Revisiting the Epworth sleepiness scale : Is excessive daytime sleepiness still a valid screening tool for obstructive sleep apnea in a population at risk?

OBJECTIVE: Obstructive sleep apnea (OSA) is a common medical problem with numerous comorbidities and high costs. Since the introduction of the Epworth sleepiness scale (ESS), excessive daytime sleepiness (EDS) has been considered the most common and prominent symptom of OSA. Aim of this study was to re-evaluate the ESS for detection of OSA in a population at risk compared to the gold standard overnight polysomnography (PSG). METHODS: A total of 266 patients (mean age 57.9 ± 11.6 years; 189 men and 77 women), referred to our sleep laboratory for probable OSA, were given ESS followed by an overnight PSG. The ESS values were compared to PSG apnea hypopnea index (AHI) with sensitivity (SE), specificity (SP), positive predictive value (PPV), negative predictive value (NPV) and diagnostic accuracy (DA) calculated for ESS. The positive cut-off value for ESS was ≥ 10 and for AHI ≥ 5. RESULTS: Only 92 (34.6%) subjects had a positive ESS. An OSA was diagnosed by PSG in 213 (80.1%) subjects: 46 having mild, 37 moderate and 130 severe apnea. Most subjects with positive ESS (88.0%) were found to have OSA but most subjects with a negative ESS (75.9%) were also positive for OSA (42% with AHI ≥ 30). The area under the receiver operating characteristic (ROC) curve for ESS was 0.60 (95% confidence interval, CI 0.54-0.66; p = 0.020) with SE 38.0%, SP 79.3%, PPV 88.0%, NPV 24.1% and DA 46.2%. CONCLUSION: It was found that excessive daytime sleepiness, measured by ESS, is not a valuable screening tool for OSA, especially when the test is negative. Other screening tests that involve additional parameters, beside daytime sleepiness alone, should be considered.

Value of Fractional Exhaled Nitric Oxide in Diagnosing Mild Asthma Responsive to Inhaled Corticosteroids.

BACKGROUND: Mild asthma is often characterized by normal spirometric values and a negative bronchodilation test (BDT), which makes accurate diagnosis challenging. The aim of our study was to evaluate the diagnostic accuracy of fractional exhaled nitric oxide (FeNO) in mild asthma. METHODS: In adults with symptoms suggestive of asthma and normal spirometry values, BDT, FeNO, BPT and skin prick testing were performed. Patients with positive BPT started inhaled corticosteroid (ICS) therapy. Those with positive response to ICS were considered asthmatics. RESULTS: There were 142 asthmatics and 140 non-asthmatics. No significant difference was found in BDT between the groups, p = 0.233. Median FeNO levels were significantly higher in the asthma group (49.5 ppb) than in the non-asthma group (23 ppb), p < 0.001. BPT was positive in 145 (51.42%) and negative in 137 (48.58%) patients. Positive response to ICS treatment was recorded in 142/145 (97.9%) patients. In diagnosing asthma, FeNO ≥ 25 ppb had a sensitivity of 75.4% and specificity of 47.9%. CONCLUSIONS: FeNO has insufficient sensitivity and specificity in mild asthma and the application of BPT is often necessary to establish an accurate diagnosis.

Autoantibodies in COVID-19, a possible role in the pathogenesis of the disease.

OBJECTIVES: In this study, we investigated whether SARS-CoV-2 stimulates autoantibody production. METHODS: The study included 91 patients hospitalized due to COVID 19, with no previous history of immunological diseases. Immunofluorescence assays were performed to detect antinuclear antibodies (ANAs) and antineutrophil cytoplasmic antibodies (ANCAs), along with tests for specific autoantibodies. RESULTS: The median age (57% male) was 74 years (range 38-95 years). Autoantibodies were positive in 67 (74%), ANA in 65 (71%), and ANCA in 11 (12%) patients. Female gender (p = 0.01), age (p = 0.005), and Charlson comorbidity index (p = 0.004) were significant predictors for the development of ANA/ANCA antibodies (p = 0.004). Nuclear mitotic apparatus (NuMA)-like, positivity was the strongest predictor of acute kidney injury (AKI), together with noninvasive ventilation and eGFR (χ2 = 49.01, P < 0.001). CONCLUSION: Positive autoantibodies in a large proportion of patients suggest a role of autoimmunity in the pathophysiology of acute COVID-19 disease. NuMA was the strongest predictor of AKI.

Causative agents of bloodstream infections in two Croatian hospitals and their resistance mechanisms.

Blood samples were collected alongside with routine blood cultures (BC) from patients with suspected sepsis, to evaluate the prevalence of different causative agents in patients with bacteraemia. Among 667 blood samples, there were 122 positive BC (18%). Haemoglobin content, platelet number, and systolic blood pressure values were significantly lower in patients with positive BC, whereas serum lactate levels, CRP, creatinine and urea content were significantly higher in patients with positive BC. The rate of multidrug (MDR) or extensively drug resistant (XDR) bacteria was 24% (n = 29): Klebsiella pneumoniae (9), Pseudomonas aeruginosa (9), Acinetobacter baumannii (4), Escherichia coli (1), vancomycin resistant Enterococcus spp (VRE) (3), and methicillin-resistant Staphylococcus aureus MRSA (3). The dominant resistance mechanisms were the production of extended-spectrum ß-lactamases, OXA-48 carbapenemase, and colistin resistance in K. pneumoniae, VIM metallo-ß-lactamases in P. aeruginosa and OXA-23-like oxacillinases in A. baumannii. The study revealed high rate of MDR strains among positive BCs in Zagreb, Croatia.

NONINVASIVE MECHANICAL VENTILATION IN COVID-19 RELATED ACUTE RESPIRATORY FAILURE.

Coronavirus disease 2019 (COVID-19) is presented with a wide range of symptoms, from asymptomatic disease to severe and progressive interstitial pneumonia. As part of interstitial pneumonia, respiratory failure is typically presented as hypoxia and is the most common cause of hospitalization. When oxygen therapy fails, continuous positive airway pressure (CPAP) or noninvasive mechanical ventilation (NIV) are used as respiratory support measures of first choice. Noninvasive respiratory support (NIRS) is applied in order to save intensive care unit resources and to avoid complications related to invasive mechanical ventilation. Emerging evidence has shown that the use of CPAP or NIV in the management of acute hypoxemic respiratory failure in COVID-19 reduces the need for intubation and mortality. The advantage of NIRS is the feasibility of its application on wards. NIV could be administered via a face mask or helmet interface. Helmet adheres better than mask and therefore leakage is reduced, a delivery of positive end-expiratory pressure is more accurate, and the risk of nosocomial transmission of infections is lowered. Patients on NIRS must be carefully monitored so that further respiratory deterioration is not overlooked and additional measures of care including timely intubation and invasive mechanical ventilation could be performed if needed.

Extracorporeal blood purification is associated with improvement in biochemical and clinical variables in the critically-ill COVID-19 patients.

This study tried to investigate the impact of oXiris filter on both clinical and laboratory parameters in critically-ill COVID-19 intensive care unit (ICU) patients receiving extracorporeal blood purification and the clinical setting for the initiation of therapy. A consecutive sample of 15 ICU patients with COVID-19 was treated with oXiris membrane for blood purification or for support of renal function due to acute kidney injury. We have included 19 non treated ICU COVID-19 patients as a control group. Two chest x-rays were analyzed for determining the chest x-ray severity score. We have found a significant decrease of SOFA score, respiratory status improved and the chest x-ray severity score was significantly decreased after 72 h of treatment. IL-6 significantly decreased after 72 h of treatment while other inflammatory markers did not. Respiratory status in the control group worsened as well as increase in SOFA score and chest x-ray severity score. Survived patients have shorter time from the onset of symptoms before starting with extracorporeal blood purification treatment and shorter time on vasoactive therapy and invasive respiratory support than deceased patients. Critically-ill patients with COVID-19 treated with extracorporeal blood purification survived significantly longer than other ICU COVID-19 patients. Treatment with oXiris membrane provides significant reduction of IL-6, leads to improvement in respiratory status, chest x-ray severity score, and reduction of SOFA score severity. Our results can suggest that ICU COVID-19 patients in an early course of a disease could be potentially a target group for earlier initiation of extracorporeal blood purification.

Psychometric Characteristics of the Croatian Version of the Zarit Burden Interview Questionnaire Among Informal Caregivers of Long-Term Mechanically Ventilated Patients.

BACKGROUND: The aim is to evaluate the reliability and validity of the Croatian version of the Zarit Caregiver Burden Interview (ZBI) among the population of informal caregivers of long-term mechanically ventilated patients. SUBJECTS AND METHODS: After a preliminary analysis, 25 participants were selected by using strictly defined criteria and they were asked to complete the Croatian version of the ZBI. The test - retest method was used for reliability assessment while an exploratory strategy of factor analysis was used to identify real-life existent subscales. RESULTS: After reliability and validity assessment, 3 items were removed from the original ZBI so that the Croatian version of the ZBI consists of 19 items. Internal consistency, observed through Cronbach's alpha for extracted subscales and for the whole questionnaire, were identified as high ranged from 0.875 to 0.922. Furthermore, exploratory factor analysis using Guttman-Kaiser criterion identified the 6 subscales for the ZBI. CONCLUSIONS: Due to the fact that approximately 30 % of targeted population was included in the study, the Croatian version of the ZBI can be accepted as a reliable and valid tool for measuring burden among informal caregivers of long-term mechanically ventilated patients. Family caregiver's burden level assessment can be crucial to enhance outcomes associated with future caregiving.

Diagnostic accuracy, sensitivity, and specificity of CT pulmonary artery to aorta diameter ratio in screening for pulmonary hypertension in end-stage COPD patients.

AIM: To determine the diagnostic accuracy of pulmonary artery to aorta ratio in screening for pulmonary hypertension in advanced chronic obstructive pulmonary disease (COPD) patients. METHODS: A prospective, diagnostic study was conducted in University Hospital Center Zagreb between January 2015 and March 2018. The study enrolled 100 patients who consecutively underwent chest computed tomography (CT), echocardiographic exam, and right heart catheterization. Two independent observers measured pulmonary artery and ascending aorta diameters. The correlation between the ratio and mean pulmonary artery pressure, measured invasively, was assessed. Patients with echocardiographic signs of moderate systolic or diastolic left ventricular dysfunction were excluded (n=44). RESULTS: Sixty-six patients (55.5% men), with a median age of 61, were identified. Median forced expiratory volume during the first second (FEV1) was 34±12, FEV1/forced vital capacity <0.70. Patients with and without pulmonary hypertension had pulmonary artery diameter of 36±7 mm and 27±4.6 mm, respectively (P<0.001). Median pulmonary artery/aorta (PA/A) ratios for patients with and without pulmonary hypertension were 1.05 and 0.81, respectively (P<0.001). PA/A ratio above 0.95 was an independent predictor of pulmonary hypertension with a specificity of 100% and a sensitivity of 74.51% (area under the curve=0.882; standard error=0.041; P<0.001). CONCLUSION: PA/A ratio as measured on chest CT images can be used as a screening tool instead of echocardiography.

Weight Gain in Lung Transplantation Patients during the COVID-19 Pandemic in Croatia.

BACKGROUND: To determine the effect of lockdown measures on lung transplant patients during the COVID-19 pandemic. SUBJECTS AND METHODS: We collected data from Croatian lung transplant patients before and after the lockdown and analyzed changes in weight, BMI, lung function and blood lipid status. RESULTS: An average increase of 3.74 kg (+4.92%) body weight during the 4 month lockdown period was observed. Lung function values and blood lipid status remained stable. CONCLUSION: Such weight gain could have detrimental effects on the morbidity and mortality of lung transplant patients. Further follow up is needed to determine the long term impacts of this observation.

Attenuation of ALS progression during pregnancy-lessons to be learned or just a coincidence?

ALS is the most frequent motor neuron disorder in adults with suggested complex relationship regarding gender. Studies investigating ALS and hormones have provided varying results. ALS onset during pregnancy is uncommon and pregnancy after the ALS symptom onset is even rarer. We present three patients with the onset of ALS symptoms before or during pregnancy and propose a putative disease modifying mechanism leading to attenuation of disease progression that we observed during the pregnancies.

Hemothorax as the first manifestation of idiopathic pulmonary arteriovenous malformation.

BACKGROUND: Pulmonary arteriovenous malformations (PAVM) are rare pulmonary vascular anomalies and hemothorax as a presenting feature of PAVM is a very rare occurrence. CASE PRESENTATION: A 45-year old woman presented with chest pain and breathlessness. A chest x-ray showed left-sided pleural effusion. An emergency MSCT scan with contrast showed no signs of pulmonary embolism but instead a probable AV malformation was shown. Diagnostic thoracocentesis revealed hemorrhagic exudate with negative cytology and microbiology findings. Thoracic drainage was performed resulting with complete regression of hemothorax. Three months later, patient was treated with transcatheter embolization of PAVM with good clinical outcome. CONCLUSIONS: We have shown that management of PAVM related hemothorax initially by thoracic drainage followed by later on performed catheter embolization of the PAVM could lead to a successful outcome.

Polymorphism 4G/5G of the plasminogen activator inhibitor 1 gene as a risk factor for the development of allergic rhinitis symptoms in patients with asthma.

Plasminogen activator inhibitor-1 (PAI-1) is a glycoprotein which has a role in tissue remodelling after inflammatory processes. The objective is to investigate the frequency of PAI-1 gene polymorphism (4G/5G) in patients with a lung ventilation dysfunction in asthma and allergic rhinitis. Genomic DNA was isolated and genotypes of polymorphism of PAI-1 4G/5G and ABO were determined using the methods of RT-PCR and PCR-SSP. Study group includes 145 adult patients diagnosed with chronic asthma, with all clinically relevant parameters and the laboratory markers of pO2, IgE and eosinophils in sputum and nasal swab. In the processing of data, appropriate statistical tests (Kolmogorov-Smirnov test, median, interquartile ranges, χ 2 and Mann-Whitney U tests) were used. Patients with symptoms of allergic rhinitis were significantly younger and had an almost four time higher levels of IgE (P = 0.001), higher pO2 (P = 0.002) and PEF (P = 0.036), compared to those who do not have these symptoms. Genotype PAI 4G/4G is significantly more common in patients with allergic rhinitis (28.1% vs. 16.1%; P = 0.017) compared to the genotype 5G/5G. Carriers of the genotype 4G/5G also have a borderline statistical significance. There were no statistically significant difference in the incidence of allergic rhinitis in the carriers of any ABO genotypes. The frequency of PAI genotype 4G/4G is significantly more common in patients with allergic rhinitis. The results suggest that the carriers of at least one 4G allele are at a higher risk for developing symptoms of allergic rhinitis in asthma.

Anemia, hypoalbuminemia, and elevated troponin levels as risk factors for respiratory failure in patients with severe exacerbations of chronic obstructive pulmonary disease requiring invasive mechanical ventilation.

AIM: To determine in-hospital and post-discharge mortality, readmission rates, and predictors of invasive mechanical ventilation (IMV) in patients treated at intensive care unit (ICU) due to acute exacerbations of chronic obstructive pulmonary disease (AECOPD). METHODS: A retrospective observational cohort study included all patients treated at a respiratory ICU for AECOPD during one year. A total of 62 patients (41 men) with mean age 68.4±10.4 years were analyzed for outcomes including in-hospital and post-discharge mortality, readmission rates, and IMV. Patients' demographic, hematologic, biochemical data and arterial blood gas (ABG) values were recorded on admission to hospital. Mean duration of follow-up time was 2.4 years. RESULTS: Of 62 patients, 7 (11.3%) died during incident hospitalization and 21 (33.9%) died during the follow-up. The overall 2.4-year mortality was 45.2%. Twenty nine (46.8%) patients were readmitted due to AECOPD. The average number of readmissions was 1.2. Multivariate analysis showed that blood pH, bicarbonate levels, low albumin, low serum chloride, and low hemoglobin were significant predictors of IMV during incident hospitalization (P<0.001 for the overall model fit). CONCLUSION: High in-hospital and post-discharge mortality and high readmission rates in our patients treated due to AECOPD at ICU indicate that these patients represent a high risk group in need of close monitoring. Our results suggested that anemia, hypoalbuminemia, and elevated troponin levels were risk factors for the need of IMV in severe AECOPD. Identification of such high-risk patients could provide the opportunity for administration of an appropriate and timely treatment.

Erlotinib-induced Rosacea-like Dermatitis.

Skin and skin adnexa toxicities are the most common side effects associated with epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) and occur in most patients receiving this therapy. The majority of these cutaneous side effects are transient, reversible, and dose dependent. Although these symptoms are in general not severe, they significantly affect quality of life and can have a serious effect on treatment compliance as well as the treatment regimen. The most common early symptoms present as papulopustules on an erythematous base, usually localized in seborrheic areas. This clinical presentation is commonly described as "acneiform", although these adverse reactions have clinical presentations, such as rosacea-like and seborrheic-like dermatitis. In this context, we report a case of a 77-year-old man with a medical history of planocellular lung cancer with ipsilateral pulmonary metastasis and mediastinum infiltration who received erlotinib as a third-line therapy, presenting with centrofacial rosaceiform rash as a side effect associated with the use of EGFR-TKIs. The patient had a negative previous history of rosacea. Therefore, symptoms probably occurred as an adverse reaction due to the oncological therapy. Current terminology of early cutaneous adverse reactions caused by EGFR-TKIs refers to "acneiform" or "papulopustular" lesions, excluding less common side effects such as rosacea-like dermatitis so these symptoms might be overlooked and misdiagnosed. Thus, we would like to emphasize the importance of developing a more accurate classification of terms in order to provide early detection of all possible cutaneous side effects, including less common ones, providing specific and timely treatment, and allowing continuation of drug therapy.

Advanced Pyoderma Gangrenosum Previously Treated as Squamous Cell Carcinoma.

Pyoderma gangrenosum is a rare, neutrophilic ulcerative skin disease of unknown etiology often associated with an underlying systemic disease. We present a case of a pyoderma gangrenosum that was initially misdiagnosed and treated as squamous cell carcinoma in another hospital. Multiple surgical treatments triggered postoperative exacerbations and further rapid progression of the lesions. History of pathergy, clinical findings, and histopathological features examined at our Department indicated pyoderma gangrenosum. The diagnosis was confirmed by excluding other diseases that could cause similar-appearing cutaneous lesions. No associated underlying disease was determined. After the diagnosis was confirmed, corticosteroid therapy was initiated until complete remission of ulcerations.

Large hemorrhagic colloid cyst in a 35-year-old male.

Colloid cysts are rare benign tumors of the third ventricle with diverse clinical presentation, which vary from incidentally found cysts to acute death. An uncommon hemorrhage in these cysts is a life threatening complication which can cause obstructive hydrocephalus with acute deterioration of the patient and sudden death. We present a case of 35-year-old man with large hemorrhagic colloid cyst of a third ventricle causing acute obstructive hydrocephalus even though magnetic resonance image with low T2 signal of the cyst suggested its clinically stable nature. Only 3 cases of in vivo diagnosed hemorrhagic colloid cysts have been reported in the literature.

Endovascular treatment of AVM-associated aneurysm of anterior inferior cerebellar artery through persistent primitive hypoglossal artery.

We present a patient with the combination of persistent primitive hypoglossal artery and the origin of left common carotid artery from the brachiocephalic trunk, who had subarachnoid haemorrhage caused by a ruptured aneurysm. The aneurysm was on distal anterior inferior cerebellar artery which was a feeder to cerebellar arterio-venous malformation.