Impact of Dexamethasone on the Pathogen Profile of Critically Ill COVID-19 Patients.

BACKGROUND: Even though several therapeutic options are available, COVID-19 is still lacking a specific treatment regimen. One potential option is dexamethasone, which has been established since the early beginnings of the pandemic. The aim of this study was to determine its effects on the microbiological findings in critically ill COVID-19 patients. METHODS: A multi-center, retrospective study was conducted, in which all the adult patients who had a laboratory-confirmed (PCR) SARS-CoV-2 infection and were treated on intensive care units in one of twenty hospitals of the German Helios network between February 2020-March 2021 were included. Two cohorts were formed: patients who received dexamethasone and those who did not, followed by two subgroups according to the application of oxygen: invasive vs. non-invasive. RESULTS: The study population consisted of 1.776 patients, 1070 of whom received dexamethasone, and 517 (48.3%) patients with dexamethasone were mechanically ventilated, compared to 350 (49.6%) without dexamethasone. Ventilated patients with dexamethasone were more likely to have any pathogen detection than those without (p < 0.026; OR = 1.41; 95% CI 1.04-1.91). A significantly higher risk for the respiratory detection of Klebsiella spp. (p = 0.016; OR = 1.68 95% CI 1.10-2.57) and for Enterobacterales (p = 0.008; OR = 1.57; 95% CI 1.12-2.19) was found for the dexamethasone cohort. Invasive ventilation was an independent risk factor for in-hospital mortality (p < 0.01; OR = 6.39; 95% CI 4.71-8.66). This risk increased significantly in patients aged 80 years or older by 3.3-fold (p < 0.01; OR = 3.3; 95% CI 2.02-5.37) when receiving dexamethasone. CONCLUSION: Our results show that the decision to treat COVID-19 patients with dexamethasone should be a matter of careful consideration as it involves risks and bacterial shifts.

[Prevalence of sleep apnea in patients with first diagnosis of hypertension]. / Prävalenz der Schlafapnoe bei Patienten mit der Erstdiagnose eines Bluthochdrucks.

BACKGROUND AND OBJECTIVES: The risk of obstructive sleep apnea (OSA) is significantly increased in patients with hypertension. In addition, OSA appears to be an independent cardiovascular risk factor. So far, sleep apnea screening is only recommended for patients with refractory hypertension and history of OSA. Therefore, OSA often remains undiagnosed in hypertensive patients. The underlying prevalence data are mainly from outpatient hypertension clinics. Data on the prevalence of OSA in patients with hypertension in primary care are not yet available. Due to the cardiovascular risk, some experts recommend screening for OSA when high blood pressure is diagnosed. The study presented here describes for the first time the prevalence of OSA in GP patients immediately after the initial diagnosis of hypertension. METHOD: 6 family practices participated in the study between December 2012 and April 2014. Cardiorespiratory polygraphy was performed on all patients diagnosed with hypertension during this period using a 24-hour blood pressure monitor (ABPM). A sleep physician evaluated the polygraphy data online. RESULTS: 50 patients were recruited, 6 patients did not meet the inclusion criteria. Thus, the data of 44 patients (19 women) were analyzed. An obstructive sleep apnea was diagnosed in 34% (n = 15) of the patients. 16% (n = 7) had a mild OSA, 16% (n = 7) a moderate OSA and 2% (n = 1) a severe OSA. CONCLUSIONS: In a relevant proportion of patients with newly diagnosed hypertension, an undiagnosed OSA was found. In order to estimate the possible effects of sleep apnea screening on hypertension patients, representative studies in the primary medical field are required.

High prevalence of obstructive sleep apnea in patients with resistant paroxysmal atrial fibrillation after pulmonary vein isolation.

OBJECTIVES: To address the question whether obstructive sleep apnea (OSA) is associated with the recurrence of paroxysmal atrial fibrillation (AF) in patients treated with ≥2 pulmonary vein isolation procedures. PATIENTS AND METHODS: In this study, we included adults with therapy-resistant symptomatic paroxysmal AF, defined as AF recurring after ≥2 PV-isolation procedures (n = 23). For comparison, we selected another cohort of patients being successfully treated by one PV isolation without AF recurrence within 6 months (n = 23). PV isolation was performed by radiofrequency with an open irrigated tip catheter. Each of the 46 participants completed an overnight polygraphic study. The two groups were matched for age, gender, and ejection fraction. Patients were late middle-aged (65 ± 7 vs 63 ± 10 years, P = 0.23), white (100%), and overweight (BMI 27.3 ± 3.6 vs. 27.2 ± 4.6 kg/m(2), P = 0.97). RESULTS: The prevalence of sleep apnea, defined as an apnea-hypopnea index (AHI) of >5 per hour of sleep, was 87% in patients with therapy-resistant AF compared to 48% in the control cohort (P = 0.005). In addition, OSA was more severe in the resistant AF group indicated by a significantly higher AHI (27 ± 22 vs 12 ± 16, P = 0.01). CONCLUSION: The extraordinarily high prevalence of sleep apnea in patients with recurrent paroxysmal AF supports its presumable role in the pathogenesis of AF and demands further controlled prospective trials. Moreover, OSA should inherently be considered in patients with therapy-resistant AF.

Severe respiratory failure due to diffuse alveolar hemorrhage: clinical characteristics and outcome of intensive care.

BACKGROUND: The aim of this study was to characterize patients and report outcome of diffuse alveolar hemorrhage (DAH) requiring intensive care unit support. PATIENTS AND METHODS: Thirty-seven patients were identified. Clinical characteristics and outcome were determined by chart review. RESULTS: Eighty-nine percent of patients presented with shortness of breath, 23% with cough, and 3% with hemoptysis. In 9% of patients, a diagnosis of DAH was suspected on admission. Diagnosis was confirmed by finding a progressively hemorrhagic bronchoalveolar lavage fluid in 89% and by a positive iron stain in 11% of patients. Vasculitis was causative in 19%, drug toxicity in 11%, thrombocytopenia in 27%, stem-cell transplantation in 5%, sepsis-associated lung injury in 22%, and unknown mechanisms in 16%. Thirty-two patients were mechanically ventilated, 4 received noninvasive ventilation, and 1 received supplemental oxygen therapy. Overall, 18 (49%) of 37 patients survived the intensive care unit stay. Survival was markedly different between patients with an immunologic/unknown etiology (82%) and patients with thrombocytopenia and/or sepsis (22%). DISCUSSION: Diffuse alveolar hemorrhage should be considered in all patients with persistent pulmonary infiltrates. Both bronchoalveolar lavage fluid and iron stain are mandatory diagnostic means. Patients with an immunologic/idiopathic pathogenetic mechanism have a relatively good prognosis, whereas the outcome in individuals with DAH secondary to cancer therapy or sepsis is poor.

Cardiac resynchronization therapy and atrial overdrive pacing for the treatment of central sleep apnoea.

AIMS: The combined therapeutic impact of atrial overdrive pacing (AOP) and cardiac resynchronization therapy (CRT) on central sleep apnoea (CSA) in chronic heart failure (CHF) so far has not been investigated. We aimed to evaluate the effect of CRT alone and CRT + AOP on CSA in CHF patients and to compare the influence of CRT on CHF between CSA positive and CSA negative patients. METHODS AND RESULTS: Thirty patients with CRT indication underwent full night polysomnography, echocardiography, exercise testing, and neurohumoral evaluation before and 3 months after CRT implantation. In CSA positive patients (60%), two additional sleep studies were conducted after 3 months of CRT, with CRT alone or CRT + AOP, in random order. Cardiac resynchronization therapy resulted in significant improvements of NYHA class, left ventricular ejection fraction, N-terminal pro-brain natriuretic peptide, VO(2)max, and quality of life irrespective of the presence of CSA. Cardiac resynchronization therapy also reduced the central apnoea-hypopnoea index (AHI) (33.6 +/- 14.3 vs. 23.8 +/- 16.9 h(-1); P < 0.01) and central apnoea index (17.3 +/- 14.1 vs. 10.9 +/- 13.9 h(-1); P < 0.01) without altering sleep stages. Cardiac resynchronization therapy with atrial overdrive pacing resulted in a small but significant additional decrease of the central AHI (23.8 +/- 16.9 vs. 21.5 +/- 16.9 h(-1); P < 0.01). CONCLUSION: In this study, CRT significantly improved CSA without altering sleep stages. Cardiac resynchronization therapy with atrial overdrive pacing resulted in a significant but minor additional improvement of CSA. Positive effects of CRT were irrespective of the presence of CSA.

Creatine phosphokinase elevation in obstructive sleep apnea syndrome: an unknown association?

STUDY OBJECTIVES: To evaluate the impact of obstructive sleep apnea syndrome (OSAS) on serum creatine phosphokinase (CK) levels. DESIGN: Single-center prospective cross-sectional study. SETTING: Academic sleep disorder center. PATIENTS: Two hundred one consecutive patients (mean [+/- SD] age, 54.9 +/- 11.0 years; 155 men and 46 women; mean body mass index, 31.3 +/- 6.9 kg/m(2)) with suspected sleep-disordered breathing. MEASUREMENTS AND RESULTS: OSAS was confirmed in182 patients (apnea-hypopnea index [AHI], > 5 events per hour) and was ruled out in 19 patients (control subjects) by standard polysomnography. Sixty-six OSAS patients and 1 control patient showed an unexplained CK elevation. The mean baseline CK level was significantly higher in patients with severe OSAS (AHI, > 30 event per hour; n = 89) compared to those with mild-to-moderate OSAS (AHI, 5 to 30 events per hour; n = 93) and control subjects (191.4 +/- 12.9 vs 134.3 +/- 7.5 vs 107.1 +/- 7.9 U/L, respectively; p < 0.01). Receiver operating curve analysis identified an optimal cutoff value of > 148 U/L (r = 0.660) for CK, which yielded a positive predictive value of 99%, a sensitivity of 43%, and a specificity of 95% for the diagnosis of OSAS. The mean nocturnal oxyhemoglobin saturation was the main predictor of CK level (r = 0.47; p < 0.001). Continuous positive airway pressure (CPAP) treatment resulted in a significant decline of CK levels both in patients with mild-to-moderate OSAS (n = 38; 129.7 +/- 13.4 vs 96.7 +/- 7.6 U/L, respectively; p < 0.001) and in patients with severe OSAS (n = 39; 187.7 +/- 18.9 vs 132.2 +/- 12.9 U/L, respectively; p < 0.001). CONCLUSIONS: One third of our study population showed a mild-to-moderate elevation in CK level, which was highly predictive of OSAS. The application of CPAP therapy in OSAS patients resulted in a significant decrease in CK level. We speculate that OSAS may account for a substantial number of cases of unexplained CK elevation (ie, hyperCKemia). Further studies should address the prevalence of OSAS in patients with mild-to-moderate hyperCKemia.

Pseudomembranous and obstructive Aspergillus tracheobronchitis - optimal diagnostic strategy and outcome.

Pseudomembranous and obstructive Aspergillus tracheobronchitis (PMATB/OATB) are still considered to be refractory to therapy and to have a fatal outcome. To evaluate the optimal diagnostic strategy and to describe factors affecting the outcome of PMATB and OATB. Retrospective analysis of four new cases of PMATB and OATB combined with 16 previously reported cases over a 10-year period (1995-2004). Among the four new cases reported and the 16 published cases, four patients survived their infection. The mortality rate was significantly higher in the group of ventilated patients [94% (15 of 16 patients)] than in the group of non-ventilated patients [25% (1 of 4 patients), P < 0.05, Fisher's exact test]. In all 20 patients, diagnosis was established by bronchoscopy. Culture examination of mucous plugs was positive in 8 of 10, culture of the tracheobronchial aspirate was positive in 8 of 12, and bronchoalveolar lavage was diagnostic in 7 of 13 patients. All bronchoscopic techniques were complementary in improving the yield of bronchoscopy. However, microscopy of mucous plugs and/or necrotic material was the best diagnostic modality [positive in 94% (17 of 18 patients)]. Prognosis of PMATB and OATB remains poor. Microscopy of respiratory specimens is the most sensitive tool to confirm the diagnosis. The characteristic appearance of the disease makes it possible to start antifungal therapy immediately.

Differential effects of fexofenadine on arachidonic acid metabolism in cultured human monocytes.

The relief of nasal congestion with the antihistamine fexofenadine in seasonal allergic rhinitis is thought to be due to its additional anti-inflammatory properties. The objective of this study was to evaluate the in vitro effects of fexofenadine on stimulated arachidonic acid metabolism. Human monocytes, isolated from blood and donated by 5 healthy volunteers, were either incubated for 20 h with 10 microg/ml lipopolysaccharide, with and without fexofenadine (10(-8)-10(-3) mol/l, n = 8-19), or were incubated for 20 h, with and without fexofenadine, and then stimulated with 0.5 mg/ml zymosan for 2 h. Leukotriene B4 (LTB4), LTC4, LTD4 and LTE4, prostaglandin E2 (PGE2) and F2alpha (PGF2alpha) production was determined by enzyme immunoassay. Zymosan-stimulated production of LTC4, LTD4 and LTE4 was significantly inhibited by clinically relevant concentrations of fexofenadine HCl: 10(-7) mol/l (22% inhibition vs. control, p = 0.008) and 10(-6) mol/l (24% inhibition vs. control, p = 0.020). Higher concentrations of fexofenadine (10(-4) and 10(-3) mol/l) inhibited LTB(4) generation. Lipopolysaccharide-stimulated production of PGE2 was significantly inhibited by fexofenadine HCl 10(-6) mol/l (26% inhibition, p = 0.035) and 10(-5) mol/l (40% inhibition, p = 0.001). Higher concentrations of fexofenadine HCl (10(-4) and 10(-3) mol/l) significantly inhibited PGF2alpha production by 50% (p = 0.026) and 63% (p = 0.001), respectively. Fexofenadine, at both clinically relevant and higher concentrations, inhibits LTC4, LTD4, LTE4 and PGE2 in cultured human monocytes. These additional anti-inflammatory properties may underlie the relief of nasal congestion observed in clinical studies.

[A case of arteria cerebri aneurysm, sepsis, and miliary lung infiltrates in a 32-year-old woman]. / Arteria-cerebri-Aneurysma, Sepsis und miliare Lungenrundherde bei einer 32-jährigen Patientin.

BACKGROUND: Miliary tuberculosis is a rare manifestation of tuberculosis with a high mortality rate. Diagnosis may easily be missed when severe neurologic symptoms are the first clinical manifestation. A typical case of miliary tuberculosis is reported, with special regard to the problems of diagnostic work-up. The need for an early empirical therapy for suspected military tuberculosis is emphasized in particular. CASE REPORT: A 32-year-old Moroccan woman was admitted to the hospital with aphasia and a hemiparesis due to an intracerebral hemorrhage caused by a ruptured septic A. cerebri media aneurysm. Despite intensive work-up no septic focus could be found. Chest radiograph and computerized tomography (CT) showed miliary consolidations in the lungs. Skin testing (Tuberkulin Behring GT5) and smears for acid-fast bacilli and polymerase chain reaction (PCR) for tuberculosis of bronchoalveolar lavage (BAL) were negative. A four-drug antituberculous regimen (rifampicin [RMP], isoniazid [INH], pyrazinamide [PZA], ethambutol [EMB]) was initiated, and resulted in normalization of temperature, blood pressure, and C-reactive protein. Subsequently, cultures of BAL yielded Mycobacterium tuberculosis. The patient was discharged, a two-drug regimen was conducted (RMP, INH) after 2 months. Follow-up of the patient showed a significant improvement of the miliary lung consolidations after 5 months in CT of the lung. Only minor neurologic symptoms persisted after cessation of the therapy. CONCLUSION: In developed countries, miliary tuberculosis is a very rare cause of septic infiltrative lung disease. However, due to the nonspecific nature of the presentation and despite improved diagnostic techniques, a high clinical suspicion is essential for successful treatment.

[Long-term outcome of intrapleural fibrinolytic therapy via small-bore catheter drainage in the management of complicated parapneumonic effusion and empyema-a case series]. / Langzeitergebnisse der intrapleuralen Fibrinolytikatherapie komplizierter parapneumonischer Pleuraergüsse und Empyeme über kleinlumige Katheter.

BACKGROUND AND PURPOSE: Complicated parapneumonic effusions (PPE) and pleural empyemas (PE) are associated with increased morbidity and mortality. Intrapleural fibrinolytic therapy (IFT) has been established, besides video-assisted thoracoscopy (VATS), in the management of PPE and PE. Combination of IFT and small-bore catheter drainage has previously not been investigated. PATIENTS AND METHODS: 15 patients consecutively referred for PPE and PE were managed with simultaneous IFT via small-bore catheter drainage (9, 12, 14 F). In addition to evaluation of primary outcome, lung function testing and radiologic studies were obtained after 3 months to predict potential pulmonary restrictive impairment and residual pleural thickening. RESULTS: Primary outcome of all 15 patients was positive. Only one patient showed a significant residual pleural thickening. None of the patients showed a restrictive lung function pattern. CONCLUSION: Proven applicability of IFT via small-bore catheter drainage seems to be effective in the face of long-term outcome. Further prospective and multicentric studies should be initiated to investigate the practicability of IFT via small-bore catheter drainage.

Outcome of patients with acute myeloid leukemia and pulmonary infiltrates requiring invasive mechanical ventilation-a retrospective analysis.

PURPOSE: To assess the prognosis of patients with acute myeloid leukemia (AML) and pulmonary infiltrates requiring mechanical ventilation. DESIGN: A retrospective cohort study. SETTING: A medical intensive care unit (ICU) in an academic tertiary care center. PATIENTS AND METHODS: We identified 30 consecutive patients with acute myeloid leukemia and pulmonary infiltrates who received invasive mechanical ventilation and compared clinical and laboratory parameters between ICU survivors and ICU non-survivors using non-parametric statistics. RESULTS: The overall mortality rate was 87% (26/30). The survival was 40 % (4/10) for patients aged 50 years or less while none (0/20) of the patients older than 50 years survived (P <.02). The median time of mechanical ventilation in survivors was 23.5 (3-45) days. No differences between survivors and non-survivors were observed for the APACHE II score, oxygenation quotient, liver function tests, creatinine, blood urea nitrogen, or prognostic parameters of acute myeloid leukemia (presence of blasts on bone marrow aspirate, cytogenetic studies, and intensity of the chemotherapy regimen). CONCLUSIONS: Age seems to be an important prognostic parameter in our cohort of 30 consecutive patients with acute myeloid leukemia and pulmonary infiltrates requiring mechanical ventilation. Prolonged ventilation does not preclude survival.