Oral semaglutide improves body composition and preserves lean mass in patients with type 2 diabetes: a 26-week prospective real-life study.

Background: Oral semaglutide is the first glucagon-like peptide-1 receptor agonist (GLP-1RA) designed for oral administration; it offers a promising opportunity to facilitate an early approach to Type 2 Diabetes (T2D). The study aimed to evaluate, in a real-life setting, the effects of oral semaglutide on the body composition of patients with T2D after 26 weeks of therapy. Methods: Thirty-two patients with T2D were evaluated at baseline (T0) and after three (T3) and six (T6) months of therapy with oral semaglutide. At each time point, body composition was assessed using a phase sensitive bioimpedance analyzer. Clinical, anthropometric and laboratory parameters, and the main biometric surrogates of liver steatosis and fibrosis, were also analyzed and compared. Results: A significant and early reduction in anthropometric and glucometabolic parameters, alanine aminotransferase, Fatty Liver Index, and Fat Mass was observed. Visceral Adipose Tissue (VAT) decreased, while Fat Free Mass and Skeletal Muscle Mass (SMM) were preserved during therapy, resulting in a beneficial increase in the SMM/VAT ratio. Finally, an overall improvement in body fluid distribution was observed. Conclusion: Our real-world data confirm the clinical efficacy of oral semaglutide and highlight its ability to improve the nutritional status of patients with T2D.

Placental Angiodysplasia: A New Sign for Prediction of Fetal Outcome?

The study of the placenta is of great importance, not only in the attempt to understand the etiopathogenesis of various maternal-fetal pathologies, but also in the attempt to understand whether it is possible to find the cause of pathological neonatal outcomes. On the other hand, abnormalities of blood vessel formation, such as angiodysplasias, have been poorly characterised in the literature, and there is a need for more studies investigating the potential impact on the fetus. In this paper, we retrospectively analysed 2063 placentas received at the Department of Pathology of the University of Bari 'Aldo Moro', among which we identified 70 placentas affected by angiodysplasia. On these placentas, we carried out histochemical staining with Masson's Trichrome, orcein-alcian blue, and, subsequently, immunostaining with anti-CD31, CD34, and desmin and actin muscle smoothness antibodies. Finally, we performed a morphometric analysis on the allantochorionic and truncal vessels and correlated the results with neonatal outcomes. We studied the characteristics of the angiodysplasias in detail, dividing the patients into two classes (A and B) according to the morphology and histochemical characteristics of the affected vessels; statistical analysis reported a statistically significant association (p < 0.05) between the ratio of maximum thickness to maximum diameter (Tmax/Dmax) and neonatal outcome, with only 30% physiological outcome in the cohort of the placentas affected by angiodysplasia. These results shed light on a rather neglected aspect in the 2015 Amsterdam Classification, as well as in the literature, and provided strong evidence that placental angiodysplasia is predictive of an increased likelihood of the pathological fetal outcome, while other factors remain in the field. Studies with larger case series and guidelines with more attention to these aspects are mandated to further investigate the predictive potential of this pathology.

Once-Weekly Subcutaneous Semaglutide Improves Fatty Liver Disease in Patients with Type 2 Diabetes: A 52-Week Prospective Real-Life Study.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is commonly observed in patients with type 2 diabetes (T2D). Semaglutide, a glucagon-like peptide 1 receptor agonist, may have a therapeutic role by targeting common mechanisms involved in the pathophysiology of T2D and NAFLD. The study aimed to assess the effectiveness of Semaglutide on NAFLD in patients with T2D. METHODS: Forty-eight patients were treated with subcutaneous Semaglutide in add-on to metformin for 52 weeks. After the baseline visit (T0), follow-up was scheduled quarterly (T3, and T6) and then at 12 months of therapy (T12). During each visit, body composition was analyzed by phase-sensitive bio-impedance, and NAFLD was diagnosed and staged by Ultrasound (US) imaging. Surrogate biomarkers of NAFLD were also calculated and followed over time. RESULTS: A significant decrease in anthropometric and glucometabolic parameters, insulin resistance, liver enzymes, and laboratory indices of hepatic steatosis was observed during treatment. Similarly, fat mass and visceral adipose tissue (VAT) decreased over time more than skeletal muscle and free-fat mass. US-assessed VAT thickness and the 12-point steatosis score also declined at T3 up to T12. Liver steatosis improved in most patients (70%), showing a reduction by at least one class in the semiquantitative US staging. CONCLUSION: Besides glucose control and body composition improvements, Semaglutide was effective in ameliorating the clinical appearance and severity of NAFLD in T2D patients.

Once-Weekly Semaglutide Induces an Early Improvement in Body Composition in Patients with Type 2 Diabetes: A 26-Week Prospective Real-Life Study.

BACKGROUND: Body weight (BW) loss is an essential therapeutic goal in type 2 diabetes (T2D). Glucagon-like peptide-1 receptor agonists are effective in reducing BW, but their effect on body composition has not yet been fully explored. The study aim was to assess the impact of Semaglutide on body composition in patients with T2D. METHODS: Forty patients with T2D were treated with subcutaneous Semaglutide and evaluated at the baseline (T0) and after three (T3) and six (T6) months. Body composition was assessed by a phase-sensitive bioimpedance analyzer. Visceral adipose tissue (VAT) thickness was also measured with an ultrasonographic method (US-VAT). Anthropometric variables, muscular strength, and laboratory tests were analyzed and compared. RESULTS: A significant decrease in VAT, the fat mass index (FMI), and BW loss was observed at all observation times. US-VAT, the skeletal mass index (SMI), the fat-free mass index (FFMI), waist circumferences, and glycated hemoglobin had lessened after three months and remained stable at T6. No variations in muscle strength, the muscle quality index, and body water were found. DISCUSSION: In a real-life setting, Semaglutide provided significant weight loss mainly due to a reduction in the FMI and VAT, with non-clinically relevant changes in the SMI, the FFMI, and muscle strength. Most importantly, the results were obtained after three months of treatment and persisted thereafter.

SARS-CoV-2, Placental Histopathology, Gravity of Infection and Immunopathology: Is There an Association?

(1) Background: As the pandemic months progress, more and more evidence shows that the placenta acts as a "barrier" to SARS-CoV-2, although rare cases of vertical transmission have been described. (2) Methods: In an attempt to investigate whether the symptoms' severity was related to different placental histological characteristics and the immune microenvironment, we subdivided 29 placentas from 29 mothers positive for SARS-CoV-2 into two groups, depending on the symptomatology (moderate/severe vs. asymptomatic/mild), performing immunohistochemical investigations for CD4 + and CD8 + T lymphocytes, as well as for CD68 + macrophage. We also evaluated the immuno-expression of the ACE2 receptor at the placental level. These two groups were compared to a control group of 28 placentas from 28 SARS-CoV-2-negative healthy mothers. (3) Results: The symptoms (likely to be related to viremia) were statistically significantly correlated (p < 0.05) with histopathological changes, such as maternal malperfusion, decidual arteriopathy, blood vessel thrombus of fetal relevance. Furthermore, the immuno-expression of ACE2 was significantly lower in SARS-CoV-2-positive groups vs. control group (p = 0.001). (4) Conclusions: There is still much to study and discover regarding the relationship between SARS-CoV-2 and histological changes in placentas and how the latter might contribute to various neonatal clinical outcomes, such as prematurity.

Lead exposure of rats during and after pregnancy induces anti-myelin proteolytic activity: a potential mechanism for lead-induced neurotoxicity.

Toxic effects of lead (Pb) are principally manifested in the central nervous system (CNS) and a mounting body of evidence indicates that excessive chronic exposure to Pb participates in the pathological processes of numerous neurodegenerative disorders in humans.In this study we evaluated whether the prolonged pre- and postnatal exposure of rat pups to lead, administrated through ingestion in drinking water, as a typical environmental exposure, can determine alterations of the protein pattern of CNS myelin and the induction of myelin-associated proteinases. Pregnant dams were given distilled water or 0.3 mg/mL lead acetate in drinking water during gestation and lactation. At postnatal day (PND) 21, pups born from mothers poisoned with Pb continued the treatment with the metal. On PND 35 and 56, pups were sacrificed, and brains were subjected to myelin purification and extraction of myelin-associated proteinases. The SDS-PAGE analysis of protein pattern of myelin incubated in vitro with an oxidative system indicated that myelin proteins from Pb-treated pups were more sensitive to the toxicity of reactive oxygen species in comparison with those from untreated pups. The zymografic analysis of NaCl-extracts from myelin of Pb-treated pups showed a band of digestion of 54 kDa that increased in pups sacrificed at PND 56 in comparison with those sacrificed at PND 35 and correlated with the concentration of Pb, detected in purified myelin. The incubation of the NaCl-extract from Pb-treated pups with purified myelin basic protein (MBP) evidenced the presence of different MBP-degrading activities. These results suggest that Pb may influence the integrity of the myelin sheath, probably through the induction of anti-myelin proteinases.

Laminar Necrosis and Hypoxic Damage of the Placenta: A Case-Control Study.

The aim of this study is to verify the role of laminar necrosis (LN) in the diagnosis of hypoxic damage of the placenta. This is a retrospective case-control study in which 50 cases with laminar necrosis were compared with 100 gestational age-matched controls without laminar necrosis in a 1:2 ratio. The parameters analyzed were: the presence of other placental lesions, obstetric characteristics and neonatal outcome. For each of the 50 cases, the area affected by the lesion was detected, and the lesions were classified into three groups based on the morphology and time of onset of the lesion in order to understand whether these characteristics of the lesion had a clinical-pathology. The results showed that including the search for LN among placental lesions generally examined is useful to guide the pathologist in the diagnosis of placental dysfunction of hypoxic origin.

Analysis of clinical factors as possible predictors of response to omalizumab and relapse after treatment discontinuation in chronic spontaneous urticaria.

Omalizumab is a monoclonal anti-IgE antibody which is effective in chronic spontaneous urticaria (CSU), although clinical response appears to be variable in the real-life setting. The aim of this study was to evaluate whether the response of CSU to omalizumab and disease relapse are associated with individual and/or clinical characteristics of patients. We retrospectively evaluated the clinical records of 124 patients treated with omalizumab for moderate to severe CSU refractory to antihistamines. Disease activity was assessed using the urticaria activity score over the last 7 days (UAS7). After 24 weeks of treatment, 91% of patients showed complete remission (UAS7 = 0) or good control (UAS7 < 7) of CSU. Omalizumab was re-administered in 45 patients because of recurrence of moderate to severe symptoms at week 8 after treatment discontinuation or later, and clinical results achieved with retreatment were similar to those observed in the first course. Among the parameters included in our analysis (age and sex of patients, documented history of atopy or autoimmune thyroid disease, CSU duration and baseline severity, concurrent angioedema, and association with chronic inducible urticaria), none was associated with response to omalizumab in our study population. Similarly, these parameters did not significantly differ between patients who experienced CSU relapse and those without relapse. Predictors of response to omalizumab treatment in CSU patients are still unclear, and further studies are needed to evaluate the presence of baseline factors that can influence treatment outcome.

Perinatal Transmission and Outcome of Neonates Born to SARS-CoV-2-Positive Mothers: The Experience of 2 Highly Endemic Italian Regions.

INTRODUCTION: COVID-19 is the disease caused by the novel coronavirus SARS-CoV-2, responsible of the pandemic declared in March 2020 and still ongoing. COVID-19 affects all ages but presents less complications and fatalities in children. Neonatal infections have rarely been reported worldwide, and vertical transmission is uncertain. METHODS: We conducted a prospective cohort study of all infants born to SARS-CoV-2-positive mothers admitted to 2 hospitals in South (Bari) and North (Varese) of Italy from April to December 2020. A molecular nasopharyngeal swab for SARS-CoV-2 using a reverse transcriptase polymerase chain reaction was made at birth for all enrolled newborns to evaluate vertical transmission of infection. We also evaluated postnatal transmission with a second nasopharyngeal swab made at 1 month of life and described maternal and neonatal clinical findings and short-term outcomes. RESULTS: 176/179 (97%) newborns were SARS-CoV-2 negative at birth and 151/156 (97%) infants were still negative at 1 month of life. All newborns were asymptomatic. Seventy percent of newborns were breastfed during hospitalization. At 1 month of life, 76% of infants were breastfed. CONCLUSION: According to our results, vertical and perinatal infection is very rare. Breastfeeding does not increase the risk of COVID-19 and should be encouraged.

Satisfaction with online teaching of medical statistics during the COVID-19 pandemic: A survey by the Education Committee of the Italian Society of Medical Statistics and Clinical Epidemiology.

On May 2020, after 2 months of online teaching with no face-to-face lectures, the Education Committee of the Italian scientific Society of Medical Statistics and Clinical Epidemiology conceived an online survey to assess satisfaction of Italian academics of medical statistics with online teaching and remote exams. This survey highlighted teachers' perceptions as well as opportunities and limitations of online teaching of medical statistics, biostatistics, and epidemiology. Although 61% of Italian academics of medical statistics declared to be favorable to provide online teaching of medical statistics, biostatistics, and epidemiology in the future, we recognize that distance education cannot substitute the unique value of teaching and knowledge exchange that could only be transmitted through a personal interaction between students and teachers. These indications may be useful to improve the quality of the teaching process in the future.

SARS-CoV-2 and Placenta: New Insights and Perspectives.

The study of SARS-CoV-2 positive pregnant women is of some importance for gynecologists, obstetricians, neonatologists and women themselves. In recent months, new works have tried to clarify what happens at the fetal-placental level in women positive for the virus, and different pathogenesis mechanisms have been proposed. Here, we present the results of a large series of placentas of Coronavirus disease (COVID) positive women, in a reference center for COVID-positive pregnancies, on which we conducted histological, immunohistochemical and electron microscopy investigations. A case-control study was conducted in order to highlight any histopathological alterations attributable to SARS-CoV-2. The prevalence of maternal vascular malperfusion was not significantly different between cases and controls (54.3% vs. 43.7% p = 0.19), whereas the differences with regard to fetal vascular malperfusion (21.1% vs. 4.2% p < 0.001) were significant. More frequent in cases with respect to controls were decidual arteriopathy (40.9% vs. 1.4% p < 0.0001), decidual inflammation (32.4% vs. 0.7% p < 0.0001), perivillous fibrin deposition (36.6% vs. 3.5% p < 0.0001) and fetal vessel thrombi (22.5% vs. 0.7% p < 0.0001). No significant differences in the percentage of terminal villous hyperplasia and chorioamnionitis were observed between the two groups. As the pandemic continues, these studies will become more urgent in order to clarify the possible mechanism of maternal-fetal transmission of the virus.

Altered Gene Expression Encoding Cytochines, Grow Factors and Cell Cycle Regulators in the Endometrium of Women with Chronic Endometritis.

To evaluate the expression of genes encoding cytokines, grow factors and cell cycle regulators in the proliferative endometrium of women with chronic endometritis (CE) compared to controls. We performed a case-control study on seven women with CE as diagnosed by hysteroscopy and histology (Cases) compared to six women without CE (Controls). All women underwent diagnostic hysteroscopy plus endometrial biopsy during the mid-proliferative phase of the menstrual cycle. Endometrial samples were divided into two different aliquots for histological and molecular analyses. The endometrial expression profile of 16 genes encoding proteins involved in the inflammatory process, proliferation and cell cycle regulation/apoptosis was assessed by using high-throughput qPCR. Study endpoints were between-group differences in the expression of VEGF A, VEGF B, VEGF C, EGF, TNF, TGF B1, IFNG, TP73, TP73L, BAXva, CDC2, CDC2va, CCND3, CCNB1, BAX and IL12. RESULTS: VEGF A, VEGF B, VEGF C, EGF, TNF, TGF B1, IFNG, TP73, TP73L, BAXva, CDC2, CDC2va, CCND3, CCNB1 were significantly overexpressed in women with CE compared to controls, while BAX and IL12 had similar expression between groups. In women with CE, we found an altered endometrial expression of genes involved in inflammatory, cell proliferation, and apoptosis processes. The dominance of proliferative and anti-apoptotic activity in CE may potentially promote the development of polyps and hyperplastic lesions.

Maternal Psychological Factors and Onset of Functional Gastrointestinal Disorders in Offspring: A Prospective Study.

BACKGROUND/OBJECTIVES: Functional gastrointestinal disorders (FGIDs) are a heterogeneous group of conditions of unclear etiology. The biopsychosocial model approach to FGIDs posits that early-life stressors may trigger a cascade of complex interactions between genetic predisposition and risk factors eventually leading to the occurrence of FGIDs. The relationship between the psychological disposition of the mother and FGIDs occurrence is poorly understood. We conducted a study to investigate if parental psychological factors may contribute to the onset of FGIDs in offspring. METHODS: We performed a prospective cohort study of parent-infant pairs who completed a battery of self-reported psychological questionnaires and a validated Rome III questionnaire for the diagnosis of infant and toddler FGIDs. The Edinburgh Postpartum Depression Scale (EPDS) was used to examine postpartum depression (PPD) symptoms; the Maternity Blues Questionnaire (MBQ) was applied to measure maternity blues severity; the Symptoms Checklist-Revised (SCL90-R) was used to assess the presence of relevant psychiatric symptoms; adult attachment style in mothers was assessed in a continuous way through the five dimensions of the Attachment Style Questionnaire (ASQ). RESULTS: Out of the 360 eligible mothers, 200 were enrolled, 113 completed the 3-month follow-up and were included in the final analysis. PPD symptoms prevalence was 20.4%, 20%, 13.2%, and 13.1% respectively at 3 days, 1 week, 1 month, and 3 months after delivery. 40.4% of mothers suffered from severe blues according to the MBQ. Relevant psychiatric symptoms (SCL90-R) were present in 7.8% and 10.9% of mothers, respectively at 1 week and 3 months after delivery. 48.7% of mothers showed a secure attachment pattern measured through the RQ. At 1-month follow-up, infant regurgitation was diagnosed in 26 (23%) of infants, infantile colic in 31 (27.4%), dyschezia in 17 (15%), and functional constipation in 9 (8%). At 3-month follow-up, FGIDs prevalence was respectively 16 (19.3%), 11 (13.3%), 4 (4.8%), and 11 (13.3%). A significant positive association between PPD symptoms starting 3 days after delivery and the presence of infantile colic on setting 1 month after birth was found (P = 0.028), as well as between PPD symptoms occurrence 7 days after delivery and infantile regurgitation beginning 1 month after birth (P = 0.042). A higher prevalence of infantile colic was found in the offspring of mothers suffering from PPD symptoms from 3 days after delivery (54.5 vs 19.8; P = 0.001). No significant association was found between FGIDs and psychiatric symptoms and maternity blues at any timepoint. On the other hand, mothers of infants with regurgitation with an onset 1 month after birth have higher insecurity score in avoidant and fearful ASQ-related attachment dimensions (respectively, P = 0.03, P = 0.042, P = 0.03). CONCLUSIONS: Maternal psychological factors might contribute to the onset of infant FGIDs in offspring. Early screening of postpartum depression symptoms and early implementation of psychological interventions within the postpartum period might promote the health of the mother-infant dyad.

Premature Birth is an Independent Risk Factor for Early Adiposity Rebound: Longitudinal Analysis of BMI Data from Birth to 7 Years.

Adiposity rebound (AR) refers to the second rise of the body mass index (BMI) curve that usually occurs physiologically between five and seven years of age. AR timing has a great impact on patients' health, since early adiposity rebound (EAR) is associated with the development of metabolic syndrome later in life. We aimed to investigate the prevalence of EAR in a cohort of inborn preterm infants admitted to the Neonatal Intensive Care Section of the Policlinico University Hospital of Bari, Italy. Secondarily, we assessed whether some determinants such as (1) gender; (2) delivery mode; (3) birth weight and classification into small, normal, or large for gestational age; (4) type of feeding; (5) breastfeeding duration; (6) timing of introduction of solid food; (7) parental education; and (8) parental pre-pregnancy body mass index (BMI) influenced EAR in this cohort. The tertiary aim was to evaluate the prevalence of obesity or being overweight at seven years of age in children according to early versus timely AR. This is a prospective, population-based longitudinal study conducted at the Neonatal Intensive Care Section of the Policlinico University Hospital of Bari, Italy. Inborn preterm infants admitted to the neonatal ward between 2009 and 2011 were eligible. Enrolled preterm infants were evaluated at birth and at 1, 3, 6, 9, 12, 15, 18, and 24 months and 3, 4, 5, 6, and 7 years of age. Weight and height data were analyzed, and BMI was calculated. AR was assessed in the growth trajectory in a body mass index (BMI) plot. Of the 250 preterm newborns included, 100 completed the seven-year follow-up and entered the final analysis, 138 were lost during the seven-year follow-up, and in 12 cases parents withdrew over the course of the study. The prevalence of EAR in our cohort of preterm newborns was 54% at seven years of age. Early adiposity rebound was associated with being large for gestational age (LGA) at birth. No other factors were associated with EAR. Early adiposity rebounders had a significantly higher BMI at seven years compared to children with timely AR (17.2 ± 2.7 vs. 15.6 ± 2.05, p = 0.021). No significant differences were found in the prevalence of obesity or being overweight at seven years of age in children with early or timely AR (29% vs. 14%, p = 0.202). Ex-preterm infants have an increased risk of EAR. Since EAR may lead to long-term detrimental health effects with the onset of various chronic diseases (e.g., obesity, metabolic syndrome, etc.), healthcare providers should be prepared to counteract its occurrence, especially in delicate sub-populations of infants.

Hydrolyzed Protein Formula for Allergy Prevention in Preterm Infants: Follow-Up Analysis of a Randomized, Triple-Blind, Placebo-Controlled Study.

Background: Allergic diseases are a major public health burden worldwide. Evidence suggests that early nutrition might play a key role in the future development of allergies and the use of hydrolyzed protein formulas have been proposed to prevent allergic disease, mainly in term infants with risk factors. Aim: To evaluate the preventive effect of a hydrolyzed protein formula vs. an intact protein formula on allergy development in preterm infants with or without risk factors. Methods: We performed a 3-year follow-up study of a previous triple-blind, placebo-controlled randomized trial. Evidence of atopic dermatitis, asthma and IgE-mediated food allergies were evaluated according to a validated parental questionnaire (Comprehensive Early Childhood Allergy Questionnaire). Food sensitization was also investigated by skin prick test at 3 years of chronological age. Results: Of the 30 subjects in the intact protein formula group and 30 in the extensively hydrolyzed formula group, respectively 18 and 16 completed the 3-year follow-up and entered the final analysis. No group differences in the incidence of atopic dermatitis, asthma, IgE-mediated food allergies, and food sensitization were found. Conclusion: Despite the small number of cases, extensively hydrolyzed protein formula seems to be ineffective in allergic diseases prevention in preterm neonates. Further adequately powered, randomized controlled trials evaluating hydrolyzed protein formula administration to prevent allergic diseases in preterm neonates are needed.

Resveratrol plus carboxymethyl-ß-glucan in infants with common cold: A randomized double-blind trial.

OBJECTIVES: To evaluate effectiveness of a nasal resveratrol/carboxymethyl-ß-glucan solution compared to nasal saline solution: a) on common cold symptoms by means of a validated measure scale (CARIFS score), b) on Rhinovirus infection and CCL2, CCL5, IL8, IL6, CXCL10 and TLR2 expression in nasal swabs, c) on frequency of relapses after 30 days of follow-up. METHODS: 89 infants with respiratory infection symptoms were randomly assigned to receive either a nasal resveratrol/carboxymethyl-ß-glucan solution or nasal saline solution.All patients were evaluated with CARIFS score at enrollment, after 48 h, 7 and 30 days by physicians and parents. Nasal swabs were obtained at enrollment, after 48 h and after one week. RESULTS: CARIFS score improved in both groups. Episodes of sneezing and cough were fewer in study group after 7 days of follow-up (p < 0.05). No significant differences were found on nasopharyngeal swabs in Rhinovirus detection and cytokines expression after 48 h, nor in 30 days relapses. TLR2 expression was significantly higher in Rhinovirus infected children of the study group. No adverse effects occurred. CONCLUSIONS: These data suggest that a solution containing resveratrol plus carboxymethyl-ß-glucan might have a positive impact on both clinical and socio-economic burden due to infant common cold.

The Lymphoscintigraphic Study of Unpredictable Head and Neck Cutaneous Melanoma Lymphatic Drainage.

Head and neck cutaneous melanoma (HNCM) does not always follow standard lymphatic drainage; typical expected lymphatic pathways are associated with unexpected ones. The aim of this study was to investigate the relation between the primary HNCM sites and all possible lymphatic drainage pathways by lymphoscintigraphy with a special focus on the unexpected sentinel lymph node (SLNs) detection. We retrospectively analyzed 67 patients (46 M, 21 F; mean age 63 years) who underwent lymphoscintigraphy from January 2004 to November 2018. 99mTc-serum albumin was injected intra-dermally at the dose of 18-37 MBq in 0.2-0.4 mL. All patients underwent dynamic and static image acquisition. For all patients, the relation between the expected and unexpected SLNs was performed using the "Sidney Melanoma Unit Database" as our reference. The relation was performed also according to the primary HNCM localization. Cohens' kappa was calculated. In 61/67 (91%) of patients, SLNs were detected only in predictable sites, while in six/67 (9%), unexpected SLNs were revealed. In all patients, the agreement proportion was 91% (95% confidence interval CI 0.8-0.96) and Cohen's K was 0.11 (95% CI 0-0.43). Regarding the primary melanoma sites, the nasolabial field HNCM showed the highest rate of concordance (K = 0.60; 95%, CI 0.32-0.89) while the preauricular region HNCM revealed the highest rate of discordance with the clinically predictable drainage. The HNCM lymphatic drainage is extremely variable in regard to both the sites and the number of involved SLNs. The lymphoscintigraphic study is highly recommended to identify all possible SLNs in order to perform an accurate staging for all patients and to avoid missing unexpected SLNs.

Long-term management of chronic heart failure patients in internal medicine.

Chronic heart failure (CHF) is one of the main disabilities in elderly patients requiring frequent hospitalizations with high health care costs. We studied the outcome of CHF outpatient management in reducing hospitalization after discharge from a division of Internal Medicine at a large 3rd referral regional Hospital. 147 CHF inpatients (M:F: 63:84; mean age 76 ± 9.6 years) admitted for acute exacerbation of CHF were followed up as outpatients at 1, 6, 12 and 24 months after discharge. At baseline, patients underwent: laboratory tests, ECG, echocardiogram and a dedicated-intensive health care educational program involving also their families. The rate of hospitalization in the same group of patients was compared with data from the previous 24 months, a period when patients had been seen elsewhere without disease management programs. Patients had high prevalence of comorbidities and the majority was in NYHA class III or IV. Hypertension and valvular heart disease were the most common causes for CHF. Systolic function was preserved (LVEF ≥ 50%) in 61.9% of cases. Functional NYHA class improved significantly after 6 months and remained stable at 24 months. There was a significant increase in the use of the renin-angiotensin system blockers, beta-blockers and diuretics compared to admission to the ward. At 24 months, hospital readmissions were decreased by 42% as compared to the previous 24 months. Risk factors for re-hospitalizations were anemia, NYHA class III or IV and previous hospitalizations. Establishing an intensive outpatient management program for CHF patients leads to long-term beneficial effects with improved clinical parameters and decreased hospitalization in the setting of Internal Medicine.

Magnesium Alginate in Gastro-Esophageal Reflux: A Randomized Multicenter Cross-Over Study in Infants.

The aims of this study were to evaluate the efficacy of magnesium alginate in decreasing functional regurgitation symptoms in infants, and to assess the cost-benefit ratio of magnesium alginate compared to a thickened formula. A multicenter perspective cross-over study was conducted in formula-fed infants with persisting regurgitation, randomly assigned to receive two weeks of a magnesium-alginate-based formulation followed by two weeks of thickened formula, or vice-versa. Infants, exclusively breast-fed, were followed up for two weeks while receiving magnesium alginate. Symptoms of gastroesophageal reflux (GER) were evaluated through the Infant Gastroesophageal Reflux Questionnaire Revised (I-GERQ-R). Direct cost of treatments was also calculated. Seventy-two infants completed the study. We found a significant reduction of I-GERQ-R scores over time (F = 55.387; p < 0.001) in all groups with no difference between the sequences of administration (F = 0.268; p = 0.848) in formula-fed infants and between exclusively breast-fed and formula-fed infants receiving magnesium alginate (t = 1.55; p = 0.126). The mean cost savings per infant was € 4.60 (±11.2) in formula-fed infants treated with magnesium alginate compared to thickened formula (t = 2.91, p < 0.0005). Conclusions were that the magnesium-alginate formulation reduces GER symptoms both in formula-fed and breast-fed infants. In formula-fed infants, clinical efficacy is similar to thickened formulas with a slightly lower cost of treatment.

Hyperhomocysteinemia is an independent risk factor of atherosclerosis in patients with metabolic syndrome.

BACKGROUND: Metabolic syndrome (MetS) is a clinical condition potentially promoting the development of atherosclerotic disease. To date, the clinical impact of elevated serum homocysteine (Hcy) levels in MetS is still under discussion. The aim of this cross sectional study was to evaluate the relationship between MetS and hyperhomocysteinemia and the potential role of Hcy in the pathogenesis of atherosclerotic complications of MetS. METHODS: We recruited 300 outpatients with MetS. All patients underwent a medical history collection, physical examination, blood sampling and carotid ultrasound echo-color Doppler. According to Hcy levels, MetS patients were divided into two groups: "normal" (< 10.7 µmol/l; n = 140, group 1) and "high" Hcy (≥ 10.7 µmol/l; n = 160, group 2). Comparisons between groups were made by Student's t-test or Chi-square test. The effects of potential covariates on group differences were evaluated by general linear models. The relationships between continuous variables were assessed by simple or multiple correlation and by linear regression. Multiple regression models were built to evaluate the effects of Hcy, together with other potential risk factors, on carotid atherosclerosis. RESULTS: Patients with high Hcy were predominantly male and slightly older than group 1 patients. Smokers and non-smokers exhibited similar Hcy levels, nor was a statistical relationship between pack-years and Hcy observed. Group 2 showed lower levels of folic acid, vitamin D, high density lipoprotein (HDL)-cholesterol and glomerular filtration rate (e-GFR) than group 1, but higher levels of C-peptide, uric acid and triglycerides. In all patients, Hcy was positively correlated with C-peptide and uric acid and negatively with folic acid and e-GFR. Intima-media thickness (IMT) and carotid stenosis degree were significantly higher in patients with high Hcy and a positive relationship between Hcy and both IMT and carotid stenosis was detected in all patients. Finally, Hcy atherogenic effects were independent of other well-known atherosclerosis risk factors. CONCLUSIONS: Our results highlight a link between MetS and hyperhomocysteinemia and a direct effect of Hcy on atherogenic process during MetS. Early correction of folic acid levels may contribute to prevent cardiovascular complications in MetS patients.