Balance and visual reliance in post-COVID syndrome patients assessed with a robotic system: a multi-sensory integration deficit.

The symptoms of SARS-CoV-2 infection are not limited to the acute phase, with vertigo, peripheral neuropathies, headache, fatigue, memory loss, and depression being the most common post-acute clinical manifestations. Such post-COVID syndrome is a new clinically relevant challenge for diagnosis and therapy. Our goal was to quantify deficit in balance and proprioception related to post-COVID syndrome and, in this sense, we prospectively analyzed data of 66 post-COVID-19 outpatients (mean age 47.3 ± 11.1 years, 50 females, 25 hospitalized), evaluated using the robotic device hunova. The dynamic balance was assessed with open (OE) and closed eyes (CE) and three indexes, proportional to subject instability, were measured: the sway path and two oscillation ranges. Hospitalized group showed the worst performance with respect to non-hospitalized patients and normality range in both visual conditions for the sway path and the oscillation ranges, with the worst performance being with CE. When compared to normality ranges, post-COVID patients were significantly more distant from normality in the OE condition compared to the CE condition. These results suggest that independently from the severity of the disease experienced, post-COVID syndrome makes the elastic balance test performances more distant from the normality when the subject integrates vision, somatosensory information, and vestibular information. In the absence of visual feedback, patients seem to implement compensatory strategies, presumably seeking more significant feedback from the lower limbs, which improve their performance. These data suggest a new mechanism of the post-COVID syndrome that deserves further investigation for its potential impact on activities of daily living.

Development and validation of an endoscopic classification of diverticular disease of the colon: the DICA classification.

BACKGROUND: A validated endoscopic classification of diverticular disease (DD) of the colon is lacking at present. Our aim was to develop a simple endoscopic score of DD: the Diverticular Inflammation and Complication Assessment (DICA) score. METHODS: The DICA score for DD resulted in the sum of the scores for the extension of diverticulosis, the number of diverticula per region, the presence and type of inflammation, and the presence and type of complications: DICA 1 (≤ 3), DICA 2 (4-7) and DICA 3 (>7). A comparison with abdominal pain and inflammatory marker expression was also performed. A total of 50 videos of DD patients were reassessed in order to investigate the predictive role of DICA on the outcome of the disease. RESULTS: Overall agreement in using DICA was 0.847 (95% confidence interval, CI, 0.812-0.893): 0.878 (95% CI 0.832-0.895) for DICA 1, 0.765 (95% CI 0.735-0.786) for DICA 2 and 0.891 (95% CI 0.845-0.7923) for DICA 3. Intra-observer agreement (kappa) was 0.91 (95% CI 0.886-0.947). A significant correlation was found between the DICA score and C-reactive protein values (p = 0.0001), as well as between the median pain score and the DICA score (p = 0.0001). With respect to the 50 patients retrospectively reassessed, occurrence/recurrence of disease complications was recorded in 29 patients (58%): 10 (34.5%) were classified as DICA 1 and 19 (65.5%) as DICA 2 (p = 0.036). CONCLUSIONS: The DICA score is a simple, reproducible, validated and easy-to-use endoscopic scoring system for DD of the colon.

Cholestatic hepatitis C after chemotherapy containing rituximab in diffuse large B cell lymphoma.

Rituximab is a chimeric anti-CD20 monoclonal antibody that is a widely used for the treatment of B cells non-Hodgkin lymphoma. The use of chemotherapy regimens containing rituximab in HCV-positive patients with non-Hodgkin lymphoma has been associated with liver dysfunction, but no cases of cholestatic hepatitis C were described. To our knowledge, this is the first case of cholestatic hepatitis C in an HCV-positive patient with diffuse large B-cell lymphoma describes in the literature. We discuss the pathogenetic mechanisms underlying this severe form of hepatitis and describe its evolution after antiviral treatment.

Long term nucleotide and nucleoside analogs treatment in chronic hepatitis B HBeAg negative genotype D patients and risk for hepatocellular carcinoma.

UNLABELLED: BACKGROUND AND RATIONALE OF THE STUDY: Effect of Long-term nucleoside/nucleotide (NUC) on hepatocellular carcinoma (HCC) incidence in a population of HBeAg-negative genotype D patients has not been adequately studied in real-life cohorts. Our aim was to evaluate the impact of liver fibrosis and other variables on HCC incidence in this population of patients. Of 745 patients with chronic hepatitis B (CHB), 306 HBeAg-negative genotype D were selected and included in this study. All patients received treatment with NUC for at least 18 months. Patients with CHB or compensated cirrhosis were included. Patients with HCC diagnosed before or during the first 18 months of NUC therapy were excluded. RESULTS: HCC was diagnosed in 2 CHB patients (1.0%) and 23 cirrhosis patients (20%) (OR = 24.41, 95% CI 5.40 < OR < 153.2; p < 0.0001). Multivariate analysis revealed that HCC risk was independently associated with age ≥ 60 years (OR = 6.45, 95% CI 1.22 to 34.0; p = 0.02) and liver cirrhosis (OR = 12.1, 95% CI 1.39 to 106.2; p = 0.02), but not with virological response (VR), and previous resistance to NUC, or rescue therapy. Multivariate analysis in cirrhosis patients revealed that only age ≥ 60 years was an independent risk factor associated with HCC (p = 0.003). CONCLUSIONS: Liver cirrhosis and age ≥ 60 years are the stronger risk factors for HCC in genotype D HBeA-gnegative patients. Previous resistance to NUC in patients that achieved a VR after rescue therapy was not a predictive factor regarding HCC. VR does not appear to significantly reduce the overall incidence of HCC when a patient has already progressed to liver cirrhosis.

Sarcopenia and Multisensory Integration Deficit in Post-COVID Syndrome Patients: The Clinical, Ultrasound and Robotic Evaluation Protocol in a Cross-sectional Study.

INTRODUCTION: Post-COVID syndrome affects relatively young outpatients with fatigue as the mostly reported symptom. We wondered whether sarcopenia could play a role. METHODS: Seventy-four outpatients (median age: 53.8 yrs, 45 females), reporting fatigue and persistent mild neurological/motor deficits, completed the Clinical, Ultrasound and Robotic Evaluation protocol 4.8 mos after the infection. RESULTS: The incidence of sarcopenia was 41%. Sarcopenic patients were older (62.7 vs. 46.4 yrs, P < 0.001), they experienced longer infection (33 vs. 24 days, P = 0.006) and higher incidence of hospitalization (86.6 vs. 29.5%, P < 0.001), they did not report more fatigue (44.5 vs. 48, P = 0.424), but they walked slower (1.27 vs. 1.5 m/sec, P = 0.027).After multivariable adjustment using multiple logistic regression, sarcopenia was dependent on age (odds ratio = 1.09) and on the duration of the disease (odds ratio = 1.04).When expressed as z score, in 79% of patients, the sway path during elastic balance shifted significantly toward negative values with closed eye, indicating multisensory integration deficit. CONCLUSIONS: Post-COVID syndrome in relatively young outpatients complaining mild motor deficit is associated with high incidence of sarcopenia. In addition, they have multisensory integration deficit that further contributes to symptoms. The Clinical, Ultrasound and Robotic Evaluation protocol is able to objectivize symptoms that common diagnostic tool cannot reveal. TO CLAIM CME CREDITS: Complete the self-assessment activity and evaluation online at http://www.physiatry.org/JournalCME. TO CLAIM CME CREDITS: Complete the self-assessment activity and evaluation online at http://www.physiatry.org/JournalCME. CME OBJECTIVES: Upon completion of this article, the reader should be able to: (1) Determine the best diagnostic algorithm for the diagnosis of sarcopenia; (2) Identify and treat two additional factors that help to explain and understand the symptoms reported by relatively young post-COVID syndrome patients; and (3) Extend their diagnostic capability through the use of technology. LEVEL: Advanced. ACCREDITATION: The Association of Academic Physiatrists is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians.The Association of Academic Physiatrists designates this Journal-based CME activity for a maximum of 1.0 AMA PRA Category 1 Credit(s) ™. Physicians should only claim credit commensurate with the extent of their participation in the activity. LEVEL: Advanced. ACCREDITATION: The Association of Academic Physiatrists is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians. The Association of Academic Physiatrists designates this Journal-based CME activity for a maximum of 1.0 AMA PRA Category 1 Credit(s) ™. Physicians should only claim credit commensurate with the extent of their participation in the activity.

Use of oxygen-ozone therapy to improve the effectiveness of antibiotic treatment on infected arthroplasty: protocol for a superiority, open-label, multicentre, randomised, parallel trial.

INTRODUCTION: Surgical site infections still remain a major public health challenge and have become an increasing universal risk, especially for the implantation of orthopaedic devices.Unfortunately, the discovery and increasingly widespread use (especially the misuse) of antibiotics have led to the rapid appearance of antibiotic-resistant strains today; more and more infections are caused by microorganisms that fail to respond to conventional treatments.Oxygen-ozone therapy has been extensively used and studied for decades across various potential medical applications and has provided consistent effects with minimal side effects.This study aims to determine the superiority of oxygen-ozone therapy in combination with oral antibiotic therapy in patients with wound infections after an orthopaedic device implantation when compared with antibiotic therapy alone. METHODS AND ANALYSIS: This is an open-label, multicentre, randomised, parallel-group study that aims to assess the efficacy and safety of oxygen-ozone therapy in combination with oral antibiotic therapy to treat infections in patients (male or female aged ≥18 years) having undergone surgery for the implant of an orthopaedic device. Patients must have at least one (but no more than three) postoperative wounds in the site of surgery (ulcers, eschars and sores) and at least one symptom (pain, burning, redness and malodour) and at least one sign (erythema, local warmth, swelling and purulent secretion) of infection of at least moderate intensity (score ≥2) in the target lesion at the screening visit (patients with wounds without signs of localised infection or with undermining wounds will be excluded).Patients (n=186) will be recruited from five Italian hospitals and studied for 7 weeks. All will be assigned to one of the two treatment groups according to a web-based, centralised randomisation procedure and placed into either the (1) intervention: oxygen-ozone therapy 2-3 times a week for 6 weeks (for a maximum of 15 sessions) simultaneously with an appropriate oral antibiotic therapy prescribed at baseline or (2) control: oral antibiotic therapy prescribed at baseline.The primary outcome is the efficacy and superiority of the treatment (ozone and oral antibiotic therapies); secondary outcomes include the resolution of signs and symptoms, modifications in lesion size and the treatment's safety and tolerability. ETHICS AND DISSEMINATION: This study has been reviewed and approved by the responsible Independent Ethics Committee (IEC) of COMITATO ETICO CAMPANIA NORD, located at 'Azienda Ospedaliera San Giuseppe Moscati di Avellino'.After completion of the study, the project coordinator will prepare a draft manuscript containing the final results of the study on the basis of the statistical analysis. The manuscript will be derived by the co-authors for comments, and after revision, it will be sent to a major scientific journal. Findings will be disseminated via online and print media, events and peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT04787575.

From Histoanatomy to Sonography in Myofascial Pain Syndrome: A EURO-MUSCULUS/USPRM Approach.

ABSTRACT: Myofascial pain is a common clinical condition, whereby accurate physical examination is usually considered as the cornerstone to identify/diagnose the "trigger point complex," that is, the characteristic finding of this syndrome. Considering the emerging role of ultrasound examination as the natural extension of physical assessment for musculoskeletal disorders, we briefly revise the histological/anatomical features of trigger points and propose a standardized, multistep sonographic approach to myofascial pain. We also imply that the integrated clinical-ultrasound evaluation could be considered as a potential tool to discriminate different phases/subsets of this challenging pathology.

HCV genotype 1a shows a better virological response to antiviral therapy than HCV genotype 1b.

BACKGROUND: The impact of viral subtype on the rate of sustained virological response (SVR) to antiviral therapy in patients chronically infected with hepatitis C genotype 1 subtype 1a and 1b has not been extensively investigated. The aim of this study is to determine whether the HCV genotype 1 subtypes 1a and 1b respond differently to treatment with PEGylated interferon (PEG-IFN) plus ribavirin. METHODS: For 48 weeks, 388 "naïve"genotype 1 patients were treated weekly with PEG-IFN α-2a or PEG-INF α-2b combined with daily ribavirin (1000-1200 mg/day). The numbers of patients in whom HCV-RNA was undetectable were compared after 4 (rapid virological response, RVR), 12 (early virological response, EVR), and 48 (end treatment virological response, ETR) weeks of treatment as well as 24 weeks after the last treatment (sustained virological response, SVR). RESULTS: The rate of SVR was higher in subtype 1a patients than subtype 1b patients (55% vs. 43%; p < 0.02). Multiple logistic regression analysis showed that infection with genotype 1a (odds ratio(OR) : 1.8; 95% confidence interval (CI): 1.4 to 4.1), age < 50 years (OR:7.0; 95% CI 1.1 to 21.2), alanine aminotransferase level (ALT)<100 IU/ml (OR:2.1; 95% CI: 1.3 to3.5), HCV-RNA < 5.6 log10 IU/ml (OR: 3.2; 95% CI: 2.7 to 6.9) and fibrosis score < S3 (OR: 3.8; 95% CI:3.2 to 7.4), were all independent predictors of SVR. CONCLUSION: Dual antiviral therapy is more effective against HCV subtype 1a than against subtype 1b and this difference is independent of other factors that may favour viral clearance. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01342003.

Porphyria cutanea tarda in an HCV-positive liver transplant patient: a case report.

INTRODUCTION: Porphyria cutanea tarda (PCT) is the most common type of porphyria. The strong association between PCT and hepatitis C virus (HCV) infection is well established. Although antiviral treatment of chronic hepatitis C may improve PCT in some cases, de novo onset of PCT has been observed in patients under- going peginterferon/ribavirin treatment. We present a rare case of a genotype 3 HCV-positive liver transplant recipient who developed PCT during antiviral treatment and discuss its probable etiopathogenesis. CASE PRESENTATION: A genotype 3 HCV-positive liver transplant recipient, a 42-year-old man, was treated with peginterferon alfa-2a (180 µg/week) combined with ribavirin (1,200 mg/day) for recurrence of HCV infection after liver transplantation. He presented with hyperferritinemia but tested negative for genetic hemochromatosis (C282Y and H63D mutations). During antiviral therapy, he developed skin lesions on his hands characterized by vesicles and erosions consistent with PCT. PCT was confirmed by skin biopsy and elevated urinary uroporphyrin levels (1,469 mg/24 h). He was treated with chloroquine (200 mg) twice weekly, resulting in gradual regression of the skin lesions. Antiviral treatment was stopped after 48 weeks, and the patient achieved a sustained virological response. In conclusion, we report an extremely rare case of PCT in a genotype 3 HCV-positive liver transplant patient treated with antiviral therapy. We believe that the combination of HCV genotype 3 infection; hemolysis due to ribavirin treatment; and increased plasma levels of cytokines, such as IL-6 and TNFα, could have altered the patient's iron metabolism and thus caused PCT.

From histo-anatomy to sonography in lymphedema: EURO-MUSCULUS/USPRM approach.

Lymphedema is a disorder characterized by the accumulation of protein-rich lymphatic fluid in the cutaneous and subcutaneous tissue. Based on the underlying causes, it is classified into primary and secondary forms. The use of ultrasound has recently become widespread in the field of lymphedema - especially for its diagnosis and treatment planning. In this study, we briefly reviewed the anatomy and histology of the skin and subcutaneous tissue - to propose a standardized ultrasound assessment of the superficial tissues in patients with upper-/lower-limb lymphedema. We believe that identification of the sono-histological patterns of the dermo-epidermal complex and subcutaneous tissue has place to serve as a simple and reproducible strategy to evaluate their edema diseases that are often subject to an inaccurate diagnosis in daily clinical practice.

From physical to ultrasound examination in lymphedema: a novel dynamic approach.

In daily practice, medical history and physical examination are commonly coupled with anthropometric measurements for the diagnosis and management of patients with lymphatic diseases. Herein, considering the current progress of ultrasound imaging in accurately assessing the superficial soft tissues of the human body; it is noteworthy that ultrasound examination has the potential to augment the diagnostic process. In this sense/report, briefly revisiting the most common clinical maneuvers described in the pertinent literature, the authors try to match them with possible (static and dynamic) sonographic assessment techniques to exemplify/propose an 'ultrasound-guided' physical examination for different tissues in the evaluation of lymphedema.

Respiratory function assessment at the time of a new respiratory virus pandemic.

We must be aware that new respiratory virus pandemic can happen frequently. Standard lung function tests should keep their crucial role to assist the clinicians in the decision-making process, but they are at risk for the spread of infection because of the generated droplets. We used opto-electronic plethysmography to investigate the post-COVID-19 syndrome on 12 patients after ICU. We found normal ventilatory pattern at rest, a restrictive pattern located in the ribcage during vital capacity and surgical mask to significantly increase minute ventilation. The attention on unconventional respiratory function tests should be sponsored for the important information they can provide.

Short versus standard treatment with pegylated interferon alfa-2A plus ribavirin in patients with hepatitis C virus genotype 2 or 3: the cleo trial.

BACKGROUND: In patients with chronic hepatitis C virus (HCV) genotype 2 or 3, 24 weeks' treatment with pegylated interferon alfa (PEG-IFN-alpha) and ribavirin induces a sustained virological response (SVR) in almost 80% of cases. Evidence suggests that a similar response rate may be obtained with shorter treatment periods, especially in patients with a rapid virological response (RVR). The aim of this study was to compare the efficacy of 12 or 24 weeks of treatment in patients with chronic HCV genotype 2 or 3 and to identify patients suitable for 12 weeks treatment. METHODS: Two hundred and ten patients received PEG-IFN-alpha-2a (180 ug/week) and ribavirin (800-1200 mg/day) for 4 weeks. Patients with a RVR (HCV RNA not detectable) were randomized (1:1) to either 12 (group A1) or 24 (group A2) weeks of combination therapy. Patients without a RVR continued with 24-weeks' combination therapy (group B). HCV RNA was monitored at weeks 4, 8, 12, and 24, and at week 24 post-treatment. RESULTS: At study end, end of treatment response (ETR) was observed in 62 (86%) patients of group A1 and in 55 (77%) patients of group A2 (p < 0.05) Relapse rate was 3% each in groups A1 and A2, and 6% in group B. Among patients with a HCVRNA test 24 weeks after the end of treatment, SVR was observed in 60 (83%) of group A1 patients and in 53 (75%) of group A2 patients. Rapid virological response, low baseline HCV RNA levels, elevated alanine aminotransferase levels and low fibrosis score, were the strongest covariates associated with SVR, independent of HCV genotype. No baseline characteristic was associated with relapse. CONCLUSION: In HCV patients with genotype 2 or 3, 12-week combination therapy is as efficacious as 24-week therapy and several independent covariates were predictive of SVR. TRIAL REGISTRATION: Trial number ISRCTN29259563.

Rehabilitation and respiratory management in the acute and early post-acute phase. "Instant paper from the field" on rehabilitation answers to the COVID-19 emergency.

COVID-19 is a respiratory infectious disease that can cause respiratory, physical and psychological long-term dysfunctions in patients. First recommendations on respiratory management were published, but they were not based on the specific needs due to COVID-19. In this paper we share the early experiences from the clinical field in Northern Italy, where the epidemic started in February. This paper summarizes the second webinar on COVID-19 (230 live attendees, 11,600 viewers of the recorded version) organized by the Italian Society of Physical and Rehabilitation Medicine about rehabilitation and in particular respiratory management in the acute (Intensive Care Unit [ICU]) and immediate post-acute phases. There is the need to prepare for the post-acute phase. ICU length of stay is relatively long, with immobilization in prone position. Some specific problems are described, including severe muscle weakness and fatigue, joint stiffness, dysphagia, (neuro)psychological problems, impaired functioning concerning mobility, activities of daily life and work. A lot is yet unknown and patients can experience long-term consequences as we know from the literature on the postintensive care syndrome, but COVID-19 has unique features to be investigated and understood. As a colleague stated during the Covinar: this is a marathon, not a sprint….

A specific home care program improves the survival of patients with chronic obstructive pulmonary disease receiving long term oxygen therapy.

OBJECTIVES: To analyze the influence of a home care (HC) program on outcomes of patients with chronic obstructive pulmonary disease (COPD) receiving long-term oxygen therapy (LTOT) in comparison with outcomes of patients receiving standard care (SC). DESIGN: A 10-year follow-up study with 2 parallel cohorts (HC vs SC). SETTING: University hospital. PARTICIPANTS: One hundred and eight patients in the HC program and 109 patients managed conventionally. INTERVENTIONS: The HC program consisted of outpatient clinical and functional evaluations every 6 months, and domiciliary assessments by a specific team including a pneumologist, a respiratory nurse, and a rehabilitation therapist every 2 to 3 months or more, as needed. MAIN OUTCOME MEASURES: Mortality; exacerbation, hospital and intensive care unit admission rate. RESULTS: One hundred and eight patients entered the HC program and 109 patients were managed conventionally. The 2 groups of patients did not differ for age, sex, body mass index, COPD severity or comorbid conditions. The overall mortality during the follow-up was 63% and the median survival was 96+/-38 months. The survival curves for HC and SC patients were statistically significantly different (log-rank, -16.04; P=.0001). In the Cox proportional hazards model, inclusion in the HC program was associated with an increased survival rate, whereas comorbid conditions and requirement of mechanical ventilation during the follow-up were associated with a decreased survival rate. During the entire follow-up, HC patients had a lower number of exacerbations/year than SC patients. CONCLUSIONS: A disease-oriented HC program is effective in reducing mortality and hospital admissions in COPD patients requiring LTOT.

Prevalence of normal tension glaucoma in obstructive sleep apnea syndrome patients.

PURPOSE: To explore the prevalence of normal tension glaucoma (NTG) among patients with obstructive sleep apnea syndrome (OSAS) and to examine OSAS as a risk factor of NTG. PATIENTS AND METHODS: Fifty-one consecutive white patients with OSAS were compared with 40 healthy subjects. All the study subjects underwent blood gas analysis, polysomnography, oxyhemoglobin saturation, and an ophthalmologic examination including visual field, visually evoked potential (VEP), and pattern electroretinography (PERG) and disc analysis with the Heidelberg Retina Tomograph II. RESULTS: Three of 51 OSAS patients (5.9%) had NTG. No patient in the control group had OSAS or NTG. The severity of OSAS correlated with intraocular pressure, the mean deviation of the visual field, the cup/disk ratio and the mean of the retinal nerve fiber layer thickness (P<0.01 to 0.001). Apnea hypopnea index and intraocular pressure were significantly greater in OSAS patients with abnormal VEP and PERG, compared to those with normal PERG and VEP. CONCLUSIONS: The present study suggests that the prevalence of NTG in our OSAS patients is higher than expected in a white population of the same age and that OSAS may be an important risk factor for NTG. Our data underline the importance of taking an accurate sleep history from patients with NTG and referring patients with sleep disturbance for polysomnography.

The safety of treatments for angioedema with hereditary C1 inhibitor deficiency.

INTRODUCTION: Angioedema is a localized and self-limiting edema of the subcutaneous and submucosal tissue. Hereditary angioedema with C1 inhibitor deficiency (C1-INH-HAE) is the best characterized form of hereditary angioedema. In C1-INH-HAE, the reduced plasma levels of C1-INH cause instability of the contact system with release of bradykinin, the key mediator of angioedema. C1-INH-HAE is characterized by recurrent skin swelling, abdominal pain, and potentially life-threatening upper airways obstruction. Knowledge of the molecular mechanisms leading from C1-INH deficiency to angioedema allowed the development of several therapies. AREAS COVERED: The aim of this review article is to discuss the safety of currently available treatments of C1-INH-HAE. The authors give an insight on the mechanism of action and safety profile of drugs for treatment of acute attacks and for short- and long-term prophylaxis. Evidence from systematic reviews, clinical trials, retrospective studies, and case reports is summarized in this review. EXPERT OPINION: C1-INH-HAE is a disabling, life-threatening condition that lasts life-long. Different therapeutic approaches with different drugs provide significant benefit to patients. Safety profiles of these therapies are critical for optimal therapeutic decision and need to be known by C1-INH-HAE treating physicians for appropriate risk/benefit evaluation.

Environmental tobacco smoke may induce early lung damage in healthy male adolescents.

STUDY OBJECTIVE: Childhood exposure to environmental tobacco smoke (ETS) adversely affects dynamic spirometric indexes as a result of combined early life (including in utero) and current exposure to parental smoking. The aim of our study was to investigate the effect of ETS on lung function and to identify the most sensitive functional parameter for evaluating lung damage. DESIGN: Cross-sectional survey. SETTING: Health survey on secondary school children. SUBJECTS: Eighty adolescents boys (mean age +/- SD, 16 +/- 1 years) classified in three groups: 21 smokers, 30 nonsmokers, and 29 passive smokers. MEASUREMENTS: Standardized questionnaire on the smoking habits of the subjects and their parents; assay of urinary cotinine level and measurement of the cotinine/creatine ratio (CCR); and lung function tests, including measurements of lung volumes, spirometric dynamic parameters, and the single-breath diffusing capacity of the lung for carbon monoxide (DLCO). RESULTS: Passive smokers presented a higher residual volume than nonsmokers, and a lower maximal expiratory flow at 25% of FVC (MEF(25)) and DLCO. Passive smokers whose mothers had smoked during pregnancy had significantly lower MEF(25) percentage, DLCO, carbon monoxide transfer coefficient, and diffusion capacity of the alveolar-capillary membrane (DM) values than did passive smokers whose mothers had given up smoking during pregnancy. Nevertheless, the MEF(25) and DM values of subjects with mothers who had given up smoking during pregnancy were lower than those observed in nonsmokers (p < 0.05), suggesting a negative effect of passive smoking independent of the mother's smoking habit during pregnancy. A statistically significant, negative correlation was found between CCR and DLCO in smokers (r = - 0.63, p < 0.01) and in passive smokers (r = - 0.91, p < 0.001), but not in nonsmokers (r = 0.26, p = not significant), suggesting a dose-effect relationship. CONCLUSIONS: Current exposure to ETS in healthy male adolescents is associated with lung function impairment independently of the effects of maternal smoking during pregnancy. More information may be obtained from determining static lung volumes and DLCO.

Nasal resistances are useful in identifying children with severe obstructive sleep apnea before polysomnography.

OBJECTIVE: In this study, we would like to show that anterior rhinometry measurement of nasal resistance would be a simple and useful test to identify severe obstructive sleep apnea (OSA) in a population of children affected by adenotonsillar hypertrophy. METHODS: Seventy-three consecutive children (44 males; mean age 5.4+/-1.2 years) with adenotonsillar hypertrophy, who complained sleep-disordered breathing, were studied. All the parents completed a questionnaire concerning the children's sleeping habits and sleep complaints before consultation; each child underwent a general paediatric examination and an evaluation of craniofacial features and upper airway patency. In all 73 children polysomnography was performed and anterior rhinometry nasal patency was measured. RESULTS: The diagnosis of OSA was confirmed in 44/73 patients (60%). Total nasal resistance showed a significant direct correlation with apnea hypopnea index, arousal index, snoring time, percentage of sleep time spent at SaO(2)<90% and a significant inverse correlation with total sleep time, sleep efficiency and the mean of SaO(2)% during sleep. Total nasal resistance was significantly related to snoring, mouth breathing and daytime sleepiness. The receiver operator characteristics (ROC) curve indicates that in the range of age of our sample a nasal resistance value of 0.59 Pa/cm(3)/s has a sensitivity of 91% and specificity of 96% for identifying the children with adenotonsillar hypertrophy affected by OSA. CONCLUSIONS: Our study shows that in children with adenotonsillar hypertrophy nasal resistance seems to be risk factor for OSA. The anterior rhinometry appears as a useful tool in routine evaluation of sleep-disordered breathing in these patients.

Sofosbuvir plus daclatasvir for post-transplant recurrent hepatitis C: potent antiviral activity but no clinical benefit if treatment is given late.

BACKGROUND: We evaluated efficacy and safety of sofosbuvir and daclatasvir±ribavirin in liver transplant recipients with severe recurrent hepatitis C. METHODS: Patients included in an international compassionate use programme for treatment with sofosbuvir and daclatasvir±ribavirin for 24 weeks were prospectively studied. Serum hepatitis C virus RNA was measured at treatment weeks 4, 12, and 24 and during follow-up at weeks 4, 8, and 12. RESULTS: Twelve patients (3 with fibrosing cholestatic hepatitis and 9 with cirrhosis; median model for end-stage liver disease score 20) received sofosbuvir 400mg/day+daclatasvir 60mg/day, and 6 patients (50%) also received ribavirin 200-800mg/day. Nine patients completed 24 weeks of treatment (75%), and all had undetectable hepatitis C virus RNA at week 24; 3 patients died (25%, liver failure, gastrointestinal bleeding and sepsis); 4 patients experienced severe liver disease-related adverse events. Post-treatment hepatitis C virus RNA was available for 5 patients (week 8, n=2; week 4, n=3) and was undetectable in all cases. Mean Child-Pugh score and albumin level improved significantly at week 24. No changes in immunosuppressant doses were needed. CONCLUSION: All-oral sofosbuvir plus daclatasvir combination shows high virological efficacy in liver transplant recipients and does not interact with immunosuppressants. All adverse events were unrelated to study drugs. These data strongly suggest that this combination must be initiated before decompensation.