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Few data are available on adverse events (AE) associated to vaccines in persons with multiple sclerosis (pwMS).to study the incidence of acute phase AE (AP-AE) related to SARS-CoV-2 mRNA vaccines in pwMS compared to a control group, and to analyze the association between AP-AE and disease modifying treatments (DMT).This was a cross-sectional study on 438 PwMS and 481 age- and sex-matched subjects not affected by dysimmune diseases that underwent two doses of SARS-CoV-2 mRNA BNT162b2 vaccine (Pfizer/BioNtech).Two hundred and twenty five (51.4%) pwMS complained of ≥1 AP-AE after the first dose, 269 (61.4%) after the second dose. A logistic regression analysis revealed that only pwMS on Fingolimod and Ocrelizumab did not show a higher risk of developing AP-AE. The likelihood to present with ≥1 AP-AE, after correcting for age and sex, was significantly higher in pwMS than controls.This study reports qualitative and quantitative features of AP-AE associated with the first and second doses of SARS-CoV-2 vaccine in a large sample of pwMS. The only risk factor identified for developing AP-AE is female gender. AntiCD-20 monoclonal antibodies and S1P inhibitors are associated with a lower risk of AP-AE occurrence.

Bone dysplasias (osteochondrodysplasias) are a large group of conditions associated with short stature, skeletal disproportion, and radiographic abnormalities of skeletal elements. Nearly all are genetic in origin. We report a series of seven children with similar findings of chondrodysplasia and growth failure following early hematopoietic stem cell transplantation (HSCT) for pediatric non-oncologic disease: hemophagocytic lymphohistiocytosis or HLH (five children, three with biallelic HLH-associated variants [in PRF1 and UNC13D] and one with HLH secondary to visceral Leishmaniasis), one child with severe combined immunodeficiency and one with Omenn syndrome (both children had biallelic RAG1 pathogenic variants). All children had normal growth and no sign of chondrodysplasia at birth and prior to their primary disease. After HSCT, all children developed growth failure, with standard deviation scores for height at or below -3. Radiographically, all children had changes in the spine, metaphyses and epiphyses, compatible with a spondyloepimetaphyseal dysplasia. Genomic sequencing failed to detect pathogenic variants in genes associated with osteochondrodysplasias. We propose that such chondrodysplasia with growth failure is a novel, rare, but clinically important complication following early HSCT for non-oncologic pediatric diseases. The pathogenesis is unknown but could possibly involve loss or perturbation of the cartilage-bone stem cell population.

Genome-wide association studies identified over 200 risk loci for multiple sclerosis (MS) focusing on common variants, which account for about 50% of disease heritability. The goal of this study was to investigate whether low-frequency and rare functional variants, located in MS-established associated loci, may contribute to disease risk in a relatively homogeneous population, testing their cumulative effect (burden) with gene-wise tests. We sequenced 98 genes in 588 Italian patients with MS and 408 matched healthy controls (HCs). Variants were selected using different filtering criteria based on allelic frequency and in silico functional impacts. Genes showing a significant burden (n = 17) were sequenced in an independent cohort of 504 MS and 504 HC. The highest signal in both cohorts was observed for the disruptive variants (stop-gain, stop-loss, or splicing variants) located in EFCAB13, a gene coding for a protein of an unknown function (p < 10–4). Among these variants, the minor allele of a stop-gain variant showed a significantly higher frequency in MS versus HC in both sequenced cohorts (p = 0.0093 and p = 0.025), confirmed by a meta-analysis on a third independent cohort of 1298 MS and 1430 HC (p = 0.001) assayed with an SNP array. Real-time PCR on 14 heterozygous individuals for this variant did not evidence the presence of the stop-gain allele, suggesting a transcript degradation by non-sense mediated decay, supported by the evidence that the carriers of the stop-gain variant had a lower expression of this gene (p = 0.0184). In conclusion, we identified a novel low-frequency functional variant associated with MS susceptibility, suggesting the possible role of rare/low-frequency variants in MS as reported for other complex diseases.

Background Although comorbidity is important in Multiple Sclerosis (MS), few validated methods for its assessment exist. Our aim is to estimate the prevalence and economic burden of major comorbidities in people with MS (pwMS) in two Northern Italy study areas (Pavia, PV and Genoa, GE), using routinely collected healthcare data. Methods We estimated prevalence of comorbid conditions in pwMS in the period 2012-2017. Anxiety, depression, cancer, leukemia, lymphoma, hypertension, heart disease, cerebrovascular diseases, vascular diseases, ischemic stroke, hyperlipidaemia, bronchopathy, diabetes, gastropathy, gastric ulcer, autoimmune diseases, chronic renal failure, connective tissue diseases and HIV/AIDS were identified by a specific algorithm currently used for monitoring prevalence of chronic diseases by Italian Local Health Authorities (BDA system). Direct healthcare costs were defined by regional and governmental contracts; the aggregated healthcare expenditure was compared between pwMS with/without comorbidities. Results The MS cases identified were 2983, 2035 in GE and 948 in PV. 55.6% of pwMS had at least one comorbidity (50.6% GE and 66.5% PV, p < 0.001). The most prevalent comorbidities were: depression (32.9%), hypertension (18.0%), cancer (10.9%), heart disease (7.8%), cerebrovascular diseases (7.0%) and hyperlipidaemia (6.1%). Comorbidity ranking was similar in the two provinces, although we observed significant differences considering specific prevalence rates. The mean direct healthcare costs of MS were substantially higher for individuals with comorbidity (36,463 €vs 26,284 €, p < 0.001), showing 39% of additive costs. Conclusions Our study provides evidence of the burden of comorbidities in MS. Comorbidity is common in MS and produce additive costs. Key messages The use of administrative data for tracking the MS comorbidity could help knowledge gaps. When additivity situation is involved, preventive policies could lead to monetary savings.

Several different operative techniques have been applied in minimally invasive right colectomy. Data reported in literature confirm the advantages of laparoscopic approach, however, there is no sure evidence of which one is the best. The pure laparoscopic technique with intracorporeal anastomosis seems to show some advantages compared to the other laparoscopic and open procedures, although for the price of technical difficulty and a longer operating time.

Background The aim of this RCT was to determine whether elective resection following successful non-operative management of a first episode of acute sigmoid diverticulitis complicated by extraluminal air with or without abscess is superior to observation in terms of recurrence rates. Methods This was a single-centre, sequential design RCT. Patients were randomized to elective surgery or observation following non-operative management and colonoscopy. Non-operative management included nil by mouth, intravenous fluids, intravenous antibiotics, CT with intravenous contrast on arrival at hospital, and repeat CT with intravenous and rectal contrast on day 3 in hospital. The primary endpoint was recurrent diverticulitis at 24 months. Patients with a history of sigmoid diverticulitis, immunosuppression or peritonitis were not included. Results Of 137 screened patients, 107 were assigned randomly to elective surgery (26) or observation (81), and underwent the allocated intervention after successful non-operative management. Conservative management failed in 15 patients. Groups were similar in age, sex, BMI, co-morbidities and colorectal POSSUM. Rates of recurrent diverticulitis differed significantly in the elective surgery and observation groups (8 versus 32 per cent; P = 0·019) at a mean(s.d.) follow-up of 37·8(8·6) and 35·2(9·2) months respectively. There was also a significant difference in time to recurrence (median 11 versus 7 months; P = 0·015). A total of 28 patients presented with recurrent diverticulitis complicated by extraluminal air and/or abscess (2 elective surgery, 26 observation), all of whom recovered with repeat non-operative management. Conclusion The majority of patients observed following conservative management of diverticulitis with local extraluminal air do not require elective surgery. Registration number: NCT01986686 (http://www.clinicaltrials.gov).

Vitamin A is a fat-soluble micronutrient involved in the regulation of several physiologic functions, such as visual acuity, epithelial tissue integrity, immune response, and gene expression, thus playing a crucial role in childhood growth and development. Although vitamin A deficiency (VAD) in resource-limited settings is still an actual issue and represents the leading cause of preventable childhood blindness, its occurrence in high-income countries is rare, although possibly underdiagnosed because of its nonspecific early manifestations. A good awareness of VAD symptoms and risk factors could aid its early diagnosis, which is fundamental to undertake a prompt treatment and to prevent ocular complications. Nevertheless, the role of restrictive dietary habits, increasingly common in developed countries, is often overlooked in infants and children. We present a case of VAD with permanent ocular sequelae in a 5-year-old girl from a high-income country. In the case described, VAD ensued from a highly restricted diet, mainly limited to oat milk, which had been followed for more than 2 years. This child presented with ocular symptoms, opportunistic infection, anemia, poor growth, and a diffuse squamous metaplasia of the bladder; after commencing retinol supplementation, a gradual healing of clinical VAD manifestations occurred, with the exception of the ocular sequelae, which resulted in irreversible visual loss.

The term osteopetrosis describes a group of rare hereditary diseases of the skeleton, characterized by an increase in bone density, caused by a defect in the development or function of osteoclasts. It comprises a clinically and genetically heterogeneous conditions ranging from infantile onset life-threatening forms to mildest adult onset forms. "Malignant" osteopetrosis is characterized by bone fragility, short stature, compressive neuropathies, hypocalcaemia, pancytopaenia. The deficiency of carbonic anhydrase II causes a moderate form, presenting classically as a triad of osteopetrosis, renal tubular acidosis (RTA), and cerebral calcification. This condition leads to specific craniofacial dysmorphisms associated with upper airway obstruction that may result in obstructive sleep apnea. Herein we report a case of osteopetrosis with RTA associated with severe OSAS successfully treated with continuous positive airway pressure (CPAP).

Background Acute mastoiditis is the main suppurative complication of acute otitis media. Its incidence ranges from 1.2 to 4.2/100.000 children/year and a rise has been reported in the last years. There are controversial data regarding risk factors for mastoiditis and its complications. Aim of the study: to evaluate demographics and clinical characteristics of children with acute mastoiditis and to identify possible risk factors for complications. Methods We retrospectively reviewed medical charts of all the children aged 1 month-14 years admitted to our Paediatric Emergency Department from January 2002 to December 2016. Results One hundred forty-seven cases (97 males and 50 females) were included in the analysis, mean age was 4.8 ± 3.6 years and 28.2% of the patients were younger than 2 years. We found an increasing number of mastoiditis per year during the last 3 years of the study. Children younger than 2 years were less treated with antibiotics for acute otitis media or treated for a shorter period (p

The inlet patch (IP) is an area of heterotopic gastric mucosa in the cervical esophagus commonly seen during upper endoscopy. Although generally asymptomatic IP has been associated with esophageal and supraesophageal symptoms and, though rare, in adult with malignant transformation. We describe two cases of recurrent episodes of laryngospasm associated with IP. In both cases there was a good response to prolonged acid suppression therapy.

Loss of function mutations in PAK3 contribute to non-syndromic X-linked intellectual disability (NS-XLID) by affecting dendritic spine density and morphology. Linkage analysis in a three-generation family with affected males showing intellectual disability, agenesis of corpus callosum, cerebellar hypoplasia, microcephaly and ichthyosis, revealed a candidate disease locus in Xq21.33q24 encompassing over 280 genes. Subsequent to sequencing all coding exons of the X chromosome, we identified a single novel variant within the linkage region, affecting a conserved codon of PAK3. Biochemical studies showed that, similar to previous NS-XLID-associated lesions, the predicted amino acid substitution (Lys389Asn) abolished the kinase activity of PAK3. In addition, the introduced residue conferred a dominant negative function to the protein that drives the syndromic phenotype. Using a combination of in vitro and in vivo studies in zebrafish embryos we show that PAK3N389 escapes its physiologic degradation and is able to perturb MAPK signaling via an uncontrolled kinase-independent function, which in turn leads to alterations of cerebral and craniofacial structures in vivo. Our data expand the spectrum of phenotypes associated with PAK3 mutations, characterize a novel mechanism resulting in a dual molecular effect of the same mutation with a complex PAK3 functional deregulation, and provide evidence for a direct functional impact of aberrant PAK3 function on MAPK signaling.

Background Posterior reversible encephalopathy syndrome is characterized by a combination of clinical-radiological findings and pathophysiologically by localized brain vasogenic edema. Many clinical illnesses may trigger the onset of posterior reversible encephalopathy syndrome and hypertension is present in about 80% of patients. Methods We describe a child with high consumption of licorice toffees who developed systemic hypertension followed by posterior reversible encephalopathy syndrome. Results This boy was hospitalized following a cluster of generalized tonic-clonic seizures. Monitoring his clinical parameters, we detected constant high blood pressure and a brain magnetic resonance scan showed a localized vasogenic edema; these symptoms suggested posterior reversible encephalopathy syndrome. He had been eating licorice toffees for a period of 4 months, consuming an estimated 72 mg of glycyrrhizic acid per day; this led to our assumption of the reason for his hypertension. Conclusion There are several reported examples of posterior reversible encephalopathy syndrome–induced licorice hypertension in adults, but none related to children. Our report examines a possible link between licorice consumption and hypertension/posterior reversible encephalopathy syndrome in children.

Juvenile dermatomyositis (JDM), an autoimmune idiopathic myositis, is characterized by rash and proximal muscle weakness. Immunohistopathology typically shows perivascular inflammatory infiltrate with predominance of CD4+ T lymphocytes, perifascicular atrophy, and upregulation of major histocompatibility complex class I. JDM has been attributed to a humoral-driven muscle microangiopathy probably implicating the type I interferon pathway. Tubulo-reticular inclusions present in endothelial cell of muscle are biomarkers of interferon exposure, and so may be an indirect data of this myopathy especially in the absence of rash and inflammatory infiltrate. We report on three patients in which electron microscopy solves the differential diagnosis among infantile myositis showing peculiar inclusions.

Ziel dieses Reviews ist die Darstellung der aktuellen Datenlage bezuglich der Behandlung der Dunndarmobstruktion. Das Thema ist auf die durch postoperative Adhasionen (Verwachsungen) bedingte Obstruktion des Dunndarms begrenzt. Andere Ursachen einer Obstruktion beim Dunndarm werden nicht angesprochen. Hier wird versucht, den Lesern einen kurz gefassten Einblick in die in der englischsprachigen Literatur verfugbaren Ergebnisse zu geben. Dieser Artikel bietet keine umfassende Darstellung des Themas; stattdessen werden einige relevante Themen herausgegriffen und dann skizziert, welche Rolle, wenn uberhaupt, die laparoskopische Operation bei der Behandlung der Dunndarmobstruktion durch Verwachsungen spielen sollte.

Objective To investigate whether preoperative noncolonic cancer stem cells in bone marrow (BM) of R0 colorectal cancer (CRC) patients are cancer cells and impact on liver metastases (LM) rates. Method Prospective data on continuous CRC patients were collected from five centres. Bone marrow aspirates, taken at laparotomy, were sent to a single lab. Noncolonic cancer stem cells were defined according to UICC. A quantity of 3 × 106 BM cells per patient was processed with monoclonal antibodies against cytokeratin 20. APC or p53 gene mutation and microsatellite instability (MSI) were assessed in primary tumours (PT) by single-strand conformation polymorphism. Noncolonic cancer stem cells in BM of PT mutation or MSI-positive patients were isolated with immunobeads coated with magnetically labelled anti-human epithelial antigen antibody and DNA-screened for mutations. Results Although 199 patients were enrolled, 162 patients were available for analysis. No patients were lost to follow-up. Twenty-five (2–170) noncolonic cancer stem cells were found in BM of 40 patients. Twenty-two patients developed LM at 36-month follow-up. Adenomatous polyposis coli (APC) or p53 gene mutation or MSI were identified in the PT of 78 patients. The same gene mutations or MSI were not found in noncolonic cancer stem cells of the BM of these patients. After adjustment, there was no significant effect of confounding factors. Noncolonic cancer stem cells in BM had no impact on LM rates, cancer-specific death rates, or all death rates. Conclusions Preoperative noncolonic cancer stem cells in BM of R0 CRC patients were not cancer cells and had no impact on LM rates.

The purpose of this article was to evaluate otological diseases in 173 patients (pts) with Turner syndrome (TS). STUDY DESIGN: One hundred and seventy-three pts, mean chronological age (CA) 12+/-6.2 yr. Patients were submitted to different therapies: GH, estrogen therapy (EE), no therapy (no tx). Seventy-nine pts (CA 11 yr) had no otological diseases. Conductive hearing loss (CHL) occurred in 38.7% (CA 11 yr) and otoscopy was: persistent secretory otitis media in 55.2%, chronic otitis media in 10.4%, pars flaccida retraction pocket in 19.4%, mostly bilateral. Cholesteatoma was present in 15%. Sensorineurinal hearing loss (SNHL) occurred in 15.6% (CA 16 yr), 11 of whom were affected by high tone loss, and 15 by loss in midfrequencies (dip between 0.5-3 kHz), bilateral in 93%. Degree of hearing loss (HL) was mild [20-40 decibel hearing level (dBHL)] in 15%, moderate (45-60 dBHL) in 31%, severe (65-80 dBHL) in 8%, profound (dBHL>85) in 2%. We found a significant association between CHL and karyotype 45, X (p

The study aim was to provide data on pattern and length of crossing of the ileocolic artery (ICA) and right colic artery (RCA) with the superior mesenteric vein (SMV). Specimens from 30 fresh human cadavers underwent corrosion casting. Methylacrylate was injected into the SMV and superior mesenteric artery (SMA). Length of crossing was measured with a scaleable ruler and copper wire. Values are mean (SD; range). ICA was present in all specimens and crossed posterior to the SMV in 19 (63.33%) of 30 specimens. Length of crossing was 17.01 (7.84; 7.09–42.89) mm. RCA was present in 19 (63.33%) of 30 specimens. RCA crossed anterior to SMV in 16 (84.21%) of 19 specimens. Length of crossing was 20.63 (8.09; 6.3–35.7) mm. ICA was always present, crossed posterior to SMV in 60% of specimens with a crossing length of 17 mm. RCA was present in 63% of specimens, crossed anterior to the SMV in 84% of specimens with a crossing length of 20 mm. Clinical implications include arterial length left behind with main nodes, arterial bleeding and safety of laparoscopic access.

We evaluated growth hormone (GH) secretion in 81 patients with Turner's syndrome (TS) (mean age 10.7+/-3.6 y) with respect to karyotype, auxological characteristics and growth response to GH treatment (1 IU/kg/wk). None of the patients had spontaneous puberty or had started replacement therapy with estrogens. Thirty-nine patients (48%) had monosomia 45X, 29 (36%) structural abnormalities of the X chromosome and 13 (16%) X mosaicism. Before the start of GH therapy, each patient underwent an evaluation of mean nocturnal GH concentration (MGHC) and 75 patients also underwent 2 pharmacological tests. MGHC of the TS patients did not differ from that of 29 prepubertal GH-deficient girls (GH peaks8 microg/l after pharmacological tests) and both groups were lower (p0.0001 and p0.0005, respectively) than MGHCs of 27 short normal girls (GH peak8 microg/l). MGHC of the patients with TS was negatively correlated (p0.001) with bodyweight excess (BWE) at multiple regression analysis. MGHC of the TS patients with BWE20% was significantly higher (p0.02) than that of the TS patients with BWE20%, but again did not differ from that of the GH-deficient patients and was lower (p0.001) than that of the short normal girls. MGHC did not significantly differ between the 3 groups subdivided according to karyotype. Forty-four percent of the TS patients showed GH responses to pharmacological tests8 microg/l. Height velocity SDS at first and second year of therapy was not influenced by MGHC levels, chronological or bone age, target height or BWE. In conclusion, spontaneous secretion in our patients with TS was lower than that of the short normal prepubertal girls and did not differ from that of GH-deficient subjects, even if we excluded overweight patients. The level of GH secretion was unable to predict GH response to treatment.

Early postoperative anastomotic complications have serious clinical implications for the patients morbidity, mortality as well as long-term results. A number of measures can be undertaken to reduce the risk of anastomotic complications, including intraoperative colorectal anastomotic integrity assessment. Methods used to assess anastomotic reliability have gradually developed from basic mechanical techniques, direct visual endoluminal inspection, to microperfusion assessment of perianastomotic tissue. Moderate benefit in terms of reduced postoperative anastomotic complications has been shown with mechanical patency testing and partly with intraoperative endoscopic visualization of colorectal anastomoses. More recently, indocyanine green (ICG) fluorescence imaging methods have emerged as major contributions to anastomotic patency assessment and intraoperative decision making during surgical colorectal procedures including decreased numbers of ileostomies.

Background: Chronic cerebrospinal venous insufficiency (CCSVI) has been proposed as a possible cause of multiple sclerosis (MS). Objectives: The CoSMo study evaluated the association between CCSVI and MS. Methods: The primary end-point of this multicentric, case-control study was to compare the prevalence of CCSVI between patients with MS, patients with other neurodegenerative diseases (ONDs) and healthy controls (HCs). Color-coded duplex sonography was performed by a sonologist and the images were sent to one of three central sonologists for a second reading. Agreement between local and central sonologists or, in case of disagreement, the predominant judgment among the three central readers, was required for a diagnosis of CCSVI. All readings, data collection and analysis were blinded. Results: The study involved 35 MS centers across Italy and included 1874 subjects aged 18–55. 1767 (94%) were evaluable: 1165 MS patients, 226 patients with ONDs and 376 HCs. CCSVI prevalence was 3.26%, 3.10% and 2.13% for the MS, OND and HC groups, respectively. No significant difference in CCSVI prevalence was found amongst the three cohorts (MS versus HC, OR = 1.55, 95%CI = 0.72–3.36, p = 0.30; OND versus HC, OR = 1.47, 95%CI = 0.53–4.11, p = 0.46; MS versus OND, OR = 1.05, 95%CI = 0.47–2.39, p = 0.99). High negative and low positive agreement was found between the local and centralized readers. Conclusions: CCSVI is not associated with MS.

Experimental models of colorectal tumor require either laparotomy for induction or anastomosis following resection. The long murine cecum avoids the need for an anastomosis, making the cecum the preferred site for induction. This study aimed to evaluate total colonoscopy with submucosal injection of cecal wall (TCWI) in rats in terms of failure rate (FR), complication rate (CR), and reproducibility (R).A bolus of bowel prep was given. Anesthesia was injected intraperitoneally. A video fiberscope (5.9 mm outer diameter, 180/90 degrees up/down bending, 100/100 degrees right/left bending, 103 cm working length, 120 degrees view field, and 2.0 mm channel) allowed for irrigation and suction. Saline 1 ml was injected in the cecal wall through a 4-mm-long, 23-gauge needle placed on a 3-mm wire, resulting in a blister. FR was a failure to reach and inject the cecum. Rats were allowed to recover. CR was measured at necropsy. R was assessed by comparing TCWI time, FR, and CR for three investigators. Sample size of 120 (type I error, 0.05; power, 80%) was based on a pilot study. Data are presented as median (range).A total of two of 122 rats (1.6%) died after prep or anesthesia. Bowel prep resulted in 99.1% evacuation of solid feces. A total of 120 male Sprague-Dawley retired breeders weighing 592 g (range, 349-780) underwent TCWI. Scope depth was 28 cm (range, 20-36). Irrigating fluid was 290 ml (range, 100-600). TCWI time was 7 min (range, 4-28). FR was 4%. In three failed cases, the scope reached the ascending colon. CR was 2%. There were two perforations in the ascending colon. All three operators had similar TCWI time (p = 0.673), FR (p0.1), and CR (p0.1). A total of 98.3% of rats survived to planned sacrifice. At 48-h necropsy, the injection site was macroscopically identified in 118 rats.A safe and reproducible TCWI rat model has been achieved, which may provide a valuable tool in the future for studies of solid colorectal tumors.

OBJECTIVE: In order to ascertain the advantages of early GH treatment in Turner syndrome (TS), we started a prospective study aimed at evaluating prepubertal height gain in a cohort of 29 girls who were treated with the same pro-kilo GH dose (1.0 IU/kg per week) since they were less than 6 years old and for at least 5 years before entering puberty. PATIENTS AND DESIGN: Following a minimum of 6 months of baseline observations, 29 girls with TS were enrolled for this prospective study provided that they (a) were less than 6 years old, (b) were below -1.0 standard deviation score (SDS) for height, (c) had a projected adult height (PAH) lower than the respective target height (TH) and (d) had a height velocity (HV) lower than -1.0 SDS. All the selected girls underwent a 5-year treatment with biosynthetic GH at a stable dose of 1.0 IU/kg per week and were periodically measured during the treatment period in order to evaluate height, HV and PAH. RESULTS: After a dramatic acceleration during the 1st year, HV was attenuated during the subsequent years, reaching its nadir at the 5th year. Height deficiency under therapy progressively decreased from entry onwards, shifting from -2.4+/-0.7 to -1.0+/-1.2 SDS. In the same period, mean PAH progressively increased, although after 5 years it remained lower than the average TH. CONCLUSIONS: (a) An effective growth-promoting strategy in TS should be based on early GH treatment, as suggested by our results. (b) This strategy could result in a prepubertal normalization of height, thus allowing the appropriate timing for the induction of puberty. (c) An initial GH dose of 1.0 IU/kg per week may be suitable during the first years of therapy, as shown by our data documenting an important waning effect of GH therapy only after the 4th year of treatment. (d) No acceleration of bone maturation was observed under this treatment regimen.

Background: Menetrier's disease is a rare form of acquired gastropathy characterized by giant rugal folds in the stomach lining and protein-losing gastropathy; in children, it rarely needs aggressive treatment and resolves spontaneously within 2–10 weeks with support therapy. Many cases of pediatric Menetrier's disease associated with cytomegalovirus (CMV) infection have been reported. Clinical findings include nausea, vomiting, abdominal pain, peripheral edema, ascites, and pleural effusion. Gastroduodenal endoscopy is useful in confirming the diagnosis and excluding other similar conditions as lymphoma, eosinophilic gastropathy, gastric varices, Zollinger-Ellison syndrome and lymphangectasia. Specific aim: We describe a case of protein-losing gastropathy, associated with primary CMV infection. Case report: An 18-month-old male presented with periorbital swelling, vomiting and food refusal. Blood tests on admission showed hypoalbuminemia, IgG hypogammaglobulinemia, hypocalcemia and a high peripheral blood eosinophil count. Metabolic, allergologic and autoimmune diseases were ruled out. His immunological profile was normal. Tests for infectious diseases revealed a primary CMV infection. The Guthrie card test for CMV PCR was negative. Endoscopy revealed a normal macroscopic picture of the digestive sections examined and histological examination of multiple oesophageal, gastric and duodenal biopsies was normal. In contrast, the ultrastructural examination of the biopsies revealed signs of viral infection. Considering the diagnostic hypothesis of protein-losing gastropathy associated with CMV infection, a proton pump inhibitor with support therapy and a dose of IgG immunoglobulins to treat the IgG hypogammaglobulinemia were administered. The child was discharged in good clinical condition, with monthly outpatient follow-up for 6 consecutive months. Conclusions: Although CMV infection appears to be the major cause of Menetrier's disease in infants, in our case, the lack of endoscopic and histological features suggestive of Menetrier's disease led us to consider a form of protein-losing gastropathy associated with CMV infection. It is important for pediatric emergency departments to consider the often misdiagnosed Menetrier's disease, together with the other causes of protein-losing enteropathy, in the differential diagnosis for edema and low albumin levels.

Background Visceral leishmaniasis (VL) is a severe disease caused by Leishmania infantum in the Mediterranean basin, and is associated with considerable morbidity and mortality. Infantile VL may begin suddenly, with high fever and vomiting, or insidiously, with irregular daily fever, anorexia, and marked splenomegaly. Delays in diagnosis of VL are common, highlighting the need for increased awareness of clinicians for VL in endemic European countries. Case presentation We report 4 cases of young children in northern Italy presenting with persistent fever of unknown origin and diagnosed with VL by serological and molecular methods. At the time of diagnosis, these patients showed an unusual echographic pattern characterized by multiple iso-hypoechoic nodules associated with splenomegaly. Conclusion We suggest that detection of spleen nodules represents a signature of VL in infants, thus helping to diagnose systemic Leishmania infantum infection in children. Electronic supplementary material The online version of this article (doi:10.1186/s12879-014-0620-2) contains supplementary material, which is available to authorized users.

The preferential association between Turner's syndrome and congenital heart defects (CHD) have been well known since the first description by Morgagni. There are few studies about the different cardiologic problems stemming from different chromosomal patterns of X monosomies. We reviewed a large series of 136 patients with Turner syndrome without cardiologic preselection, 29 of whom had some kind of CHD (21.5%). Partial anomalous pulmonary venous drainage (PAPVD; 2.9%), aortic valve disease (stenosis and/or incompetence) (AoVD; 5. 1%), aortic coarctation (AoCo; 4.4%), and bicuspid aortic valve (BicAo; 14.7%) are much more frequent in Turner's syndrome than in the normal population, with the difference being statistically highly significant. In our cases, only the 45, X subjects showed severe CHD and multiple lesions, whereas the X-ring pattern was associated with an elevated prevalence of BicAo. Patients with X-deletion showed no signs of congenital heart malformations. Eleven patients, all with 45, X pattern, and significant CHD, underwent cardiac surgery at a mean age of 7.7 +/- 5.3 years (range 7 days-18 years) without complications. At follow-up of 3-18 years (8.6 +/- 5. 2), we were unable to observe any type of evolution of the remaining untreated cardiovascular anomalies.

Knowledge about the balance between heritable and nonheritable risk in multiple sclerosis (MS) is based on twin studies in high-prevalence areas. In a study that avoided ascertainment limitations and directly compared continental Italy (medium-prevalence) and Sardinia (high-prevalence), we ascertained 216 pairs from 34,549 patients. This gives a twinning rate of 0.62% among MS patients, significantly less than that of the general population. In continental Italy, probandwise concordance was 14.5% (95% confidence interval, 5.1-23.8) for monozygotic and 4.0% (95% confidence interval, 0.8-7.1) for dizygotic twins. Results in Sardinia resemble those in northern populations but in limited numbers. Monozygotic concordance was 22.2% (95% confidence interval, 0-49.3) probandwise, but no concordant dizygotic pairs were identified. A questionnaire on 80 items possibly related to disease cause was administered to 70 twin pairs, 135 sporadic patients, and 135 healthy volunteers. Variables positively (7) or negatively (2) associated with predisposition and concordance in twins largely overlapped and were mainly linked to infection. If compared with previous studies, our data demonstrate that penetrance in twins appears to correlate with MS prevalence. They highlight the relevance of nonheritable variables in Mediterranean areas. The apparent underrepresentation of MS among Italian twins draws attention to protective factors, shared by twins, that may influence susceptibility.

Real-time ultrasonography was performed in 142 patients with Turner syndrome, aged 0.57 to 21 years, with different karyotypes (45,X [4896], X mosaicism [17%], and X structural abnormalities [35%]). Ovarian and uterine volumes were calculated and the data collected in a mixed longitudinal and cross-sectional mode. Thirty-eight patients were followed longitudinally during pubertal age (10 to 18 years bone age) for ovarian data. Patients with Turner syndrome were divided into two groups according to the presence or absence of detectable ovaries. Patients with Turner syndrome with detectable ovaries showed the first increase in ovarian volume at about 9 years of bone age; this increase was continuous and more evident only after 14 years of age and appeared later than in control subjects. When followed longitudinally during puberty, the ovaries showed a hormonal function in some cases. Girls with X mosaicism had the highest percentage of bilateral detectable ovaries and the greatest total ovarian volume; about 50% of them had spontaneous breast appearance and 38.5% had spontaneous menarche. They showed also the lowest gonadotropin levels, when bilateral ovaries were present during puberty. On the contrary, patients with the 45,X karyotype had the lowest percentage of detectable ovaries, ovarian volume, and spontaneous breast appearance. In our patients with Turner syndrome, uterine measures increased significantly with age and this was more evident in subjects with detectable ovaries after 13 years of bone age. Compared with control subjects, they showed significantly lower uterine measures, and patients with X mosaicism had greater and more progressive increments. In conclusion, pelvic ultrasonography in Turner syndrome is particularly useful in detecting ovaries and their possible increase in volume. These data, linked with karyotype pattern and gonadotropin levels, have prognostic value in predicting the future sexual development of these patients.

Eighteen Italian patients presenting with sporadic, bilateral, simultaneous, or sequential optic neuritis (ON) were evaluated for 14 base changes in mitochondrial DNA (mtDNA) previously found associated with Leber′s hereditary optic neuropathy (LHON), aiming to identify at a molecular level LHON cases with nontypical phenotypes. During a 36-month follow-up, 11 ON patients developed clinical or laboratory features allowing diagnosis of clinically definite multiple sclerosis (MS). None was positive for any of the "primary" LHON-associated mutations. However, single or multiple "secondary" LHON-associated sequence changes at 4216/ND1, 4917/ND2, and 13708/ND5 were detected in ON and ON-MS patients. MS controls without visual failure as well as healthy control subjects harbored the same base changes at similar frequencies. In addition, coexistence of three sequence changes was found in two cases (1 ON-MS patient and 1 MS control patient). We also report finding two new neutral sequence base changes in the ND-4 gene which were identified by SSCP and confirmed by automated DNA sequence analysis. The results suggest that these secondary mutations do not contribute to MS susceptibility in these patients, but rather represent neutral mitochondrial DNA polymorphisms. In addition, whether there are biochemical abnormalities related to single and multiple secondary mtDNA sequence changes remain to be demonstrated.

This randomized controlled trial (RCT) was performed to test the hypothesis that adverse event rates following primary anastomosis (PRA) are not inferior to those following nonrestorative colon resection for perforated diverticulitis with peritonitis.Patients admitted for perforated diverticulitis with peritonitis were randomly assigned to PRA (left colon resection with PRA and loop ileostomy) or nonrestorative colon resection (left colon resection with end colostomy). The endpoint was adverse events defined as mortality and morbidity following PRA or nonrestorative colon resection and stoma reversal. The estimated sample size was 300 patients in each study arm (alpha 0.10; 90% power).During a 9-year period, 90 patients were randomly assigned to undergo PRA or nonrestorative colon resection in 14 centres in eight countries. Thirty-four PRA patients were comparable to 56 nonrestorative colon resection patients for age (P = 0.481), gender (P = 0.190), APACHE III (P = 0.281), Hinchey stage III vs IV (P = 0.394) and Mannheim Peritonitis Index (P = 0.145). There were no differences in operating time (P = 0.231), surgeries performed at night (P = 0.083), open vs laparoscopic approach (P = 0.419) and litres of peritoneal irrigation (P = 0.096). There was no significant difference in mortality (2.9 vs 10.7%; P = 0.247) and morbidity (35.3 vs 46.4%; P = 0.38) following PRA or nonrestorative colon resection. After a similar lag time (P = 0.43), 64.7% of PRA patients and 60% of nonrestorative colon resection patients underwent stoma reversal (P = 0.659). Adverse event rates following stoma reversal differed significantly after PRA and reversal of nonrestorative resection (4.5 vs 23.5%; P = 0.0589).No conclusions may be drawn on preference of one treatment over another from this RCT because it was prematurely terminated following accrual of 15% of its sample size.

Turner syndrome (TS) is one of the most common chromosomal abnormalities, occurring in about 50 per 100,000 female live births characterized by the total or partial loss of one X-chromosome in all or some cells. Frequently observed manifestations of TS include short stature, lymphedema, cardiac abnormalities, gonadal dysgenesis, dysmorphic features, ear and hearing problems, and a variety of other problems. Conductive hearing loss (CHL) in patients (pts) with TS is due to recurrent otitis media with effusion, chronic middle ear infection, and cholesteatoma probably as the result of malfunction of the Eustachian tube associated with lymphedema and anatomic shortening of the skull base. The high prevalence of middle ear infections and CHL in TS are probably due to growth disturbances of the structures from the first and second branchial arches. Sensorineural hearing loss (SNHL) is also reported in TS and the hearing decline seems to consist of two patterns: a mid-frequency dip (0.5–3 kHz region) (MF-HL) and a high-frequency loss (>3 kHz region) (HF-HL). SNHL is associated with genotype and phenotype. It seems that SNHL in these pts can become clinically evident during childhood or adolescence, progressive with time, and is independent of middle ear diseases. The evaluation in follow-up of hearing impairment shows that the high-frequency HL remained stable in time. Instead, SNHL with typical dip had a progressive decline. The rate of hearing loss is high at all frequencies but most prominent in the mid-frequency region and the presence of a mid-frequency dip is an especially strong predictor for a progressive decline of hearing. Hearing loss (HL) could have an important impact on social functioning for pts with TS. Clinicians proposed a regular audiological follow-up in TS, especially during childhood, to prevent important middle ear anatomic sequelae and to identify HL at an early stage.

The study was performed to evaluate factors influencing postoperative adverse events after Hartmann's reversal (HR).This was a retrospective study of unselected patients who underwent HR after the Hartmann's procedure (HP) for left colonic perforation with peritonitis at a single institution. Data were retrieved from an Institutional Review Board-approved database. The study end-point was postoperative adverse events, which included mortality, complications, reoperations and 30-day readmission. Lag time was defined as the time from HP to HR. The results are expressed as mean±SD.From 1997 to 2007, 204 (39.1%) of all patients who underwent the HP [60±16 years of age; 58% men; body mass index (BMI) 27.6±5.7; 2% were American Society of Anesthesiology (ASA) 1, 50.2% were ASA 2, 39.9% were ASA 3 and 7.9% were ASA 4) underwent HR at an interval of 158±107 days. There were 24 laparoscopic and 180 open HRs, with no deaths. The operating time was 167±64 min, estimated blood loss was 245±283 ml and the 30-day readmission rate was 4.9%. Eleven (5.4%) patients developed 14 (6.8%) complications and five (2.4%) of these patients required a new stoma at the time of HR or later. On multivariate analysis controlling for confounders, chronic renal failure requiring dialysis (OR=21.0; 95% CI: 1.5-284; P=0.02) was significantly associated with increased adverse events.The study showed that chronic renal failure requiring dialysis was the only independent predictor of postoperative adverse event rates following HR.

This study aimed to evaluate circumferential resection margin (CRM) involvement in patients with rectal adenocarcinoma after laparoscopic abdominoperineal excision (APR). Prospectively collected data were analyzed on consecutive patients who underwent laparoscopic APR for histologically proven rectal cancer following neoadjuvant chemotherapy, from 1998 to 2006. Patients with no sphincter involvement were not included and underwent intersphincteric resection with coloanal anastomosis. CRM involvement was defined as ≤ 2 mm using a standardized pathology protocol. Data were presented as mean ± SD or as median (range).Seventy-four patients (60 ± 14 years of age; body mass index = 29.7 ± 7.9 kg/m(2) ) underwent laparoscopic APR. The distance of the tumour from the anal verge was 3.1 ± 0.93 cm. All patients had sphincter involvement. The operative time was 180 ± 73 min, and estimated blood loss was 269 ± 149 ml. There were no conversions and no postoperative mortality. The adverse event rate was 11%. There were two reoperations and three readmissions. Seventy-one patients had a T3 tumour and three patients had a T4 tumour. The median tumour size was 3.1 (range, 0-10) × 3 (range, 0-8.5) × 2 (range, 0-3.6) cm, and 26 (range, 3-41) lymph nodes were harvested. The median CRM was 7 (range, 1-11) mm. This was localized at the waist of the specimen in 12 (16.2%) of patients. Adjuvant therapy was given to 92% and 97% of patients with an involved and an uninvolved CRM, respectively. At 50 ± 27 months of follow up of 73 patients, 12 had CRM involvement and had a significantly decreased cancer-specific survival (log rank test, P = 0.002).Laparoscopic APR resulted in CRM involvement in 16.2% of patients with rectal cancer.