Analyzing Neck Circumference as an Indicator of CPAP Treatment Response in Obstructive Sleep Apnea with Network Medicine.

We explored the relationship between obstructive sleep apnea (OSA) patients' anthropometric measures and the CPAP treatment response. To that end, we processed three non-overlapping cohorts (D1, D2, D3) with 1046 patients from four sleep laboratories in Western Romania, including 145 subjects (D1) with one-night CPAP therapy. Using D1 data, we created a CPAP-response network of patients, and found neck circumference (NC) as the most significant qualitative indicator for apnea-hypopnea index (AHI) improvement. We also investigated a quantitative NC cutoff value for OSA screening on cohorts D2 (OSA-diagnosed) and D3 (control), using the area under the curve. As such, we confirmed the correlation between NC and AHI (ρ=0.35, p<0.001) and showed that 71% of diagnosed male subjects had bigger NC values than subjects with no OSA (area under the curve is 0.71, with 95% CI 0.63-0.79, p<0.001); the optimal NC cutoff is 41 cm, with a sensitivity of 0.8099, a specificity of 0.5185, positive predicted value (PPV) = 0.9588, negative predicted value (NPV) = 0.1647, and positive likelihood ratio (LR+) = 1.68. Our NC =41 cm threshold classified the D1 patients' CPAP responses-measured as the difference in AHI prior to and after the one-night use of CPAP-with a sensitivity of 0.913 and a specificity of 0.859.

Long-Term Effects of Continuous Positive Airway Pressure (CPAP) Therapy on Obesity and Cardiovascular Comorbidities in Patients with Obstructive Sleep Apnea and Resistant Hypertension-An Observational Study.

BACKGROUND: We sought to investigate whether long-term continuous positive airway pressure (CPAP) treatment in patients with obstructive sleep apnea (OSA) and resistant hypertension (RHTN) could attenuate the cardiovascular disease risk by lowering their body-mass index (BMI). METHODS: This was a long-term observational study of RHTN patients diagnosed with OSA. Patients were evaluated with polysomnography initially and after a mean follow-up period of four years. The patients were divided into two groups based on their compliance to CPAP therapy. RESULTS: 33 patients (aged 54.67 ± 7.5, 18 men, 54.5%) were included in the study, of which 12 were compliant to CPAP therapy. A significant reduction in BMI at follow-up was noted in patients compliant to CPAP therapy (1.4 ± 3.5 vs. -1.6 ± 2.5, p = 0.006). We also noted a large effect size reduction in abdominal circumference at follow-up in the CPAP group. At follow-up evaluation, the mean heart rate (b/min) was lower in the CPAP group (58.6 ± 9.5 vs. 67.8 ± 7.8), while arrhythmia prevalence increased between initial (28.6%) and follow-up (42.9%) evaluation with an intermediate effect size in non-compliant patients. CONCLUSIONS: In our cohort of OSA patients with RHTN, long-term adherence to CPAP therapy was associated with weight loss and improvement in cardiac rhythm outcomes.

Particularities of Older Patients with Obstructive Sleep Apnea and Heart Failure with Mid-Range Ejection Fraction.

Background and objectives: Obstructive sleep apnea syndrome (OSAS) and heart failure (HF) are increasing in prevalence with a greater impact on the health system. The aim of this study was to assess the particularities of patients with OSAS and HF, focusing on the new class of HF with mid-range ejection fraction (HFmrEF, EF = 40%-49%), and comparing it with reduced EF (HFrEF, EF < 40%) and preserved EF (HFpEF, EF ≥ 50%). Materials and Methods: A total of 143 patients with OSAS and HF were evaluated in three sleep labs of "Victor Babes" Hospital and Cardiovascular Institute, Timisoara, Western Romania. We collected socio-demographic data, anthropometric sleep-related measurements, symptoms through sleep questionnaires and comorbidity-related data. We performed blood tests, cardio-respiratory polygraphy and echocardiographic measurements. Patients were divided into three groups depending on ejection fraction. Results: Patients with HFmrEF were older (p = 0.0358), with higher values of the highest systolic blood pressure (mmHg) (p = 0.0016), higher serum creatinine (p = 0.0013), a lower glomerular filtration rate (p = 0.0003), higher glycemic levels (p = 0.008) and a larger left atrial diameter (p = 0.0002). Regarding comorbidities, data were presented as percentage, HFrEF vs. HFmrEF vs. HFpEF. Higher prevalence of diabetes mellitus (52.9 vs. 72.7 vs. 40.2, p = 0.006), chronic kidney disease (17.6 vs. 57.6 vs. 21.5, p < 0.001), tricuspid insufficiency (76.5 vs. 84.8 vs.59.1, p = 0.018) and aortic insufficiency (35.3 vs.42.4 vs. 20.4, p = 0.038) were observed in patients with HFmrEF, whereas chronic obstructive pulmonary disease(COPD) (52.9 vs. 24.2 vs.18.3, p = 0.009), coronary artery disease(CAD) (82.4 vs. 6.7 vs. 49.5, p = 0.026), myocardial infarction (35.3 vs. 24.2 vs. 5.4, p < 0.001) and impaired parietal heart kinetics (70.6 vs. 68.8 vs. 15.2, p < 0.001) were more prevalent in patients with HFrEF. Conclusions: Patients with OSAS and HF with mid-range EF may represent a new group with increased risk of developing life-long chronic kidney disease, diabetes mellitus, tricuspid and aortic insufficiency. COPD, myocardial infarction, impaired parietal kinetics and CAD are most prevalent comorbidities in HFrEF patients but they are closer in prevalence to HFmrEF than HFpEF.

SAS score: Targeting high-specificity for efficient population-wide monitoring of obstructive sleep apnea.

PROPOSAL: This paper investigates a novel screening tool for Obstructive Sleep Apnea Syndrome (OSAS), which aims at efficient population-wide monitoring. To this end, we introduce SASscore which provides better OSAS prediction specificity while maintaining a high sensitivity. METHODS: We process a cohort of 2595 patients from 4 sleep laboratories in Western Romania, by recording over 100 sleep, breathing, and anthropometric measurements per patient; using this data, we compare our SASscore with state of the art scores STOP-Bang and NoSAS through area under curve (AUC), sensitivity, specificity, negative predictive value (NPV), and positive predictive value (PPV). We also evaluate the performance of SASscore by considering different Apnea-Hypopnea Index (AHI) diagnosis cut-off points and show that custom refinements are possible by changing the score's threshold. RESULTS: SASscore takes decimal values within the interval (2, 7) and varies linearly with AHI; it is based on standardized measures for BMI, neck circumference, systolic blood pressure and Epworth score. By applying the STOP-Bang and NoSAS questionnaires, as well as the SASscore on the patient cohort, we respectively obtain the AUC values of 0.69 (95% CI 0.66-0.73, p < 0.001), 0.66 (95% CI 0.63-0.68, p < 0.001), and 0.73 (95% CI 0.71-0.75, p < 0.001), with sensitivities values of 0.968, 0.901, 0.829, and specificity values of 0.149, 0.294, 0.359, respectively. Additionally, we cross-validate our score with a second independent cohort of 231 patients confirming the high specificity and good sensitivity of our score. When raising SASscore's diagnosis cut-off point from 3 to 3.7, both sensitivity and specificity become roughly 0.6. CONCLUSIONS: In comparison with the existing scores, SASscore is a more appropriate screening tool for monitoring large populations, due to its improved specificity. Our score can be tailored to increase either sensitivity or specificity, while balancing the AUC value.

Long-term effects of nocturnal continuous positive airway pressure therapy in patients with resistant hypertension and obstructive sleep apnea.

Obstructive sleep apnea (OSA) is often linked to high blood pressure and has a particularly high prevalence in patients with resistant hypertension. The effect of continuous positive airway pressure (CPAP) therapy on blood pressure (BP) values has been evaluated in several short-term clinical trials with conflicting results. Our aim was to investigate the role of long-term CPAP treatment in achieving BP control in patients who associate OSA and resistant hypertension. We have included in the study 33 patients with resistant hypertension, diagnosed with OSA in our sleep lab. Data was collected initially and after a mean follow-up period of 4 years. Patients were divided into 2 groups according to the use of CPAP therapy. Patients under CPAP therapy (n = 12) exhibited a higher reduction in both systolic and diastolic pressure and BP control was achieved in 75% of cases, while patients without CPAP treatment (n = 21) remained with refractory hypertension in proportion of 90.5%. A de-escalation of antihypertensive drug regimen by discontinuation of 1 or more drugs was observed in 41.6% (n = 5) of patients from CPAP group and in the other 33.4% (n = 4) the medication remained unchanged, but BP control was reached. Using a direct logistic regression model for examining the impact of different confounders on the probability of diagnosis of resistant hypertension at follow-up, the only statistically significant predictor found was the lack of CPAP usage.

Sildenafil Reduces Inflammation and Prevents Pulmonary Arterial Remodeling of the Monocrotaline - induced Disease in the Wistar Rats.

OBJECTIVES: Pulmonary arterial hypertension (PAH) is a rare and severe disease with incompletely under stood pathogenesis. PAH is associated with pulmonary arterial remodeling and inflammation. We evaluated the effects of Sildenafil on the Monocrotaline (MCT) -induced disease in Wistar rats, for potential benefit in the early phases of inflammation and vascular remodeling. MATERIAL AND METHODS: MCT-injected rats, MCT-injected sildenafil-treated rats (starting day 1 with 2 x 0.2 mg/day; total of 2 mg/kgc/day) and saline-injected control rats were evaluated at day 14 and day 28 following MCT for pulmonary morphological changes - lesions, inflammation (inflammator y index), arterial morphometry (hypertrophy index), immunohistochemistry for smooth muscle cell marker. OUTCOMES: The administration of sildenafil following MCT significantly reduced the severity of inflammation in the acute stage of the disease (reduction of the inflammatory index by 6.038% (p <0.05)) and prevented pulmonary arterial remodeling (reduction of the hypertrophy index by 7.306% (p<0.001)). It also improved survival in the early phase with a mortality rate during the first 14 days of 4 in the MCT- exposed rats vs 1 in the MCT-exposed sildenafil-treated rate. CONCLUSIONS: Early administration of sildenafil in the MCT experimental PAH improves inflammation and survival, and prevents pulmonary vascular remodeling. Our study suggests that one of the mechanisms involved, besides vasodilatation and anti-proliferative effect, could be a direct anti-inflammatory effect of sildenafil.

[Sleep apnea syndrome -- cause of resistance to treatment of arterial hypertension]. / Sindromul de apnee în somn -- factor de rezistenta la tratament a hipertensiunii arteriale.

The prevalence of sleep apnea syndrome is relatively high in population (5%). The mortality is significantly higher in those with apnea-hypopnea index >20. There is an increased rate of car accidents in the subjects with OSA compared to those who don't have this syndrome (31% versus 6%). The impact of OSA on mortality is also given by its association with a significant number of cardiovascular diseases. The association between OSA and hypertension has been much debated. The prevalence of hypertension among patients with OSA varies between 50-58%, while the prevalence of OSA in hypertensive patients is 30%. A particular association is OSA and resistant hypertension, i.e. blood pressure that remains above goal in spite of the concurrent use of three antihypertensive agents of different classes, one to be a diuretic and all pharmacological agents being prescribed at recommended doses. Secondary causes of hypertension are common in patients with resistant hypertension. Among these causes, one of the most frequent is sleep apnea syndrome. Some of the mechanisms by which sleep apnea contributes to the development of hypertension are intermittent hypoxia and/or increased upper airway resistance associated with sleep apnea that induces a sustained increase in sympathetic nervous system activity. Treatment of sleep apnea with continuous positive airway pressure devices (CPAP) improves blood pressure control, although the benefit of CPAP evaluated in clinical trials is variable.

Interstitial cells of Cajal in pancreas.

We show here (presumably for the first time) a special type of cell in the human and rat exocrine pancreas. These cells have phenotypic characteristics of the enteric interstitial cells of Cajal (ICC). To identify pancreatic interstitial cells of Cajal (pICC) we used routine light microscopy, non-conventional light microscopy (less than 1 mum semi-thin sections of Epon-embedded specimens cut by ultramicrotomy and stained with Toluidine blue), transmission electron microscopy (TEM), and immunocytochemistry. The results showed that pICC can be recognized easily by light microscopy, particularly on semi-thin sections, as well as by TEM. Two-dimensional reconstructions from serial photos suggest a network-like spatial distribution of pICC. pICC represent 3.3+/-0.5% of all pancreatic cells, and seem to establish close spatial relationships with: capillaries (43%), acini (40%), stellate cells (14%), nerve fibres (3%). Most of pICC (88%) have 2 or 3 long processes (tens of mum) emerging from the cell body. TEM data show that pICC meet the criteria for positive diagnosis as ICC (e.g. numerous mitochondria, 8.7+/-0.8% of cytoplasm). Immunocytochemistry revealed that pICC are CD117/c-kit and CD34 positive. We found pICC positive (40-50%) for smooth muscle alpha-actin or S-100, and, occasionally, for CD68, NK1 neurokinin receptor and vimentin. The reactions for desmin and chromogranin A were negative in pICC. At present, only hypotheses and speculations can be formulated on the possible role of the pICC (e.g., juxtacrine and/or paracrine roles). In conclusion, the quite-established dogma: "ICC only in cavitary organs" is overpassed.

[Structural and immunohistochemical changes of conjunctiva induced by topical glaucoma medication]. / Tratamentul topic antiglaucomatos--modificarile conjunctivale structurale si imunohitochimice.

PURPOSE: The topical medication represents the first line therapy for the primary open angle glaucoma. The study is aimed at assessing the structural and immunohistochemical changes of conjunctiva induced by topical glaucoma medication. METHODS: For this purpose, we carried out a 40 weeks, prospective, experimental, epidemiological-operational and randomized study enrolling 18 patients (36 eyes) with recently primary open angle glaucoma. The eyes were divided into treatment (non-selective beta blockers or selective, prostaglandin analogues, topical carbonic anhydrase inhibitors) in four groups. The assessment was performed by comparison with control group (4 patients) who was instilled with natural tears (with different preservative). Both the cytology and the conjunctival biopsy specimens were investigated by histological exams and immunohistochemistry using different monoclonal antibodies. The study was performed by collaboration with The National Institute of Research and Development in Pathology and Biomedical Sciences-"V. Babes"-Bucharest. RESULTS: The morphometric analysis of histological sections of conjunctiva showed the following changes: squamous metaplasia (significant increases in the thickness and number of epithelial cell layers), inflammation (increase the number of lymphocytes, macrophages and fibroblasts) and subconjunctival fibrosis. According to the type of medication, we observed the significant increase of subepithelial collagen density and degenerative changes of fibrocytes, the reduction of extracellular matrix and also the up-regulation of antibodies against matrix metalloproteinase and allergic changes. According to structural changes, the immunohistochemistry confirmed the tendency of chronic inflammation. CONCLUSIONS: This study revealed important structural and immunohistochemical changes of conjunctiva after topical glaucoma medication. The category and the intensity of these changes are dependent on the sort of therapy and the topical treatment period. The findings showed that benzalkonium chloride (the most common preservative of antiglaucoma drugs) is a major factor for conjunctival metaplasia.

[Clinical course of an ileal carcinoid with mesenteric metastasis]. / Evolutie particulara a unui carcinoid ileal cu metastaza ganglionara în baza mezenterului.

This paper aim is to present the case of a male patient, age 63 admitted in hospital for non-specific gastroenterologic symptoms easily attributed to colecyst calculosis; the anamnesis and careful clinical examination have avoided a useless cholecystectomy and permitted to establish indication for laparotomy; during that was found an ileal tumor with massive metastasis in the base of mesentery. The surgical attitude was dictated by histological diagnostic difficulties (prostate adenocarcinoma metastasis), so it has given up the idea of tumor excision (unjustified intraoperative risk for a metastasis), performing a bypass of the ileal tumor by an enteroenterostomy, then the patient was sent to the Oncological Department. Postoperative evaluation of the patient finally permitted to establish the neuroendocrine origin of the tumor; after oncological treatment (chemotherapy), about 10 months after operation the patient didn't present any sign of tumor (tumor markers and CT scan within normal). The paper emphasizes the problem of practicing an aggressive surgical treatment for carcinoid intestinal tumors with mesenteric metastasis but also brings attention to nonsymptomatic forms of cholecyst calculosis that may hide associated malignant tumors undetected by laparoscopic cholecystectomy.

[Conjunctival changes related to topical treatment and effectiveness of surgery in glaucoma]. / Modificarile conjunctivale legate de tratamentul topic si eficienta chirurgiei filtrante în glaucom.

PURPOSE: The topical treatment for a long run in glaucoma rises histopathological changes of conjunctiva. The study is aimed at assessing the correlations between conjunctival changes bound of the type and duration of medical glaucoma therapy and the efficiency of subsequent filtering surgery. METHOD: For this purpose, we carried out a three years clinical prospective study (01.05.2000-30.04.2003), with a mean follow-up period of 18.5 months, enrolling 22 cases (38 eyes) operated by trabeculectomy for primary open angle glaucoma (POAG), with the same technique and the same surgeon. There were excluded both the patients with previous ophthalmic surgical interventions and ocular/systemic chronic inflammatory disease. The cases were divided according to type and duration of topical treatment. There were recorded the conjunctival changes (by histological exam and immunohistochemistry), dynamic evolution of intraocular pressure (IOP) and the morphological aspects of filtering blebs. Statistical analysis was performed by Wilcoxon test. RESULTS: In all groups, the efficiency of filtering surgery was correlated with the duration of topical medication; the survey presents the correlations between topical treatment, conjunctival changes and postoperative evolution. CONCLUSIONS: These results suggest that exhaustive topical treatment in POAG, for a long period, with many drugs may represent a negative prognostic factor for the subsequent filtering surgery. Therefore it is necessary an individual approach for the first line therapy in POAG.