Vitamin D deficiency is a risk factor for infections in patients affected by HCV-related liver cirrhosis

Objectives: To evaluate the prevalence of vitamin D deficiency and its impact on infections in HCV-related liver cirrhosis. Methods: We enrolled 291 patients affected by HCV-related liver cirrhosis. Serum vitamin D levels were dosed at enrolment. The presence of infection was assessed at baseline and during follow-up based on physical examination and laboratory analyses. Results: Vitamin D deficiency (15 (p = 0.003), Child-Pugh class B/C vs A (p < 0.001), and active hepatocellular carcinoma (HCC) (p < 0.001). At multivariate analysis, vitamin D deficiency (p < 0.01), HCC (p < 0.05), hospitalization (p < 0.001) and exposure to immunosuppressant agents (p < 0.05) were independent risk factors for infection at baseline. Conclusions: Vitamin D may play a role in the development of infections in patients affected by liver cirrhosis, and preventive strategies with vitamin D supplementation are to be evaluated in randomized controlled trials

Anti-HBc positivity was associated with histological cirrhosis in patients with chronic hepatitis C

Introduction. In patients with chronic hepatitis C it is still debated whether previous exposure to the hepatitis B virus, diagnosed from the presence of the anti-HBc antibody, is linked to a greater risk of severe hepatitis. The aim of the study was to evaluate whether the presence of anti-HBc antibodies is associated with cirrhosis in patients with HBsAg-negative chronic hepatitis C. Material and methods. Two hundred twenty-two consecutive HBsAg-negative patients with HCV-related chronic hepatitis were enrolled at their first liver biopsy. Ishak's scoring system was used to grade necroinflammation and fibrosis and the patients with stage 5 or 6 were considered as having histological cirrhosis. Results. Patients with histological cirrhosis had a higher mean age, AST, ALT, a lower platelet count and prothrombin activity compared to those with milder fibrosis. The presence of anti-HBc was identified in 21 (63.6%) of the 33 patients with fibrosis score 5 or 6 and in 56 (29.6%; p < 0.001) of the 189 with score ≤ 4. Patients with cirrhosis had a significantly higher grading than those without cirrhosis (median = 8, IQR 6-11 vs. Median = 6, IQR = 4-8, respectively, p < 0.001). A multivariate logistic regression analysis showed that age, sex and anti-HBc positivity were independent predictors of histological cirrhosis. Conclusion. Our data support the idea that in patients with chronic hepatitis C the presence in serum of anti-HBc is associated with histological cirrhosis and is therefore a marker of clinical value

Allergic reactions to midazolam: A case series from an Italian allergy unit.

Midazolam is a short-acting benzodiazepine with central nervous system depressing action, commonly used for conscious sedation for various procedures and for its pharmacologic properties. In literature, severe adverse reactions to this drug are described, but only in few cases positive allergological tests were demonstrated. The authors collected herein five clinical cases of different allergic reactions to midazolam demonstrated by positive skin tests. The 1° case is a suspected Kounis syndrome with cardiorespiratory arrest during an elective video laparoscopic cholecystectomy. The 2° and 5° cases are two systemic reactions with involvement of the skin and the gastrointestinal/respiratory system during elective surgeries in two patients with clinical history of atopia, while the 3° and 4° cases are local skin reactions in correspondence with the infusion site of midazolam during the execution of a colonoscopy. All the patients performed a complete allergological evaluation for the reaction involved drugs. In all cases, only the intradermal test (IDT) with midazolam at 0.5 mg/mL was positive.Allergological tests performed in 10 healthy controls with negative results supported the diagnosis. Therefore, midazolam is often considered a safe drug, because it does not have any active metabolites, in rare cases, it could cause different types of allergic adverse reactions: from severe anaphylaxis with cardiorespiratory arrest to simple local skin reactions. Skin tests remain the first line in the diagnosis of an immediate-type hypersensitivity to midazolam; even if they could lose in sensitivity with increasing latency from the event. However the concentrations recommended by current guidelines of European Network for Drug Allergy (ENDA) and the European Academy of Allergy and Clinical Immunology (EAACI) drug allergy interest groups might not rule out some false-positive reactions due to an irritant effect that should be considered. In doubt cases, other allergological or laboratory tests (i.e., basophil activation tests, serum tryptase, or provocation tests) remain useful to support the diagnosis of an IgE-mediated reaction. Midazolam associated anaphylaxis is relatively rare and the risk factors associated with this event are actually unknown; however, it remains important to obtain a detailed allergic history and each surgical/endoscopic examination unit should be prepared to handle any situation or emergency that may occur

Puzzling Out the Genetic Architecture of Endometriosis: Whole-Exome Sequencing and Novel Candidate Gene Identification in a Deeply Clinically Characterised Cohort

Endometriosis (EM) is a common multifactorial gynaecological disorder. Although Genome-Wide Association Studies have largely been employed, the current knowledge of the genetic mechanisms underlying EM is far from complete, and other approaches are needed. To this purpose, whole-exome sequencing (WES) was performed on a deeply characterised cohort of 80 EM patients aimed at the identification of rare and damaging variants within 46 EM-associated genes and novel candidates. WES analysis detected 63 rare, predicted, and damaging heterozygous variants within 24 genes in 63% of the EM patients. In particular, (1) a total of 43% of patients carried variants within 13 recurrent genes (FCRL3, LAMA5, SYNE1, SYNE2, GREB1, MAP3K4, C3, MMP3, MMP9, TYK2, VEGFA, VEZT, RHOJ); (2) a total of 8.8% carried private variants within eight genes (KAZN, IL18, WT1, CYP19A1, IL1A, IL2RB, LILRB2, ZNF366); (3) a total of 24% carried variants within three novel candidates (ABCA13, NEB, CSMD1). Finally, to deepen the polygenic architecture of EM, a comprehensive evaluation of the analysed genes was performed, revealing a higher burden (p < 0.05) of genes harbouring rare and damaging variants in the EM patients than in the controls. These results highlight new insights into EM genetics, allowing for the definition of novel genotype–phenotype correlations, thereby contributing, in a long-term perspective, to the development of personalised care for EM patients

L’inconsistenza della diagnosi di cancro duttale in situ

Background: Classifying ductal carcinoma in situ (DCIS) remains problematical for interpretation of specified histological features and field selection where morphology is heterogeneous. Emphasis is placed on the role of intraductal proliferative lesions as risk factors of variable magnitude in subsequent development of invasive breast carcinoma. The present study is designed to investigate the relative contribution of diagnostic and treatment paradigms on the lack of consistency in the analysis of these lesions. Materials and methods: A cohort of in situ lesions of the breast was reviewed according to ductal intraepithelial neoplasia (DIN) classification adopted by the World Health Organization (WHO). In this retrospective study 458 patients with DIN diagnosed by core needle biopsy had undergone conservative or radical surgical treatment and SLNB in cases of DIN1C-DIN3. Results: Breast conservative surgery was the definitive treatment in 80% of cases. All the SLNs sampled showed 1.2 % (4/336) positivity of metastatic or micrometastatic nodal involvement by H&E stain while the IHC assessment for cytokeratin showed 4.5% (15/336) positivity. Conclusions: The widely recognised variation in the growth pattern of DCIS makes difficult to identify uniform indications for clinical procedure. Although the incidence of metastases in patient with initial diagnosis of DIN is considered to be low, SLNB remains an attractive option to guarantee oncological safety. In patients at high risk occult invasion does occur and without lymphatic analysis, undertreatment is possible

Beyond the 2D Field‐Effect Charge Transport Paradigm in Molecular Thin‐Film Transistors

Organic field-effect transistors (OFETs) are considered almost purely interfacial devices with charge current mainly confined in the first two semiconducting layers in contact with the dielectric with no active role of the film thickness exceeding six to eight monolayers (MLs). By a combined electronic, morphological, structural, and theoretical investigation, it is demonstrated that the charge mobility and source–drain current in 2,20-(2,20-bithiophene-5,50-diyl)bis(5-butyl-5H-thieno[2,3-c]pyrrole-4,6)-dione (NT4N) organic transistors directly correlate with the out-of-plane domain size and crystallite orientation in the vertical direction, well beyond the dielectric interfacial layers. Polycrystalline films with thickness as high as 75 nm (≈30 MLs) and 3D molecular architecture provide the best electrical and optoelectronic OFET characteristics, highlighting that the molecular orientational order in the bulk of the film is the key-enabling factor for optimum device performance. X-ray scattering analysis and multiscale simulations reveal the functional correlation between the thickness-dependent molecular packing, electron mobility, and vertical charge distribution. These results call for a broader view of the fundamental mechanisms that govern field-effect charge transport in OFETs beyond the interfacial 2D paradigm and demonstrate the unexpected role of the out-of-plane domain size and crystallite orientation in polycrystalline films to achieve optimum electronic and optoelectronic properties in organic transistors

Nutritional Rehabilitation of HIV-Exposed Infants in Malawi: Results from the Drug Resources Enhancement Against AIDS and Malnutrition Program

Infant malnutrition in sub-Saharan Africa is a public health priority and a challenge in high HIV prevalence areas. The Drug Resources Enhancement Against AIDS and Malnutrition program, with multiple medical centers in Sub-Saharan Africa, developed an innovative intervention for the surveillance and control of malnutrition. In a pilot initiative, 36 HIV-exposed children were evaluated at baseline upon presentation for malnutrition and at six months post- treatment. Parameters included HIV-free survival, nutritional status and change in diet. Food diary data was entered and processed using the Nutrisurvey (WHO) software. At 6 months post-intervention, a significant improvement in anthropometric parameters was noted. Slowing of linear growth was observed in patients with malaria with a mean gain in centimetres of 4.4 ± 1.7 as compared to 5.6 ± 1.7 in children with no malaria, p < 0.048 (CL 95%: −2.32, −0.01). Dietary diversity scores increased from 5.3 ± 1.9 to 6.5 ± 1.3, p < 0.01 at 6 months. A significant increase (+25%, p < 0.02) in the number of children eating fish meals was noted. Our pilot data describes positive outcomes from a rehabilitative nutritional approach based on use of local foods, peer education, anthropometric and clinical monitoring in areas of high food insecurity. The relationship between malaria and linear growth retardation requires further investigation

Guidelines for the use and interpretation of diagnostic methods in adult food allergy

Food allergy has an increasing prevalence in the general population and in Italy concerns 8 % of people with allergies. The spectrum of its clinical manifestations ranges from mild symptoms up to potentially fatal anaphylactic shock. A number of patients can be diagnosed easily by the use of first- and second-level procedures (history, skin tests and allergen specific IgE). Patients with complex presentation, such as multiple sensitizations and pollen-food syndromes, frequently require a third-level approach including molecular diagnostics, which enables the design of a component-resolved sensitization profile for each patient. The use of such techniques involves specialists' and experts' skills on the issue to appropriately meet the diagnostic and therapeutic needs of patients. Particularly, educational programs for allergists on the use and interpretation of molecular diagnostics are needed

Pediatric trauma and emergency surgery: an international cross-sectional survey among WSES members

Background: In contrast to adults, the situation for pediatric trauma care from an international point of view and the global management of severely injured children remain rather unclear. The current study investigates structural management of pediatric trauma in centers of different trauma levels as well as experiences with pediatric trauma management around the world. Methods: A web-survey had been distributed to the global mailing list of the World Society of Emergency Surgery from 10/2021-03/2022, investigating characteristics of respondents and affiliated hospitals, case-load of pediatric trauma patients, capacities and infrastructure for critical care in children, trauma team composition, clinical work-up and individual experiences with pediatric trauma management in response to patients´ age. The collaboration group was subdivided regarding sizes of affiliated hospitals to allow comparisons concerning hospital volumes. Comparable results were conducted to statistical analysis. Results: A total of 133 participants from 34 countries, i.e. 5 continents responded to the survey. They were most commonly affiliated with larger hospitals (&gt; 500 beds in 72.9%) and with level I or II trauma centers (82.0%), respectively. 74.4% of hospitals offer unrestricted pediatric medical care, but only 63.2% and 42.9% of the participants had sufficient experiences with trauma care in children ≤ 10 and ≤ 5&nbsp;years of age (p = 0.0014). This situation is aggravated in participants from smaller hospitals (p &lt; 0.01). With regard to hospital size (≤ 500 versus &gt; 500 in-hospital beds), larger hospitals were more likely affiliated with advanced trauma centers, more elaborated pediatric intensive care infrastructure (p &lt; 0.0001), treated children at all ages more frequently (p = 0.0938) and have higher case-loads of severely injured children &lt; 12&nbsp;years of age (p = 0.0009). Therefore, the majority of larger hospitals reserve either pediatric surgery departments or board-certified pediatric surgeons (p &lt; 0.0001) and in-hospital trauma management is conducted more multi-disciplinarily. However, the majority of respondents does not feel prepared for treatment of severe pediatric trauma and call for special educational and practical training courses (overall: 80.2% and 64.3%, respectively). Conclusions: Multi-professional management of pediatric trauma and individual experiences with severely injured children depend on volumes, level of trauma centers and infrastructure of the hospital. However, respondents from hospitals at all levels of trauma care complain about an alarming lack of knowledge on pediatric trauma management