One session laparoscopic management of Mirizzi syndrome: feasible and safe in specialist units

BACKGROUND:To evaluate the laparoscopic management of Mirizzi syndrome, seldom diagnosed preoperatively causing difficulty when performing cholecystectomy and increasing complication risks. METHODS:Analysis of a prospective single-surgeon database of 5700 laparoscopic cholecystectomies found 58 Mirizzi syndrome cases. They were managed with an intention to treat during the index admission according to protocol of single-session management of bile duct stones. RESULTS:38/58 patients were females (65.5%). The median age was 55 years. 53 cases were emergency admissions. 34 cases (58.6%) only had ultrasound scanning. Operative difficulty was Grade IV in 34 cases (58.6%) and Grade V in 20 (34.5%) (Nassar Scale). There were 33 Mirizzi Type IA, 7 Type IB, 16 Type II and one each of Type III and Type IV. Bile duct exploration was performed in 94.8% through choledochotomy/ transfistula in 58.6% or transcystic in 36.2%. Four cases required conversion to open. Postoperative morbidity occurred in 29%. Two 30-day mortalities occurred from pneumonia in two elderly patients who were late referrals. CONCLUSION:Although the utilization of the laparoscopic approach in managing bile duct stones is not currently widely practiced it was safer in this series than in reported series of open surgery in Mirizzi Syndrome. The optimal approach to Mirizzi Type II is via cholecystocholedochal fistula to explore the bile duct then drain with T-tube through the fistula. It is unnecessary to perform bilioenteric bypass in majority of cases, reducing the morbidity and mortality

Achieving the critical view of safety in the difficult laparoscopic cholecystectomy: a prospective study of predictors of failure

Background: Bile duct injury rates for laparoscopic cholecystectomy (LC) remain higher than during open cholecystectomy. The “culture of safety” concept is based on demonstrating the critical view of safety (CVS) and/or correctly interpreting intraoperative cholangiography (IOC). However, the CVS may not always be achievable due to difficult anatomy or pathology. Safety may be enhanced if surgeons assess difficulties objectively, recognise instances where a CVS is unachievable and be familiar with recovery strategies. Aims and methods: A prospective study was conducted to evaluate the achievability of the CVS during all consecutive LC performed over four years. The primary aim was to study the association between the inability to obtain the CVS and an objective measure of operative difficulty. The secondary aim was to identify preoperative and operative predictors indicating the use of alternate strategies to complete the operation safely. Results: The study included 1060 consecutive LC. The median age was 53 years, male to female ratio was 1:2.1 and 54.9% were emergency admissions. CVS was obtained in 84.2%, the majority being difficulty grade I or II (70.7%). Displaying the CVS failed in 167 LC (15.8%): including 55.6% of all difficulty grade IV LC and 92.3% of difficulty grade V. There were no biliary injuries or conversions. Conclusion: All three components of the critical view of safety could not be demonstrated in one out of 6 consecutive laparoscopic cholecystectomies. Preoperative factors and operative difficulty grading can predict cases where the CVS may not be achievable. Adapting instrument selection and alternate dissection strategies would then need to be considered

Invasive micropapillary carcinoma of the breast overexpresses MUC4 and is associated with poor outcome to adjuvant trastuzumab in HER2-positive breast cancer

Invasive micropapillary carcinoma of the breast (IMPC) is a histological tumor variant that occurs with low frequency characterized by an inside-out formation of tumor clusters with a pseudopapillary arrangement. IMPC is an aggressive tumor with poor clinical outcome. In addition, this histological subtype usually expresses human epidermal growth factor receptor 2 (HER2) which also correlates with a more aggressive tumor. In this work we studied the clinical significance of IMPC in HER2-positive breast cancer patients treated with adjuvant trastuzumab. We also analyzed mucin 4 (MUC4) expression as a novel biomarker to identify IMPC.Fil: Mercogliano, María Florencia. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Inurrigarro, Gloria. Sanatorio Mater Dei Hermanas de María de Schoenstatt; ArgentinaFil: de Martino, Mara. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Venturutti, Leandro. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Rivas, Martin Alfredo. Cornell University; Estados UnidosFil: Cordo Russo, Rosalia Ines. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Proietti Anastasi, Cecilia Jazmín. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Fernandez, Elmer Andres. Universidad Católica de Córdoba; ArgentinaFil: Frahm, Isabel. Sanatorio Mater Dei Hermanas de María de Schoenstatt; ArgentinaFil: Barchuk, Sabrina. Gobierno de la Ciudad de Buenos Aires. Hospital General de Agudos ; ArgentinaFil: Allemand, Daniel H.. Gobierno de la Ciudad de Buenos Aires. Hospital General de Agudos ; ArgentinaFil: Figurelli, Silvina. Gobierno de la Ciudad de Buenos Aires. Hospital General de Agudos ; ArgentinaFil: Gil Deza, Ernesto. Instituto Oncológico Henry Moore; ArgentinaFil: Ares, Sandra. Instituto Oncológico Henry Moore; ArgentinaFil: Gercovich, Felipe G.. Instituto Oncológico Henry Moore; ArgentinaFil: Cortese, Eduardo. Ministerio de Defensa. Fuerza Aérea Argentina. Hospital Aeronáutico Central ; ArgentinaFil: Amasino, Matías. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Guzmán, Pablo. Universidad de La Frontera; ChileFil: Roa, Juan C.. Universidad de La Frontera; ChileFil: Elizalde, Patricia Virginia. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Schillaci, Roxana. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentin

Search for composite and exotic fermions at LEP 2

A search for unstable heavy fermions with the DELPHI detector at LEP is reported. Sequential and non-canonical leptons, as well as excited leptons and quarks, are considered. The data analysed correspond to an integrated luminosity of about 48 pb^{-1} at an e^+e^- centre-of-mass energy of 183 GeV and about 20 pb^{-1} equally shared between the centre-of-mass energies of 172 GeV and 161 GeV. The search for pair-produced new leptons establishes 95% confidence level mass limits in the region between 70 GeV/c^2 and 90 GeV/c^2, depending on the channel. The search for singly produced excited leptons and quarks establishes upper limits on the ratio of the coupling of the excited fermio

Search for lightest neutralino and stau pair production in light gravitino scenarios with stau NLSP

Promptly decaying lightest neutralinos and long-lived staus are searched for in the context of light gravitino scenarios. It is assumed that the stau is the next to lightest supersymmetric particle (NLSP) and that the lightest neutralino is the next to NLSP (NNLSP). Data collected with the Delphi detector at centre-of-mass energies from 161 to 183 \GeV are analysed. No evidence of the production of these particles is found. Hence, lower mass limits for both kinds of particles are set at 95% C.L.. The mass of gaugino-like neutralinos is found to be greater than 71.5 GeV/c^2. In the search for long-lived stau, masses less than 70.0 to 77.5 \GeVcc are excluded for gravitino masses from 10 to 150 \eVcc . Combining this search with the searches for stable heavy leptons and Minimal Supersymmetric Standard Model staus a lower limit of 68.5 \GeVcc may be set for the stau mas

Social mobility and healthy behaviours from a gender perspective in the Spanish multicase-control study (MCC-Spain)

There is evidence for the influence of socioeconomic status (SES) on healthy behaviours but the effect of social mobility (SM) is not yet well known. This study aims to analyse the influence of origin and destination SES (O-SES and D-SES) and SM on healthy behaviours and co-occurrence, from an integrated gender and age perspective. Data were obtained from the controls of MCC-Spain between 2008-2013 (3,606 participants). Healthy behaviours considered: healthy diet, moderate alcohol consumption, non-smoking and physical activity. SM was categorized as stable high, upward, stable medium, downward or stable low. Binary and multinomial logistic regression models were adjusted. Those aged <65, with a low O-SES, D-SES and stable low SM are less likely to have healthy behaviours in the case of both women (physically active: OR = 0.65 CI = 0.45-0.94, OR = 0.71 CI = 0.52-0.98, OR = 0.61 CI = 0.41-0.91) and men (non-smokers: OR = 0.44 CI = 0.26-0.76, OR = 0.54 CI = 0.35-0.83, OR = 0.41 CI 0.24-0.72; physically active: OR = 0.57 CI = 0.35-0.92, OR = 0.64 CI = 0.44-0.95, OR = 0.53 CI = 0.23-0.87). However, for those aged ≥65, this probability is higher in women with a low O-SES and D-SES (non-smoker: OR = 8.09 CI = 4.18-15.67, OR = 4.14 CI = 2.28-7.52; moderate alcohol consumption: OR = 3.00 CI = 1.45-6.24, OR = 2.83 CI = 1.49-5.37) and in men with a stable low SM (physically active: OR = 1.52 CI = 1.02-1.26). In the case of men, the same behaviour pattern is observed in those with a low O-SES as those with upward mobility, with a higher probability of co-occurring behaviours (three-to-four behaviours: OR = 2.00 CI = 1.22-3.29; OR = 3.13 CI = 1.31-7.48). The relationship of O-SES, D-SES and SM with healthy behaviours is complex and differs according to age and gender.This research was supported by the “Acción Transversal del Cancer”, approved by the Spanish Council of Ministers on 11th October 2007, by the Instituto de Salud Carlos III-FEDER [grant number:PI08/1770, PI08/0533, PI08/1359, PS09/00773-Cantabria, PS09/01286-León, PS09/01903-Valencia, PS09/02078-Huelva, PS09/ 01662-Granada, PI11/01403, PI11/01889-FEDER, PI11/00226, PI11/01810, PI11/02213, PI12/00488, PI12/00265, PI12/01270, PI12/00715, PI12/00150, PI14/01219, PI14/0613, PI15/00069, PI15/00914, PI15/01032, PI11/01810, PI14/01219, PI11/02213, PIE16/00049, PI17/01179, PI17-00092], by the Fundación Marqués de Valdecilla [grant number: API 10/09], by the ICGC International Cancer Genome Consortium CLL (The ICGC CLL-Genome Project is funded by Spanish Ministerio de Economía y Competitividad (MINECO) through the Instituto de Salud Carlos III (ISCIII)), by the Red Temática de Investigación del Cáncer (RTICC) del ISCIII [grant number: RD12/0036/0036], by the Junta de Castilla y León [grant number: LE22A10-2], by the Consejería de Salud of the Junta de Andalucía [grant number: PI-0571-2009, PI-0306-2011, salud201200057018tra], by the Conselleria de Sanitat of the Generalitat Valenciana [grant number: AP_061/10], by the Recercaixa [grant number: 2010ACUP00310], by the Regional Government of the Basque Country, by the Consejería de Sanidad de la Región de Murcia, by the European Commission [grant number: FOOD-CT-2006-036224-HIWATE], by the Spanish Association Against Cancer (AECC) Scientific Foundation [grant number: GCTRA18022MORE], by the Catalan Government-Agency for Management of University and Research Grants (AGAUR) [grant number: 2014SGR647, 2014SGR850 and 2017SGR723], by the Fundación Caja de Ahorros de Asturias and by the University of Oviedo. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.S

The ICARUS Experiment, A Second-Generation Proton Decay Experiment and Neutrino Observatory at the Gran Sasso Laboratory

The final phase of the ICARUS physics program requires a sensitive mass of liquid Argon of 5000 tons or more. The T600 detector stands today as the first living proof that such large detector can be built and that liquid Argon imaging technology can be implemented on such large scales. After the successful completion of a series of technical tests to be performed at the assembly hall in Pavia, the T600 detector will be ready to be transported into the LNGS tunnel. The operation of the T600 at the LNGS will allow us (1) to develop the local infrastructure needed to operate our large detector (2) to start the handling of the underground liquid argon technology (3) to study the local background (4) to start the data taking with an initial liquid argon mass that will reach in a 5-6 year program the multi-kton goal. The T600 is to be considered as the first milestone on the road towards a total sensitive mass of 5000 tons: it is the first piece of the detector to be complemented by further modules of appropriate size and dimensions, in order to reach in a most efficient and rapid way the final design mass. In this document, we describe the physics program that will be accomplished within the first phase of the program

Genetic landscape of 6089 inherited retinal dystrophies affected cases in Spain and their therapeutic and extended epidemiological implications

Inherited retinal diseases (IRDs), defined by dysfunction or progressive loss of photoreceptors, are disorders characterized by elevated heterogeneity, both at the clinical and genetic levels. Our main goal was to address the genetic landscape of IRD in the largest cohort of Spanish patients reported to date. A retrospective hospital-based cross-sectional study was carried out on 6089 IRD affected individuals (from 4403 unrelated families), referred for genetic testing from all the Spanish autonomous communities. Clinical, demographic and familiar data were collected from each patient, including family pedigree, age of appearance of visual symptoms, presence of any systemic findings and geographical origin. Genetic studies were performed to the 3951 families with available DNA using different molecular techniques. Overall, 53.2% (2100/3951) of the studied families were genetically characterized, and 1549 different likely causative variants in 142 genes were identified. The most common phenotype encountered is retinitis pigmentosa (RP) (55.6% of families, 2447/4403). The most recurrently mutated genes were PRPH2, ABCA4 and RS1 in autosomal dominant (AD), autosomal recessive (AR) and X-linked (XL) NON-RP cases, respectively; RHO, USH2A and RPGR in AD, AR and XL for non-syndromic RP; and USH2A and MYO7A in syndromic IRD. Pathogenic variants c.3386G > T (p.Arg1129Leu) in ABCA4 and c.2276G > T (p.Cys759Phe) in USH2A were the most frequent variants identified. Our study provides the general landscape for IRD in Spain, reporting the largest cohort ever presented. Our results have important implications for genetic diagnosis, counselling and new therapeutic strategies to both the Spanish population and other related populations.This work was supported by the Instituto de Salud Carlos III (ISCIII) of the Spanish Ministry of Health (FIS; PI16/00425 and PI19/00321), Centro de Investigación Biomédica en Red Enfermedades Raras (CIBERER, 06/07/0036), IIS-FJD BioBank (PT13/0010/0012), Comunidad de Madrid (CAM, RAREGenomics Project, B2017/BMD-3721), European Regional Development Fund (FEDER), the Organización Nacional de Ciegos Españoles (ONCE), Fundación Ramón Areces, Fundación Conchita Rábago and the University Chair UAM-IIS-FJD of Genomic Medicine. Irene Perea-Romero is supported by a PhD fellowship from the predoctoral Program from ISCIII (FI17/00192). Ionut F. Iancu is supported by a grant from the Comunidad de Madrid (CAM, PEJ-2017-AI/BMD7256). Marta del Pozo-Valero is supported by a PhD grant from the Fundación Conchita Rábago. Berta Almoguera is supported by a Juan Rodes program from ISCIII (JR17/00020). Pablo Minguez is supported by a Miguel Servet program from ISCIII (CP16/00116). Marta Corton is supported by a Miguel Servet program from ISCIII (CPII17/00006). The funders played no role in study design, data collection, data analysis, manuscript preparation and/or publication decisions

The genetic architecture of type 2 diabetes

The genetic architecture of common traits, including the number, frequency, and effect sizes of inherited variants that contribute to individual risk, has been long debated. Genome-wide association studies have identified scores of common variants associated with type 2 diabetes, but in aggregate, these explain only a fraction of heritability. To test the hypothesis that lower-frequency variants explain much of the remainder, the GoT2D and T2D-GENES consortia performed whole genome sequencing in 2,657 Europeans with and without diabetes, and exome sequencing in a total of 12,940 subjects from five ancestral groups. To increase statistical power, we expanded sample size via genotyping and imputation in a further 111,548 subjects. Variants associated with type 2 diabetes after sequencing were overwhelmingly common and most fell within regions previously identified by genome-wide association studies. Comprehensive enumeration of sequence variation is necessary to identify functional alleles that provide important clues to disease pathophysiology, but large-scale sequencing does not support a major role for lower-frequency variants in predisposition to type 2 diabetes