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Anabolic deficiencies play a pivotal role in left-sided heart failure. Little is known about their impact on idiopathic pulmonary arterial hypertension (iPAH). Therefore, the aim of this study was to assess the impact of multiple hormone-metabolic deficiencies on clinical features and outcomes in idiopathic pulmonary arterial hypertension. We have demonstrated that the assessment of anabolic hormone levels in patients with iPAH allows the identification of a subpopulation with worse exercise capacity, pulmonary hemodynamics, right ventricular size, and function generating the hypothesis about the potential role of hormonal replacement therapy. These data should be confirmed by larger studies.

The purpose of this multicenter case-control study was to evaluate a group of patients at least 1 year after coronavirus disease 2019 (COVID-19) with Sniffin' Sticks tests and to compare the results with a control population to quantify the potential bias introduced by the underlying prevalence of olfactory dysfunction (OD) in the general population. The study included 170 cases and 170 controls. In the COVID-19 group, 26.5% of cases had OD (anosmia in 4.7%, hyposmia in 21.8%) versus 3.5% in the control group (6 cases of hyposmia). The TDI score (threshold, discrimination, and identification) in the COVID-19 group was significantly lower than in the control group (32.5 [interquartile range, 29-36.5] vs 36.75 [34-39.5], P < .001). The prevalence of OD was significantly higher in the COVID-19 group, confirming that this result is not due to the underlying prevalence of OD in the general population.

BackgroundThe long-term recovery rate for coronavirus disease 2019 related chemosensory disturbances has not yet been clarified.MethodsOlfactory and gustatory functions were assessed with psychophysical tests in patients in the first seven days from coronavirus disease 2019 onset and one, two, three and six months after the first evaluation.ResultsA total of 300 patients completed the study. The improvement in olfactory function was significant at the two-month follow up. At the end of the observation period, 27 per cent of the patients still experienced a persistent olfactory disturbance, including anosmia in 5 per cent of cases. As for taste, the improvement in the psychophysical scores was significant only between the baseline and the 30-day control. At the 6-month evaluation, 10 per cent of the patients presented with a persistent gustatory disturbance with an incidence of complete ageusia of 1 per cent.ConclusionSix months after the onset of coronavirus disease 2019, about 6 per cent of patients still had a severe persistent olfactory or gustatory disturbance.

In recent years, several observations reported that intolerance of physical exertion and other cardinal symptoms in heart failure (HF) are closely related to the functionality of the right ventricular (RV), regardless of left heart. It has been demonstrated that the RV dysfunction complicates the course, aggravates the quality of life, and increases the mortality of HF patients. The present review is aimed to report tips physicians about the current therapeutic management of right HF during acute stage and chronic phase, shedding light on the RV and its failure and providing physicians with essential information for everyday clinical practice.

Long-term weight loss maintenance represents a big challenge for the management of obesity. This narrative review aims to provide an overview of the main endocrine mechanisms involved in weight regain in subjects with obesity and to review the current evidence on the best lifestyle approaches, including diet and physical activity. Weight regain after weight loss occurs in about 50% of subjects with obesity in the absence of lifestyle changes. The primary endocrine mechanism responsible for weight regain involves the brain-gut axis, which encourages food intake and thus weight regain through the secretion and action of several gastrointestinal hormones, such as ghrelin, leptin and cholecystokinin. Several evidence reported changes of secretion of these hormones during weight loss and weight loss maintenance programs. Endurance training is the most effective physical activity to lose and keep weight loss; the association of endurance with resistance training is recommended for remodelling body shape.

Aims The association between hyperglycemia at hospital admission and relevant short- and long-term outcomes in elderly population is known. We assessed the effects on mortality of hyperglycemia, disability, and multimorbidity at admission in internal medicine ward in patients aged ≥ 65 years. Methods Data were collected from an active register of 102 internal medicine and geriatric wards in Italy (RePoSi project). Patients were recruited during four index weeks of a year. Socio-demographic data, reason for hospitalization, diagnoses, treatment, severity and comorbidity indexes (Cumulative Illness rating Scale CIRS-SI and CIRS-CI), renal function, functional (Barthel Index), and cognitive status (Short Blessed Test) and mood disorders (Geriatric Depression Scale) were recorded. Mortality rates were assessed in hospital 3 and 12 months after discharge. Results Of the 4714 elderly patients hospitalized, 361 had a glycemia level ≥ 250 mg/dL at admission. Compared to subjects with lower glycemia level, patients with glycemia ≥ 250 mg/dL showed higher rates of male sex, smoke and class III obesity. These patients had a significantly lower Barthel Index (p = 0.0249), higher CIRS-SI and CIRS-CI scores (p = 0.0025 and p = 0.0013, respectively), and took more drugs. In-hospital mortality rate was 9.2% and 5.1% in subjects with glycemia ≥ 250 and p = 0.0010). Regression analysis showed a strong association between in-hospital death and glycemia ≥ 250 mg/dL (OR 2.07; [95% CI 1.34–3.19]), Barthel Index ≤ 40 (3.28[2.44–4.42]), CIRS-SI (1.87[1.27–2.77]), and male sex (1.54[1.16–2.03]). Conclusions The stronger predictors of in-hospital mortality for older patients admitted in general wards were glycemia level ≥ 250 mg/dL, Barthel Index ≤ 40, CIRS-SI, and male sex.

In December 2019, several patients were hospitalized and diagnosed with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, which subsequently led to a global pandemic. To date, there are no studies evaluating the relationship between the respiratory phageome and the SARS-CoV-2 infection. The current study investigated the phageome profiles in the nasopharyngeal swabs collected from 55 patients during the three different waves of coronavirus disease 2019 (COVID-19) in the Campania Region (Southern Italy). Data obtained from the taxonomic profiling show that phage families belonging to the order Caudovirales have a high abundance in the patient samples. Moreover, the severity of the COVID-19 infection seems to be correlated with the phage abundance.

This study aims to analyse the relationship between the incidence of bad splits and the surgical tools adopteded to perform bilateral sagittal split ramus osteotomy (BSSRO).BSSROs performed by the same experienced surgeon period were reviewed, retrospectively. The patients were divided into three groups according to the surgical instrument used to perform the osteotomy: a Lindemann burr, reciprocating saw or piezosurgery. Among the 1120 BSSROs performed, 5 bad fractures were detected during the observation period: 3 among patients operated with the Lindemann burr (0.8%) and 2 among those operated with a reciprocating saw (0.5%). There was no significant correlation between the bad split rate and age and gender of the patients, the type of malocclusion or the type of instrument used to perform the osteotomy. Within the limitations of the study it seems that the the choice of the osteotomy tool for BSSRO does not influence the rate of bad fractures and, therefore, the selection of the osteotmy tool should be left to the discretion of the surgeon.

The X-linked gene encoding aristaless-related homeobox (ARX) is a bi-functional transcription factor capable of activating or repressing gene transcription, whose mutations have been found in a wide spectrum of neurodevelopmental disorders (NDDs); these include cortical malformations, paediatric epilepsy, intellectual disability (ID) and autism. In addition to point mutations, duplications of the ARX locus have been detected in male patients with ID. These rearrangements include telencephalon ultraconserved enhancers, whose structural alterations can interfere with the control of ARX expression in the developing brain. Here, we review the structural features of 15 gain copy-number variants (CNVs) of the ARX locus found in patients presenting wide-ranging phenotypic variations including ID, speech delay, hypotonia and psychiatric abnormalities. We also report on a further novel Xp21.3 duplication detected in a male patient with moderate ID and carrying a fully duplicated copy of the ARX locus and the ultraconserved enhancers. As consequences of this rearrangement, the patient-derived lymphoblastoid cell line shows abnormal activity of the ARX-KDM5C-SYN1 regulatory axis. Moreover, the three-dimensional (3D) structure of the Arx locus, both in mouse embryonic stem cells and cortical neurons, provides new insight for the functional consequences of ARX duplications. Finally, by comparing the clinical features of the 16 CNVs affecting the ARX locus, we conclude that—depending on the involvement of tissue-specific enhancers—the ARX duplications are ID-associated risk CNVs with variable expressivity and penetrance.

Exercise intolerance represents a typical feature of heart failure with preserved ejection fraction (HFpEF), and is associated with a poor quality of life, frequent hospitalizations, and increased all-cause mortality. The cardiopulmonary exercise test is the best method to quantify exercise intolerance, and allows detection of the main mechanism responsible for the exercise limitation, influencing treatment and prognosis. Exercise training programs improve exercise tolerance in HFpEF. However, studies are needed to identify appropriate type and duration. This article discusses the pathophysiology of exercise limitation in HFpEF, describes methods of determining exercise tolerance class, and evaluates prognostic implications and potential therapeutic strategies.

Recent pharmacological research on milk whey, a byproduct of the dairy industry, has identified several therapeutic properties that could be exploited in modern medicine. In the present study, we investigated the anticancer effects of whey from Mediterranean buffalo (Bubalus bubalis) milk. The antitumour effect of delactosed milk whey (DMW) was evaluated using the HCT116 xenograft mouse model of colorectal cancer (CRC). There were no discernible differences in tumour growth between treated and untreated groups. Nevertheless, haematoxylin and eosin staining of the xenograft tissues showed clearer signs of different cell death in DMW-treated mice compared to vehicle-treated mice. Detailed biochemical and molecular biological analyses revealed that DMW was able to downregulate the protein expression levels of c-myc, phospho-Histone H3 (ser 10) and p-ERK. Moreover, DMW also activated RIPK1, RIPK3, and MLKL axis in tumour tissues from xenograft mice, thus, suggesting a necroptotic effect. The necroptotic pathway was accompanied by activation of the apoptotic pathway as revealed by increased expression of both cleaved caspase-3 and PARP-1. At the molecular level, DMW-induced cell death was also associated with (i) upregulation of SIRT3, SIRT6, and PPAR-γ and (ii) downregulation of LDHA and PPAR-α. Overall, our results unveil the potential of whey as a source of biomolecules of food origin in the clinical setting of novel strategies for the treatment of CRC.

Background Noonan and Noonan-like syndromes are multisystem genetic disorders, mainly with autosomal dominant trasmission, caused by mutations in several genes. Missense pathogenetic variants of SOS1 gene are the second most common cause of Noonan syndrome (NS) and account approximately for 13% to 17% of cases. Subjects carrying a pathogenetic variant in SOS1 gene tend to exhibit a distinctive phenotype that is characterized by ectodermal abnormalities. Cutis verticis gyrata (CVG) is a rare disease, congenital or acquired, characterized by the redundancy of skin on scalp, forming thick skin folds and grooves of similar aspect to cerebral cortex gyri. Several references in the literature have reported association between nonessential primary form of CVG and NS. Case presentation we report two cases of newborns with CVG and phenotype suggestive for NS who have been diagnosed to harbour the same pathogenetic variant in SOS1 gene. Conclusions previously described patients with NS presenting CVG had received only clinical diagnosis. Therefore we report the first patients with CVG in which the clinical suspicion of NS is confirmed by molecolar analysis.

SUMMARY OBJECTIVE: A multicentric, cross-sectional study was carried out to determine the prevalence and risk factors for Coronavirus disease 2019 in medical students and residents from four universities and affiliated hospitals in Brazil. METHODS: A survey about contamination risk and symptoms was sent to all participants through email and WhatsApp. Prevalence was measured by the self-report of positive polymerase chain reaction or serological test. Univariate and multivariate analyses were performed, and odds ratio and 95% confidence interval were calculated. RESULTS: Prevalence of infection by Sars-CoV-2 was 14.9% (151/1011). The disease was more prevalent in residents and interns than in undergraduate students. Contact with an infected relative outside the hospital or with colleagues without using personal protective equipment was associated with higher contamination. Contact with patients without wearing goggles and higher weekly frequency of contact were the two factors independently associated with the infection by Coronavirus disease 2019 in the multivariate analysis. CONCLUSIONS: Medical students, interns, and residents have a higher prevalence of Coronavirus disease 2019 than the general population, in which the last two groups are significantly at higher risk. Contacting patients at a higher weekly frequency increases the risk for infection. The use of goggles should be reinforced when contacting patients.

The aim of this study has been to describe our experience with pleomorphic adenomas of the parapharyngeal space (PPS) treated with trans-oral robotic surgery (TORS). Tumors arising from the PPS comprise less than 0.5% of all head and neck tumors. Salivary gland tumors account for 40% to 50% of PPS lesions with pleomorphic adenomas representing the most common salivary tumors (80%-90%). Parapharyngeal space tumors cause nonspecific symptoms and may be difficult to diagnose.In our study a preoperative diagnosis was conducted by fine needle aspiration biopsy and magnetic resonance imaging and the results were used to plan the correct surgical approach.In all cases we were able to employ TORS, a minimally invasive procedure that allows us to operate in narrow and anatomically complex spaces that we can only reach thanks to the use of well-articulated hand pieces.This report indicates that TORS is a safe surgical procedure for the excision of benign tumors of the PPS in selected cases.

We aimed to analyze the representativeness of women surgeons in academic and leadership positions in Brazil. We investigated women representativeness across surgical departments of 25 Brazilian universities (2020); across boards of 10 Brazilian surgical societies (2020), and, as speakers, in 281 surgical events (Jan-2014 to Dec-2020). From 383 individuals in university departments, 43 (11.2 %) were women (p 0.001). Only three universities had women as department chairs. From 163 positions in surgical societies, only 14 positions (8.6 %) were held by women (p 0.001). The underrepresentation is worse in prestigious positions (presidency and vice-presidency), in which only 1 (5 %) were women. In 281 surgical events, there were 6686 speakers, of which only 886 (13.3 %) of these were women (p 0.001). Further studies are needed to elucidate the possible causes for the gender gap in these scenarios in Brazil, so as to implement effective strategies to improve gender representativeness in surgery in the country.

Aims: Limited data are available regarding cardiac expression of molecules involved in heart failure (HF) pathophysiology. The majority of the studies have focused on end-stage HF with reduced ejection fraction (HFrEF) without comparison with healthy subjects, while no data are available with regard to HF with preserved ejection fraction (HFpEF). HFpEF is a condition whose multiple pathophysiological mechanisms are still not fully defined, with many proposed hypotheses remaining speculative due to limited access to human heart tissue. This study aimed at evaluating cardiac expression levels of key genes of interest in human biopsy samples from patients affected with HFrEF and HFpEF in order to possibly point out distinct phenotypes. Methods and results: Total RNA was extracted from left ventricular cardiac biopsies collected from stable patients with HFrEF (n=6) and HFpEF (n=7) and healthy subjects (n=9) undergoing elective cardiac surgery for valvular replacement, mitral valvuloplasty, aortic surgery, or coronary artery bypass. Real-time PCR was performed to evaluate the mRNA expression levels of genes involved in somatotropic axis regulation [IGF-1, IGF-1 receptor (IGF-1R), and GH receptor (GHR)], in adrenergic signalling (GRK2, GRK5, ADRB1, and ADRB2), in myocardial calcium handling (SERCA2), and in TNF-α. Patients with HFrEF and HFpEF showed reduced serum IGF-1 circulating levels when compared with controls (102±35.6, 138±11.5, and 160±13.2ng/mL, P&nbsp

This retrospective multicenter cohort study aimed to evaluate the clinical outcomes (mortality rate, operative time, complications) of elective laparoscopic cholecystectomy (LC) when performed by a surgical resident in comparison to experienced consultant in the backdrop of Italian academic centers.Retrospective review of all patients undergoing elective LC between January 2016 and January 2022 at six teaching hospitals across Italy was performed. Cases were identified using the Current Procedural Terminology (CPT) code 5123 (LC without cholangiogram). All cases of emergency surgery, ASA score 3, or when cholecystectomy was performed with another surgical procedure, were excluded. All suitable cases were divided into 2 groups based on primary surgeon: consultant or senior resident. Main outcome was complication rates (intraoperative and peri/postoperative); secondary outcomes included operative time, the length of stay, and the rate of conversion to open.A total of 2331 cases (1425 females) were included, of which, consultants performed 1683 LCs (72%), while the residents performed 648 (28%) surgeries. The groups were statistically comparable regarding demographics, history of previous abdominal surgery, operative time, or intraoperative complications. The rate of conversion to open cholecystectomy was 1.42% for consultant and none for resident (p = 0.02). A statistically significant difference was observed between groups regarding the average length of stay (2.2 ± 3 vs 1.6 ± 1.3 days p = 0.03). Similarly, postoperative complications (1.7% vs 0.5%) resulted in statistically significant (p = 0.02) favoring resident group.Our study demonstrates that in selected patients, senior residents can safely perform LC when supervised by senior staff surgeons.

Aims To explore the feasibility of upper limbs cardiopulmonary exercise test (CPET) in Friedreich ataxia (FRDA) patients and to compare the results with sex, age, and body mass index (BMI) matched cohort of healthy controls (HC). Methods and results Cardiopulmonary exercise test was performed using an upper limbs cycle ergometer on fasting subjects. Peak oxygen uptake (peak VO2) was recorded as the mean value of VO2 during a 20 s period at the maximal effort of the test at an appropriate respiratory exchange rate. The ventilatory anaerobic threshold (AT) was detected by the use of the V-slope method. We performed echocardiography with an ultrasound system equipped with a 2.5 MHz multifrequency transducer for complete M-mode, two-dimensional, Doppler, and Tissue Doppler Imaging analyses. We studied 55 FRDA and 54 healthy matched controls (HC). Peak VO2 showed a significant 31% reduction in FRDA patients compared to HC (15.2 ± 5.7 vs. 22.0 ± 6.1 mL/kg/min; P Conclusions Upper limb CPET is useful in the assessment of exercise tolerance and a possible tool to determine the functional severity of the mitochondrial oxidative defect in patients with FRDA. The cardiopulmonary exercise test is an ideal functional endpoint for Phases II and III trials through a simple, non-invasive, and safe exercise test.

Background Although type 1 diabetes (T1D) represents one of the most common chronic diseases in pediatric age, few studies on the epidemiology of T1D exist globally and the exact prevalence and incidence rates of the disease are unknown. In many countries, including Italy, national registries are missing. Methods This study aims to assess T1D incidence in the pediatric population of the Calabria region (southern Italy) in the period 2019–2021. The secondary objective was to describe the main demographical, clinical and immunological features of incident cases. Case ascertainment and all clinical data were assessed by retrospectively reviewing the electronic medical records of children and adolescents diagnosed with diabetes at any Pediatric Diabetes Center belonging to the Rete Diabetologica Calabrese (Calabria Region Diabetes Network), from January 2019 to December 2021. The incidence of T1D was estimated for the entire region and was stratified according to age group (0–4 years, 5–9 years, and 10–14 years) and gender. Standardized incidence ratios for each province in the region were also calculated. Results The crude incidence of T1D was 20.6/100,000 person/years. Incidence rates were higher among females and children aged 5–9 years. The crude incidence of T1D was higher in the province of Reggio Calabria (26.5/100,000 person-years). The provinces of Crotone, Catanzaro, and Vibo Valentia showed significantly lower standardized incidence ratios. The annual incidence in the region progressively increased by 43% during the study period. Conclusions Our study revealed a relatively high incidence in the Calabria region. The marked increasing incidence trend over the past two years could be related to the global impact of the COVID-19 pandemic, but further long-scale population-based studies are needed to confirm these findings.

Background Findings from the T.O.S.CA. Registry recently reported that patients with concomitant chronic heart failure (CHF) and impairment of insulin axis (either insulin resistance—IR or diabetes mellitus—T2D) display increased morbidity and mortality. However, little information is available on the relative impact of IR and T2D on cardiac structure and function, cardiopulmonary performance, and their longitudinal changes in CHF. Methods Patients enrolled in the T.O.S.CA. Registry performed echocardiography and cardiopulmonary exercise test at baseline and at a patient-average follow-up of 36 months. Patients were divided into three groups based on the degree of insulin impairment: euglycemic without IR (EU), euglycemic with IR (IR), and T2D. Results Compared with EU and IR, T2D was associated with increased filling pressures (E/e′ratio: 15.9 ± 8.9, 12.0 ± 6.5, and 14.5 ± 8.1 respectively, p 2) in TD2 vs EU and IR patients was recorded (respectively, 15.8 ± 3.8 ml/Kg/min, 18.4 ± 4.3 ml/Kg/min and 16.5 ± 4.3 ml/Kg/min, p 2 in the T2D group (+ 13% increase in RV dimension, − 21% decline in TAPSE/PAPS ratio and − 20% decrease in peak VO2). Conclusion The higher risk of death and CV hospitalizations exhibited by HF-T2D patients in the T.O.S.CA. Registry is associated with progressive RV ventricular dysfunction and exercise impairment when compared to euglycemic CHF patients, supporting the pivotal importance of hyperglycaemia and right chambers in HF prognosis. Trial registration ClinicalTrials.gov identifier: NCT023358017

We have read with interest the recent article by Lerner et al.,which analyzed the clinical features of parosmia following coronavirus disease 2019(COVID-19). Congratulating the authors for the quality of their study, we would like to discuss some important points regarding pathogenetic hypotheses and the epidemiological implications emerging from their results.

The aim of this study was to identify features mainly involved in determining the partial response (PR) to the Electrochemotherapy (ECT) in patients with recurrent and/or metastatic head and neck (HN) tumor; the identified features were also used in a decision chart in order to provide the clinician with a support tool in deciding further therapies.131 patients (186 treatment sessions) with recurrent and/or metastatic HN neoplasm were subjected to ECT. Treatment response was evaluated based on Response Evaluation Criteria in Solid Tumors (RECIST) v. 1.1 two months after the ECT. The grade of bleeding and pain before, at the end and one week after ECT treatment were evaluated. Univariate and multivariate analysis were performed to identify features involved in determining the patient PR.In the context of the univariate analysis, tumor size significantly influenced the response to ECT, with higher PR rate of 58.3%: 28 among 48 patients with lesion size ≤ 3 centimeters (p-value0.001 at Chi-square test). Pain and bleeding pre-treatment were positively correlated to PR (p-value0.001 at Chi-square test). A difference in the current flowing in the tissue during treatment was also observed in partially responsive patients, where the median current value (6.6 A) was higher than that achieved in patients that did not show PR (3.3 A). In the context of the multivariate analysis, the best performances are achieved with the BART method (accuracy of 84%). The main clinical factors to predict the partial response, among investigated features, that have shown to be considered were the pain value felt before performing the treatment and the median current delivered during the ECT treatment. A decision-making support tool to predict the patient prognosis in terms of response rate could be represented by the decision tree obtained with CART algorithm, where a pain pre-treatment more than 5 and a median delivered current not less than 2.8 A led to the prediction a partial responsive patient with an accuracy of 75%.The study confirmed that ECT is an interesting antitumoral therapy in advanced chemo- and radio-refractory HN neoplasms, able to reduce frequent symptoms and to improve the quality of life. Pain pre-treatment and delivered current are the most important variables when predicting the partial response of patients.

Background and aims: Quick and reliable diagnostic tools play an important role in controlling the spread of the SARS-Cov-2 pandemic. The aim of this study was to evaluate the diagnostic accuracy of a new cyto-salivary antigen test aimed at detecting the presence of antigens for SARS-CoV-2, as compared by the gold standard RT-PCR and a lateral flow test. Methods: A total of 433 healthy volunteers were enrolled in the study and the sensitivity and specificity of the new cyto-salivary antigen test were calculated, as compared to the RT-PCR nasopharyngeal swab and to the lateral flow test. Results: A total of 433 samples were collected and tested at the Mediterranean Fair in Palermo from February 2021 until April 2021. The new cyto-salivary antigen had a sensitivity of 100% and a specificity of 94.2%. The sensitivity and the specificity of the lateral flow test were 55% and 100%, respectively. Conclusions: The new cyto-salivary antigen test detected more positive cases than the RT-PCR in a sample of asymptomatic subjects, demonstrating to be a promising tool for a more sensitive diagnosis of COVID-19. Further studies are warranted to better characterize its diagnostic accuracy.

La sindrome da apnee notturne: correlazione con l’obesità e gestione del paziente obeso.La sindrome da apnee notturne è una malattia caratterizzata da ostruzione delle vie aeree superiori durante il sonno, abbastanza frequente nella popolazione generale, anche se sottovalutata. Russamenti, apnee notturne e ipersonnia diurna sono comuni in questi pazienti. L’obesità svolge un ruolo chiave: riduce le dimensioni e modifica la conformazione delle vie aeree superiori, oltre a prevenire l’espansione polmonare, con conseguente riduzione dei volumi polmonari. Le persone obese sono anche resistenti alla leptina, che stimola fisiologicamente la ventilazione; di conseguenza, questo provoca uno scarso risveglio durante l’apnea. La diagnosi si basa sulla combinazione di parametri clinici, come indice di apnea / ipopnea (AHI), anamnesi, valutazione clinica e Mallampati score. La prima indagine strumentale per identificare pazienti OSAHS è la polisonnografia seguita dalla sleep endoscopy. La terapia prevede in primo luogo la riduzione del peso corporeo, seguita dalla ventilazione a pressione positiva continua delle vie aeree (CPAP), che rimane ancora ad oggi il trattamento di scelta nella maggior parte dei pazienti, dispositivi di avanzamento mandibolare (MAD) e infine diversi approcci chirurgici. Tra le tecniche chirurgiche la faringoplastica (BRP), rappresenta la tecnica prescelta.Obstructive sleep apnoea/hypopnoea syndrome (OSAHS) is a disease characterised by upper airway obstruction during sleep, quite frequent in the general population, even if underestimated. Snoring, sleep apnoea and diurnal hypersomnia are common in these patients. Central obesity plays a key role: it reduces the size and changes the conformation of the upper airways, besides preventing lung expansion, with consequent reduction of lung volumes. Furthermore, obese people are also resistant to leptin, which physiologically stimulates ventilation; as a result, this causes scarce awakening during apnoea. OSAHS diagnosis is based on the combination of clinical parameters, such as apnoea/hypopnoea index (AHI), medical history, physical examination and Mallampati score. The first objective reference method to identify OSAHS is polysomnography followed by sleep endoscopy. Therapy provides in the first instance reduction of body weight, followed by continuous positive airway pressure (CPAP), which still remains the treatment of choice in most patients, mandibular advancement devices (MAD) and finally otolaryngology or maxillofacial surgery. Among surgical techniques, central is barbed reposition pharyngoplasty (BRP), used in the field of multilevel surgery.

During the sixth World Symposium on Pulmonary Hypertension, the threshold of mean pulmonary arterial pressure (mPAP) for the definition of pulmonary hypertension (PH) has been lowered to a value of greater than 20 mmHg, measured by means of right heart catheterization at rest. In this review, we aim at describing the impact of the new definition of PH, analyzing the available data from the latest scientific literature concerning subjects with mPAP between 21 and 24 mmHg (defined as "mildly elevated PH"), discussing the impact of the new threshold for mPAP in the clinical practice, and highlighting the new perspectives in this field.

Klinefelter syndrome (KS), also known as 47, XXY, shows increased mortality when compared with mortality rates among the general population. Cardiovascular, hemostatic, metabolic diseases are implicated. Moreover, cardiac congenital anomalies in KS can contribute to the increase in mortality.In this study, we have systematically reviewed the relationships between KS and the cardiovascular system and the management of cardiovascular complication. In summary, patients with KS display increased cardiovascular risk profile, characterized by increased prevalence of metabolic alterations including dyslipidemia, diabetes mellitus (DM), and abnormalities in biomarkers of cardiovascular disease. KS subjects are characterized by subclinical abnormalities in endothelial function and in left ventricular (LV) systolic and diastolic function, which - when associated with chronotropic incompetence - may negatively influence cardiopulmonary performance. Moreover, KS patients appear to be at a higher risk for cardiovascular disease, due to thromboembolic events with high prevalence of recurrent venous ulcers, venous insufficiency, recurrent venous and arterial thromboembolism leading to deep venous thrombosis or pulmonary embolism.Considering the unequivocal finding of increased mortality of KS patients, we suggest a periodic cardiovascular follow up in specialized centers with multidisciplinary care teams that comprise endocrinologists and cardiologists dedicated to KS syndrome.

Since it was first synthesized in 1935, testosterone (T) has been viewed as the mythical Fountain of Youth, promising rejuvenation, restoring sexual appetites, growing stronger muscles, and quicker thinking. T is endowed with direct effects on myocardial and vascular structure and function, as well as on risk factors for cardiovascular (CV) disease. Indeed, low serum T levels are a risk factor for diabetes, metabolic syndrome, inflammation, and dyslipidaemia. Moreover, many studies have shown that T deficiency per se is an independent risk factor of CV and all-cause mortality. On this background and due to direct-to-patient marketing by drug companies, we have witnessed to the widespread use of T replacement therapy without clear indications particularly in late-life onset hypogonadism. The current review will dwell upon current evidence and controversies surrounding the role of T in the pathophysiology of CV diseases, the link between circulating T levels and CV risk, and the use of replacing T as a possible adjuvant treatment in specific CV disorders. Specifically, recent findings suggest that heart failure and type 2 diabetes mellitus represent two potential targets of T therapy once that a state of hypogonadism is diagnosed. However, only if ongoing studies solve the CV safety issue the T orchid may eventually ‘bloom’.

We have read with interest the recent article by Reis et al. which underlines the high frequency of persistent olfactory and gustatory dysfunctions in subjects infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).

Objective To compare the efficacy and safety characteristics of different materials used for oval window sealing during stapedotomy. Methods A systematic review was conducted according to the PRISMA guidelines. Published international English literature from January 1, 2000 to December 2021 was screened, checking for studies that compared different materials utilization in patients undergoing stapedotomy surgery for otosclerosis or congenital stapes fixation. Data related to the efficacy and safety of each material were extracted. The primary outcome measure was the air–bone gap (ABG) closure after surgical intervention. Results Six studies were included in the metanalysis. Because of the heterogeneity of the treatments adopted, we assessed the use of the fat compared to all other treatments, and the use of the gelfoam compared to all other treatments. In the former analysis (fat vs others) we did not identify differences in ABG closure between the groups (p = 0.74), with a low heterogeneity of the results (I2 = 28.36%; Hedge’s g = 0.04, 95% CI − 0.19 0.27); similarly, we did not identify differences between the use of gelfoam and other treatments (p = 0.97), with a low heterogeneity of the results (I2 = 28.91%; Hedge’s g = 0.00, 95% CI − 0.20 0.21). Conclusions Numerous options are available for oval window sealing during stapedotomy, with acceptable safety and effectiveness profiles. Based on the current data, no definitive recommendation can be made regarding the choice of one material over another, and the convenience of sealing over no sealing at all.

We read with interest the article by Messer et al.1 reporting a significant increase in time in range (TIR, +9%, P

Objective To evaluate the six-month impact of the advanced automated functions of a closed-loop control (CLC) system (Control-IQ) and a virtual educational camp (vEC) on emotions and time in range (TIR) of children and adolescents with type 1 diabetes. Methods Children and their parents participated in a three-day vEC. Clinical, glucose, and emotion data were evaluated before, just after, and six months after the vEC. Emotions were evaluated using adapted Plutchik's and Geneva Emotion Wheels. Results Forty-three children and adolescents (7–16 years) showed significant improvements in positive emotions immediately and six months after the vEC (67% and 65% vs 38%, p < 0.05, respectively), while mixed emotions were reduced (32% and 15% vs 61%, p < 0.05 and p < 0.001, respectively). The median percentage TIR increased from 64% (IQR 54–72) to 75% (IQR 70–82) with Control-IQ (p < 0.001) six months after the vEC. Conclusions Positive emotions (joy, serenity, and satisfaction) significantly improved while mixed emotions were significantly worse six months after the initiation of a CLC system (Control-IQ) and a vEC.

Interstitial pneumonia is an important complication of COVID-19 and a reliable negative prognostic factor. This study aimed to analyze the correlation between olfactory psychophysical scores and severity of lung involvement detected by chest computed tomography in COVID-19 patients suspected of having interstitial pneumonia. We also evaluated whether severity of respiratory disease predicted recovery of olfactory dysfunction .

The appropriate surgical management of early-stage oral tongue squamous cell carcinoma (OTSCC) remains a debated topic. The aim of this study is to investigate the role of the pre-treatment neutrophil to lymphocyte ratio (NLR) and tumor depth of invasion (DOI) in predicting the presence of occult neck metastases in early-stage OTSCC. A retrospective analysis of patients affected by early-stage (cT1-T2 cN0) OTSCC who were submitted to elective neck dissection (END) was performed. Tumors were classified retrospectively according to the 8th TNM classification, the DOI was assessed on the pre-operative magnetic resonance imaging, and the pre-treatment NLR was calculated for each patient. A logistic regression model to estimate the probability π (x) of cervical metastases by studying the NLR and DOI was carried out. Next, the correlation between the two variables, the NLR and DOI, was preliminarily studied. A cohort of 110 patients was analyzed (mean age, 62 years old; male to female ratio 1.2:1). The patients were staged as cT1 in 53 cases and cT2 in 57 cases. A DOI greater than 5.4 mm and a NLR greater than 2.93 are associated with an increased risk of presenting occult cervical metastases. Furthermore, the variables NLR and DOI are linearly associated with a positive correlation, proved by Spearman's rank correlation coefficient rho of 0.64, with a unitary increase in the DOI of 1 mm directly associated with an increase of 0.47 in the NLR. The DOI and NLR can be effectively used to predict the occurrence of occult neck metastasis and therefore to plan an END in early-stage OTSCC.

Objectives To analyze the demographic data, surgical and adjuvant treatment data and the survival outcomes in adult patients affected by acinic cell carcinoma of the parotid gland (AciCC). Methods A retrospective multicenter analysis of patients treated for AciCC of the parotid gland from 2000 to 2021 was performed. Exclusion criteria were pediatric (0–18 years) patients, the absence of follow-up and patients with secondary metastatic disease to the parotid gland. Multivariable logistic regression was used to determine factors associated with survival. Results The study included 81 adult patients with AciCC of the parotid gland. The median age was 46.3 years (SD 15.81, range 19–84 years), with a gender female prevalence (F = 48, M = 33). The mean follow-up was 77.7 months (min 4–max 361, SD 72.46). The 5 years overall survival (OS) was 97.5%. The 5 years disease-free survival (DFS) was 60%. No statistical differences have been found in prognosis for age (p > 0.05). Conclusion This study did not find prognostic factor for poorest outcome. In contrast with the existing literature, our results showed how also high-grade tumours cannot be considered predictive of recurrence or aggressive behaviour.

The determinants of the susceptibility to severe acute respiratory syndrome‐coronavirus‐2 (SARS‐CoV‐2) infection and severe coronavirus disease 2019 (COVID‐19) manifestations are yet not fully understood. Amino‐bisphosphonates (N‐BPs) have anti‐inflammatory properties and have been shown to reduce the incidence of lower respiratory infections, cardiovascular events, and cancer. We conducted a population‐based retrospective observational cohort study with the primary objective of determining if oral N‐BPs treatment can play a role in the susceptibility to development of severe COVID‐19. Administrative International Classification of Diseases, Ninth Revision, Clinical ModificationI (ICD‐9‐CM) and anatomical‐therapeutic chemical (ATC) code data, representative of Italian population (9% sample of the overall population), were analyzed. Oral N‐BPs (mainly alendronate and risedronate) were included in the analysis, zoledronic acid was excluded because of the low number of patients at risk. Incidence of COVID‐19 hospitalization was 12.32 (95% confidence interval [CI], 9.61–15.04) and 11.55 (95% CI, 8.91–14.20), of intensive care unit (ICU) utilization because of COVID‐19 was 1.25 (95% CI, 0.38–2.11) and 1.42 (95% CI, 0.49–2.36), and of all‐cause death was 4.06 (95% CI, 2.50–5.61) and 3.96 (95% CI, 2.41–5.51) for oral N‐BPs users and nonusers, respectively. Sensitivity analyses that excluded patients with prevalent vertebral or hip fragility fractures and without concomitant glucocorticoid treatment yielded similar results. In conclusion, we found that the incidence of COVID‐19 hospitalization, intensive care unit (ICU) utilization, and COVID‐19 potentially related mortality were similar in N‐BPs–treated and nontreated subjects. Similar results were found in N‐BPs versus other anti‐osteoporotic drugs. We provide real‐life data on the safety of oral N‐BPs in terms of severe COVID‐19 risk on a population‐based cohort. Our results do not support the hypothesis that oral N‐BPs can prevent COVID‐19 infection and/or severe COVID‐19; however, they do not seem to increase the risk. © 2021 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

Since their advent in daily clinical practice, continuous subcutaneous insulin infusion (CSII) systems have been increasingly improved, leading to a high percentage of both adult and pediatric patients with diabetes now using insulin pumps. Different types of CSII systems are currently available, which are characterized by different settings and technical features. This longitudinal observational study aims to evaluate real-word glycemic outcomes in children and adolescents with type 1 diabetes using three different CSII devices: hybrid closed-loop (HCL) systems, predictive low glucose (PLGS) systems, and non-automated insulin pumps. The secondary objective was to identify clinical variables that may significantly influence the achievement of therapeutic goals in our study cohort. One-hundred-and-one patients on CSII therapy attending our pediatric diabetes center were enrolled. When compared with the non-automated group, patients using HCL systems showed higher levels of time in target glucose range (p = 0.003) and lower glucose variability (p = 0.008). Similarly, we found significantly better glucose metrics in HCL users in comparison to PLGS patients (time in range p = 0.008; coefficient of variation p = 0.009; time above 250 mg/dL p = 0.007). Multiple linear regression models showed that HCL systems (time in range p < 0.001) and high daily percentage of glycemic sensor use (time in range p = 0.031) are predictors for good glycemic control. The introduction and increasing availability of novel technologies for diabetes represent a promising strategy to improve glycemic control and quality of life in pediatric patients with type 1 diabetes. Our real-world data confirm the superiority of HCL systems in terms of improvement of time spent in the target glucose range, prevention of hypoglycemia, and reduction of glycemic variability.

La Crosse virus (LACV) is a major cause of pediatric encephalitis and aseptic meningitis in the Midwestern, Mid-Atlantic, and Southern United States, where it is an emerging pathogen. The LACV Gc glycoprotein plays a critical role in the neuropathogenesis of LACV encephalitis as the putative virus attachment protein. Previously, we identified and experimentally confirmed the location of the LACV fusion peptide within Gc and generated a panel of recombinant LACVs (rLACVs) containing mutations in the fusion peptide as well as the wild-type sequence. These rLACVs retained their ability to cause neuronal death in a primary embryonic rat neuronal culture system, despite decreased replication and fusion phenotypes. To test the role of the fusion peptide in vivo, we tested rLACVs in an age-dependent murine model of LACV encephalitis. When inoculated directly into the CNS of young adult mice (P28), the rLACV fusion peptide mutants were as neurovirulent as the rLACV engineered with a wild-type sequence, confirming the results obtained in tissue culture. In contrast, the fusion peptide mutant rLACVs were less neuroinvasive when suckling (P3) or weanling (P21) mice were inoculated peripherally, demonstrating that the LACV fusion peptide is a determinant of neuroinvasion, but not of neurovirulence. In a challenge experiment, we found that peripheral challenge of weanling (P21) mice with fusion peptide mutant rLACVs protected from a subsequent WT-LACV challenge, suggesting that mutations in the fusion peptide are an attractive target for generating live-attenuated virus vaccines. Importantly, the high degree of conservation of the fusion peptide amongst the Bunyavirales and, structurally, other arboviruses suggests that these findings are broadly applicable to viruses that use a class II fusion mechanism and cause neurologic disease.

In this study, we investigated whether treatment with palmitoylethanolamide and luteolin (PEA-LUT) leads to improvement in the quantitative or qualitative measures of olfactory dysfunction or relief from mental clouding in patients affected by long COVID. Patients with long COVID olfactory dysfunction were allocated to different groups based on the presence (“previously treated”) or absence (“naïve”) of prior exposure to olfactory training. Patients were then randomized to receive PEA-LUT alone or in combination with olfactory training. Olfactory function and memory were assessed at monthly intervals using self-report measures and quantitative thresholds. A total of 69 patients (43 women, 26 men) with an age average of 40.6 + 10.5 were recruited. PEA-LUT therapy was associated with a significant improvement in validated odor identification scores at the baseline versus each subsequent month; assessment at 3 months showed an average improvement of 10.7 + 2.6, CI 95%: 6–14 (p < 0.0001). The overall prevalence of parosmia was 79.7% (55 patients), with a significant improvement from the baseline to 3 months (p < 0.0001), namely in 31 patients from the Naïve 1 group (72%), 15 from the Naïve 2 group (93.7%), and 9 from the remaining group (90%). Overall, mental clouding was detected in 37.7% (26 subjects) of the cases, with a reduction in severity from the baseline to three months (p = 0.02), namely in 15 patients from the Naïve 1 group (34.8%), 7 from the Naïve 2 group (43.7%), and 4 from the remaining group (40%). Conclusions. In patients with long COVID and chronic olfactory loss, a regimen including oral PEA-LUT and olfactory training ameliorated olfactory dysfunction and memory. Further investigations are necessary to discern biomarkers, mechanisms, and long-term outcomes.

Aims Recent evidence supports the occurrence of multiple hormonal and metabolic deficiency syndrome (MHDS) in chronic heart failure (CHF). However, no large observational study has unequivocally demonstrated its impact on CHF progression and outcome. The T.O.S.CA. (Trattamento Ormonale nello Scompenso CArdiaco; Hormone Treatment in Heart Failure) Registry has been specifically designed to test the hypothesis that MHDS affects morbidity and mortality in CHF patients. Methods and Results The T.O.S.CA. Registry is a prospective, multicentre, observational study involving 19 Italian centres. Thyroid hormones, insulin-like growth factor-1, total testosterone, dehydropianoandrosterone sulfate, insulin resistance, and the presence of diabetes were evaluated. A MHDS was defined as the presence of ≥2 hormone deficiencies (HDs). Primary endpoint was a composite of all-cause mortality and cardiovascular hospitalizations. Four hundred and eighty heart failure patients with ejection fraction ≤45% were enrolled. MHDS or diabetes was diagnosed in 372 patients (77.5%). A total of 271 events (97 deaths and 174 cardiovascular hospitalizations) were recorded, 41% in NO-MHDS and 62% in MHDS (P Conclusion MHDS is common in CHF and independently associated with increased all-cause mortality and cardiovascular hospitalization, representing a promising therapeutic target. Trial registration ClinicalTrials.gov identifier: NCT023358017

Major surgical societies advised using non-operative management of appendicitis and suggested against laparoscopy during the COVID-19 pandemic. The hypothesis is that a significant reduction in the number of emergent appendectomies was observed during the pandemic, restricted to complex cases. The study aimed to analyse emergent surgical appendectomies during pandemic on a national basis and compare it to the same period of the previous year. This is a multicentre, retrospective, observational study investigating the outcomes of patients undergoing emergent appendectomy in March–April 2019 vs March–April 2020. The primary outcome was the number of appendectomies performed, classified according to the American Association for the Surgery of Trauma (AAST) score. Secondary outcomes were the type of surgical technique employed (laparoscopic vs open) and the complication rates. One thousand five hundred forty one patients with acute appendicitis underwent surgery during the two study periods. 1337 (86.8%) patients met the inclusion criteria: 546 (40.8%) patients underwent surgery for acute appendicitis in 2020 and 791 (59.2%) in 2019. According to AAST, patients with complicated appendicitis operated in 2019 were 30.3% vs 39.9% in 2020 (p = 0.001). We observed an increase in the number of post-operative complications in 2020 (15.9%) compared to 2019 (9.6%) (p 24 h after admission (+ 58%), open surgery (+ 112%) and conversion to open surgery (+ 166%). In Italian hospitals, in March and April 2020, the number of appendectomies has drastically dropped. During the first pandemic wave, patients undergoing surgery were more frequently affected by more severe appendicitis than the previous year's timeframe and experienced a higher number of complications. Trial registration number and date: Research Registry ID 5789, May 7th, 2020

Objectives This study aimed to determine the effect of the use of a bipolar coagulator on postoperative pain and complications when used during connective tissue harvesting from the palate. Material and methods A randomized controlled clinical trial was conducted with 57 sequential patients requiring a connective tissue graft for periodontal or implant surgery. All samples were harvested superficially and de‐epithelized outside the mouth. The patients were randomly allocated to two groups: in one group, the bipolar coagulator was used before suturing to control bleeding, and in the other group, the coagulator was not used. The surgeon was unaware of the randomization until the end of the harvesting phase. Self‐reported maximum pain, number of painkillers used, bleeding events, emergency visits at the clinic were recorded 7 days after surgery. Results Fifty patients were randomized and treated (seven were excluded for different reasons). The mean harvested area was 75.24 mm2 (SD, 33.96), and the mean thickness of the samples was 2.47 mm (SD, 0.75). The mean self‐reported pain value on the visual analog scale was 3.37 (SD, 2.30), and the mean number of pain medications used was 7.1 (SD, 6.60). Seven patients made an emergency visit each, and 17 delayed bleeding events were reported by 15 patients. No statistically significant differences were reported in postoperative pain, postoperative bleeding, and emergency visit to the clinic between the groups that did and did not use the bipolar coagulator. When smoking habits were taken into consideration, the number of pain medications was higher among male smokers and older smokers than among male non‐smokers and younger smokers. This study was not able to find a relationship between harvested sample dimension or thickness and postoperative discomfort. Conclusions The bipolar coagulator can be used during connective tissue harvesting from the palate to control bleeding without influencing postoperative pain.

Skin involvement is an overlooked aspect in the management of paediatric patients with type 1 diabetes. A comprehensive search of published literature using the PubMed database was carried out using the following key terms: “children”, “pediatric/paediatric patients”, “skin”, “skin disorders”, “type 1 diabetes”. Dermatological side effects are frequently observed among diabetic children and adolescents. Insulin-induced lipodystrophies and allergic contact dermatitis caused by insulin pumps or glycaemic sensors are the most common skin reactions in these patients. Furthermore, several diabetes-associated skin diseases such as necrobiosis lipoidica, granuloma annulare, vitiligo, and bullosis diabeticorum may already be present in paediatric age. Paediatric diabetes specialists should pay attention to their patients’ skin so as to recognize these disorders, identify the potential causes, and choose the most suitable treatment. Finally, the evaluation of skin concentrations of advanced glycation end-products using non-invasive diagnostic techniques may be used to assess the risk of chronic complications of diabetes as early as adolescence.

"Chronic heart failure (CHF) is a complex syndrome characterized by symptoms and signs supported by different forms of cardiac impairment. The link between multiple hormonal and metabolic derangements and the development of CHF and the beneficial effects seen with hormonal replacement therapy suggest that a reduction of anabolic pathways might contribute to the onset of CHF. Therefore, an imbalance between anabolic and catabolic forces could be responsible for the development of CHF. There are sufficient evidence to support the screening in patients with CHF of hormonal deficiencies and their correction with replacement therapy."

Background: The contribution of gut dysfunction to heart failure (HF) pathophysiology is not routinely assessed. We sought to investigate whether biomarkers of gut dysfunction would be useful in assessment of HF (eg, severity, adverse outcomes) and risk stratification.Methods: A panel of gut-related biomarkers including metabolites of the choline/carnitine- pathway (acetyl-L-carnitine, betaine, choline, γ-butyrobetaine, L-carnitine and trimethylamine-N-oxide [TMAO]) and the gut peptide, Trefoil factor-3 (TFF-3), were investigated in 1,783 patients with worsening HF enrolled in the systems BIOlogy Study to TAilored Treatment in Chronic Heart Failure (BIOSTAT-CHF) cohort and associations with HF severity and outcomes, and use in risk stratification were assessed.Results: Metabolites of the carnitine-TMAO pathway (acetyl-L-carnitine, γ-butyrobetaine, L-carnitine, and TMAO) and TFF-3 were associated with the composite outcome of HF hospitalization or all-cause mortality at 3 years (hazards ratio [HR] 2.04-2.93 [95% confidence interval {CI} 1.30-4.71] P≤.002). Combining the carnitine-TMAO metabolites with TFF-3, as a gut dysfunction panel, showed a graded association; a greater number of elevated markers was associated with higher New York Heart Association class (PConclusions: A panel of biomarkers of gut dysfunction showed graded association with severity of HF and adverse outcomes. Biomarkers as surrogate markers are potentially useful for assessment of gut dysfunction to HF pathophysiology and in risk stratification.