Complications of laparoscopic lymphadenectomy for gynecologic malignancies. Experience of 372 patients

Evaluation of lymph nodes is an integral part in the management of women with gynecologic cancers, which is why the pelvic and aortic lymphadenectomy is widely used as a staging and/ or prognostic procedure in such malignancies. The purpose of this study was to describe our experience with pelvic and aortic laparoscopic lymphadenectomy and evaluate the safety and feasibility of this procedure for gynecologic malignancies. From January 2004 to December 2015, a laparoscopic pelvic and/or aortic lymphadenectomy was performed in 372 women at the Department of Gynecology Oncology of the University General Hospital of Castellon and at the Department of Obstetrics and Gynecology of Sant Pau and Santa Tecla Tarragona Hospitals. Out of the 372 cases, 240 combined pelvic and paraaortic lymphadenectomies were performed, while 108 and 24 patients underwent pelvic and aortic lymphadenectomy respectively. The mean operative times were 40 min (20-89) in order to perform a complete pelvic lymphadenectomy, 62 min (21-151) for transperitoneal aortic lymphadenectomy and 45 min (35-65) for a retroperitoneal approach. A conversion to laparotomy was needed in 1.6% of patients. Twenty-three (6.1%) complications were encountered in 372 patients undergoing laparoscopic lymphadenectomy. Nine (2.4%) major complications occurred intraoperatively while fourteen (3.7%) appeared postoperatively. The most frequent intraoperatory complication was vascular injury (1.3%). Laparoscopic lymphadenectomy can be considered a safe and achievable procedure, and could be considered the golden standard procedure for staging gynecologic malignancies

The folding of a metallopeptide

We have applied solid-phase synthesis methods for the construction of tris(bipyridyl) peptidic ligands that coordinate Fe(II) ions with high affinity and fold into stable mononuclear metallopeptides. The main factors influencing the folding pathway and chiral control of the peptidic ligands around the metal ions have been studied both by experimental techniques (CD, UV-vis and NMR) and molecular modeling tools. Amongst the numerous molecular variables that have been studied, this study clearly illustrates how the chirality of a given set of aminoacids (proline in this case) of the peptide dictates the chirality of the metal center of the resulting metallopeptide. Moreover, the relatively hydrophobic peptidic models used in this work show that the most stable structures present reduced solvent contacts and, in counterpart, stabilize the cis configuration of the proline residuesWe are thankful for the support given by the Spanish grants SAF2013-41943-R, CTQ2012-31341, CTQ2011-23336 and CTQ2013-49317-EXP; the ERDF and the European Research Council (Advanced Grant 340055); the Xunta de Galicia grants GRC2013-041 and PGIDIT08CSA-047209PR and the Generalitat de Catalunya grant 2009SGR68. Support of COST Action CM1105 is kindly acknowledged. G.R. thanks the INL for his PhD fellowshipS

Unambiguous discrimination between two unknown qudit states

We consider the unambiguous discrimination between two unknown qudit states in $n$-dimensional ($n\geqslant2$) Hilbert space. By equivalence of unknown pure states to known mixed states and with the Jordan-basis method, we demonstrate that the optimal success probability of the discrimination between two unknown states is independent of the dimension $n$. We also give a scheme for a physical implementation of the programmable state discriminator that unambiguously discriminate between two unknown states with optimal probability of success.Comment: 8 pages, 3 figure

STI epidemic re-emergence, socio-epidemiological clusters characterisation and HIV coinfection in Catalonia, Spain, during 2017-2019 : A retrospective population-based cohort study

Objectives To describe the epidemiology of sexually transmitted infections (STIs), identify and characterise socio-epidemiological clusters and determine factors associated with HIV coinfection. Design Retrospective population-based cohort. Setting Catalonia, Spain. Participants 42 283 confirmed syphilis, gonorrhoea, chlamydia and lymphogranuloma venereum cases, among 34 600 individuals, reported to the Catalan HIV/STI Registry in 2017-2019. Primary and secondary outcomes Descriptive analysis of confirmed STI cases and incidence rates. Factors associated with HIV coinfection were determined using logistic regression. We identified and characterized socio-epidemiological STI clusters by Basic Health Area (BHA) using K-means clustering. Results The incidence rate of STIs increased by 91.3% from 128.2 to 248.9 cases per 100 000 population between 2017 and 2019 (p<0.001), primarily driven by increase among women (132%) and individuals below 30 years old (125%). During 2017-2019, 50.1% of STIs were chlamydia and 31.6% gonorrhoea. Reinfections accounted for 10.8% of all cases and 6% of cases affected HIV-positive individuals. Factors associated with the greatest likelihood of HIV coinfection were male sex (adjusted OR (aOR) 23.69; 95% CI 16.67 to 35.13), age 30-39 years (versus <20 years, aOR 18.58; 95% CI 8.56 to 52.13), having 5-7 STI episodes (vs 1 episode, aOR 5.96; 95% CI 4.26 to 8.24) and living in urban areas (aOR 1.32; 95% CI 1.04 to 1.69). Living in the most deprived BHAs (aOR 0.60; 95% CI 0.50 to 0.72) was associated with the least likelihood of HIV coinfection. K-means clustering identified three distinct clusters, showing that young women in rural and more deprived areas were more affected by chlamydia, while men who have sex with men in urban and less deprived areas showed higher rates of STI incidence, multiple STI episodes and HIV coinfection. Conclusions We recommend socio-epidemiological identification and characterisation of STI clusters and factors associated with HIV coinfection to identify at-risk populations at a small health area level to design effective interventions

Diagnostic potential of western blot analysis of sera from dogs with Leishmaniasis in endemic areas and significance of the pattern.

Serum samples collected from 237 dogs in Catalonia (northeastern Spain) were screened by Western blot analysis to detect the presence of antibodies specific to different Leishmania infantum polypeptide fractions. Leishmaniasis was confirmed in 72 of these dogs by direct examination and/or culture. Another 165 animals from the Priorat region were studied periodically for 2-8 years between 1987 and 1995, giving a total of 565 determinations. A control group of 93 dogs from nonendemic areas was also studied. Sera from dogs with leishmaniasis recognized antigens with molecular weights ranging from 12 to 85 kD. The most sensitive antigens were those of 70, 65, 46, 30, 28, 14, and 12 kD, which were recognized by 75%, 75%, 78%, 75%, 81%, 79%, and 75%, respectively, of the sera from dogs with positive parasitologic examination results. Antigens of 70 and 65 kD were also recognized by two dogs from nonendemic areas. Antigens of 14 and 12 kD were the first to be recognized by sera of asymptomatic dogs with titers less than the cut-off value of the dot-ELISA that increased during the longitudinal study, and the presence of antibodies specific for these fractions was observed for up to six years before seroconversion observed by dot-ELISA. These antibodies were also the first to disappear in dogs in which the disease was self-limited. The study corroborates the high sensitivity and specificity of Western blots in the diagnosis of canine leishmaniasis when the bands of low molecular weight (less than 46 kD) are considered, and indicates that fractions of 14 and 12 kD are useful in detecting early forms of the disease

Pervasive lesion segregation shapes cancer genome evolution

Cancers arise through the acquisition of oncogenic mutations and grow through clonal expansion. Here we reveal that most mutagenic DNA lesions are not resolved as mutations within a single cell-cycle. Instead, DNA lesions segregate unrepaired into daughter cells for multiple cell generations, resulting in the chromosome-scale phasing of subsequent mutations. We characterise this process in mutagen-induced mouse liver tumours and show that DNA replication across persisting lesions can produce multiple alternative alleles in successive cell divisions, thereby generating both multi-allelic and combinatorial genetic diversity. The phasing of lesions enables the accurate measurement of strand biased repair processes, quantification of oncogenic selection, and fine mapping of sister chromatid exchange events. Finally, we demonstrate that lesion segregation is a unifying property of exogenous mutagens, including UV light and chemotherapy agents in human cells and tumours, which has profound implications for the evolution and adaptation of cancer genomes.This work was supported by: Cancer Research UK (20412, 22398), the European Research Council (615584, 682398), the Wellcome Trust (WT108749/Z/15/Z, WT106563/Z/14/A, WT202878/B/16/Z), the European Molecular Biology Laboratory, the MRC Human Genetics Unit core funding programme grants (MC_UU_00007/11, MC_UU_00007/16), and the ERDF/Spanish Ministry of Science, Innovation and Universities-Spanish State Research Agency/DamReMap Project (RTI2018-094095-B-I00)

Hydroxychloroquine for Early Treatment of Adults With Mild Coronavirus Disease 2019: A Randomized, Controlled Trial

No effective treatments for coronavirus disease 2019 (COVID-19) exist. We aimed to determine whether early treatment with hydroxychloroquine (HCQ) would be efficacious for outpatients with COVID-19.The authors thank Gerard Carot-Sans, PhD, for providing medical writing support during the revisions of the subsequent drafts of the manuscript; the personnel from the Fights Aids and Infectious Diseases Foundation for their support in administration, human resources and supply chain management; Eric Ubals (Pierce AB) and Òscar Palao (Opentic) for website and database management; Óscar Camps and OpenArms nongovernmental organization for nursing home operations; and Anna Valentí and the Hospital Germans Trias i Pujol Human Resources Department for telephone monitoring. We thank Consorci Sanitari del Maresme, Centre Sociosanitari El Carme, l'Hospital General de Granollers and occupational hazards department of Hospital Germans Trias i Pujol for their contribution with patient enrollment. We are very grateful to Marc Clotet and Natalia Sánchez who coordinated the JoEmCorono crowd-funding campaign. We thank the Hospital Germans Trias Pujol Institutional Review Board and the Spanish Agency of Medicines and Medical Devices for their prompt action for consideration and approvals to the protocol. Financial support. This work was mainly supported by the crowd-funding campaign JoEmCorono (https://www.yomecorono.com/) with contributions from more than 72 000 citizens and corporations. The study also received financial support from Laboratorios Rubió, Laboratorios Gebro Pharma, Zurich Seguros, SYNLAB Barcelona, and Generalitat de Catalunya. Laboratorios Rubió also contributed to the study with the required doses of hydroxychloroquine (Dolquine®). Foundation Dorneur partly funded lab equipment at Irsi-Caixa.Peer reviewe