hemodynamic and respiratory status were recorded at diagnosis, admission to pulmonary unit and prior to thrombolytic therapy. Patient survival was assessed at 30 of 90 days from diagnosis by CTA. Results All low risk patients (36%) per sPESI survived. Among the 117 remaining patients, 31% received IV-tPA. Respiratory failure was associated with decreased age-adjusted survival (P = 0.005). Among patients with respiratory failure selected for IV-tPA, age-adjusted survival was improved significantly compared to others (P = 0.043). Conclusions Thrombolytic therapy for hemodynamically stable PE patients with respiratory failure may improve survival. Trial registration MMC-0216-14

Salisphere-derived adult epithelial cells have been used to improve saliva production of irradiated mouse salivary glands. Importantly, optimization of the cellular composition of salispheres could improve their regenerative capabilities. The Rho Kinase (ROCK) inhibitor, Y27632, has been used to increase the proliferation and reduce apoptosis of progenitor cells grown in vitro. In this study, we investigated whether Y27632 could be used to improve expansion of adult submandibular salivary epithelial progenitor cells or to affect their differentiation potential in different media contexts. Application of Y27632 in medium used previously to grow salispheres promoted expansion of Kit+ and Mist1+ cells, while in simple serum-containing medium Y27632 increased the number of cells that expressed the K5 basal progenitor marker. Salispheres derived from Mist1CreERT2; R26TdTomato mice grown in salisphere media with Y27632 included Mist1-derived cells. When these salispheres were incorporated into 3D organoids, inclusion of Y27632 in the salisphere stage increased the contribution of Mist1-derived cells expressing the proacinar/acinar marker, Aquaporin 5 (AQP5), in response to FGF2-dependent mesenchymal signals. Optimization of the cellular composition of salispheres and organoids can be used to improve the application of adult salivary progenitor cells in regenerative medicine strategies. Keywords: Salivary gland, Salisphere, Organoid, Proacinar differentiation, Y27632

Sjogren's syndrome is associated with chronic cough, but sicca symptoms are missing from cough evaluation guidelines. We evaluated patients with unexplained cough for undiagnosed Sjogren's syndrome. Patients referred to our pulmonary clinic (Sheba Medical Center, 2009 to 2012) with unexplained cough and concomitant dry eyes were selected for evaluation. Unexplained cough was defined as chronic cough of unknown etiology despite algorithm-based evaluation and treatment. Patients were evaluated in a dedicated clinic by a pulmonologist, rheumatologist, and ophthalmologist specializing in autoimmune disease. Patients completed the Leicester Cough Questionnaire, spirometry, antibody testing for anti Ro/La, ophthalmologic examination with visual acuity, eyelid, ocular surface fluorescein staining, tear break-up time and Schirmer's test, full slit lamp, and fundus examinations. Four-year follow-up was conducted by telephone questionnaire. We identified 24 patients among which 22 (21 females) agreed for evaluation. Eight patients (36%), seven initially, and one during follow-up were diagnosed with Sjogren's syndrome (SS) (six secondary and two primary SS). At 4-year follow-up, cough tended to persist and improve in only 37% with SS. These include 2 (Scl and RA) who received rituximab and 1 (stage 1 sarcoidosis) with spontaneous improvement. In contrast, cough improved in most (64%) patients without SS; the majority (eight/nine) report intensified disease-specific treatment (five allergic and three GERD). We describe patients in whom unexplained chronic cough was associated with dry eyes. Focused workup revealed undiagnosed Sjogren's syndrome in 36%. Dry eyes, with or without SS, is under-recognized and should be added to diagnostic algorithms for unexplained cough.

Pulmonary embolism (PE) is the third most frequently occurring cardiovascular disease. However, the clinical presentation in patients with PE is variable.To evaluate the prevalence of radiological findings detected in contrast-enhanced computed tomography angiography (CTA) and their significance in patients with PE; and to assess whether the CTA findings differed in patients receiving tissue plasminogen activator (tPA) therapy from those who did not.We retrospectively reviewed CTA scans of 186 patients diagnosed with acute PE. Incidental findings on CTA scan were assessed, including mediastinal and parenchymal lymph nodes, pleural effusion, space-occupying lesions, consolidations, emphysema, and pericardial effusion.Patients receiving tPA (19.9%) were less likely to have pleural effusion (29.7% vs. 50.3%, P = 0.024). Other CTA findings did not differ between the tPA and non-tPA groups, including lung infiltrates (40.5% vs. 38.9, P = 0.857), space-occupying lesions (5.4% vs. 6.7%, P = 1), pericardial effusion (8.1% vs. 8.7%, P = 1), emphysema (21.6% vs. 17.4%, P = 0.557), lung (18.9% vs. 24.2%, P = 0.498), and mediastinal ( 24.3% vs. 25.5%, P = 0.883) lymph nodes, respectively.The prevalence of pleural effusion (unilateral or bilateral) was higher in patients not treated with tPA. Therefore, in patients with a borderline condition, the presence of pleural effusion could support the decision not to give tPA treatment.

A ground glass opacity (GGO) lung lesion may represent early stage adenocarcinoma, which has an excellent prognosis upon prompt surgical resection. However, GGO lesions have broad differential diagnoses, including both benign and malignant lesions. Our objective was to study telomere length and telomerase activity in patients with suspected lung cancer in which GGO was the predominant radiographic feature. Knowledge of telomere biology may help distinguish malignant from benign radiographic lesions and guide risk assessment of these lesions. Peripheral blood samples were taken from 22 patients with suspected adenocarcinoma with the GGO radiographic presentation. Multidisciplinary discussion confirmed the need for surgery in all cases. We used an age and gender‐matched group without known lung disease as a control. Telomere length and aggregates were assessed by quantitative fluorescence in situ hybridization (QFISH) and quantitative PCR. Cell senescence was evaluated by senescence‐associated heterochromatin foci. Subjects with GGO lesions had a higher percentage of lymphocytes with shorter telomeres (Q‐FISH, P = 0.003). Furthermore, relative telomere length was also reduced among the GGO cases (qPCR, P < 0.05). Increased senescence was observed in the GGO group compared to controls (P < 0.001), with significant correlation between the senescence‐associated heterochromatin foci and aggregate formation (r = −0.7 and r = −0.44 for cases and controls, respectively). In conclusion, patients with resectable early adenocarcinoma demonstrate abnormal telomere length and cell senescence in peripheral blood leukocytes compared to control subjects. Abnormal telomere biology in the peripheral blood may increase suspicion of early adenocarcinoma among patients with GGO lesions.

Yoram Neuman,1,3 Matthew Koslow,2,3 Alona Matveychuk,2,3 Avigdor Bar-Sef,1 Alexander Guber,2,3 David Shitrit2,3 1Division of Cardiology, 2Pulmonary Department, Meir Medical Center, Kfar Saba, Israel; 3Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel Background and objective: Patients with pulmonary hypertension (PH) are considered to be at risk for complications associated with flexible bronchoscopy (FB), but data concerning the degree of PH are often lacking. We investigated whether COPD patients with PH who undergo bronchoscopy are at greater risk for complications. Methods: This prospective study included 207 consecutive COPD patients undergoing FB. All underwent an echo-Doppler to evaluate pulmonary artery pressure on the day of the bronchoscopy procedure. Pulmonologists were blinded to the echocardiogram results. Results: A total of 167 patients (80.7%) had normal pulmonary pressure. The remaining 40patients (19.3%) had PH: 27 (13.0%) mild, eight (3.9%) moderate, and five (2.4%) severe. Noninvasive hemodynamic parameters between groups before and after FB were similar. Two patients with normal pulmonary pressure developed supraventricular tachycardia. None developed hemodynamically significant dysrhythmia. Bleeding episodes between groups in bronchoalveolar lavage (BAL) and transbronchial biopsy (TBB) did not differ. PH patients who underwent BAL and TBB had decreased O2 saturation during the procedure compared with the non-PH group (23.5% vs 6.9%, P=0.033). No deaths were attributable to FB. Conclusion: PH is common among COPD patients undergoing FB. PH patients undergoing BAL and TBB are at higher risk of decreased O2 saturation than those without PH. Further studies should assess the risk among COPD patients with moderate-to-severe PH. Keywords: bronchoscopy, hypoxemia, pulmonary hypertension

The objective of this study was to identify clinical and imaging features that distinguish rheumatoid lung nodules from malignancy. We conducted a retrospective review of 73 rheumatoid patients with histologically-proven rheumatoid and malignant lung nodules encountered at Mayo Clinic, Rochester, MN (2001–2016). Medical records and imaging were reviewed including a retrospective blinded review of CT and PET/CT studies. The study cohort had a mean age of 67 ± 11 years (range 45–86) including 44 (60%) women, 82% with a smoking history, 38% with subcutaneous rheumatoid nodules, and 78% with rheumatoid factor seropositivity. Subjects with rheumatoid lung nodules compared to malignancy were younger (59 ± 12 vs 71 ± 9 years, p

Objective.Interstitial lung diseases (ILD) form a diverse group of parenchymal lung disorders. Currently, a multidisciplinary team (MDT) including pulmonologists, radiologists, and pathologists is the gold standard for ILD diagnosis. Recently, additional subtypes of connective tissue disease (CTD)-ILD with autoimmune features were defined, making the rheumatological assessment increasingly important. We aimed to assess the effect of adding a rheumatologist to the MDT for routine rheumatology assessment.Methods.A prospective study that assessed newly diagnosed ILD patients by 2 parallel blinded arms; all patients were evaluated by both MDT (e.g., history, physical examination, blood tests, pulmonary function tests, and biopsies, if needed) and a rheumatologist (e.g., history, physical examination, blood and serological tests).Results.Sixty patients were assessed with the mean age of 67.3 ± 12 years, 55% male, and 28% smokers. The rheumatological assessment reclassified 21% of the idiopathic pulmonary fibrosis as CTD. Moreover, the number of CTD-ILD with autoimmune features was increased by 77%. These included antineutrophil cytoplasmic antibody–associated vasculitis, antisynthetase syndrome, and IgG4-related ILD. Retrospectively, rheumatological evaluation could have saved 7 bronchoscopies and 1 surgical biopsy.Conclusion.Adding routine rheumatology assessments could significantly increase diagnostic accuracy and reduce invasive procedures.

To present the diagnostic accuracy and safety of a novel technique for CT-guided transthoracic needle aspiration biopsy (TNAB) of lung lesions suspected of malignancy.A novel technique for coaxial CT-guided TNAB is reported in this single-centre, retrospective study. A 22-gauge guide wire is used to accurately locate the lesion prior to biopsy. The technique enables penetration of lung lesions in various locations with less risk of harm to adjacent organs. Malignant and benign diagnoses were confirmed by histology or radiologic resolution.Clinical features of 181 patients included 59% men. Mean lesion size was 24 ± 14.9 mm with a mean depth of 13.6 ± 18.3 mm. Among 160 (88.4%) confirmed malignancies, 151 (94.4%) were diagnosed with TNAB. Among the 13 (7.2%) confirmed benign diagnoses, 11 (84.6%) received a specific, benign diagnosis with TNAB. The overall diagnostic accuracy of CT-TNAB was 93.6% among all confirmed diagnoses (173/181). Complications included 48 (26.5%) with pneumothorax, of which 77.8% resolved spontaneously, 20% by aspiration and 2.2% required chest drain insertion. Intrapulmonary haemorrhage was observed in 3.9% and hemoptysis in 6.0% without clinical significance.The guide wire technique provides a novel method for needle biopsy of lung lesions with improved accuracy and safety.Lung cancer screening has increased the detection of lung lesions. The guide wire technique is a novel method to biopsy lung lesions. The guide wire technique for lung biopsy demonstrates improved accuracy and safety. The chest tube insertion rate is reduced with aspiration during the procedure.

OBJECTIVE: The clinical significance of vertebral osteomyelitis and infectious endocarditis co-infection is unclear. This study investigates the rate, clinical features, and outcome of vertebral osteomyelitis with and without concomitant infectious endocarditis. METHODS: A retrospective study of all cases of osteomyelitis with spinal imaging (n ¼ 176), from January 2007 to April 2013, that were diagnosed as vertebral osteomyelitis. Sixty-two patients with spontaneous vertebral osteomyelitis were identified after excluding postsurgical, decubitus ulcers and spinal metastases. Seventeen (27%) were identified with concomitant infectious endocarditis. RESULTS: All patients presented with back pain and 59% were diagnosed with infectious endocarditis subsequent to vertebral osteomyelitis. Distinguishing features among the co-infection group include the increased use of transesophageal echocardiography (94% vs 58%, P ¼ .004), predisposing cardiac conditions (59% vs 16%, P ¼ .001), and Gram-positive bacteremia, of which Streptococcus sp. and Enterococcus sp. were more common (35% vs 11%, P ¼ .026). Adverse neurologic events were increased significantly in the co-infection group (59% vs 22%, P ¼ .006). On transesophageal echocardiography, 88% of co-infection patients had highly mobile vegetations, 9 of which measured 10 mm or more. The overall mortality was 41% and 29% in the co-infection and lone vertebral osteomyelitis groups, respectively (P ¼ .356). One-year mortality was identical for both groups at 24% (P ¼ .999), and higher than previously reported (11.3% for lone vertebral osteomyelitis). CONCLUSIONS: Patients with vertebral osteomyelitis, in whom infectious endocarditis is not excluded, are at increased risk for adverse neurologic events and mortality. The prompt diagnosis of infectious endocarditis, and associated high-risk features that may benefit from surgical intervention, require early evaluation by transesophageal echocardiography.