Mara Bulgheroni

Risk of Obstructive Sleep Apnea with Daytime Sleepiness Is Associated with Liver Damage in Non-Morbidly Obese Patients with Nonalcoholic Fatty Liver Disease

Background A high prevalence of obstructive sleep apnea syndrome (OSAS) has been reported in severely obese patients with nonalcoholic fatty liver disease (NAFLD), but few studies have evaluated OSAS in non-morbidly obese NAFLD patients. Aims To determine the prevalence of risk for OSAS with or without daytime sleepiness in non-morbidly obese patients with NAFLD and evaluate the association with the severity of liver damage. Methods We considered 159 consecutive patients with histological NAFLD and body mass index (BMI) <35 Kg/m2, and 80 controls without ultrasonographic steatosis matched for age, sex, and BMI. OSAS risk was determined by positivity for Berlin questionnaire (BQ), and daytime sleepiness by the Sleepness Epworth Scale (ESS). Liver damage was evaluated according to the NAFLD activity score. Results In NAFLD patients, BQ alone was positive in 39 (25%), ESS in 8 (5%), and both in 13 (8%, OSAS with sleepines); p = ns vs. controls without steatosis. In NAFLD patients at risk for OSAS with (but not in those without) sleepiness, we observed a higher prevalence of nonalcoholic steatohepatitis (NASH; 11/13, 85% vs. 72/146, 49%; p = 0.018), and of clinically significant fibrosis (stage>1; 9/13, 69% vs. 39/146, 27%; p = 0.003). At multivariate logistic regression analysis, OSAS with sleepiness was strongly associated with NASH and fibrosis>1 independently of known clinical risk factors such as age, gender, BMI, diabetes, and ALT levels (OR 7.1, 95% c.i. 1.7–51, p = 0.005 and OR 14.0, 95% c.i. 3.5–70, p = 0.0002, respectively). Conclusions A proportion of NAFLD patients without severe obesity is at risk for OSAS with daytime sleepiness, which is associated with the severity of liver damage independently of body mass and other cofactors.

Is hospital admission valuable in managing syncope? Results from the STePS study

The proper way to test the usefulness of hospitalization in syncope patients would be to conduct a randomized controlled trial. However, this approach is characterized by major theoretical and ethical limitations which make this procedure unfeasible. Data from observational studies indirectly show that hospitalization might help reduce the short-term risk of death and adverse events by promptly identifying and treating life-threatening events or conditions. Future research should focus on identifying which patients will benefit from hospitalization. In this regard, we should be able both to correctly risk-stratify patients and to analyze syncope observation units and protocols, which may provide a safe alternative for the evaluation of intermediate-risk patients.

Increased complexity of short-term heart rate variability in hyperthyroid patients during orthostatic challenge

Hyperthyroidism is a pathological condition characterized by an altered autonomic cardiovascular control, resulting in an increase of the sympathetic and a decrease of the parasympathetic modulation of heart rate variability. Recently, the entropy-based indices derived from short-term heart period variability have been proved to be helpful in evaluating the autonomic cardiovascular modulation. The aim of our study was to evaluate the autonomic cardiovascular modulation of hyperthyroid subjects at rest and during standing using spectral parameters and corrected conditional entropy indices derived from short-term heart period variability in 12 hyperthyroid (HYPTH) and 9 normal healthy (N) females. Mean heart period was significantly decreased by standing both in N and HYPTH and the LF power expressed in normalized units was increased. The respiratory rate was faster in the HYPTH group compared to N and complexity was significantly greater in HYPTH compared to N during standing. Results suggested an enhanced complexity of cardiovascular control in HYPTH, more evident in a condition of sympathetic activation. The increased complexity of the cardiovascular regulation is probably not completely due to autonomic control but also to other influences, such as metabolic effects of thyroid hormones impinging upon respiratory control mechanisms and, therefore, on cardiorespiratory coupling.

When Water Hurts

Deglutition syncope refers to an uncommon cause of neurally mediated syncope induced by swallowing. We briefly review a case of a 66‐year‐old man who experienced recurrent syncope episodes during ingestion of beverages, mainly water. Our investigations documented several short asymptomatic episodes of asystole and one prolonged complete atrioventricular block of around 15 seconds associated with the syncopal events, during swallowing. Barium x‐ray and manometry evaluations revealed only a nonspecific esophageal dysmotility. An underlying sick‐sinus syndrome was found on electrophysiologic study. A DDD pacemaker implantation was performed leading to total disappearance of patients symptoms.

Autonomic Cardiovascular Control in Hyperthyroid Women during Sleep

Hyperthyroidism is characterized by hyperadrenergic symptoms (i.e., tachycardia, anxiety, and increased metabolic state). Although hyperthyroid patients often complain about an impairment of sleep, no data are available on sleep characteristics and autonomic cardiovascular control during sleep in these patients. We aimed to assess sleep qualitative indices and autonomic cardiovascular regulation during sleep in hyperthyroidism (Hyperthyr) and after treatment. Six subjects with a first diagnosis of Graves’ disease or hyperfunctioning nodule underwent a complete polysomnographic study (PSG) at the time of diagnosis and after the treatment, when they became euthyroid (Euthyr). ECG and respiratory signals were extracted and samples of consecutive 250–300 beats were analyzed using linear spectral and nonlinear entropy analysis of heart rate variability (HRV), during the different sleep stages. Heart rate was decreased and total power increased in Euthyr compared to Hyperthyr, both during wake and sleep; no changes of the sympathovagal balance were observed. Entropy analysis showed that regularity index was reduced in Euthyr compared to Hyperthyr, suggesting changes in the complexity of the cardiovascular control. Periodic leg movements (PLM) were reduced in Euthyr compared to Hyperthyr. In conclusion, hyperthyroidism seems to be associated with an increased sleep fragmentation, due to PLM and an altered cardiac autonomic control.

Pulmonary involvement complicating plasma cell proliferative disorders: a case report and review of the literature.

A 60-year-old woman, affected by IgG lambda monoclonal gammopathy of undetermined significance (MGUS), diagnosed 13 years prior, presented with progressive dyspnoea, persistent dry cough, and a 6-month history of unilateral recurring pleural effusion. Recently, the patient developed severe pulmonary hypertension. The past medical history was significant for sinus tachycardia, which presented 5 years prior. The family history was not relevant. Respiratory function tests revealed a restrictive pattern, while a computed tomography (CT scan) performed 5 months prior to admission showed a ground glass opacification in the superior pulmonary lobes, bilateral diffuse pleural thickening, and enlarged mediastinal lymph nodes. Pulmonary and pleural biopsies, obtained by thoracoscopy 1 month prior to admission, showed nonspecific chronic inflammation of the parietal pleura and septal fibrosis of the pulmonary parenchyma. At presentation, the patient was tachypnoic (respiratory rate 36 breaths/min) and tachycardic (94 beats/min). The blood pressure was 110/70 mmHg. Elevated jugular venous pressure and leg edema were noted. The entire right hemithorax was dull to percussion, with decreased breath sounds; crackles were present at the contra lateral base. Arterial blood gas analyses on room air revealed pH 7.52, pO2 91 mmHg, pCO2 36 mmHg, HCO3 29 mmol/L. Further laboratory workup showed normocytic anemia (Hb 10 g/dL, MCV 88 fl), mild kidney failure [serum creatinine 1.14 mg/dL; chronic kidney disease (CKD) stage II], LDH 539 U/L, b2 microglobulin 2.6 mg/L, calcium 8.9 mg/dL, AST 32 UI/L, ALT 37 UI/L. Serum protein electrophoresis confirmed a monoclonal spike in the gamma fraction (1.2 g/dL), and serum immunoelectrophoresis demonstrated the presence of monoclonal IgG lambda chains; the urine test for Bence Jones protein was positive (IgG lambda). Pro-brain natriuretic peptide (proBNP) was 2,008 pg/mL (n.v. 0–1,800 pg/mL). A chest CT scan ruled out pulmonary embolism and confirmed pulmonary ground glass opacities with enlarged mediastinal lymph nodes and a massive organized rightsided effusion. On the fourth day of hospitalization, the patient suddenly developed a right-sided hemiparesis. ECG confirmed a sinus rhythm. Echocardiography demonstrated left ventricular concentric thickening with ‘‘sparkling’’ appearance of the myocardium, slight right ventricular diastolic dysfunction, and pulmonary hypertension (estimated pulmonary arterial pressure 53 mmHg, similar to previous data). The Doppler ultrasound scan showed a small fibrotic plaque, causing low-grade stenosis in the left-internal carotid artery. After 2 h, a head CT scan showed no hemorrhagic lesions; subsequently, neurological impairment improved. The patient underwent another head CT scan 48 h after the onset of hemiparesis, which showed a mesial-temporal ischemic stroke and another ischemic area in the left thalamus. M. Bulgheroni (&) L. Airaghi S. Fargion Internal Medicine 1B, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, University of Milan, Via Francesco Sforza 35, 20122 Milan, Italy e-mail: mara.bulgheroni@gmail.com