Effect of High-Risk Obstructive Sleep Apnea on Clinical Outcomes in Adults with Coronavirus Disease 2019: A Multicenter, Prospective, Observational Clinical Trial.

Rationale: Coronavirus disease (COVID-19) is an ongoing pandemic, in which obesity, hypertension, and diabetes have been linked to poor outcomes. Obstructive sleep apnea (OSA) is associated with these conditions and may influence the prognosis of adults with COVID-19. Objectives: To determine the effect of OSA on clinical outcomes in patients with COVID-19. Methods: The current prospective observational study was conducted in three hospitals in Istanbul, Turkey from March 10 to June 22, 2020. The participants were categorized as high-risk or low-risk OSA according to the Berlin questionnaire that was administered in the out-patient clinic, in hospital, or shortly after discharge from hospital blinded to the clinical outcomes. A modified high-risk (mHR)-OSA score based on the snoring patterns (intensity and/or frequency), breathing pauses, and morning/daytime sleepiness, without taking obesity and hypertension into account, were used in the regression models. Results: The primary outcome was the clinical improvement defined as a decline of two categories from admission on a 7-category ordinal scale that ranges from 1 (discharged with normal activity) to 7 (death) on Days 7, 14, 21, and 28, respectively. Secondary outcomes included clinical worsening (an increase of 1 category), need for hospitalization, supplemental oxygen, and intensive care. In total, 320 eligible patients (median [interquartile range] age, 53.2 [41.3-63.0] yr; 45.9% female) were enrolled. In all, 121 (37.8%) were categorized as known (n = 3) or high-risk OSA (n = 118). According to the modified scoring, 70 (21.9%) had mHR-OSA. Among 242 patients requiring hospitalization, clinical improvement within 2 weeks occurred in 75.4% of the mHR-OSA group compared with 88.4% of the modified low-risk-OSA group (P = 0.014). In multivariate regression analyses, mHR-OSA (adjusted odds ratio [OR], 0.42; 95% confidence interval [CI], 0.19-0.92) and male sex (OR, 0.39; 95% CI, 0.17-0.86) predicted the delayed clinical improvement. In the entire study population (n = 320), including the nonhospitalized patients, mHR-OSA was associated with clinical worsening (adjusted hazard ratio, 1.55; 95% CI, 1.00-2.39) and with the need for supplemental oxygen (OR, 1.95; 95% CI, 1.06-3.59). Snoring patterns, especially louder snoring, significantly predicted delayed clinical improvement, worsening, need for hospitalization, supplemental oxygen, and intensive care. Conclusions: Adults with mHR-OSA in our COVID-19 cohort had poorer clinical outcomes than those with modified low-risk OSA independent of age, sex, and comorbidities. Clinical trial registered with www.clinicaltrials.gov (NCT04363333).

Appropriate use of tocilizumab in COVID-19 infection.

OBJECTIVE: This study aimed to describe the effectiveness and optimum use of tocilizumab (TCZ) treatment by the support of clinical, laboratory and radiologic observations. METHODS: All patients were followed up in the hospital with daily interleukin-6 (IL-6), C-reactive protein (CRP), ferritin, d-dimer, full blood count, and procalcitonin. Thoracic computed tomography (CT) was performed on admission, when oxygen support was necessary, and seven days after TCZ started. Disease course of the patients was grouped as severe or critical, according to their clinical, laboratory and radiologic evaluations. RESULTS: Forty-three patients were included: 70% were male; the median age was 64 years (minimum-maximum: 27-94); and six (14%) patients died. The median duration of oxygen support before the onset of TCZ was shorter among the severe patient group than the critical patient group (1 vs. 4 days, p < 0.001). Three cases of 21 (14%) who received TCZ in the ward were transferred to ICU, and none of them died. The levels of IL-6, CRP, ferritin, d-dimer, and procalcitonin were significantly lower in the severe cases group than the critical cases group (p = 0.025, p = 0.002, p = 0.008, p = 0.002, and p = 0.001, respectively). Radiological improvement was observed in severe cases on the seventh day of TCZ. Secondary bacterial infection was detected in 41% of critical cases, but none of the severe ones. CONCLUSION: Earlier use of TCZ in COVID-19 infection was beneficial for survival, length of hospitalization and duration of oxygen support. The recommendation for administration of TCZ was based on an increase in requirement of oxygen support, progression in thoracic CT, and elevation of inflammation markers, including IL-6, CRP, ferritin, and d-dimer, and decrease in % lymphocytes.

Bortezomib induced pulmonary toxicity: a case report and review of the literature.

Bortezomib is widely used in the treatment of Multiple Myeloma. While the most common side effects are neurological and gastrointestinal related complications, severe pulmonary problems are rarely described. The present case is a 72-year old male with multiple myeloma, who received Lenalidomide, Bortezomib, and Dexamethasone (RVD) combination regimen. He underwent 30 Gy palliative radiotherapy to the thoracic 5-9 and lumbar L1-3 vertebra due to pain and fracture risk. During the third cycle, he was admitted to hospital with dyspnea and dizziness. The thoracic CT revealed bilateral pleural effusions, a diffuse reticular pattern on the parenchyma, and ground-glass opacities that were compatible with drug-induced lung injury. The microbiological and molecular analysis excluded infectious disease, and lung biopsy confirmed the diagnosis of Bortezomib Lung Injury. The time from the first dose of Bortezomib to the lung injury was 57 days, and it was five days from the last dose of Bortezomib. His symptoms were refractory to IV steroids and supportive care. Our patient was lost despite steroids and intensive care support. Even Bortezomib induced lung injury is a rare adverse effect, based on high mortality rate, we would like to emphasize the clinical importance of this clinical scenario in light of the published literature and our presented case.

The role of atopy in the pathogenesis of bleomycin pulmonary toxicity.

INTRODUCTION: Bleomycin pulmonary toxicity (BPT) is a potentially life-threatening consequence of bleomycin usage in patients. An overproduction of epithelium-derived cytokines, habitually linked to allergic inflammation, has been recently revealed in experimental models of BPT. METHODS: We assessed retrospectively our cohort of patients with Hodgkin Lymphoma treated with bleomycin between 2014 and 2016 for their demographic, clinical features, including BPT development, atopy status and risk factors for BPT. Then they were invited for allergy testing and blood sample collection. The samples were stimulated with different stimuli (Bleomycin, IL-33, TSLP) for 24 h on cell culture. The culture supernatants were analysed for TGF-ß, Galectin3, Arginin, Amphiregulin, Eotaxin, IFNγ, TNFα, IL1ß, 4, 5, 6, 10, 13, 17, MIP-1α, and bleomycin hydrolase (BLH) levels. RESULTS: The cohort consisted of 51 patients showed that atopy was the only significant risk factor for BPT occurrence (OR: 7.2, p = 0.007). Fourteen subjects were included for blood analysis. The analysis of supernatants at the unstimulated condition revealed that BLH and Amphiregulin were significantly lower in patients who had BPT than controls. The BLH cut-off that best identified a history of BPT was 175.31 (Sensitivity: 62.5%, specificity: 100%). Following the stimulation, BLH reduced compared to the unstimulated condition and the difference between groups remained significant (p < 0.05). CONCLUSION: Our study is the first to report that low levels of bleomycin hydrolase in allergic individuals may be predisposing to a possible pathway of fibrosis.

Isolated omental metastasis of renal cell carcinoma after extraperitoneal open partial nephrectomy: A case report.

INTRODUCTION: Metachronous metastatic spread of clinically localized renal cell carcinoma (RCC) affects almost 1/3 of the patients. They occur most frequently in lung, liver, bone and brain. Isolated omental metastasis of RCC has not been reported so far. CASE PRESENTATION: A 62-year-old patient previously diagnosed and treated due to pulmonary sarcoidosis has developed an omental metastatic lesion 13 years after having undergone open extraperitoneal partial nephrectomy for T1 clear-cell RCC. Constitutional symptoms and imaging findings that were attributed to the presence of a sarcomatoid paraneoplastic syndrome triggered by the development this metastatic focus complicated the diagnostic work-up. Biopsy of the [18F]-fluorodeoxyglucose (+) lesions confirmed the diagnosis of metastatic RCC and the patient was managed by the resection of the omental mass via near-total omentectomy followed by targeted therapy with a tyrosine kinase inhibitor. DISCUSSION: Late recurrence of RCC has been reported to occur in 10-20% of the patients within 20 years. Therefore lifelong follow up of RCC has been advocated by some authors. Diffuse peritoneal metastases have been reported in certain RCC subtypes with adverse histopathological features. However, isolated omental metastasis without any sign of peritoneal involvement is an extremely rare condition. CONCLUSION: To our knowledge, this is the first reported case of metachronously developed, isolated omental metastasis of an initially T1 clear-cell RCC. Constitutional symptoms, despite a long interval since nephrectomy, should raise the possibility of a paraneoplastic syndrome being associated with metastatic RCC. Morphological and molecular imaging studies together with histopathological documentation will be diagnostic.

A case of uncontrolled severe asthma patient with coexisting carcinoid tumor presenting as pneumomediastinum.

INTRODUCTION: Patients with inadequately controlled or uncontrolled asthma are at a greater risk of attacks for asthma requiring emergency room visits or hospital admissions. There is a significant correlation between the severity of the disease and the severity of exacerbations. Patients with poorly controlled asthma are at a higher risk for complications. CASE STUDY: We present a 24-year-old aspirin-intolerant, uncontrolled asthma patient with the complication of pneumomediastinum. RESULTS: Severe symptoms persisted after the resolution of the pneumomediastinum despite intense anti-inflammatory and anti-obstructive therapy. A bronchoscopy revealed an endobronchial lesion and she was diagnosed with a carcinoid tumor. CONCLUSION: This case is an example of the importance of re-evaluating asthma patients who do not respond to standard medical treatment. Clinicians should be aware of the complications associated with asthma attacks such as pneumomediastinum and the possibility of a differential diagnosis that worsen asthma symptoms such as a carcinoid tumor.

Use of PET-CT for the assessment of treatment results in patients with sarcoidosis.

BACKGROUND AND AIM: Sarcoidosis is a multisystem disease of unknown origin. Determining the involvement and the response to the treatment is important. The aim of this study was to identify the effects of methylprednisolone and indomethacine on metabolic activity and pulmonary function test parameters in patients with sarcoidosis. MATERIAL AND METHODS: A total of 24 pulmonary sarcoidosis patients were enrolled in the study. All the patients underwent spirometry and [(18)F]fluorodeoxyglucose positron emission tomography-computed tomography (FDG PET-CT) scan before treatment and were divided into two groups according to the necessity of corticosteroid treatment or not. Patients who did not have corticosteroid indication were treated with indomethacine. Symptomatic patients and patients who did not respond to indomethacine treatment received methylprednisolone. Patients were followed up on a monthly basis to determine the response. FDG uptakes as the disease activity were re-evaluated before ending the treatment at the sixth month. RESULTS: Mean age of patients (16 male, 8 female) was 39.79 (9.3) years. Besides mediastinum and pulmonary parenchyma, extrapulmonary sites were also involved in patients with pulmonary sarcoidosis (distant lymph nodes (upper abdominal, supraclavicular, inguinal, and axillary), liver, and spleen). Although maximum standard uptake values of methylprednisolone group regressed significantly (p < 0.001) after treatment, indomethacine group did not have significant regression (p = 0.345). Despite metabolic regressions, spirometry values of patients did not significantly increase (p > 0.005). CONCLUSION: FDG PET-CT may be useful for determining activity and the efficacy of treatments. Methylprednisolone is effective in reducing metabolic activity but does not lead to improvement in functional parameters.

Clinical presentations and diagnostic work-up in sarcoidosis: a series of Turkish cases (clinics and diagnosis of sarcoidosis).

Sarcoidosis is an idiopathic granulomatous disease. It usually affects the lung. The diagnosis may be problematic since the known causes of granulomatous inflammation must be excluded. This multicenter study aimed to evaluate the clinical presentations and diagnostic approaches of sarcoidosis. The study protocol was sent via internet, and the participants were asked to send the information (clinical, radiological and diagnostic) on newly diagnosed sarcoidosis cases. 293 patients were enrolled within two years. Pulmonary symptoms were found in 73.3% of the patients, and cough was the most common one (53.2%), followed by dyspnea (40.3%). Constitutional symptoms were occured in half of the patients. The most common one was fatigue (38.6%). The most common physical sign was eritema nodosum (17.1%). The most common chest radiograhical sign was bilateral hilar lymphadenomegaly (78.8%). Staging according to chest X-ray has revealed that most of the patients were in Stage I and Stage II (51.9% and 31.7%, respectively). Sarcoidosis was confirmed histopathologically in 265 (90.4%) patients. Although one-third of the bronchoscopy was revealed normal, mucosal hyperemi (19.8%) and external compression of the bronchial wall (16.8%) were common abnormal findings. The 100% success rate was obtained in mediastinoscopy among the frequently used sampling methods. Transbronchial biopsy was the most frequently used method with 48.8% success rate. Considering sarcoidosis with its most common and also rare findings in the differential diagnosis, organizing the related procedures according to the possibly effected areas, and the expertise of the team would favour multimodality diagnosis.

Extrapulmonary involvement in patients with sarcoidosis in Turkey.

BACKGROUND AND OBJECTIVE: Extrapulmonary sarcoidosis is common, and is almost always associated with concomitant thoracic involvement. Extrapulmonary manifestations vary on the basis of gender, age at presentation and ethnicity. The aim of this study was to investigate extrapulmonary involvement in patients with sarcoidosis in Turkey. METHODS: This study was conducted by Turkish Thoracic Society Clinical Problems Study Group. New cases of sarcoidosis between 1 June 2004 and 31 May 2006 were recorded on electronic case record forms sent to all potential investigators and information about extrapulmonary involvement was collected. RESULTS: One hundred and nineteen of 293 patients (83 female, 36 male, mean age = 45 ± 12 years) had extrapulmonary involvement in this study (40.6%). The median time to diagnosis was 6 months and this was longer than patients with just thoracic sarcoidosis (P = 0.001). Extrapulmonary symptoms were present in 181 (61.8%) patients, and skin lesions, arthralgia and back pain were the commonest (33.4%, 20.8% and 16.4%, respectively). Incidence of organ involvement was independent of age with the exception of ocular involvement, which was higher in those under the age of 40 years (P = 0.007). CONCLUSIONS: Skin and peripheral lymph node involvement were the most common sites of extrapulmonary involvement and ocular involvement was more common in those under the age of 40 years in patients with sarcoidosis in a Turkish population.

[Position of occupational diseases in medical education in Turkey]. / Türkiye'de tip egitiminde is sagligi konusunun agirligi.

Currently, economical and socio-political changes seem to influence the point of view on occupational health all over the world. Duration of the occupational health education in medical schools decreases day by day and treatment based medical practice seems to be much more popular than preventive medicine activities. The aim of our study is to determine the quality and level of the occupational health education both during the education period and post post-graduation period of medical schools in Turkey. Two questionnaires on the occupational health education were sent to the medical schools of state universities. 65% of the medical schools answered the questionnaires. The average education time of the topic was 6.7 hours during pre-graduate period. Education was usually given by a faculty staff in respiratory medicine (73%) and in public health departments (52%). It was found that, only in six of 19 universities, the faculty staff members had a specific education on occupational health. In the post-graduate period, 15 respiratory medicine unite (62%) gives education on occupational health. As a conclusion, we can say that, there isn't a standardized and structured education program on occupational health/occupational diseases during the medical education during both the education period and post-graduation period of medical schools in Turkey. The duration and the quality of the present education programs seem to be insufficient.

Comparison of three clinical scoring methods in patients with pulmonary thromboembolism.

The clinical diagnosis is not reliable in pulmonary thromboembolism (PTE) because the symptoms are mostly nonspecific. Different clinical prediction rules for PTE have been described recently. These rules are used to aid clinicians in assigning a pre-test probability to patients with clinical signs and symptoms of disease. The aim of this study was to assess the clinical probability of PTE using three different models (Wells, Wicki and modified Hyers scores) and to find their power to determine PTE probability. Clinical probabilities of patients with PTE were determined with Wells, Wicki and modified Hyers scores. Cramer's, contingency coefficient (CC), Spearman's rho, Kendal's tau-b and kappa tests were used for statistical analysis. The study included 248 patients (119 male, 129 female; mean age= 57 +/- 16.7 years). Although 61.3% of the patients were assigned high clinical probability with modified Hyers score, 56% and 50% of them were assigned moderate clinical probability with Wicki and Wells scores, respectively. The correlations of the clinical probabilities was low according to kappa correlation test and moderate according to the Cramer's, CC, Spearman's rho and Kendal's tau-b tests among these three scores. In conclusion, modified Hyers score showed higher percentage of high probability compared to Wells and Wicki scoring systems and the best correlation was found between the modified Hyers and Wells scores.

Hereditary thrombophilic risk factors and venous thromboembolism in Istanbul, Turkey: the role in different clinical manifestations of venous thromboembolism.

The aim of this study was to investigate the hereditary thrombophilic risk factors in patients with venous thromboembolism (VTE) and whether these risk factors play a different role in patients with isolated pulmonary embolism (PE) as compared with patients with deep vein thrombosis (DVT) and patients with PE + DVT. The protein C (PC), protein S, antithrombin activities, homocysteine levels, and factor V Leiden (FVL) G1691A and prothrombin G20210A mutations were evaluated in 191 patients with VTE and 191 controls. The prevalence of FVL and PC deficiency were higher in patients (P = .003 and P = .02, respectively). There was no significant difference for the other risk factors. The combination of thrombophilic risk factors was significantly higher in patients with DVT + PE as compared with patients with isolated PE or DVT (P = .04). In conclusion, the most important hereditary risk factors for VTE in this study were the FVL mutation and PC deficiency.

Platelet glycoprotein Ia 807C/T and 873G/A polymorphisms in patients with venous thromboembolism.

Two silent polymorphisms (807C/T and 873G/A) within glycoprotein Ia (GPIa) gene have been implicated in increased risk of developing thrombosis and myocardial infarction in affected individuals. The aim of this study was to investigate the GPIa gene polymorphism in patients with venous thromboembolism (VTE). A multiplexed allele specific-polymerase chain reaction (AS-PCR)-based method was used to determine the GPIa 807T/873A allele frequency in 77 patients with VTE and 106 healthy controls. The allelic frequency for 807T/873A was 33% in the patient group and 38% in the control group. The allelic frequency for 807C/873G was 66% in the patient group and 62% in the control group. The genotypic frequencies were 8% for 807TT/873AA, 42% for 807CC/GG, and 50% for 807CT/GA in the patient group. In the control group, the frequencies were 12% for 807TT/873AA, 35% for 807CC/873GG, and 52% for 807CT/873GA. As a result, the glycoprotein Ia 807C/T and 873G/A dimorphisms were not shown as risk factors for VTE.

Increased risk of tuberculosis in health care workers: a retrospective survey at a teaching hospital in Istanbul, Turkey.

BACKGROUND: Tuberculosis (TB) is an established occupational disease affecting health care workers (HCWs). Determining the risk of TB among HCWs is important to enable authorites to take preventative measures in health care facilities and protect HCWs. This study was designed to assess the incidence of TB in a teaching hospital in Istanbul, Turkey. A retrospective study of health records of HCWs in our hospital from 1991 to 2000. RESULTS: The mean workforce of the hospital was 3359 + 33.2 between 1991 and 2000. There were 31 cases (15 male) meeting the diagnostic criteria for TB, comprising eight doctors, one nurse and 22 other health professionals. Mean incidence of TB was 96 per 100,000 for all HCWs (relative risk: 2.71), 79 per 100,000 for doctors (relative risk: 2.2), 14 per 100,000 for nurses and 121 per 100,000 (relative risk: 3.4) for other professionals. The mean incidence of TB in Turkey between 1991 and 2000 was 35.4 per 100,000. Incidence of TB was similar in the Departments of Chest Diseases and Clinical Medicine but there were no TB cases in the Basic Science and Managerial Departments. CONCLUSION: HCWs in Turkey who work in clinics have an increased risk for TB. Post-graduate education and prevention programs reduce the risk of TB. Control programs to prevent nosocomial transmission of TB should be established in hospitals to reduce risk for HCWs.