Search

BACKGROUND: The main goal of neonatologist performed echocardiography is to timely assess hemodynamic changes in order to properly manage unsteady neonates. Detailed structural heart assessment remains the domain of pediatric cardiologists. Nonetheless, many neonatologists take on an additional role in diagnosis of congenital heart defects, mostly compelled by the lack of in-house pediatric cardiology services. The experience of neonatologist performed echocardiography in an Italian neonatal unit was reported and the risk benefit profile of this practice was discussed. MATERIAL AND METHODS: We retrospectively reviewed the echocardiograms undertaken by the neonatologist on infants admitted to the neonatal unit and postnatal ward of the Hospital San Pio in Benevento, over a 2-year period. Details of scans and concordance between neonatologist and cardiologist were analyzed. RESULTS: A total of 160 echocardiographic studies were done by the neonatologist on 136 infants. The ECG was requested in a minority of infants. The most common reason for performing the echocardiogram was admission to the neonatal care unit. Around half of the echocardiograms were normal. The remaining scans resulted in functional and structural abnormalities, transitional changes, and doubtful findings. Cardiac anomalies were significantly more likely found in cases of echocardiograms performed for fetal indications. Only 28 patients were eventually referred to the cardiology services. The inter-rater agreement was satisfactory. CONCLUSIONS: The hemodynamic assessment of sick infants, as well as triaging and referral of neonates with structural heart diseases are valuable advantages of the echocardiography run by neonatologists. Collaboration with pediatric cardiologists and robust training and accreditation programs are essential to ensure safety and quality service.

The development of inhibitors against factor VIII (FVIII) concentrates is a severe complication of treatment for patients with haemophilia. We investigated annualized bleeding rates (ABRs) in patients in Argentina with haemophilia A with inhibitors and analysed potential differences between treatment strategies. This multicentre, retrospective, real-world data, cohort design study comprised ambulatory paediatric and adult patients with congenital haemophilia A and FVIII inhibitors treated according to standard clinical practice, with 12-months follow-up. Of 69 included patients, 39 (56.5%) received on-demand treatment, 13 (18.8%) received prophylactic treatment, and 17 (24.6%) received immune tolerance induction (ITI) therapy. The mean overall ABR was 7.68 ± 8.18, with similar rates for on-demand (8.59 ± 9.69), prophylaxis (5.54 ± 4.71), and ITI (7.24 ± 6.23) subgroups. In the negative binomial regression model, prophylactic treatment [incidence rate ratio (IRR) 0.41, 95% confidence interval (CI): 0.21-0.79, P

Background/Aims Impaired intestinal motility seems to play a crucial role in symptomatic uncomplicated diverticular disease (SUDD), although the mechanism is not clear. The aim of the present study is to explore the contractility patterns of colonic smooth muscle strips (MS) and smooth muscle cells (SMCs) and to assess mucosal integrity in SUDD patients. Methods MS or SMCs were isolated from specimens of human distal colon of 18 patients undergoing surgery for non-obstructive colonic cancer, among them 9 with SUDD. Spontaneous phasic contractions on strips and morpho-functional parameters on cells were evaluated in basal conditions and in response to acetylcholine (ACh). Mucosal integrity of SUDD colonic biopsies was evaluated by the Ussing Chamber system. Immunohistochemical staining for tight junction protein complex and for Toll-like receptor 4 (TLR4) was performed. Results Colonic MS of SUDD group showed a significant reduced basal tone and ACh-elicited contraction, compared to the control group (9.5 g and 47.0% in the SUDD group; 14.16 g and 69.0% in the control group; P < 0.05). SMCs of SUDD group showed a maximal contractile response to ACh significantly reduced compared to control group (8.8% vs 16.5%, P < 0.05). SUDD patients displayed lower transepithelial electrical resistance and increased paracellular permeability compared to control group. Immunohistochemical expression of TLR4 was not different in both groups, while tight junction protein complex expression was lower in SUDD patients compared to control group patients. Conclusion It could be hypothesized that in SUDD, in absence of severe inflammation, an increased intestinal mucosal permeability is related to altered colonic motility probably responsible for symptoms genesis.

Common bile duct stones are frequently diagnosed worldwide and are one of the main indications for endoscopic retrograde cholangio-pancreatography. Endoscopic sphincterotomy (EST) has been used for the removal of bile duct stones for the past 40 years, providing a wide opening to allow extraction. Up to 15% of patients present with complicated choledocholithiasis. In this context, additional therapeutic approaches have been proposed such as endoscopic mechanical lithotripsy, intraductal or extracorporeal lithotripsy, or endoscopic papillary large balloon dilation (EPLBD). EPLBD combined with EST was introduced in 2003 to facilitate the passage of large or multiple bile duct stones using a balloon greater than 12 mm in diameter. EPLBD without EST was introduced as a simplified technique in 2009. Dilation-assisted stone extraction (DASE) is the combination of two techniques: EPLBD and sub-maximal EST. Several studies have reported this technique as safe and effective in patients with large bile duct stones, without any increased risk of adverse events such as pancreatitis, bleeding, or perforation. Nevertheless, it is difficult to analyze the outcomes of DASE because there are no standard techniques and definitions between studies. The purpose of this paper is to provide technical guidance and specific information about the main issues regarding DASE, based on current literature and daily clinical experience in biliary referral centers.

Previous research has shown that genes play a substantial role in determining a person’s susceptibility to age-related hearing impairment. The existing studies on this subject have different results, which may be caused by difficulties in determining the phenotype or the limited number of participants involved. Here, we have gathered the largest sample to date (discovery n = 9,675; replication n = 10,963; validation n = 356,141), and examined phenotypes that represented low/mid and high frequency hearing loss on the pure tone audiogram. We identified 7 loci that were either replicated and/or validated, of which 5 loci are novel in hearing. Especially the ILDR1 gene is a high profile candidate, as it contains our top SNP, is a known hearing loss gene, has been linked to age-related hearing impairment before, and in addition is preferentially expressed within hair cells of the inner ear. By verifying all previously published SNPs, we can present a paper that combines all new and existing findings to date, giving a complete overview of the genetic architecture of age-related hearing impairment. This is of importance as age-related hearing impairment is highly prevalent in our ageing society and represents a large socio-economic burden.

Background Intraductal papillary neoplasm of the bile duct (IPNB) is a rare variant of bile duct tumors, characterized by an exophytic growth exhibiting a papillary mass within the bile duct lumen and it can be localized anywhere along the biliary tree, with morphological variations and occasional invasion. Case summary We present a patient with obstructive jaundice who was diagnosed with IPNB using cholangioscopy during endoscopic retrograde cholangio-pancreatography. Using the SpyGlass DS II technology, we were able to define tumor extension and obtain targeted Spy-byte biopsies. After multidisciplinary evaluation, the patient was scheduled for surgical resection of the tumor, which was radically removed. Conclusion Cholangioscopy appears to be crucial for the rapid and clear diagnosis of lesions in the bile duct to achieve radical surgical resection.

Approximately 10% of infants at birth require some assistance to breathe and 1% require vigorous resuscitation. As such, midwives need appropriate education and training on newborn life support (NLS) techniques.We conducted a survey on Italian territory about the correlation between obstetric education and the management of the neonatal resuscitation in the delivery room. The study was led through a web survey based on 23 questions, given anonymously online through the Google Drive platform.272 women aged from 19 to 59 years answered the questions (83% midwives and 17% midwifery students). 93% of them attended an NLS course before graduation, while only 57% have repeated it afterwards once or more times. The midwives working in hospitals with neonatal intensive care units (NICUs) experienced more involvement within the emergency neonatal resuscitation team than the others working in other kind of hospitals (hospital with NICU 79%, hospital without NICU 57%, private hospital 48%;In spite of NLS techniques are taught to near all midwives, only working in hospitals within a NICU and longer work experience are directly related with greater involvement of a midwife in the neonatal resuscitation team.

Hypochondroplasia (HCH) is a rare autosomal dominant skeletal dysplasia condition caused by FGFR3 mutations leading to disproportionate short stature. Classically HCH presents in toddlers or school-age children, as limb-to-trunk disproportion and is often mild and easily overlooked during infancy. We report experiences from a single-center UK HCH-cohort of 31 patients, the rate of antenatal HCH detection in our cohort (13/31, 41.9%) and describe relevant case-data for this subset of 13 patients. Inclusion criteria were patients with confirmed molecular HCH diagnosis (by age 3 years) and presenting with short long-bones or large head size on antenatal ultrasound scan. We then conducted a systematic literature review using PUBMED and MEDLINE, analyzing patients with HCH and related antenatal findings. Antenatally suspected (with subsequent molecular confirmation) HCH has been reported 15 times in the literature (2004-2019). Key markers (consistent in both groups) included reduced; femur length, humeral length and increased; biparietal diameter and head circumference. HCH is increasingly detected both antenatally and in infancy, contrary to previous descriptions. This is likely due to greater HCH awareness, improved imaging, and easier molecular testing. Thus, one should consider HCH outside the classical presenting period. Studying the natural history of younger patients with HCH is important with the advent of several targeted FGFR3 therapies currently in trials for Achondroplasia, that may soon be trialed in HCH.

Duodenal hyperpermeability and low-grade inflammation in functional dyspepsia is potentially related to duodenal acid exposure. We aimed to evaluate in healthy volunteers the involvement of mast cell activation on the duodenogastric reflex and epithelial integrity during duodenal acidification. This study consisted of 2 parts: (1) Duodenal infusion of acid or saline during thirty minutes in a randomized, double-blind cross-over manner with measurement of intragastric pressure (IGP) using high resolution manometry and collection of duodenal biopsies to measure epithelial barrier function and the expression of cell-to-cell adhesion proteins. Mast cells and eosinophils were counted and activation and degranulation status were assessed. (2) Oral treatment with placebo or mast cell stabilizer disodiumcromoglycate (DSCG) prior to duodenal perfusion with acid, followed by the procedures described above. Compared with saline, acidification resulted in lower IGP (P

Achondroplasia is associated with foramen magnum stenosis. We report a male infant with achondroplasia and centrally mediated obstructive apnoea who underwent two foramen magnum decompression due to bone regrowth. He presented at six weeks of age with breath holding and apnoeic episodes associated with significant desaturation, requiring non-invasive ventilation. Craniospinal imaging revealed a narrow foramen magnum without signal change in the spinal cord. Sleep studies showed obstructive, but not central, apnoea. Respiratory abnormalities persisted and reimaging at two months showed development of significant signal changes at the cervicomedullary junction (CMJ). He underwent emergency foramen magnum decompression with initial clinical improvement. Ten days later he relapsed with further apnoeic episodes requiring respiratory support. After extensive re-investigations including CT and MRI, incomplete initial decompression and foramen magnum restenosis were considered and confirmed with a CT head scan 15 weeks after the initial operation. Repeat decompression of bone and removal of thickened dural bands resulted in complete resolution of the apnoeic episodes. Obstructive sleep apnoea can be centrally mediated and further decompression of foramen magnum stenosis should be considered, especially if significant respiratory compromise persists or recurs.

BackgroundAchondroplasia is associated with foramen magnum stenosis (FMS) and significant risk of morbidity and sudden death in infants. A sensitive and reliable method of detecting infants who require decompressive surgery is required. This study aims to describe the incidence and severity of FMS in an unselected, sequential series of infants using a novel MRI score and retrospectively correlate severity with clinical examination and cardiorespiratory sleep (CRS) studies.MethodsThe Achondroplasia Foramen Magnum Score (AFMS) was developed and scores were retrospectively correlated with clinical and CRS data over a 3-year period.ResultsOf 36 infants (M:F, 18:18), 2 (5.6%) did not have FMS (AFMS0); 13 (36.1%) had FMS with preservation of the cerebrospinal fluid (CSF) spaces (AFMS1); 3 (8.3%) had FMS with loss of the CSF space but no spinal cord distortion (AFMS2); 13 (36.1%) had FMS with flattening of the cervical cord without signal change (AFMS3); and 5 (13.9%) had FMS resulting in cervical cord signal change (AFMS4). Mean Total Apnea and Hypopnea Index (TAHI) for AFMS0–4 was 3.4, 6.41, 2.97, 10.5 and 25.8, respectively. Severe TAHI had a specificity of 89% but only a 59% sensitivity for AFMS3–4. Neurological examination was normal in 34/36 (94%) patients. Overall, 9/36 (25%) infants required neurosurgery with minimal surgical complications.ConclusionsClinical examination and CRS have a low sensitivity for predicting the effects of foramen stenosis on the spinal cord. Routine screening with MRI using AFMS can aid in detecting early spinal cord changes and has the potential to reduce infant morbidity and mortality.

Se analizó el impacto de un programa de salud para adolescentes con problema de obesidad. La intervención duró 14 semanas, consistió en tres condiciones (control, experimental y experimental con fototerapia) y los indicadores fueron medidas del perfil metabólico y cinco dimensiones del autoconcepto (Inventario de autoconcepto forma AF-5). Diseño cuasi-experimental con mediciones pre-post. La condición de control únicamente fue evaluada en dos ocasiones. Un grupo experimental recibió orientación nutricional y realizó actividad física (bicomponente). El segundo grupo experimental recibió, además, sesiones de fototerapia. Se analizaron las diferencias basales (pretest) encontrando diferencias entre las tres condiciones en triglicéridos y autoconcepto familiar. Los resultados finales indicaron que la administración de orientación nutricional, actividad física y fototerapia se relacionó con mejoras en el pliegue tricipital, triglicéridos y glicemia (p < .05). La administración de cualquiera de las condiciones experimentales, incluyeran o no fototerapia, se correspondía con mejor autoconcepto social respecto del grupo de control. Se concluye que la participación en un programa de salud que incluye orientación nutricional y actividad física puede producir en corto plazo cambios en la distribución de la adiposidad y el autoconcepto social en adolescentes con obesidad.Abstract. The impact of a health program for adolescents with obesity problem was analyzed. The intervention lasted 14 weeks, consisted of three conditions (control, experimental, and experimental with phototherapy) and the indicators were measures of the metabolic profile and five dimensions of the Self-concept Inventory Form. A quasi-experimental design with pre-post measurements was applied. Control condition was only evaluated twice. An experimental group received nutritional guidance and performed physical activity. The second experimental group additionally received phototherapy sessions. Baseline differences (pretest) were analyzed, finding differences between the three conditions in triglycerides and family self-concept. Final results indicated that nutritional guidance, physical activity and phototherapy were related to improvements in the tricipital fold, triglycerides and glycemia (p < .05). The administration of any of the experimental conditions, with or without phototherapy, corresponded with better social self-concept with respect to the control group. Participation in a health program that includes nutritional guidance and physical activity can produce changes in the distribution of adiposity and social self-concept in adolescents with obesity in the short term.

El ejercicio físico ha tomado presencia en el campo investigativo como complemento del tratamien-to para el trastorno depresivo mayor (TDM). Por tanto, el objetivo fue analizar las diferentes interven-ciones de programas de ejercicio aeróbico y tratamiento farmacológico en pacientes hospitalizados con TDM. Se realizó una busque bibliográfica en PubMed, Cochrane Library y Scopus, entre el año 2000 y 2019, seleccionando estudios con pacientes hospitalizados de 18 años en adelante diagnosticados con TDM bajo tratamiento farmacológico en conjunto a una intervención de ejercicio aeróbico. De los artículos seleccionados se obtuvo información como tipo de ejercicio y duración, entre otras características. De un total de 599 artículos, se identificaron 10 artículos potenciales evidenciando una respuesta positiva de los programas de ejercicios aeróbicos sobre los síntomas depresivos de los pacientes. Sin embargo, la frecuencia y duración fueron variables. En conclusión, hay necesidad de estandarizar un programa de ejercicio en hospitales psiquiátricos como tratamiento coadyuvante para el TDM Physical exercise has taken presence in the research field as a complement to the treatment for major depressive disorder (MDD). Therefore, the objective was to analyse the different interventions of aerobic exercise and pharmacology treatment programs in hospitalized patients with MDD. A bibliogra-phic search was carried out in PubMed, Cochrane Lybrary, Scopus databases from 2000-2019, selecting studies with hospitalized patients aged 18 years, and older diagnosed with MDD under pharmacologi-cal treatment with an aerobic exercise intervention. Information was obtained from the selected arti-cles, such as type of exercise and duration, among other characteristics. From 599 articles, ten potential articles were identified, evidencing a positive response from aerobic exercise programs to patients’ depressive symptoms. However, the frequency and duration were variable. In conclusion, there is a need to standardize an exercise program in psychiatric hospitals as an adjunctive treatment for MDD

OBJECTIVE To report the clinical outcomes of the use of acellular fish skin grafts (FSGs) for the management of complex soft tissue wounds of various etiologies in dogs and cats. ANIMALS 13 dogs and 4 cats with complex wounds treated with FSGs between February 2019 and March 2021. PROCEDURES Medical records were reviewed for information regarding cause, location, size of the wound, management techniques, complications, and clinical outcomes. RESULTS In dogs, the number of FSG applications ranged from 1 to 4 (median, 2 graft applications). The time between each application ranged from 4 to 21 days (median, 9.5 days). Time to application of the first FSG ranged from 9 to 210 days (median, 19 days). Wounds closed by second-intention healing following the first fish skin application between 26 and 145 days (median, 71 days; n = 12). In cats, 1 or 2 FSGs were used, and the wounds of 3 of 4 cats healed completely by secondary intention. The wounds of 1 dog and 1 cat did not heal. There were no adverse events attributed to the use of the FSGs. CLINICAL RELEVANCE For dogs and cats of the present study, complete healing of most wounds occurred with the use of FSGs, the application of which did not require special training, instruments, or bandage materials.

The QT interval is an electrocardiographic measure representing the sum of ventricular depolarization (QRS duration) and repolarization (JT interval). Abnormalities of the QT interval are associated with potentially fatal ventricular arrhythmia. We conducted genome-wide multi-ancestry analyses in >250,000 individuals and identified 177, 156 and 121 independent loci for QT, JT and QRS, respectively, including a male-specific X-chromosome locus. Using gene-based rare-variant methods, we identified associations with Mendelian disease genes. Enrichments were observed in established pathways for QT and JT, with new genes indicated in insulin-receptor signalling and cardiac energy metabolism. In contrast, connective tissue components and processes for cell growth and extracellular matrix interactions were significantly enriched for QRS. We demonstrate polygenic risk score associations with atrial fibrillation, conduction disease and sudden cardiac death. Prioritization of druggable genes highlighted potential therapeutic targets for arrhythmia. Together, these results substantially advance our understanding of the genetic architecture of ventricular depolarization and repolarization.

The objective of this research was to explore current communication practices for positive newborn bloodspot screening results for congenital hypothyroidism from the newborn bloodspot screening laboratory to clinicians and then families, in order to (i) understand how the pathway is implemented in practice, (ii) highlight regional differences and (iii) identify barriers and facilitators. A qualitative exploratory design was employed using semi-structured interviews across 13 newborn bloodspot screening laboratories in England. Participants included 35 clinicians and 17 NBS laboratory staff across the 13 laboratories and 18 members of relevant clinical teams. Findings illuminated variations in how positive newborn bloodspot screening results for congenital hypothyroidism are communicated in practice. This included regional variations due to historical arrangements and local resources. Contacting the appropriate person could be challenging and obtaining feedback from clinical teams to the laboratory after the child has been seen could be time consuming for those involved. Standardised communication model(s) for positive newborn bloodspot screening results for congenital hypothyroidism, which include named contact individuals, defined pathways of care and processes for feeding back to laboratories, may help to ensure the process is less labour intensive, particularly from a laboratory perspective.

INTRODUCTION AND OBJECTIVE:Klinefelter's syndrome (KS) affects 1 in 660 males and is one of the most common congenital chromosomal disorders. Management of KS involves input from multiple specialti...

El objetivo del estudio fue determinar las características de la conducta de actividad física realizada al inicio de la fase 3 de contingencia epidemiológica por COVID-19 en personas mayores de 18 años. Se presenta una investigación cuantitativa, comparativa y transversal. Participaron 2116 profesionistas afiliados en asociaciones de Educación Física y Deporte de Norteamérica, Centro y Sudamérica. Los resultados muestran que los principales motivos para realizar ejercicio fueron la condición física (32.5%), el disfrute o gusto (27.8%) y la apariencia física (16.3%). Más de uno de cada cinco reportó no tener tiempo para realizar ejercicio. Existen diferencias por región y sexo para la realización de actividad física durante el aislamiento social (p < .05). Pese a que las personas reconocen los beneficios del ejercicio para la salud, la salud no es considerada dentro de las principales motivaciones para su realización. The objective of the study was to determine the characteristics of the physical activity behavior carried out at the beginning of phase 3 of the epidemiological contingency due to COVID-19 in people over 18 years of age. It is presented a quantitative comparative and cross-sectional study. Two thousand one hundred sixteen professionals affiliated with Physical Education and Sports associations in North, Central and South America participated. In this sample, the main reasons for exercising were physical condition (32.5%), enjoyment (27.8%) and physical appearance (16.3%). More than one in five reported not having time to exercise. There were differences by region and sex for the performance of physical activity during social isolation (p < .05). Even though people recognize the benefits of exercise for health, health is not considered among the main motivations for its performance.

OBJECTIVE: To document the appearance of artifacts created by commonly encountered surgical conditions and instrumentation on optical coherence tomography (OCT) and to compare these findings with histopathology. STUDY DESIGN: Ex vivo study. ANIMALS: Five canine cadavers. METHODS: Skin, subcutaneous fat, skeletal muscle, and fascia samples were obtained from fresh canine cadavers. Blood pooling, hemostatic crushing, scalpel blade cut, monopolar electrosurgery, bipolar vessel sealing device, and ultrasonic energy surgical artifacts were induced on each tissue type. Each specimen was imaged with OCT and subsequently histologically processed. RESULTS: Most surgical instrumentation used for tumor excision created a high-scattering region with local architectural disruption. Blood pooling was visible as a high-scattering layer overlying tissue with normal architecture. Only the scalpel blade created a focal, low-scattering area representing a sharply demarcated cut within the tissue distinct from the appearance of other instrumentation. CONCLUSION: Common surgical instruments and conditions encountered during tumor excision produced high-scattering OCT artifacts in tissues commonly seen at surgical margins. CLINICAL SIGNIFICANCE: The clinical value of OCT hinges on the ability of personnel to interpret this novel imaging and recognize artifacts. Defining and describing the appearance of common surgical artifacts provides a foundation to create image libraries with known histological and OCT interpretation, ultimately improving the diagnostic accuracy of OCT for assessment of surgical margins.

Background Skeletal dysplasia (SD) conditions are rare genetic diseases of the skeleton, encompassing a heterogeneous group of over 400 disorders, and represent approximately 5% of all congenital anomalies. Developments in genetic and treatment technologies are leading to unparalleled therapeutic advances; thus, it is more important than ever to molecularly confirm SD conditions. Data on ‘rates-of-molecular yields’ in SD conditions, through exome sequencing approaches, is limited. Figures of 39% and 52.5% have been reported in the USA (n = 54) and South Korea (n = 185) respectively. Methods We discuss a single-centre (in the UK) experience of whole-exome sequencing (WES) in a cohort of 15 paediatric patients (aged 5 months to 12 years) with SD disorders previously molecularly unconfirmed. Our cohort included patients with known clinical diagnoses and undiagnosed skeletal syndromes. Extensive phenotyping and expert radiological review by a panel of international SD radiology experts, coupled with a complex bioinformatics pipeline, allowed for both gene-targeted and gene-agnostic approaches. Results Significant variants leading to a likely or confirmed diagnosis were identified in 53.3% (n = 8/15) of patients; 46.7% (n = 7/15) having a definite molecular diagnosis and 6.7% (n = 1/15) having a likely molecular diagnosis. We discuss this in the context of a rare disease in general and specifically SD presentations. Of patients with known diagnoses pre-WES (n = 10), molecular confirmation occurred in 7/10 cases, as opposed to 1/5 where a diagnosis was unknown pre-test. Thus, diagnostic return is greatest where the diagnosis is known pre-test. For WGS (whole genome sequencing, the next iteration of WES), careful case selection (ideally of known diagnoses pre-test) will yield highest returns. Conclusions Our results highlight the cost-effective use of WES-targeted bioinformatic analysis as a diagnostic tool for SD, particularly patients with presumed SD, where detailed phenotyping is essential. Thorough co-ordinated clinical evaluation between clinical, radiological, and molecular teams is essential for improved yield and clinical care. WES (and WGS) yields will increase with time, allowing faster diagnoses, avoiding needless investigations, ensuring individualised patient care and patient reassurance. Further diagnoses will lead to increased information on natural history/mechanistic details, and likely increased therapies and clinical trials.

KIAA0753-related skeletal ciliopathy is a recently described recessive disorder causing skeletal dysplasia and overlapping features of certain ciliopathies; Joubert, Jeune and Oro-facial-digital syndromes. We describe a ninth case that expands the phenotype; a 10-year-old girl with rhizomelic short stature (-5.6 SD), macrocephaly, developmental delay, CNS anomalies (thin corpus callosum, bilateral ventriculomegaly), cone-rod dystrophy, nystagmus, mild conductive hearing loss and recurrent chest infections secondary to confirmed ciliary dyskinesia. Testing for FGFR3 achondroplasia-related hotspots and mucopolysaccharidosis were negative. Whole-exome sequencing, aged eight, via skeletal dysplasia panel analysis and subsequent whole-genome sequencing (via the 100,000 genomes project) found no cause. WGS data reanalysis using exomiser uncovered compound heterozygous pathogenic KIAA0753 variants (frameshift and splice site). Further clinical and radiological surveys were consistent with the expected phenotype. We discuss the emerging phenotype of this uncommon disorder. This report details the sixth published case of skeletal dysplasia in all cases of KIAA0753-related disease and the first case to describe a novel c.1830-2A>G splice variant. Our case is the eldest woman reported to date (aged ten years) and the only known case to report associated hearing loss, leg-length discrepancy, pectus carinatum, respiratory ciliary dyskinesia and late-onset (9 years old) neuro-degenerative regression.

Chlorpyrifos (CPF), the most used insecticide in Argentina, can act as an endocrine disruptor at low doses. We previously demonstrated that chronic exposure to CPF induces hormonal imbalance in vivo. The aim of this work was to study the effects of low concentrations of CPF (0.01 and 1 mg/kg/day) on the reproductive system of virgin adult rats. In the ovary, we studied the effects of CPF on steroidogenesis by determining steroid hormone content by RIA and CYP11 and CYP19 enzyme expression by qRT-PCR. The estrous cycle was evaluated by microscopic observation of vaginal smear, as well as by changes in uterine histology. In endometrium, we determined the fractal dimension and expression of PCNA, ERα and PR by IHC. Our results showed that chronic exposure to CPF affects ovarian steroid synthesis, causing alterations in the normal cyclicity of animals. In addition, CPF induced proliferative changes in the uterus, suggesting that it could affect reproduction or act as a risk factor in the development of uterine proliferative pathologies.

Intestinal dysbiosis seems to play a role in the pathophysiology of irritable bowel syndrome (IBS). The present pilot study aimed to elucidate the association between nutrient intake and Mediterranean diet (MD) adherence with IBS symptoms and gut microbiota in IBS patients. The nutrient intake of 28 IBS patients and 21 controls was assessed through a food diary, the reference intake ranges (RIs) for energy-yielding macronutrients and the MD serving score (MDSS) index. MD adherence and nutrients intake were compared to IBS symptoms and fecal microbiota, obtained by 16S rRNA targeted-metagenomics. In IBS patients MDSS index was altered compared to controls (p &lt, 0.01). IBS patients with low-MD score reported severe abdominal pain and higher flatulence point-scales. Through Linear discriminant analysis effect size (LEfSe), Erysipelotrichaceae were detected as a microbial biomarker in IBS patients with altered RIs for macronutrients intake, compared to controls. Lactobacillaceae and Lactobacillus were associated to an altered carbohydrates intake in IBS patients, while specific taxonomic biomarkers, such as Aldercreuzia, Mogibacteriaceae, Rikenellaceae, Parabacteroides and F. prausnitzii were associated with an adequate intake of nutrient in these patients. This study supports an association between dietary patterns and gut microbial biomarkers in IBS patients. Further investigations are needed to clarify these connections.

Objectives Emergency department (ED) providers face pressure to meet sepsis mandates such as prompt administration of antibiotic therapy, which can lead to the overuse of broad-spectrum antibiotics. In recent years, there has also been a push to adhere to institutional antibiotic stewardship goals including decreasing inappropriate antibiotic therapy and limiting duration of therapy. Previous literature has demonstrated that the incorporation of clinical decision support (CDS) tools in electronic medical records can aid in guiding appropriate antibiotic prescribing. Therefore, the objective of this study was to determine whether the implementation of a CDS tool could improve antibiotic selection for pneumonia management in the ED. Methods This was a retrospective single-centre observational study conducted in patients that presented to the ED with pneumonia. In November 2018, a CDS tool was incorporated into the ED sepsis order set to guide practitioners in selecting appropriate antibiotics for pneumonia. Antibiotic prescribing patterns were assessed pre-CDS (January–February 2018) and post-CDS (January–February 2019) implementation. Patients were included if they were 18 years of age or older, had an ED visit with ICD10 code reflective of pneumonia, and had at least one antibiotic ordered from the ED sepsis order set. The primary endpoint was the percentage of patients prescribed appropriate antibiotic therapy for pneumonia based on patient risk factors pre- and post-CDS implementation. Key findings There were 161 patients in the pre-CDS group and 119 patients in the post-CDS group included in the study. There was a significant improvement in the selection of appropriate antibiotics in the post-CDS group (31.9% versus 65.3%, P < 0.0001) with no significant differences in duration of antibiotics, intubation rates, vasopressor initiation, length of stay, mortality or 30-day readmission. Conclusion The implementation of a CDS tool for empiric management of pneumonia in the ED significantly improved the selection of appropriate antibiotics.

Oxidative stress is a key mediator of autoimmune/neurodegenerative disorders. The antioxidant/anti-inflammatory effect of a synthetic conjugated linoleic acid (CLA) mixture in MRL/MpJ-Fas lpr mice (MRL/lpr), an animal model of neuropsychiatric lupus, was previously associated with the improvement of nuclear factor-E2-related factor 2 (Nrf2) defenses in the spleen and liver. However, little is known about the neuroprotective ability of a CLA mixture. This study investigated the age-dependent progression of oxidative stress and the hyperactivation of redox-sensitive compensatory pathways (macroautophagy, Nrf2) in old/diseased MRL/lpr mice brains and examines the effect produced by dietary CLA supplementation. Disrupted redox homeostasis was evidenced in the blood, liver, and brain of 21- to 22-week-old MRL/lpr (Old) mice compared with 8- to 10-week-old MRL/lpr (Young) animals. This alteration was associated with significant hyperactivation of compensatory mechanisms (macroautophagy, Nrf2, and astrocyte activation) in the brains of Old mice. Five-week daily supplementation with CLA (650 mg/kg-1 body weight) of 16-week-old (CLA+Old) mice diminished all the pathological hallmarks at a level comparable to Young mice or healthy controls (BALB/c). Such data demonstrated that MRL/lpr mice can serve as a valuable model for the evaluation of the effectiveness of neuroprotective drugs. Notably, the preventive effect provided by CLA supplementation against age-associated neuronal damage and hyperactivation of compensatory mechanisms suggests that the activation of an adaptive response is at least in part accountable for its neuroprotective ability.

Context: The Global Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) pandemic has resulted in explosive patterns of transmission in most countries. Nasopharyngeal swabs were the specimen’s collection tools recommended for the diagnosis of SARS-CoV-2 infection, and for monitoring infection outbreaks in communities. Our objective was to report the quality and efficacy of unsupervised self-collected mid turbinate “dry FLOQSwabs” (MT FLOQSwabs) (56380CS01, Copan). There were 111 specimens collected for the study: 36 by health care personnel, from themselves, to verify the quality and efficacy of mid-turbinate swabs, 75 to compare and assess the diagnostic performance, among health care personnel, of nasopharyngeal swabs and self-collected mid-turbinate FLOQSwabs. A collection of 51 specimens was enrolled to define the efficacy of the Testami program (validation). Our analyses demonstrate that self-collected mid-turbinate dry swabs ensure an accuracy of 97.3%, as compared to the standard nasopharyngeal swabs collected by health care workers. Furthermore, the mid-turbinate FLOQSwabs can be stored without medium for six days at room temperature without affecting the molecular diagnosis of the SARS-CoV-2 virus infection. Self-collection of diagnostic specimens at home could offer an avenue to increase testing availability for SARS-CoV-2 infection without asking people to travel to a clinic or a laboratory, thus reducing people’s exposure to infection. Our findings demonstrate that unsupervised self-collection swabs, transported dry, are sensitive, practical and easy-to-use tools and should be considered for diagnosis of SARS-COV-2 and coronavirus disease 2019 (COVID-19) surveillance.

Dietary supplementation with pure cis9, trans11 isomer of Conjugated Linoleic Acid –known as Rumenic Acid (RA)– improves cytoprotective defenses downstream through the activation of nuclear factor-E2-related factor-2(Nrf2). This capability, when Rumenic Acid is consumed in the form of foods, is still unknown. The ability of standard (St) or cow milk naturally-enriched in RA (En) to activate Nrf2 pathway and its impact on dextran sodium sulfate (DSS)-induced colitis was comparatively evaluated. Activity of Nrf2 pathway was investigated in colonic tissue of BALB/c mice, receiving 4-week supplement with skimmed milk (SK), St or St reinforced with pure RA (RSt) providing increasing RA dose (0, 124 or 404 mg RA/kg-1 b.w, respectively). Next, the anti-oxidant/ anti-inflammatory effect produced by St or En treatment (383 mg RA/kg-1 b.w.) was explored. Finally, macroscopic and histomorphologic features of colitis were evaluated in animals challenged with 5% (w/v) DSS, at the end of St or En treatment. Significant activation of Nrf2 pathway is associated with RSt and En intake (P

Chronic kidney disease (CKD) is responsible for a public health burden with multi-systemic complications. Through trans-ancestry meta-analysis of genome-wide association studies of estimated glomerular filtration rate (eGFR) and independent replication (n = 1,046,070), we identified 264 associated loci (166 new). Of these, 147 were likely to be relevant for kidney function on the basis of associations with the alternative kidney function marker blood urea nitrogen (n = 416,178). Pathway and enrichment analyses, including mouse models with renal phenotypes, support the kidney as the main target organ. A genetic risk score for lower eGFR was associated with clinically diagnosed CKD in 452,264 independent individuals. Colocalization analyses of associations with eGFR among 783,978 European-ancestry individuals and gene expression across 46 human tissues, including tubulo-interstitial and glomerular kidney compartments, identified 17 genes differentially expressed in kidney. Fine-mapping highlighted missense driver variants in 11 genes and kidney-specific regulatory variants. These results provide a comprehensive priority list of molecular targets for translational research.

Objective Different surgical set-ups for endoscopic transsphenoidal surgery (ETS) have been described, but studies on their ergonomics are limited. The aim of this article is to describe present trends in the ergonomics of ETS. Design and Participants A 33-question, web-based survey was sent to North American Skull Base Society members in 2018 and 116 responded to it (16% of all members). Most respondents were from North America (76%), in academic practice (87%), and neurosurgeons (65%); they had more than 5 years of experience in ETS (73%), had received specific training (66%), and performed at least 5 procedures/mo (55%). Results Mean reported time for standard and complex procedures were 3.7 and 6.3 hours, respectively. The patient's body is usually positioned in a straight, supine position (84%); the head is in a neutral position (46%) or rotated to the side (38%). Most surgeons perform a binostril technique, work with a partner (95%), and operate standing (94%), holding suction (89%) and dissector (83%); sometimes the endoscope is held by the primary surgeon (22–24%). The second surgeon usually holds the endoscope (72%) and irrigation (42%). During tumor removal most surgeons stand on the same side (65–66%). Many respondents report strain at the dorsolumbar (50%) or cervical (26%) level. Almost one-third of surgeons incorporate a pause during surgery to stretch, and approximately half exercise to be fit for surgery; 16% had sought medical attention for ergonomic-related symptoms. Conclusion Most respondents value ergonomics in ETS. The variability in surgical set-ups and the relatively high report of complaints underline the need for further studies to optimize ergonomics in ETS.

Rapid decline of glomerular filtration rate estimated from creatinine (eGFRcrea) is associated with severe clinical endpoints. In contrast to cross-sectionally assessed eGFRcrea, the genetic basis for rapid eGFRcrea decline is largely unknown. To help define this, we meta-analyzed 42 genome-wide association studies from the Chronic Kidney Diseases Genetics Consortium and United Kingdom Biobank to identify genetic loci for rapid eGFRcrea decline. Two definitions of eGFRcrea decline were used: 3 mL/min/1.73m(2)/year or more ("Rapid3"; encompassing 34,874 cases, 107,090 controls) and eGFRcrea decline 25% or more and eGFRcrea under 60 mL/min/1.73m(2) at follow-up among those with eGFRcrea 60 mL/min/1.73m(2) or more at baseline ("CKDi25"; encompassing 19,901 cases, 175,244 controls). Seven independent variants were identified across six loci for Rapid3 and/or CKDi25: consisting of five variants at four loci with genome-wide significance (near UMOD-PDILT (2), PRKAG2, WDR72, OR2S2) and two variants among 265 known eGFRcrea variants (near GATM, LARP4B). All these loci were novel for Rapid3 and/or CKDi25 and our bioinformatic follow-up prioritized variants and genes underneath these loci. The OR2S2 locus is novel for any eGFRcrea trait including interesting candidates. For the five genome-wide significant lead variants, we found supporting effects for annual change in blood urea nitrogen or cystatin-based eGFR, but not for GATM or (LARP4B). Individuals at high compared to those at low genetic risk (8-14 vs. 0-5 adverse alleles) had a 1.20-fold increased risk of acute kidney injury (95% confidence interval 1.08-1.33). Thus, our identified loci for rapid kidney function decline may help prioritize therapeutic targets and identify mechanisms and individuals at risk for sustained deterioration of kidney function., Zweitveröffentlichungen der Universität Potsdam : Reihe der Digital Engineering Fakultät; 19

Introduction: The COVID-19 Pandemic has mandated limiting routine visit frequency for patients with chronic cardiovascular (CV) diseases. In patients with heart failure (HF) followed longitudinally, the period of clinical trial participation provides an opportunity to evaluate the influence of high-frequency per-protocol in-person visits compared to less frequent routine visits during longitudinal clinical care. Hypothesis: Patients enrolled in clinical trials will have a lower CV and HF event rates during periods of trial enrollment than during non-trial periods. Methods: We examined clinical characteristics, CV and HF hospitalization rates, and outcomes in patients with HF receiving longitudinal HF care at a single center. We evaluated hospitalization rates during the 1-year preceding trial enrollment and hospitalization and death rates during enrollment in clinical trials and for up to 1 year following trial completion. Results: Among the 121 patients enrolled in HF clinical trials, 72% were HFrEF (age 62±11, 19% females, BMI 30.4±6.0, LVEF 25±7, NYHA 2.7±0.6, NT-proBNP 2336±2671) and 28% were HFpEF (age 69±9, BMI 32.1±5.5, 29% females, LVEF 60±10, NYHA 2.4±0.5, NT-proBNP 957±997). Average clinical trial exposure was 8±6.6 months. Per-protocol visit frequency was 16±7 per year during clinical trial enrollment. In the one-year pre-trial period, compared to the within-trial period, CV hospitalizations were 0.88/patient-year vs. 0.32/patient-year (p Conclusion: In HF patients followed longitudinally at a single center, periods of clinical trial enrollment were associated with high visit frequency and lower CV and HF hospitalization rates. These findings highlight the potential benefits of trial enrollment and high-frequency visits for HF patients at a time when routine visit frequency is being carefully considered during the COVID-19 Pandemic.

Histopathologic surgical margin assessment in veterinary patients is an imprecise science with assessment limited to a small proportion of the surgical margin due to time and finances. Incomplete excision of canine mast cell tumours (MCTs) alters treatment recommendations and prognosis. Optical coherence tomography (OCT) is a novel imaging modality that has been reported in a single veterinary study for surgical margin assessment. Twenty-five dogs with 34 MCTs were enrolled in a prospective pilot-study to assess the imaging characteristics of canine MCTs with OCT and to evaluate the feasibility and utility of OCT-guided histopathology. All dogs underwent routine surgical excision of MCTs. OCT imaging was used to assess the entire surgical margin prior to placement in formalin. Either normal areas or areas suspected of incomplete MCT excision were inked. Standard histopathologic sectioning and tangential sectioning of inked areas were performed and compared to OCT results. OCT identified MCT near the surgical margin in 10 of 26 specimens (38.4%). Four specimens suspicious for incomplete margins on OCT had incomplete MCT excision that was missed on standard histopathologic sectioning. Six specimens had OCT-guided sections taken as suspicious, which did not show MCT on histopathology. OCT-guided pathology sections were able to detect incompletely excised MCT near the surgical margin with a sensitivity of 90% and specificity of 56.2% in this preliminary study. OCT imaging shows promise for guiding pathologists to areas of interest to improve the diagnostic accuracy of surgical margin assessment in excised canine MCTs.

Background Most of Harm Reduction Service (HRS) users represent a crucial high-risk population for blood borne infections, including HCV. With the advent of new direct antiviral agents (DAAs), HCV micro-elimination in this setting has become feasible. We evaluated HCV treatment cascade in two HRSs located in Milan. Methods We collected data on demographics, substance abuse history, HIV prevalence, HCV prevalence, testing and treatment on all register HRS users on 1 January 2019. Data collection was closed on 1 January 2020. Results A total of 881 HRS users (732M,149F) were included (median age: 45). The majority was addicted to heroin 67.5% (595), 24.1%(212) to cocaine, 5.3%(47) to THC and 3.1%(27) to other substances. The 28.0%(247/881) reported current or prior judiciary problems, 168/881(19.1%) were under psychiatric treatment. HCV serological screening (HCVAb) was performed for 587/881(66.7%), 113/881(12.8%) were in process, 2/881(0.2%) refused, 179/881(20.3%) were not HRS user anymore. 364/587(62%) resulted HCVAb positive, of whom 288(79.1%) were tested for HCV RNA. Among them 123/324(37.9%) were positive, 165/324(50.9%) were negative. Among HCVAb positive, 116/364(31.9%) were tested for HIV and 92(79.3%) resulted HIV positive. Among HCV RNA positive 92/123(74.8%) were initiated on DAAs treatment. Compliance to treatment was high; one treatment failure was registered. Individuals tested for HCV and HCVAb positive people had an average age significantly higher than the individuals not tested and HCVAb negative people (p Conclusions Our study demonstrate that it is feasible to achieve good efficacy and compliance for HCV treatment among people who use drugs when decentralising treatment to HRS. To achieve the viral hepatitis elimination agenda goals, HRS-based model of treatment provision needs to be implemented at larger scale. Key messages Decentralising HCV test and treatment to harm reduction services is an effective strategy to achieve HCV micro-elimination among people who use drugs. Young people and people who are addicted to other substance than heroin resulted more difficult to link to HCV care through the harm reduction services. They require tailored intervention.

The outbreak of the COVID-19 pandemic has radically changed the daily hospital care activity for all medical specialists. Although the predominant symptoms of this new coronavirus infection are respiratory, the gastrointestinal tract is also significantly involved. In this short report, we will discuss a new and unexpected clinical presentation related to COVID-19 colonization of upper gastrointestinal tract.

Objective: To evaluate the course of fecal calprotectin (FC) in very preterm infants over the first 15 days of life in relation to the type of milk diet. Methods: This study was part of a randomized controlled trial comparing two different ways of integrating the own mother's milk (OMM) for the evaluation of feeding tolerance in very preterm infants. In infants with gestational age of ≤ 32 weeks randomized to receive preterm formula (PF group) or pasteurized donor human milk (PDHM group) as a supplement to the OMM insufficient or unavailable, FC level was planned to be measured at the first meconium passage and at days 8 and 15 of life (T0, T1, and T2, respectively). Results: FC data were available for all the 70 infants randomized, 35 in the PF group, and 35 in the PDHM group. The mean FC levels were similar in the two study groups at T0 and T1, whereas they were significantly higher in the PF group than the PDHM group at T2. FC values decreased over the first week of life in both groups and significantly increased over the second week of life only in the PF group. Conclusions: Our study demonstrates a significant increase in FC levels when PF is used as a supplement to the OMM compared to the use of PDHM. Further studies are needed to establish if the higher FC levels in infants receiving PF are the expression of a normal immunological maturation rather than an initial inflammatory process.

Optical coherence tomography (OCT) is an optical imaging modality that has been investigated for real-time surgical margin evaluation in human breast cancer patients. Previous veterinary OCT studies have been limited to surgical margin imaging for soft tissue sarcoma (STS) tumors. To the authors knowledge, OCT has never been used to characterize or evaluate other types of neoplasia in dogs. The goal of this study was to characterize the OCT imaging appearance of apocrine gland anal sac adenocarcinoma (AGASACA) in excised ex vivo specimens from five client-owned dogs. All excised tissue surgical margins were imaged using a clinical spectral domain OCT system and two to four areas suspicious for incomplete surgical margins were selected. These areas were inked and sections were trimmed for histopathology. This enabled OCT imaging from each area of interest to be compared to corresponding H&E stained histology imaging from the same location. OCT was able to identify the presence of AGASACA at or within 1 mm of the surgical margin in all areas of interest. AGASACA, similar to the previously described canine STS, generated a dense, highly scattering image without any specific textural architecture. This study was able to validate the ability of OCT to accurately identify another type of tumor presence at or close to the surgical margin in the dog. Further study is needed to assess OCT accuracy at identifying other tumor types in dogs to understand its potential clinical applications. This article is protected by copyright. All rights reserved.

Endoscopic transsphenoidal surgery is a surgical technique introduced in the last 20 years for the treatment of skull base pathologies and, in particular, pituitary tumours. Although the prevalence of work-related musculoskeletal disorders is usually significantly higher in endoscopists and minimally invasive surgeons compared to other surgical and medical specialties, reviews on the prevalence of disorders among neurosurgeons dedicated to endoscopic transsphenoidal surgery are not available. This article performs a systematic review to identify the work-related musculoskeletal disorders among transsphenoidal neurosurgeons, their prevalence and the ergonomic interventions proposed to reduce risk factors and prevent disorders. The results show that the ergonomics of transsphenoidal neurosurgeons is an under-investigated topic. Indeed, specific prevalence data are not available. In addition, only a few papers suggest interventions and guidelines, but without objective assessment of the outcomes to confirm the ergonomic benefit. Based on these gaps in the literature, a future research agenda is proposed.

OBJECTIVE To determine the influence of stapling on leakage pressures after canine partial gastrectomy. STUDY DESIGN Ex vivo study. SAMPLE POPULATION Gastric specimens from 24 adult canine cadavers. METHODS Partial gastrectomy constructs were assigned to one of three closure techniques (n = 8 per group): group 1, stapled closure with a 90-mm thoracoabdominal stapling device and a 4.8-mm staple cartridge; group 2, hand-sewn double-layer inverting suture closure with 3-0 glycomer 631; and group 3, staple line reinforcement with an inverting Cushing suture pattern. Leakage and pressure testing were performed. Initial leakage pressure (ILP), maximal leakage pressure (MLP), and leakage location were recorded. Significance was set at P

The fast spread of the novel coronavirus (SARS-CoV-2) has become a global threat hitting the worldwide fragile health care system. In Italy, there is a continued COVID-19 growth of cases and deaths that requires control measures for the correct management of the epidemiological emergency. To contribute to increasing the overall knowledge of COVID-19, systematic tests in the general population are required.Here, we describe the first Italian survey performed in 727 employees belonging to a Mother-Child Research hospital tested for both viral (nasopharyngeal and oropharyngeal swabs) and antibody presence. Individuals were divided into three risk categories (high, medium and low) according to their job activity. Only one subject was positive at the swab test while 17.2% of the cohort was positive for the presence of antibodies. Results highlighted that the presence of Positive antibodies is significantly associated with high and medium risk exposure occupation (p-value=0.026) as well as cold and conjunctivitis symptoms (p-value=0.016 and 0.042 respectively). Moreover, among healthcare professionals, the category of medical doctors showed a significant association with the presence of antibodies against SARS-CoV-2 (p-value=0.0127). Finally, we detected a rapid decrease in antibody intensity between two assessments performed within a very short period (p-value=0.009). Overall, the present study increases our knowledge of the epidemiological data of COVID-19 infection in Italy, suggesting a high prevalence of immune individuals (i.e. at least among at-risk categories) and the efficacy of the combined diagnostic protocol to monitor the possible outbreak.

Brain abscess (BA) is an encapsulated infection and can be the consequence of head and cranio-maxillo-facial surgery or trauma, or may be secondary to cavernous thrombophlebitis, but is most frequently due to hematogenous septic dissemination from an adjacent site of infection, such as the paranasal sinuses, middle ear or oral cavity. We report a rare and unfortunate case of multiple BA caused by dental procedures in a young man with undiagnosed patent foramen ovale (PFO). Simple routine dental procedures, such as tooth brushing and professional oral hygiene, can predispose to life-threatening conditions. This case report and literature review highlights that multiple BA after professional tooth cleaning is extremely rare, but cardiac defects (in first place PFO which is a potential source of paradoxical embolism) promote BA formation.

Background The management of metastatic Renal Cell Carcinoma (RCC) has changed dramatically in the last 20 years, and the role of surgery in the immunotherapy’s era is under debate. Metastatic lesions interesting pancreas are infrequent, but those harbouring from RCC have an high incidence. If metachronous resections are not rare, synchronous resection of primary RCC and its pancreatic metastasis is uncommonly reported, and accounts for a bad prognosis. Case presentation We report the case of a 68 years old woman, who presented hematuria at hospital incoming, with radiological appearance of a 13 cm left renal mass, with a 2.5 cm single pancreatic tail metastasis. Work-up of staging ruled out other distant metastases, urothelial cancer and there was no evidence of inferior vena cava thrombosis. We choose a 5-port trans-peritoneal robotic approach using lazy right lateral decubitus. Synchronous robotic radical nephrectomy and spleen-sparing pancreatic resection was performed. The pancreatic mass was completely enucleated from pancreatic parenchyma using a latero-medial dissection. Peri-operative hemoglobine loss was 2.4 g/dL. Total operative time was 213 min. No post-operative complications were recorded and patient was discharged in 7th post-operative day. Histopathological examination showed a pT2b N0 M1 RCC, Fuhrman grade II, with pancreatic tail metastasis; both, primary and metastatic lesions had the same histological characteristics with negative surgical margins. After 9 months patient had no evidence of disease recurrence at radiological studies. Conclusions The rationale for surgical removal of disseminated tumor, followed by immunotherapy, includes improving prognosis and enhancing the potential of an immune-mediated response to systemic treatment. A spleen-sparing procedure can adequately preserve post-operative immunologic capabilities. In our experience, the correct assessment of pre-operative imaging data and surgeon skills in robotic surgery seem to play a key role in the success of these procedures. Robotic surgery seems to enhance the possibility to control multiple vessels encountered during dissection. Such a conservative approach may be helpful in future research aimed at uncovering biological features, and also leading to better targeted preventive interventions and more individualized and effective treatments. Electronic supplementary material The online version of this article (10.1186/s12893-018-0371-x) contains supplementary material, which is available to authorized users.

Approximately 30% of healthy volunteers (HVs) show dilated intercellular spaces in the esophageal epithelium suggesting a functionally reduced epithelial integrity. We aimed to evaluate the presence of an altered epithelial integrity in HVs and whether physiological acid could explain such a difference.Biopsies for Ussing chamber experiments were taken between 3 cm and 5 cm proximal to the gastroesophageal junction. Twenty-four-hour impedance-pH (MII-pH) monitoring was performed in the same 15 HVs. MII-pH tracings from 24 HVs before and after treatment with esomeprazole (40 mg b.i.d., two weeks), a proton pump inhibitor, were analyzed. Reflux parameters and impedance baseline (IB) at different levels of the esophagus were calculated.Epithelial integrity in the distal esophagus presents a large variability in vivo and in vitro (transepithelial electrical resistance 196.9 ± 16.27Ω. cmA subgroup of HVs presents a low epithelial integrity in the distal esophagus probably due to the increased presence of physiological acid reflux. Whether these individuals have a higher chance to develop gastroesophageal reflux disease is unknown. The role of epithelial integrity in symptom perception needs to be further explored.

BACKGROUND. Bacteriocins are peptides with antimicrobial efficacy produced by certain bacterial species. Probiotics indeed seem a promising method in the prevention of upper respiratory infections and our study would like to contribute to the results available in the literature, in order to underlie their true therapeutic potential role. MATERIAL AND METHODS. Our multicenter pilot prospective study investigates 366 patients from September 2015 to February 2016. All the patients were treated with a topical device made up of a suspension of two specific bacterial strains: Streptococcus salivarius 24SMB and Streptococcus oralis 89a to be administered as nasal spray. The nasal spray was administered twice daily for 7 days per month for three consecutive months. A questionnaire about the subjective efficacy of the therapy correlated to an improvement of symptoms was also collected from patients. RESULTS. After one year from the enrolment, a 70.07% reduction in the number of events compared with the number of expected episodes was observed. CONCLUSION. The aim of our data is to propose a new therapeutic approach to treat the recurrence of upper airway infection and to support an adequate therapy in all cases where the traditional antibiotic therapeutic protocol did not obtain completely efficient results in terms of recurrence.

Background: Among rate-control or rhythm-control strategies, there is conflicting evidence as to which is the best management approach for non-valvular atrial fibrillation (AF) in elderly patients. Design: We performed an ancillary analysis from the ‘Registro Politerapie SIMI’ study, enrolling elderly inpatients from internal medicine and geriatric wards. Methods: We considered patients enrolled from 2008 to 2014 with an AF diagnosis at admission, treated with a rate-control-only or rhythm-control-only strategy. Results: Among 1114 patients, 241 (21.6%) were managed with observation only and 122 (11%) were managed with both the rate- and rhythm-control approaches. Of the remaining 751 patients, 626 (83.4%) were managed with a rate-control-only strategy and 125 (16.6%) were managed with a rhythm-control-only strategy. Rate-control-managed patients were older (p=0.002), had a higher Short Blessed Test (SBT; p=0.022) and a lower Barthel Index (p=0.047). Polypharmacy (p=0.001), heart failure (p=0.005) and diabetes (p=0.016) were more prevalent among these patients. Median CHA2DS2-VASc score was higher among rate-control-managed patients (p=0.001). SBT [odds ratio (OR) 0.97, 95% confidence interval (CI) 0.94–1.00, p=0.037], diabetes (OR 0.48, 95% CI 0.26–0.87, p=0.016) and polypharmacy (OR 0.58, 95% CI 0.34–0.99, p=0.045) were negatively associated with a rhythm-control strategy. At follow-up, no difference was found between rate- and rhythm-control strategies for cardiovascular (CV) and all-cause deaths (6.1 vs. 5.6%, p=0.89; and 15.9 vs. 14.1%, p=0.70, respectively). Conclusion: A rate-control strategy is the most widely used among elderly AF patients with multiple comorbidities and polypharmacy. No differences were evident in CV death and all-cause death at follow-up.