Initial experience with intraoperative testing and repair of colorectal anastomosis using a TAMIS approach after a positive leak test.

Anastomotic leak is one of the most feared complications of colorectal anastomosis. Different techniques have been described for intraoperative testing of anastomotic integrity. These include air insufflation, methylene blue and endoscopic visualisation. If an anastomotic leak is identified intraoperatively, there are various management options. Redo anastomosis is a possibility, but may be difficult in some cases. Defunctioning is another option, but there is an associated morbidity and signficant detrimental effect on quality of life. Direct transanal repair is only possible when a low anastomosis has been performed. When the anastomotic leak occurs high in the rectum or a partial mesorectal excision is performed a transanal approach is technically very challenging. We present our experience with transanal minimally invasive surgery (TAMIS) approach for anastomotic assessment and repair in four patients. In all cases, a colorectal anastomosis was performed and the air insufflation test was positive. We assessed the anastomosis with TAMIS. In three cases, a defect was found and subsequently sutured. In one case, a scar in the rectal mucosa was found and reinforced with a suture. A protective ileostomy was performed in two cases, while in the other two cases, no stoma was added. All four patients were discharged with no further complications. Both protective ileostomies were taken down after radiological and endoscopic confirmation of anastomotic integrity and all 4 anastomoses remain intact after follow-up. TAMIS intraoperative assessment and repair of anastomotic leak is a safe and feasible technique whcih may avoid the need for a defunctioning stoma.

Polymorphisms within the ARNT2 and CX3CR1 Genes Are Associated with the Risk of Developing Invasive Aspergillosis.

Invasive aspergillosis (IA) is a life-threatening infection that affects an increasing number of patients undergoing chemotherapy or allo-transplantation, and recent studies have shown that genetic factors contribute to disease susceptibility. In this two-stage, population-based, case-control study, we evaluated whether 7 potentially functional single nucleotide polymorphisms (SNPs) within the ARNT2 and CX3CR1 genes influence the risk of IA in high-risk hematological patients. We genotyped selected SNPs in a cohort of 500 hematological patients (103 of those had been diagnosed with proven or probable IA), and we evaluated their association with the risk of developing IA. The association of the most interesting markers of IA risk was then validated in a replication population, including 474 subjects (94 IA and 380 non-IA patients). Functional experiments were also performed to confirm the biological relevance of the most interesting markers. The meta-analysis of both populations showed that carriers of the ARNT2rs1374213G, CX3CR1rs7631529A, and CX3CR1rs9823718G alleles (where the RefSeq identifier appears as a subscript) had a significantly increased risk of developing IA according to a log-additive model (P value from the meta-analysis [PMeta] = 9.8 · 10-5, PMeta = 1.5 · 10-4, and PMeta =7.9 · 10-5, respectively). Haplotype analysis also confirmed the association of the CX3CR1 haplotype with AG CGG with an increased risk of IA (P = 4.0 · 10-4). Mechanistically, we observed that monocyte-derived macrophages (MDM) from subjects carrying the ARNTR2rs1374213G allele or the GG genotype showed a significantly impaired fungicidal activity but that MDM from carriers of the ARNT2rs1374213G and CX3CR1rs9823718G or CX3CR1rs7631529A alleles had deregulated immune responses to Aspergillus conidia. These results, together with those from expression quantitative trait locus (eQTL) data browsers showing a strong correlation of the CX3CR1rs9823718G allele with lower levels of CX3CR1 mRNA in whole peripheral blood (P = 2.46 · 10-7) and primary monocytes (P = 4.31 · 10-7), highlight the role of the ARNT2 and CX3CR1 loci in modulating and predicting IA risk and provide new insights into the host immune mechanisms involved in IA development.

[Pharmaceutical care for older adults. Application of STOPP-START criteria]. / Atención farmacéutica de adultos mayores. Aplicación de los criterios STOPP-START.

INTRODUCTION: Drug-related problems can be caused by potentially inappropriate prescribing (PIP), one of the most used tools for its identification are the STOPP (Older Persons' potentially inappropriate Prescriptions) - START (Screening Tool to Alert doctors to Right Treatment) criteria. The objective of this study is to determine PIP in older adults who receive pharmaceutical care in the Pharmacotherapy Optimization Unit (POU)-Rosario. MATERIALS AND METHODS: Pharmacoepidemiological observational study, which evaluates the quality of medication use. Workplace: POU-Rosario. Population under study: adults over 60 years of age, who received pharmacotherapy follow-up during the period March 2017 to February 2018. PIPs were identified using the STOPP-START criteria, 2014 version; selecting the most appropriate criteria to assess outpatient pharmacotherapy. Prevalence of PIP and amount of PIP per active principle were estimated. RESULTS: 50 patients older than 60 years received pharmacotherapy follow-up in the POU; 47 patients (94.0%) had at least one PIP corresponding to a STOPP criterion; 17 STOPP criteria were found among the 41 initially selected, leading to 145 PIPs identified. And 7 START criteria among the 11 initially selected, leading to 50 PIPs identified. Medications with a higher amount of PIPs: benzodiazepines and proton pump inhibitors. CONCLUSIONS: This study allowed the identification of a high prevalence of PIP. The data obtained show the usefulness of these criteria. The STOPP-START criteria have been included to support decision making during pharmacotherapy follow-up to propose pharmaceutical interventions, in order to enhance pharmacotherapy. These activities contribute to patient safety, a dimension of health quality.

Polymorphisms in Host Immunity-Modulating Genes and Risk of Invasive Aspergillosis: Results from the AspBIOmics Consortium.

Recent studies suggest that immune-modulating single-nucleotide polymorphisms (SNPs) influence the risk of developing cancer-related infections. Here, we evaluated whether 36 SNPs within 14 immune-related genes are associated with the risk of invasive aspergillosis (IA) and whether genotyping of these variants might improve disease risk prediction. We conducted a case-control association study of 781 immunocompromised patients, 149 of whom were diagnosed with IA. Association analysis showed that the IL4Rrs2107356 and IL8rs2227307 SNPs (using dbSNP numbering) were associated with an increased risk of IA (IL4Rrs2107356 odds ratio [OR], 1.92; 95% confidence interval [CI], 1.20 to 3.09; IL8rs2227307 OR, 1.73; 95% CI, 1.06 to 2.81), whereas the IL12Brs3212227 and IFNγrs2069705 variants were significantly associated with a decreased risk of developing the infection (IL12Brs3212227 OR, 0.60; 95% CI, 0.38 to 0.96; IFNγrs2069705 OR, 0.63; 95% CI, 0.41 to 0.97). An allogeneic hematopoietic stem cell transplantation (allo-HSCT)-stratified analysis revealed that the effect observed for the IL4Rrs2107356 and IFNγrs2069705 SNPs was stronger in allo-HSCT (IL4Rrs2107356 OR, 5.63; 95% CI, 1.20 to 3.09; IFNγrs2069705 OR, 0.24; 95% CI, 0.10 to 0.59) than in non-HSCT patients, suggesting that the presence of these SNPs renders patients more vulnerable to infection, especially under severe and prolonged immunosuppressive conditions. Importantly, in vitro studies revealed that carriers of the IFNγrs2069705C allele showed a significantly increased macrophage-mediated neutralization of fungal conidia (P = 0.0003) and, under stimulation conditions, produced higher levels of gamma interferon (IFNγ) mRNA (P = 0.049) and IFNγ and tumor necrosis factor alpha (TNF-α) cytokines (P value for 96 h of treatment with lipopolysaccharide [PLPS-96 h], 0.057; P value for 96 h of treatment with phytohemagglutinin [PPHA-96 h], 0.036; PLPS+PHA-96 h = 0.030; PPHA-72 h = 0.045; PLPS+PHA-72 h = 0.018; PLPS-96 h = 0.058; PLPS+PHA-96 h = 0.0058). Finally, we also observed that the addition of SNPs significantly associated with IA to a model including clinical variables led to a substantial improvement in the discriminatory ability to predict disease (area under the concentration-time curve [AUC] of 0.659 versus AUC of 0.564; P-2 log likehood ratio test = 5.2 · 10(-4) and P50.000 permutation test = 9.34 · 10(-5)). These findings suggest that the IFNγrs2069705 SNP influences the risk of IA and that predictive models built with IFNγ, IL8, IL12p70, and VEGFA variants can used to predict disease risk and to implement risk-adapted prophylaxis or diagnostic strategies.

Formación de un residente de cirugía general en la unidad de cirugía mayor ambulatoria de un hospital de tercer nivel / General surgery trainee education in the ambulatory surgery setting of a tertiary hospital

Objetivos: la cirugía mayor ambulatoria ha adquirido entidad propia dentro de las unidades asistenciales, con un importante papel en la formación del residente. El objetivo de este estudio es valorar la formación actual de un residente de cirugía general en la unidad de cirugía ambulatoria de un hospital de tercer nivel. Materiales y método: se trata de un estudio retrospectivo, observacional y descriptivo. Las variables estudiadas han sido meses de rotación, intervenciones realizadas como cirujano principal, primer o segundo ayudante, sesiones de la unidad y tiempo de consulta. Resultados: en nuestro hospital dedicamos 6 meses de la residencia a la unidad de cirugía ambulatoria (2 en el primer año, 4 en el tercero), abarcando patologías de la pared abdominal, proctología básica, colelitiasis, patología benigna de la mama y patología de piel y partes blandas. El primer año se intervienen una media de 125 pacientes (36,16% como cirujano principal, 56% como primer ayudante y 7,84% como segundo). Durante el tercer año se realiza patología más compleja, llevándose a cabo una media de 206 intervenciones (68,40% como cirujano, 30,90% como primer ayudante y el 0,70% como segundo ayudante). Durante estos meses se realiza además actividad asistencial en consultas externas, sesiones clínicas relacionadas con patología de la unidad y sesión conjunta semanal sobre la evolución de los pacientes de pared compleja. Conclusión: dicha rotación realizada por un residente de cirugía general es imprescindible ya que en ella adquiere los cimientos para futuras intervenciones más complejas (AU)

Objectives: Ambulatory surgery has become entity within the health care units, with an important role in the learning of residents. The aim of this study is to assess the current training of general surgery residents in a ambulatory surgery unit of a tertiary hospital. Materials and methods: We show a retrospective, observational and descriptive study. The variables studied have been months of rotation, as chief surgeon interventions, first or second assistant, unit meetings and consultation time. Results: In our hospital, we dedicated 6 months of our residence period in the ambulatory surgery unit (two in the first year, four in the third), including diseases of the abdominal wall, basic proctology, cholelithiasis, benign breast disease and pathology of skin and soft tissue. The first year we operate an average of 125 procedures (36.16% as surgeon, 56% as first assistant and 7.84% as second). During the third year, there is a more complex pathology index, with an average of 206 interventions (68.40% as surgeon, 30.90% as first assistant and 0.70 as second). During these months we also participate in outpatient care activities, clinical sessions and a weekly staff session. Conclusions: This period is essential in a general surgery resident learning because it stablish the basis for their future more complex technics (AU)

[Association between genetic polymorphism in the promotor region of CD209 and propensity to develop invasive pulmonary aspergillosis]. / Asociación de un polimorfismo genético en la región promotora del gen CD209 y propension a la aspergilosis pulmonar invasiva.

Fungi of the genus Aspergillus are found everywhere in the natural environment; they cause invasive pulmonary aspergillosis (IPA), an infectious complication common in immunocompromised individuals, which has a mortality rate of up to 90% in patients with hematological malignancy. The first line of defense of innate immunity is the recognition of Aspergillus conidia by dendritic cells or alveolar macrophages. DC-SIGN is an integrin directly involved in this recognition; its degree of expression in immune cells and its functionality may be partly determined by genetic variations. The objective of this study was to determine whether the presence of polymorphisms of a single nucleotide in the DC-SIGN gene increases the risk of invasive pulmonary aspergillosis. For this purpose, the variants DC-SIGN-139A/G (rs2287886) and DC-SIGN+11C/G (rs7252229) were analyzed In 314 subjects (152 patients with hematologic malignancy and 162 healthy controls). Of the 152 hematologic cancer patients, 81 were diagnosed with demonstrated invasive pulmonary aspergillosis per EORTC/IFICG criteria, and the remaining 71 patients had no symptoms of the infection. An association was found between the variant DC-SIGN-139(A/G) and resistance to IPA. Carriers of the allele A (A/A + A/G) were significantly more resistant to the infection than patients with the G/G genotype (p = 0.0574). Analysis of the serum concentration of the galactomannan antigen supported the hypothesis that this polymorphism may be implicated in the susceptibility to suffer invasive pulmonary aspergillosis. Although the difference was not statistically significant, carriers of the allele G had a higher frequency of positive galactomannans than subjects with the genotype A/A (p = 0.1921). These results suggest that the variant DC-SIGN-139(A/G) in the DC-SIGN gene promoter influences the risk of invasive pulmonary aspergillosis and may therefore be used as a genetic biomarker to stratify patients according to risk.

Comorbidity and clinical features in elderly patients with dementia: differences according to dementia severity.

OBJECTIVES: To evaluate comorbidity and clinical features in elderly patients with dementia to determine differences according to dementia severity. DESIGN: Observational study with medical record review. SETTING: Eight hospitals in the Barcelona area. PARTICIPANTS: 515 consecutive admissions aged > 64 years with dementia, 89.1% of whom lived in the community. MEASUREMENTS: We collected data on sociodemographic variables, type of dementia, Barthel Index (BI), Lawton and Brody Index (LI), Mini-Mental State Examination (MMSE), Charlson Index and the total number of drugs chronically prescribed. We stratified the population into two groups according to disease severity with the Global Deterioration Scale (GDS): mild-moderate (GDS 3-5) and severe (GDS 6-7). RESULTS: There were a total of 515 participants of which 364 females (70%) and 151 males with a mean age of 81 +/- 6 years old. The total number of chronic prescription drugs was 5.6 +/- 2.4. The mean Charlson Index score was 2 +/- 1.2. The 270 (52.5%) patients with a GDS score of 3-5 were compared with the 245 patients with a GDS score of 6-7. In the multivariate analysis, a GDS score of 6-7 was associated with poorer LI, BI, and MMSE scores and greater neuroleptic therapy. CONCLUSIONS: Important comorbidity conditions are common in elderly individuals with dementia. The patients with more severe dementia had poor functional status and higher frequency of neuroleptic use. Medical comorbidities should be taken into account in the management of patients with dementia.

Segmental disorders of the nephron: histopathological and imaging perspective.

Recent advances in molecular genetics and immunocytochemistry have clarified the cell of origin in many renal disorders. Several renal disorders are thought to involve specific segments of the nephron. Renin-secreting tumours arise from juxtaglomerular cells. Clear cell and papillary renal cell carcinoma (RCC) recapitulate the epithelium of the proximal tubules. Oncocytoma and chromophobe RCC differentiate towards Type A and Type B intercalated cells of the cortical collecting duct, respectively. Medullary collecting ducts are the target sites for the development of autosomal recessive polycystic kidney disease, collecting duct carcinoma and medullary carcinoma. Renal papillae are susceptible to unique changes such as necrosis or papillitis. The purpose of our article is threefold: to illustrate the imaging findings of renal disorders that show segmental involvement of the nephron, to describe proximal and distal nephron disorders and to correlate imaging findings of some entities with histopathological features.

Synthesis and biological evaluation of 1,3,4-triaryl-3-pyrrolin-2-ones, a new class of selective cyclooxygenase-2 inhibitors.

The synthesis and structure activity relationships (SAR) of a series of novel selective COX-2 inhibitors are reported. The results show that some of the 1,3,4-triaryl-3-pyrrolin-2-ones 1 are more potent as COX-2 inhibitors than celecoxib, and that lactam Id has the same selectivity.

Endothelin-receptor interactions. Role of a putative sulfhydryl on the endothelin receptor.

The mechanism of action of endothelin-receptor interactions was studied, using radioligand binding assays and SDS-PAGE, to investigate the possibility of disulfide interchange. Electrophoretic analysis suggested involvement of disulfide bond(s) in the receptor-ligand complex. Treatment of Et receptors with sulfhydryl-specific alkylating reagents (NEM or others) resulted in decreased ability to bind [125I]Et-1. [Dpr1-Asp15]Et-1, an antagonist homologous to Et but with an amide link replacing one of the disulfides, bound to Et receptors reversibly, but binding of Et-1 was less reversible. Preincubation of receptors with Et-1, but not with [Dpr1-Asp15]Et-1, protected receptors from alkylation with [14C]NEM. The data suggest that the Et receptor has a sulfhydryl group at or near the Et binding site. A model is proposed in which the role of the putative sulfhydryl group is discussed.