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Goals The present survey from the Italian Society of Digestive Endoscopy (SIED-Societa Italiana di Endoscopia Digestiva) was aimed at reporting infection control practice and outcomes at Digestive Endoscopy Units in a high-incidence area. Background Lombardy was the Italian region with the highest coronavirus disease-2019 (COVID-19) prevalence, at the end of March 2020 accounting for 20% of all worldwide deaths. Joint Gastro-Intestinal societies released recommendations for Endoscopy Units to reduce the risk of the contagion. However, there are few data from high-prevalence areas on adherence to these recommendations and on their efficacy. Methods A survey was designed by the Lombardy section of SIED to analyze (a) changes in activity and organization, (b) adherence to recommendations, (c) rate of health care professionals' (HCP) infection during the COVID-19 outbreak. Results In total, 35/61 invited centers (57.4%) participated; most modified activities were according to recommendations and had filtering face piece 2/filtering face piece 3 and water-repellent gowns available, but few had negative-pressure rooms or provided telephonic follow-up; 15% of HCPs called in sick and 6% had confirmed COVID-19. There was a trend (P=0.07) toward different confirmed COVID-19 rates among endoscopists (7.9%), nurses (6.6%), intermediate-care technicians (3.4%), and administrative personnel (2.2%). There was no correlation between the rate of sick HCPs and COVID-19 incidence in the provinces and personal protective equipment availability and use, whereas an inverse correlation with hospital volume was found. Conclusions Adherence to recommendations was rather good, though a minority were able to follow all recommendations. Confirmed COVID-19 seemed higher among endoscopists and nurses, suggesting that activities in the endoscopy rooms are at considerable viral spread risk.

Gastric leak is a serious complication of sleeve gastrectomy with a well-documented morbidity and mortality. Depending on the series the leak rate ranges between 1 and 5%. The treatment of sleeve gastrectomy leak is still challenging. Different procedures have been described in management of gastric leak, both surgical and endoscopic. The treatment of gastric leaks depends on the extent of the staple-line leak, the site of the leak and its association with stenosis. As published data are limited, there are no still standardized guidelines on best treatment. One of the most commonly used option in the treatment of gastric leak is esophageal stent. Its success rate reaches 70–80% but it is burdened by some complications. Stent migration is the most common complication in the placement of esophageal stent.We present a challenging surgical in which case the use of an esophageal stent for the treatment of a sleeve gastrectomy leak gained the resolution of the leak but was complicated by bowel obstruction due to migration of the stent.

Introduction: The 2q37.3 deletion syndrome is a disorder caused by the microdeletion of a subband on chromosome 2, whose epidemiology is approximately 150 cases worldwide, and the prevalence of 1: 10000. Its characteristics are developmental delay, facial dysmorphia, musculoskeletal abnormalities, and increased risk of congenital diseases. The purpose is to present, for the first time in the literature, the oral and dental clinical findings associated with the syndrome. Case report: The main physical characteristics of the syndrome were identified during the physical examination: thin upper lip, prominent columella, and epicanthic folds. In the intraoral examination, dental characteristics were reported, which may be associated with the syndrome: accumulation of dental calculus, hypomineralization and hypoplasia, crossbite, open bite, agenesis, taurodontism, and dentigerous cyst. The dental treatment consisted of the application of behavior management techniques, hygiene and diet instruction, prophylaxis, supragingival scraping, topical fluoride application, and extraction of the lower second molar. This is the first report of oral characteristics of the 2q37.3 deletion syndrome, giving importance to the characteristics observed in this patient. Such findings will be useful in the characterization of the syndrome, which is extremely rare, and may contribute to the clinical diagnosis of these patients, in addition to subsidizing the dental treatment of other individuals. Conclusion: We present oral clinical findings such as hypomineralization and hypoplasia, crossed and an open bite, agenesis, taurodontism, and dentigerous cyst present in the patient with the syndrome and we suggest that the involved gene or its deletion may be responsible for such findings., Introdução: A síndrome de deleção 2q37.3 é uma desordem causada pela microdeleção de uma sub-banda no cromossomo 2, cuja epidemiologia é de aproximadamente 150 casos no mundo, e a incidência de 1:10000. As características da síndrome são: atraso no desenvolvimento, dismorfia facial, anormalidades musculoesqueléticas e aumento ao risco de doenças congênitas. O objetivo deste relato de caso é apresentar, pela primeira vez na literatura, os achados clínicos orais e dentários associados à síndrome. Relato de caso: As principais características físicas da síndrome foram identificadas na paciente durante o exame físico: lábio superior fino, columela proeminente e dobras epicânticas. No exame intraoral, relatou-se as características odontológicas, que podem estar associadas à síndrome: acúmulo de cálculo dental, hipomineralização e hipoplasia, mordida cruzada, mordida aberta, agenesias, taurodontia e cisto dentígero. O tratamento dental consistiu na aplicação de técnicas de manejo de comportamento, instrução de higiene e de dieta, profilaxia, raspagem supragengival, aplicação tópica de flúor, além da extração do segundo molar decíduo inferior. Este é o primeiro relato de características orais da síndrome de deleção 2q37.3 dando importância às características observadas nesta paciente. Tais achados também serão úteis na caracterização da síndrome, que é extremamente rara, podendo contribuir para o diagnóstico clínico desses pacientes, além de subsidiar o tratamento odontológico de outros indivíduos. Conclusão: Apresentamos os achados clínicos orais como hipomineralização e hipoplasia, mordida cruzada e aberta, agenesia, taurodontia e cisto dentígero presentes na paciente com a síndrome e sugerimos que o gene envolvido ou sua deleção possam ser responsáveis por tais achados.

AIM To evaluate several factors that might interfere with the use of electronic root canal length measurement devices (ERCLMDs) in a laboratory setting, including two different embedding media (alginate and electroconductive gel), three different types of devices and the radiographic view on the assessment of the electronic readings. METHODOLOGY Thirty single-rooted extracted human mandibular premolars were selected. After access and canal pre-flaring, a size 10 K-file was inserted in the canal up to the major apical foramen under magnification (×10), and this length was recorded as the actual length (AL) of the canal. Teeth were mounted on a specific endodontic training kit platform (ProTrain). Two different embedding media (electroconductive gel and alginate) and three different ERCLMDs: Apex ID (SybronEndo, Glendora, CA, USA), CanalPro Apex Locator (Coltene-Endo, Cuyahoga Falls, OH, USA) and the Root ZX II (J. Morita, Tokyo, Japan), were tested. Following the measurement at the 0.5 mark of each ERCLMD using alginate, two periapical radiographs (bucco-lingual and proximal views) were taken. The difference between the electronic readings and the AL, as well as the distance from the file tip to the apex of the roots on the radiographs, was calculated. Data were analysed statistically (two-way anova, Tukey's and chi-squared tests) at 5% significance level. RESULTS The incidence of over-extended readings was significantly greater (P

Objectives to investigate the association between dental caries, developmental defects of enamel (DDE) and genetic polymorphisms in vitamin D receptor (VDR) in Brazilian children. Methods Children examination to access the DMFT index was performed according to the World Health Organization's recommendations and the children were classified according their caries experience into ‘No caries experience’ (DMFT = 0), and ‘Caries experience’ (DMFT ≤1), and ‘Low caries experience’ (DMFT ≤3) or ‘High caries experience’ (DMFT≥4) groups. DDE were diagnosed using the modified DDE index based on the Federation Dentaire Internationale (FDI) recommendation. Children were included in the DDE group when presented at least one tooth with a DDE. Genomic DNA was extracted and genetic polymorphisms (rs2228570 and rs739837) were genotyped by TaqMan chemistry and end-point analysis. Chi-square or Fisher exact tests were used to compare genotype and allele distribution among the groups. Epi Info 7 was used to analyze data. The established alpha of this study was 5%. Results Among 157 included children, 19 children (12.1%) were caries free and were in the ‘No caries experience’ group, while 138 children (87.9%) were in the ‘Caries experience’ group. Sixty-seven children (42.7%) were in the ‘Low caries experience’ group while 90 children (57.3%) were in the ‘High caries experience’ group. Five children presented primary dentition, 29 presented mixed dentition and 123 presented permanent dentition. Forty-one (26.1%) children presented at least one tooth with DDE. Caries experience was not associated with DDE (p = 0.71). The polymorphisms rs2228570 and rs739837 were not associated with dental caries, neither DDE (p > 0.05). Allele distributions were also not associated with dental caries, neither DDE (p > 0.05). Conclusions The genetic polymorphisms rs2228570 and rs739837 were not associated with dental caries and developmental defects of enamel in Brazilian children.

The reference standard for assessing transjugular intrahepatic portosystemic shunt (TIPS) function is venography with portosystemic pressure gradient (PPG) measurement. This procedure is invasive and expensive; thus, we assessed the feasibility, reproducibility and diagnostic accuracy of color-Doppler ultrasound (CDUS) and spleen and liver stiffness (LS) measurements for identifying TIPS dysfunction. Twenty-four patients (15 undergoing TIPS placement and nine undergoing TIPS revision) consecutively underwent CDUS examination and LS and spleen stiffness (SS) determination by transient elastography (TE) and point shear-wave elastography (pSWE). All parameters were taken before TIPS placement/revision (1–15 d before) and 24 h after, just before revision by venography. pSWE inter-observer agreement was assessed by intra-class correlation coefficient (ICC). CDUS and elastographic data were correlated (Pearson coefficient) with pressure gradients (hepatic venous pressure gradient [HVPG], PPG). Main determinants of TIPS dysfunction were investigated by linear regression. Forty-nine paired examinations were performed in total: 49 (100%) SS reliable measurements by pSWE and 38 (88%) by TE. The ICC for pSWE values was 0.90 (95% confidence interval [CI] 0.81‒0.94). SS values significantly correlated with HVPG and PPG (R = 0.51, p = 0.01). The area under the Receiver-Operating Characteristic (AUROC) curve of SS for diagnosing TIPS dysfunction was 0.86 (95% CI 0.70‒0.96) using a 25 kPa cutoff. At multivariate analysis, the flow direction of the intrahepatic portal vein branches and SS values were independently associated to TIPS dysfunction. The intrahepatic portal vein branches flow direction and SS value are two simple, highly sensitive parameters accurately excluding TIPS dysfunction. SS measurement by pSWE is feasible, reproducible and both positively and significantly correlates with HVPG and PPG values.

Background & aim Although acute lower GI bleeding (LGIB) represents a significant healthcare burden, prospective real-life data on management and outcomes are scanty. Present multicentre, prospective cohort study was aimed at evaluating mortality and associated risk factors and at describing patient management. Methods Adult outpatients acutely admitted for or developing LGIB during hospitalization were consecutively enrolled in 15 high-volume referral centers. Demographics, comorbidities, medications, interventions and outcomes were recorded. Results Overall 1,198 patients (1060 new admissions;138 inpatients) were included. Most patients were elderly (mean-age 74±15 years), 31% had a Charlson-Comorbidity-Index ≥3, 58% were on antithrombotic therapy. In-hospital mortality (primary outcome) was 3.4% (95%CI 2.5–4.6). At logistic regression analysis, independent predictors of mortality were increasing age, comorbidity, inpatient status, hemodynamic instability at presentation, and ICU-admission. Colonoscopy had a 78.8% diagnostic yield, with significantly higher hemostasis rate when performed within 24-hours than later (21.3% vs.10.8%, p = 0.027). Endoscopic hemostasis was associated with neither in-hospital mortality nor rebleeding. A definite or presumptive source of bleeding was disclosed in 90.4% of investigated patients. Conclusion Mortality in LGIB patients is mainly related to age and comorbidities. Although early colonoscopy has a relevant diagnostic yield and is associated with higher therapeutic intervention rate, endoscopic hemostasis is not associated with improved clinical outcomes [ClinicalTrial.gov number: NCT 04364412].

Transmission with endoscopes, particularly duodenoscope, of potential lethal infections prompted different scientific societies to deliver recommendations aimed reducing this risk. Some International societies extended recommendations on microbial surveillance to all the endoscopes and devices used in the reprocessing procedure. Considering the relevance of the topic, 8 Italian scientific societies of physicians, nurses and technical operators prepared a concerted document taking into account Institutional advisories and facilities in Italy. The rules for a correct microbial surveillance on endoscopes were detailed in term of what, how and when to perform the procedure, also suggesting behaviors in case of contamination.

Background: the lack of standardized pathways for patients with gastrointestinal bleeding may have led to differences in their management and inequity to medical care access. The "Hub & Spoke" model was adopted to fill this gap in many disciplines, but, to our knowledge, no data exist on its efficacy on mortality in GI bleeding. We aimed to evaluate if the "Hub & Spoke" organizational model has an impact on mortality risk from UGIB. Methods: from January 2014 to December 2015, 3324 consecutive patients admitted for UGIB in 50 Italian hospitals were enrolled (1977 patients in hospitals within the "Hub & Spoke" network for digestive hemorrhagic emergency and 1347 in hospitals outside the "Hub & Spoke" network). Clinical, endoscopic and organizational data were recorded. Results: we observed no differences in mortality between patients admitted to hospitals included or not included in the "Hub & Spoke" network (5.2% vs 6.1%, p = 0.3). On multivariate analysis, admission in gastroenterology wards (OR 0.61, p = 0.001) or an academic hospital (OR 0.65, p < 0.056) were independent protective factors while being in "Hub & Spoke" organization system did not affect mortality (OR 1.09, p = 0.57). Conclusion: the "Hub & Spoke" model per sé does not impact on mortality while being treated in academic hospital or gastroenterology wards improved survival.

Description, The CaCTS algorithm nominates cancer cell master transcription factors and guides a model of ovarian cancer regulatory circuitry., Critical developmental “master transcription factors” (MTFs) can be subverted during tumorigenesis to control oncogenic transcriptional programs. Current approaches to identifying MTFs rely on ChIP-seq data, which is unavailable for many cancers. We developed the CaCTS (Cancer Core Transcription factor Specificity) algorithm to prioritize candidate MTFs using pan-cancer RNA sequencing data. CaCTS identified candidate MTFs across 34 tumor types and 140 subtypes including predictions for cancer types/subtypes for which MTFs are unknown, including e.g. PAX8, SOX17, and MECOM as candidates in ovarian cancer (OvCa). In OvCa cells, consistent with known MTF properties, these factors are required for viability, lie proximal to superenhancers, co-occupy regulatory elements globally, co-bind loci encoding OvCa biomarkers, and are sensitive to pharmacologic inhibition of transcription. Our predictions of MTFs, especially for tumor types with limited understanding of transcriptional drivers, pave the way to therapeutic targeting of MTFs in a broad spectrum of cancers.

Inflammatory and replacement tooth resorption are common outcomes following tooth replantation, biological mediators involved in these processes are widely unknown. The aim study was to investigate molecules involved in tooth resorption following permanent tooth avulsion and delayed replantation. Dog premolars were extracted and kept dry for 20, 60 and 90 minutes (n= 30). The teeth were replanted, splinted. After 120 days, the animals were euthanized and tissues were removed for histological processing. Slides were stained for microscopic analysis, submitted to tartrate resistant acid phosphatase (TRAP) histoenzymology and immunostained for RANK, RANKL, OPG, alkaline phosphatase and periostin. Data obtained were submitted to statistical analysis using the chi-square, Fisher and one-way ANOVA tests (alpha= 0.05). In inflammatory resorption areas, TRAP + and RANK + osteoclasts surrounding the replanted teeth were identified, regardless of the extra-alveolar time. RANKL synthesis in this region was higher in longer extra-alveolar times and was more intense after keeping the tooth dry for 90 minutes compared to other periods. In the replacement reabsorption area, there was lower synthesis of periostin and higher alkaline phosphatase production. Inflammatory resorption was characterized by osteoclast recruitment and RANKL synthesis and replacement resorption was characterized by inhibition of periostin and alkaline phosphatase syntheses.

Objective: To report the safety and efficacy of trans-arterial embolization (TAE) for upper gastrointestinal bleeding (UGIB) and lower gastrointestinal bleeding (LGIB) due to different etiologies in 91 patients for ten years. Methods: A retrospective analysis of GIB treated between January 2010 and December 2020 was performed. TAE was performed using different embolic agents (coils, particles, glue, gelatin sponge, and EVOH-based agents). Technical success, secondary technical success, clinical success, and complications were evaluated. Results: Technical success was achieved in 74/91 (81.32%) patients. Seventeen patients (18.68%) required re-intervention. Secondary technical success was achieved in all cases (100.0%). Clinical success was achieved in 81/91 patients (89.01%). No major complications were recorded, overall, minor complications occurred in 20/91 patients. Conclusions: TAE is a technically feasible and safe therapeutic option for patients with GIB from a known or blind anatomic source where endoscopic therapy has failed or is deemed unfeasible.

Background & aim To investigate the association between the genetic polymorphisms FokI (rs2228570) and BglI (rs739837) in vitamin D receptor (VDR) with dental caries and gingivitis susceptibility. Design This study included 353 Brazilian children (8 to 11 years old). Dental caries was assessed using ICDAS (International System for Detection and Assessment of Carious Lesions) and gingival bleeding using Community Periodontal Index (CPI). The presence of visible biofilm was also evaluated. DNA was extracted from saliva, and real-time PCR was used to evaluate genetic polymorphisms in VDR: rs2228570 (FokI, A>G/Met>Thr) and rs739837 (BglI, G>T). Dental caries was evaluated as a continuous data (mean and standard deviation-SD) and was also categorized (ICDAS0 versus ICDAS1-6 or ICDAS1-2 versus ICDAS3-6). Gingivitis was categorized in with and without. One-way ANOVA was used for comparisons of caries among genotypes. Chi-square test, logistic regression, and haplotype analysis were performed (P Results Biofilm was associated with dental caries susceptibility and gingivitis (P .05). Genotype distributions among caries groups (in the two different cut-offs) and among gingivitis and non-gingivitis groups were not statistically significant (P > .05). Conclusion The polymorphisms FokI and BglI in VDR were not associated with dental caries or gingivitis.

A obesidade e uma enfermidade preocupante que vem atingindo proporcoes epidemicas. A incidencia dos individuos que se submetem a bariatrica cresce em numeros significativos e, portanto, merecem tratamento, atencao especial e diferenciada pelos pesquisadores da area da saude. Sexo masculino, submetido a cirurgia bariatrica ha 10 anos e relatou que desde entao apresentava quadro de hernia, de grande dimensao, abdominal incisional proveniente de uma protusao de uma fracao intestinal, e, como consequencia, resultava em dor refrataria. Na avaliacao do abdome presenca de hernia de tamanho significativo com alteracao trofica da pele, discreta hiperemia em regiao inferior, dor a palpacao difusa e ruidos hidroaereos discretamente aumentados com timbre metalico. Devido ao quadro, o paciente foi admitido para a realizacao de uma hernioplastia incisional, enterectomia segmentar e dermolipectomia. E possivel inferir que a realizacao da cirurgia bariatrica pode trazer inumeros beneficios ao paciente, mas e imperativo estar que procedimento pode gerar efeitos colaterais, como a formacao de hernias incisionais, as quais necessitam de precoce intervencao cirurgica, afim de evitar maiores complicacoes.

OBJECTIVE. Genome-wide association studies (GWASs) for epithelial ovarian cancer (EOC) have focused largely on populations of European ancestry. We aimed to identify common germline variants associated with EOC risk in Asian women. METHODS. Genotyping was performed as part of the OncoArray project. Samples with >60% Asian ancestry were included in the analysis. Genotyping was performed on 533,631 SNPs in 3238 Asian subjects diagnosed with invasive or borderline EOC and 4083 unaffected controls. After imputation, genotypes were available for 11,595,112 SNPs to identify associations. RESULTS. At chromosome 6p25.2, SNP rs7748275 was associated with risk of serous EOC (odds ratio [OR] = 1.34, P = 8.7 × 10(−9)) and high-grade serous EOC (HGSOC) (OR = 1.34, P = 4.3 × 10(−9)). SNP rs6902488 at 6p25.2 (r(2) = 0.97 with rs7748275) lies in an active enhancer and is predicted to impact binding of STAT3, P300 and ELF1. We identified additional risk loci with low Bayesian false discovery probability (BFDP) scores, indicating they are likely to be true risk associations (BFDP

The outcome of root canal treatment has been reported as intimately related to the host response. Genetic polymorphisms might be associated with apical periodontitis repair. The aim of this study was to evaluate the association between receptor activator of nuclear factor kappa B (RANK), receptor activator of nuclear factor kappa B ligand (RANKL), and osteoprotegerin (OPG) genetic polymorphisms with persistent apical periodontitis (PAP) in Brazilian subjects.Subjects with at least 1 year of follow-up after nonsurgical root canal therapy were recalled. Sixty-four subjects with signs/symptoms of PAP and 86 subjects with root canal-treated teeth exhibiting healthy periradicular tissues (healed) were included. Genomic DNA was extracted from saliva and used for RANK (rs3826620), RANKL (rs9594738), and OPG (rs2073618) genotyping by real-time exact tests, and odds ratio were implemented using Epi Info 3.5.2 (Centers for Disease Control and Prevention, Atlanta, GA). A logistic regression analysis was also performed using the time of follow-up as the covariate. All tests were performed with an established alpha of 0.05 (P = .05).An association between allele distribution and the polymorphism in RANK was observed. Subjects who carry the T allele had a lower risk of having PAP (P.05). In RANKL polymorphism, the genotype distribution was statistically significant different between the PAP and healed groups (P = .05). The time of follow-up was associated with PAP (P.05). In the logistic regression analysis using time as a covariant, RANK (P.05) and RANKL (P.05) were associated with PAP. The polymorphism rs2073618 in OPG was not associated with PAP (P.05).These findings suggest that polymorphisms in RANK and RANKL genes are associated with PAP.

Stem cells in platelet-rich plasma (PRP) scaffolds may be a promising treatment for cartilage repair. Human dental pulp stem cell (hDPSC) subpopulations have been identified to have substantial angiogenic, neurogenic and regenerative potential when compared with other stem cell sources. The present study evaluated the potential of hDPSCs in a PRP scaffold to regenerate full-thickness cartilage defects in rabbits. Full-thickness articular cartilage defects were created in the patellar groove of the femur of 30 rabbits allocated into three experimental groups: Those with an untreated critical defect (CTL), those treated with PRP (PRP) and those treated with stem cells in a PRP scaffold (PRP+SC). The patellar grooves of the femurs from the experimental groups were evaluated macroscopically and histologically at 6 and 12 weeks post-surgery. The synovial membranes were also collected and evaluated for histopathological analysis. The synovial lining cell layer was enlarged in the CTL group compared with the PRP group at 6 weeks (P=0.037) but not with the PRP+SC group. All groups exhibited low-grade synovitis at 6 weeks and no synovitis at 12 weeks. Notably, macroscopic grades for the area of articular cartilage repair for the PRP+SC group were significantly improved compared with those in the CTL (P=0.001) and PRP (P=0.049) groups at 12 weeks. Furthermore, histological scores (modified O'Driscoll scoring system) of the patellar groove articular cartilage in the PRP+SC and PRP groups, in which the articular cartilage was primarily hyaline-like, were significantly higher compared with those in the CTL group at 12 weeks (P=0.002 and P=0.007, respectively). The present results support the therapeutic use of hDPSCs for the treatment of full-thickness articular cartilage defects.

The role played by family caregivers in delivering long-term care is crucial: they enhance the quality of care perceived by the patients and support the shift to out-of-hospital care. However, taking care of a relative entails a huge burden that usually begins with the patient’s hospital discharge and may mean that caregivers become patients in need of care as well. Owing to socio-demographic trends, informal caregiving is the most important source of care in community settings; hence targeting the caregivers’ burden properly is crucial. This study explores how action research (AR) can be used to develop new hospital practices to manage the burden borne by family caregivers when patients are discharged from hospital. The 7-month-long action research reported in this paper consisted of three stages (burden identification, burden sharing, and burden management) and it was conducted in a teaching hospital in Rome (Italy). Both quantitative (surveys) and qualitative (focus groups and simulation sessions) techniques were used to engage participants. The AR demonstrates that there is a feasible way in which hospital managers can address proactively the caregivers’ needs in the hospital discharge process, to the advantage of the patients and the entire community.

PURPOSE: Genetic and epidemiologic studies have shown that lipid genes and High Density Lipoproteins (HDL) are implicated in age-related macular degeneration (AMD). We studied circulating lipid levels in relation to AMD in a large European dataset, and investigated whether this relationship is driven by certain sub fractions. DESIGN: (Pooled) analysis of cross-sectional data. PARTICIPANTS: 30,953 individuals aged 50+ participating in the E3 consortium; and 1530 individuals from the Rotterdam Study with lipid sub fraction data. METHODS: In E3, AMD features were graded per eye on fundus photographs using the Rotterdam Classification. Routine blood lipid measurements were available from each participant. Data on genetics, medication and confounders such as body mass index, were obtained from a common database. In a subgroup of the Rotterdam Study, lipid sub fractions were identified by the Nightingale biomarker platform. Random-intercepts mixed-effects models incorporating confounders and study site as a random-effect were used to estimate the associations. MAIN OUTCOME MEASURES: early, late or any AMD, phenotypic features of early AMD, lipid measurements. RESULTS: HDL was associated with an increased risk of AMD, corrected for potential confounders (Odds Ratio (OR) 1.21 per 1mmol/L increase (95% confidence interval[CI] 1.14-1.29); while triglycerides were associated with a decreased risk (OR 0.94 per 1mmol/L increase [95%CI 0.91-0.97]). Both were associated with drusen size, higher HDL raises the odds of larger drusen while higher triglycerides decreases the odds. LDL-cholesterol only reached statistical significance in the association with early AMD (p=0.045). Regarding lipid sub fractions: the concentration of extra-large HDL particles showed the most prominent association with AMD (OR 1.24 [95%CI 1.10-1.40]). The CETP risk variant (rs17231506) for AMD was in line with increased-HDL levels (p=7.7x10-7); but LIPC risk variants (rs2043085, rs2070895) were associated in an opposite way (p=1.0x10-6 and 1.6x10-4). CONCLUSIONS: Our study suggests that HDL-cholesterol is associated with increased risk of AMD and triglycerides negatively associated. Both show the strongest association with early AMD and drusen. Extra-large HDL sub fractions seem to be drivers in the relation with AMD, variants in lipid genes play a more ambiguous role in this association. Whether systemic lipids directly influence AMD or represent lipid metabolism in the retina remains a question to be answered.

Contains fulltext : 237689.pdf (Publisher’s version ) (Open Access) Familial, sequencing, and genome-wide association studies (GWASs) and genetic correlation analyses have progressively unraveled the shared or pleiotropic germline genetics of breast and ovarian cancer. In this study, we aimed to leverage this shared germline genetics to improve the power of transcriptome-wide association studies (TWASs) to identify candidate breast cancer and ovarian cancer susceptibility genes. We built gene expression prediction models using the PrediXcan method in 681 breast and 295 ovarian tumors from The Cancer Genome Atlas and 211 breast and 99 ovarian normal tissue samples from the Genotype-Tissue Expression project and integrated these with GWAS meta-analysis data from the Breast Cancer Association Consortium (122,977 cases/105,974 controls) and the Ovarian Cancer Association Consortium (22,406 cases/40,941 controls). The integration was achieved through application of a pleiotropy-guided conditional/conjunction false discovery rate (FDR) approach in the setting of a TWASs. This identified 14 candidate breast cancer susceptibility genes spanning 11 genomic regions and 8 candidate ovarian cancer susceptibility genes spanning 5 genomic regions at conjunction FDR < 0.05 that were >1 Mb away from known breast and/or ovarian cancer susceptibility loci. We also identified 38 candidate breast cancer susceptibility genes and 17 candidate ovarian cancer susceptibility genes at conjunction FDR < 0.05 at known breast and/or ovarian susceptibility loci. The 22 genes identified by our cross-cancer analysis represent promising candidates that further elucidate the role of the transcriptome in mediating germline breast and ovarian cancer risk.

BACKGROUND: In recent years, several articles have reported considerable results with the Mini/One Anastomosis Gastric Bypass (MGB/OAGB) in terms of both weight loss and resolution of comorbidities. Despite those positive reports, some controversies still limit the widespread acceptance of this procedure. Therefore, a multicenter retrospective study, with the aim to investigate complications following this procedure, has been designed. PATIENTS AND METHODS: To report the complications rate following the MGB/OAGB and their management, and to assess the role of this approach in determining eventual complications related especially to the loop reconstruction, in the early and late postoperative periods, the clinical records of 2678 patients who underwent MGB/OAGB between 2006 and 2015 have been studied. RESULTS: Intraoperative and early complications rates were 0.5 and 3.1%, respectively. Follow-up at 5 years was 62.6%. Late complications rate was 10.1%. A statistical correlation was found for perioperative bleeding both with operative time (p < 0.001) or a learning curve of less than 50 cases (p < 0.001). A statistical correlation was found for postoperative duodenal-gastro-esophageal reflux (DGER) with a preexisting gastro-esophageal-reflux disease (GERD) or with a gastric pouch shorter than 9 cm, (p < 0.001 and p = 0.001), respectively. An excessive weight loss correlated with a biliopancreatic limb longer than 250 cm (p < 0.001). CONCLUSIONS: Our results confirm MGB/OAGB to be a reliable bariatric procedure. According to other large and long-term published series, MGB/OAGB seems to compare very favorably, in terms of complication rate, with two mainstream procedures as standard Roux-en-Y gastric bypass (RYGBP) and laparoscopic sleeve gastrectomy (LSG).

Objectives To assess the prevalence of probable sarcopenia according to 3 different definitions (“strength, assistance with walking, rise from a chair, climb stairs, falls”- SARC-F score, low grip strength, and the guidelines indicated by the European Working Group on Sarcopenia in Older People 2 - EWGSOP2) and assess the association of probable sarcopenia with functional disability and falls among community-dwelling older adults. Methods Cross-sectional study with 419 older adults. Probable sarcopenia was assessed by 3 definitions: a SARC-F ≥ 4, low grip strength (< 27 kg for men and < 16 kg for women), and the EWGSOP2 criteria. Associations were investigated using Pearson's chi-square test and prevalence ratios were estimated by Poisson regression (P, Highlights • 23.0% of the SARC-F≥4, 33.7% of low grip strength and 10.4% of EWGSOP2. • Higher prevalence of difficulty climbing stairs and strength in SARC-F≥4. • Highest prevalence of IADL disability was found individuals with probable sarcopenia. • Highest prevalence of had fallen was found in individuals with probable sarcopenia. • IADL disability and falls were associated with SARC-F≥4 and EWGSOP2.

C.A., a 57 years old male, was admitted to our hospital in October 2017 for the occurrence of ascites. He was diagnosed with decompensated liver cirrhosis with a double etiology: hepatitis C virus infection (HCV, genotype I) and chronic alcohol abuse. He was treated with large-volume paracentesis, albumin supplementation, and diuretic therapy with clinical benefit. Despite subsequent treatment with direct antiviral agents and stopping alcohol consumption, he developed refractory ascites. For this reason, in July 2019, he was treated with the placement of a trans-jugular intrahepatic porto-systemic shunt (TIPS). We used color doppler ultrasound and elastography to assess TIPS patency and estimate the reduction of portal hypertension.

Background and study aims COVID-19 has dramatically impacted endoscopy practice because upper endoscopy procedures can be aerosol-generating. Most elective procedures have been rescheduled. Endoscopic retrograde cholangiopancreatography (ERCP) is frequently performed in emergency or urgent settings in which rescheduling is not possible. We evaluated the impact of the COVID-19 pandemic on ERCP in Italy during the SARS-CoV-2 lockdown, in areas with high incidence of COVID-19. Patients and methods We performed a retrospective survey of centers performing ERCP in high COVID-19 prevalence areas in Italy to collect information regarding clinical data from patients undergoing ERCP, staff, case-volume and organization of endoscopy units from March 8, 2020 to April 30, 2020. Results We collected data from 31 centers and 804 patients. All centers adopted a triage and/or screening protocol for SARS-CoV-2 and performed follow-up of patients 2 weeks after the procedure. ERCP case-volume was reduced by 44.1 % compared to the respective 2019 timeframe. Of the 804 patients undergoing ERCP, 22 (2.7 %) were positive for COVID-19. Adverse events occurred at a similar rate to previously published data. Of the patients, endoscopists, and nurses, 1.6 %, 11.7 %, and 4.9 %, respectively, tested positive for SARS-CoV-2 at follow up. Only 38.7 % of centers had access to a negative-pressure room for ERCP. Conclusion The case-volume reduction for ERCP during lockdown was lower than for other gastrointestinal endoscopy procedures. No definitive conclusions can be drawn about the percentage of SARS-CoV-2-positive patients and healthcare workers observed after ERCP. Appropriate triage and screening of patients and adherence to society recommendations are paramount.

Common genetic variation in a region on chromosome 15q26 confers susceptibility to breast and ovarian cancer. The P53 interacting gene RCCD1 in this region is a candidate susceptibility gene for both cancers. In this study, a colocalization analysis of breast and ovarian cancer case-control genetic association studies in over 145,000 and 146,000 controls fine mapped the shared association in this region to 17 pleiotropic credible causal risk variants (Pbreast< 1.16 × 10−14andPovary< 7.50 × 10−7). These variants were strongly associated with the expression of RCCD1 in normal breast and ovarian tissues. Circular chromosome conformation capture (4C) analysis ofRCCD1in breast and ovarian cancer cells identified similar patterns ofcis-interaction and significant binding site enrichment for theBRCA2interacting geneEMSY(Padjusted= 9.24 × 10−6). The 4C analysis pinpointed a single 2kB RCCD1 cis-interaction that contained two of the 17 shared risk variants. RCCD1trans-interacting regions mapped to previously identified genome wide significant (P < 5 × 10−8) breast cancer risk loci (1p34.2 and 3p14.1) and to the pleiotropic breast-ovarian cancer risk locus at chromosome 9q34.2. Stable overexpression of RCCD1 in breast and ovarian cancer precursor cells identified 13 and 11 differentially expressed genes (DEGs) respectively associated with breast and ovarian cancer risk at genome-wide significance (PMAGMA< 2.6 × 10−6after Bonferroni correction). Eighty-two DEGs shared between breast and ovarian cancer were strongly enriched in TP53 (P = 9.9 × 10−4), Hippo (P = 2.51 × 10−3) and TNF signaling (P = 4.7 × 10−3) pathways.

Langerhans cell histiocytosis (LCH) is an inflammatory myeloid neoplasia commonly affecting children with frequent somatic mutations in MAPK pathway genes including BRAFV600E and MAP2K1. Some studies suggest that LCH cells can recruit and modulate inflammatory cells, which could provide reciprocal survival signals. To characterize the immune profile of infiltrating inflammatory cells, and to clarify their participation in LCH pathogenesis, a detailed immunohistochemical analysis was performed. Fifteen (10 children, 5 adults) LCH cases were assessed through macrophage (CD68 and CD163), mature dendritic cell (mDC; CD83 and CD208), regulatory T cell (Treg; CD4, CD25 and FOXP3) and cytotoxic lymphocyte (CL; CD56, CD57, perforin and granzyme B) immunomarkers. Moreover, lymphocytic and LCH markers were also analysed. All cases were S100, CD1a, CD207 and CD4-positive. Bcl-2 and cyclin D1 expression was observed in 13 of 15 cases. In the immune microenvironment, M2-polarized macrophages and Tregs were the predominant cell populations, followed by significantly (P < .005) smaller levels of mDCs and CLs. Additionally, the number of CD3 + cells was significantly higher than that of CD20 + cells. In the CD3 + cell population, there were a significantly higher number of CD4 + cells than CD8 + cells. While there were no differences when comparing the paediatric and adult populations, FOXP3 + cells were significantly higher in patients with multisystem involvement and treated with chemotherapy, than single-site cases and those without chemotherapy. Our results suggest that M2-polarized macrophages and Treg infiltration can promote LCH development and survival, probably through pro-tumoral, immunosuppressive and/or cytokine-mediated mechanisms. This work highlights the need for further exploration of immune-targeted therapy for LCH.

Most studies on gender and psychosis have focused on gender differences at illness onset or on the long-term outcome, whereas little is known about the impact of gender on the first years after psychosis onset. A total of 185 first episode psychosis (FEP) patients were followed for 5 years after psychosis onset, and gender differences were explored in psychopathology (PANSS), needs for care (CAN), and insight (SAI-E). Male patients showed more negative symptoms than females over time, whereas female patients showed higher levels of depressive symptoms than males throughout the study period. In addition, female patients presented more functioning unmet needs for care, but higher levels of insight into illness than males. Therapy and rehabilitative programs for FEP patients should be gender-targeted, as gender has proved to impact on psychopathology, needs for care, and insight in the very first years following psychosis onset.

Recent studies suggested that genetics contribute to differences in dental fluorosis (DF) susceptibility among individuals having the same environmental exposure. This study evaluated if MMP2, MMP9 and MMP20 are expressed during enamel development and assessed the association between polymorphisms in these genes with DF. Mice susceptible and resistant to DF were used to evaluate if MMPs were candidate genes for DF. The animals received fluoride and their enamels were used for immunohistochemistry. Additionally, 481 subjects from a city with fluoridation of public water supplies were recruited. Genotyping was performed using real time PCR. Allele/genotype frequencies were compared between groups. MMP2, MMP9 and MMP20 immunostaining was detected in both animal groups. DF was observed in 22.4% of the subjects. A borderline association was observed in MMP2 (rs243865), MMP9 (rs17576) and in MMP20 (rs1784418) (p = 0.06, p = 0.08 and p = 0.06 respectively). Briefly, MMPs were expressed during enamel maturation and genetic polymorphisms were not associated with DF.

Objectives Superficial swab sampling of American tegumentary leishmaniasis (ATL) lesions shows higher amounts of Leishmania than those from biopsy. Subcutaneous involvement is also important in ATL, but parasite quantification according to lesion depth has not been evaluated. We aim to present the best depth at which sampling should be performed for molecular exams of ATL. Methods Patients with a clinical presentation compatible with ATL were allocated to ATL and control groups. Qualitative and quantitative qPCR assays were performed using SYBR Green and primers amplifying the kDNA minicircle of Leishmania spp. in different skin layers, including the epidermis, the superior dermis, the inferior dermis, and the hypodermis. Results Fifty-nine patients were included in this study, including 40 who had been diagnosed with ATL and 19 controls. The number of parasites was greater in samples of the epidermis and superior dermis (159.1 × 106, range 4.0–781.7, and 75.4 × 106, range 8.0–244.5, mean Leishmania parasite equivalents per μg of tissue DNA, respectively) than those in samples of the inferior dermis and hypodermis (54.6, range 8.0–256.6, and 16.8 × 106, range 8.0–24.1, mean Leishmania parasite equivalents per μg of tissue DNA, respectively). The best diagnostic accuracy was achieved in the superior dermis (77.9%) and was significantly greater than that in the hypodermis (63.3%; p 0.039). Conclusions We conclude that superficial sampling can retrieve a greater quantity of parasites. Future studies of the role of transepidermal elimination as a mechanism of host defence in ATL must be performed as there is a considerable quantity of Leishmania kDNA in the epidermis.

Background and aims Restarting activity in Endoscopic Departments (ED) after COVID-19 lockdown raises critical issues. This survey investigates strategies and uncertainties on resumption of elective activity. Methods Directors of 55 EDs in Northern Italy received a questionnaire focusing on the impact of pandemic on activity and organization and on the resources available at re-opening. A section was devoted to gather forecasts and proposals on the return path to normality. Results All centres had reduced their activities of at least 50% of the pre-COVID-19 period. A rate of endoscopists (13.6%), nurses (25.2%), and health assistants (14%) were not available since infected, or relocated to other departments. One third of endoscopic rooms were converted to COVID-19 care. Two third had the waiting or the recovery areas too small for distancing. A dedicated pathway for infected patients could not be guaranteed in 20% of EDs. Only one third of EDs judged realistic to completely restore a pre-crisis workload by the next months. Optimizing appropriateness of procedures, closer interaction with GPs and triaging patients with telemedicine were the proposals to re-open EDs. Conclusions The critical issues while re-opening EDs calls for reducing the workload in the endoscopy units through appropriate rescheduling of procedures. Funding None

Made available in DSpace on 2021-06-25T10:48:29Z (GMT). No. of bitstreams: 0 Previous issue date: 2020-11-01 Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) We report a 7-year-old boy who presented with a nodule on the upper lip. A previous clinical history of mechanical trauma in the lesional area had been noted. After surgical excision, microscopy revealed fibrocollagenous fascicles associated with neurovascular bundles and skeletal striated muscle fibers in diffuse subepithelial distribution, suggesting rhabdomyomatous mesenchymal hamartoma. However, strict clinicopathological correlation favored a healing process with trapped striated skeletal muscle tissue. After three years of follow-up, an improvement in the aesthetic appearance of the upper lip was observed. To the best of our knowledge, a case of pseudo-rhabdomyomatous mesenchymal hamartoma has not been reported to date. Department of Pediatric Dentistry School of Dentistry of Ribeirão Preto FORP/USP University of Sao Paulo Oral Medicine Department of Diagnosis and Surgery Araraquara Dental School Universidade Estadual Paulista (UNESP) Oral Pathology Department of Stomatology Public Oral Health and Forensic Dentistry School of Dentistry of Ribeirão Preto FORP/USP University of São Paulo Oral Medicine Department of Diagnosis and Surgery Araraquara Dental School Universidade Estadual Paulista (UNESP) FAPESP: 2016/02713-2

The aim of this study was to investigate the association between genetic polymorphisms in MMP8, MMP13, and MMP20 with caries experience and developmental defects of enamel (DDE) in children from the Amazon region of Brazil. Den tal caries and DDE data were collected through clinical examination from 216 children. Genomic DNA was extracted from saliva, and genotyping of selected polymorphisms in MMP8 (rs17099443 and rs3765620), MMP13 (rs478927 and rs2252070), and MMP20 (rs1784418) was performed using TaqMan chemistry and endpoint analysis. χ2 or Fisher’s exact tests were used to compare allele and genotype distributions between children with caries experience and caries-free children and between DDE-affected and -unaffected children with an established alpha of 5%. The polymorphism rs478927 in MMP13 was associated with caries experience and DDE (p < 0.05). The analysis performed comparing children with both conditions (caries experience plus DDE) and children with neither of the conditions (caries-free chil dren without DDE) demonstrated that children carrying the MMP13 rs478927 TT genotype were more likely to have concomitant occurrence of these two conditions (OR = 5.8, 95% CI 2.1–15.8; p = 0.0003). In conclusion, the genetic polymorphism rs478927 in MMP13 was associated with caries experience and DDE.

BackgroundDistinct genome-wide methylation patterns have consistently clustered pituitary neuroendocrine tumors (PT) into molecular groups associated with specific clinicopathological features. Here we aim to identify, characterize and validate the methylation signatures that objectively classify PT into those molecular groups.MethodsCombining in-house and publicly available data, we conducted an analysis of the methylome profile of a comprehensive cohort of 177 tumor and 20 non-tumor specimens from the pituitary gland. We also retrieved methylome data from an independent pituitary tumor (PT) cohort (N=86) to validate our findings.ResultsWe identified three methylation clusters associated with functional status and adenohypophyseal cell lineages using an unsupervised approach. We also identified signatures based on differentially methylated CpG probes (DMP), some of which overlapped with pituitary-specific transcription factors genes (SF1 and Tpit), that significantly distinguished pairs of clusters related to functional status and adenohypophyseal cell lineage. These findings were reproduced in an independent cohort, validating these methylation signatures. The DMPs were mainly annotated in enhancer regions associated with pathways and genes involved in cell identity and tumorigenesis.ConclusionsWe identified and validated methylation signatures that distinguished PT by distinct functional status and adenohypophyseal cell lineages. These signatures, annotated in enhancer regions, indicate the importance of these elements in pituitary tumorigenesis. They also provide an unbiased approach to classify pituitary tumors according to the most recent classification recommended by the WHO 2017 using methylation profiling.Key-pointsDistinct methylation landscapes define PT groups with specific functional status/subtypes and adenohypophyseal lineages subtypes.Methylation abnormalities in each cluster mainly occur in CpG annotated in distal regions overlapping predicted enhancers regions associated with pathways and genes involved in cell identity and tumorigenesis.DNA methylation signatures provide an unbiased approach to classify PT.Importance of the studyThis study harnessed the largest methylome data to date from a comprehensive cohort of pituitary specimens obtained from four different institutions. We identified and validated methylation signatures that distinguished pituitary tumors into molecular groups that reflect the functionality and adenohypophyseal cell lineages of these tumors. These signatures, mainly located in enhancers, are associated with pathways and genes involved in cell identity and tumorigenesis. Our results show that methylome profiling provides an objective approach to classify PT according to the most recent classification of PT recommended by the 2017 WHO.