Consecutive strabismus after infantile nystagmus syndrome surgery and potential risk factors.

PURPOSE: The aim of this study is to evaluate the incidence of consecutive strabismus after infantile nystagmus surgery and its potential risk factors. METHODS: A retrospective study including 89 patients was conducted. Patients presented infantile nystagmus (idiopathic or ocular disease-associated nystagmus) without previous or coincidental strabismus. Sex, age at surgery, amblyopia, botulinum toxin (BT) injection before surgery, spherical equivalent, anisometropia, surgery procedure (Anderson's or retroequatorial recessions of four horizontal recti), and follow-up were analyzed. Kaplan-Meier and univariate Cox regression were performed. RESULTS: The median age at surgery was 5 years. The median follow-up was 36 months. The incidence of consecutive strabismus was 11.2%. There were eight patients with exotropia and two patients with esotropia. Consecutive strabismus was associated with severe bilateral amblyopia (p = 0.036), previous treatment with BT injection (p = 0.025), and large recessions of the four horizontal muscles (p = 0.001). The hazard ratio for patients with severe bilateral amblyopia was 5.4 (95% CI 1.1-25.8), and for patients previously treated with BT was 6.1 (1.3-29.3). The survival rate was 95.4% at 6 months and 88.5% at 3 years. CONCLUSION: Severe bilateral amblyopia, previous BT treatment, and type of surgery seem to be associated with consecutive strabismus after infantile nystagmus surgery. Most cases appear within the first months after surgery.

Prophylactic closed-incision negative-pressure wound therapy is associated with decreased surgical site infection in high-risk colorectal surgery laparotomy wounds.

AIM: Surgical site infection in colorectal surgery is associated with significant healthcare costs, which may be reduced by using a closed-incision negative-pressure therapy device. The aim of this study was to assess the impact of closed-incision negative-pressure therapy on the incidence of surgical site infection. METHOD: In this retrospective cohort study we evaluated all patients who had undergone high-risk open colorectal surgery at a single tertiary care centre from 2012 to 2016. We compared the incidence of surgical site infection between those receiving standard postoperative wound care between 2012 and 2014 and those receiving closed-incision negative-pressure therapy via a customizable device (Prevena Incision Management System, KCI, an Acelity company, San Antonio, Texas, USA) between 2014 and 2016. A validated surgical site infection risk score was used to create a 1:1 matched cohort subset. RESULTS: Negative pressure therapy was used in 77 patients and compared with 238 controls. Negative pressure patients were more likely to have a stoma (92% vs 48%, P < 0.01) and to be smokers (33% vs 15%, P < 0.01). Surgical site infection was higher in control patients (15%, n = 35/238) compared with negative pressure patients (7%, n = 5/77) (P = 0.05). On regression analysis, negative pressure therapy was associated with decreased surgical site infection (OR 0.27; 95% CI 0.09-0.78). These differences persisted in the matched analysis. CONCLUSION: Negative pressure therapy was associated with decreased surgical site infection. Negative pressure therapy offers significant potential for quality improvement.

Identification of a founder BRCA1 mutation in the Moroccan population.

Breast cancer (BC) is the most frequent cancer among women in Morocco. However, the role of the most prevalent BC-predisposing genes, BRCA1 and BRCA2, has been largely unexplored. To help define the role of BRCA1 in BC in Morocco, we characterized the first potential BRCA1 founder mutation in this population. Genetic testing of BRCA1 and BRCA2 in BC high-risk families identified mutation BRCA1 c.5309G>T, p.(Gly1770Val) or G1770V in five independent families from Morocco, suggesting a founder effect. To confirm this hypothesis, haplotype construction was performed using seven intragenic and flanking BRCA1 microsatellite markers. Clinical data were also compiled. Clinical data from carriers of mutation G1770V correspond to data from carriers of BRCA1 pathogenic mutations. Microsatellite analysis showed a common haplotype for the five families in a region comprising 1.54 Mb, confirming G1770V as the first specific founder BRCA1 mutation in the Moroccan population. Our findings contribute to a better understanding of BC genetics in the Moroccan population. Nevertheless, comprehensive studies of mutation G1770V in large series of BC patients from Morocco are needed to assess the real prevalence of this mutation and to improve genetic testing and risk assessment in this population.

Status of Competency-Based Medical Education in Endoscopy Training: A Nationwide Survey of US ACGME-Accredited Gastroenterology Training Programs.

OBJECTIVES: The Accreditation Council for Graduate Medical Education (ACGME) emphasizes the importance of medical trainees meeting specific performance benchmarks and demonstrating readiness for unsupervised practice. The aim of this study was to examine the readiness of Gastroenterology (GI) fellowship programs for competency-based evaluation in endoscopic procedural training. METHODS: ACGME-accredited GI program directors (PDs) and GI trainees nationwide completed an online survey of domains relevant to endoscopy training and competency assessment. Participants were queried about current methods and perceived quality of endoscopy training and assessment of competence. Participants were also queried about factors deemed important in endoscopy competence assessment. Five-point Likert items were analyzed as continuous variables by an independent t-test and χ(2)-test was used for comparison of proportions. RESULTS: Survey response rate was 64% (94/148) for PDs and 47% (546/1,167) for trainees. Twenty-three percent of surveyed PDs reported that they do not have a formal endoscopy curriculum. PDs placed less importance (1­very important to 5­very unimportant) on endoscopy volume (1.57 vs. 1.18, P<0.001), adenoma detection rate (2.00 vs. 1.53, P<0.001), and withdrawal times (1.96 vs. 1.68, P=0.009) in determining endoscopy competence compared with trainees. A majority of PDs report that competence is assessed by procedure volume (85%) and teaching attending evaluations (96%). Only a minority of programs use skills assessment tools (30%) or specific quality metrics (28%). Specific competencies are mostly assessed by individual teaching attending feedback as opposed to official documentation or feedback from a PD. PDs rate the overall quality of their endoscopy training and assessment of competence as better than overall ratings by trainees. CONCLUSIONS: Although the majority of PDs and trainees nationwide believe that measuring specific metrics is important in determining endoscopy competence, most programs still rely on procedure volume and subjective attending evaluations to determine overall competence. As medical training transitions from an apprenticeship model to competency-based education, there is a need for improved endoscopy curricula which are better suited to demonstrate readiness for unsupervised practice.

Identification of a founder EPCAM deletion in Spanish Lynch syndrome families.

Germline deletions at the 3'-end of EPCAM have been involved in the etiology of Lynch syndrome (LS). The aim of this study was to characterize at the molecular level Spanish families harboring EPCAM deletions. Non-commercial multiplex ligation-dependent probe amplification (MLPA) probes and long-range polymerase chain reaction (PCR) amplification were used to characterize each deletion. Haplotyping was performed by analyzing eight microsatellite markers and five MSH2single nucleotide polymorphisms (SNPs). Methylation of MSH2 was analyzed by methylation specific-MLPA. Tumors diagnosed in seven Spanish families harboring EPCAM deletions were almost exclusively colorectal. Mosaicism in MSH2 methylation was observed in EPCAM deletion carrier samples, being average methylation levels higher in normal colon and colorectal tumors (27.6% and 31.1%), than in lymphocytes and oral mucosa (1.1% and 0.7%). Three families shared the deletion c.858 + 2568_*4596del, with a common haplotype comprising 9.9 Mb. In two families the novel EPCAM deletion c.858 + 2488_*7469del was identified. This study provides knowledge on the clinical and molecular characteristics of mosaic MSH2 epimutations. The identification of an EPCAM founder mutation has useful implications for the molecular diagnosis of LS in Spain.

Natural disaster alters the adaptive benefits of sociality in a primate.

Weather-related disasters can radically alter ecosystems. When disaster-driven ecological damage persists, the selective pressures exerted on individuals can change, eventually leading to phenotypic adjustments. For group-living animals, social relationships are believed to help individuals cope with environmental challenges and may be a critical mechanism enabling adaptation to ecosystems degraded by disasters. Yet, whether natural disasters alter selective pressures on patterns of social interactions and whether group-living animals can, as a result, adaptively change their social relationships remains untested. Here, we leveraged unique data collected on rhesus macaques from 5 years before to 5 years after a category 4 hurricane, leading to persistent deforestation which exacerbated monkeys' exposure to intense heat. In response, macaques increased tolerance for and decreased aggression toward other monkeys, facilitating access to scarce shade critical for thermoregulation. Social tolerance predicted individual survival for 5 years after the hurricane, but not before it, revealing a clear shift in the adaptive function of social relationships in this population. We demonstrate that an extreme climatic event altered selection on sociality and triggered substantial and persistent changes in the social structure of a primate species. Our findings unveil the function and adaptive flexibility of social relationships in degraded ecosystems and identify natural disasters as potential evolutionary drivers of sociality. One-Sentence Summary: Testard et al. show that a natural disaster altered selection on sociality in group-living primates triggering persistent changes in their social structure.

Ligilactobacillus salivarius V4II-90 eradicates Group B Streptococcus colonisation during pregnancy: a randomised, double-blind, placebo-controlled trial.

Group B Streptococcus (GBS) is the leading cause of bacterial neonatal sepsis. This study aimed to confirm the effect of Ligilactobacillus salivarius V4II-90 on GBS colonisation during pregnancy. A randomised, multicentre, double-blind, placebo-controlled, parallel-group study was conducted in seven hospitals in Madrid, Spain. The sample was broken down into two groups with 20 participants each (n = 40) in order to show reduced GBS colonisation frequency in the probiotic versus the placebo group. Pregnant participants positive for vaginal-rectal colonisation before or during the 13th week of gestation were randomly assigned to either the placebo or the probiotic group. The probiotic, L. salivarius V4II-90 at 1 × 109 cfu/day was administered for 12 weeks, starting at week 21-23 of gestation. The primary outcome was the percentage of participants with vaginal and/or rectal GBS colonisation at the end of the intervention period (35 weeks of gestation). Secondary outcomes were changes in the microbial composition of vaginal and rectal exudates; premature delivery; premature rupture of membranes; intrapartum antibiotics; new-borns with early or late-onset GBS sepsis; adverse events (AEs); and GBS test results performed at the hospital at week 35 of gestation. Of the 481 participants included, 44 were vaginal-rectal colonised with GBS and randomised. 43 completed the study (20 in the probiotic group and 23 in the placebo group). After intervention, GBS was eradicated in six participants (27%) from the placebo group and in twelve participants (63%) from the probiotic group ( P = 0.030). None of the 185 AEs reported were identified as possibly, probably, or definitely related to the investigational product. In conclusion, oral administration of L. salivarius V4II-90 is a safe and successful strategy to significantly decrease the rates of GBS colonisation at the end of pregnancy and, therefore, to reduce the exposure of subjects and their infants to intrapartum antibiotic prophylaxis. Trial registered at ClinicalTrials.gov: number NCT03669094.

Ecological disturbance alters the adaptive benefits of social ties.

Extreme weather events radically alter ecosystems. When ecological damage persists, selective pressures on individuals can change, leading to phenotypic adjustments. For group-living animals, social relationships may be a mechanism enabling adaptation to ecosystem disturbance. Yet whether such events alter selection on sociality and whether group-living animals can, as a result, adaptively change their social relationships remain untested. We leveraged 10 years of data collected on rhesus macaques before and after a category 4 hurricane caused persistent deforestation, exacerbating monkeys' exposure to intense heat. In response, macaques demonstrated persistently increased tolerance and decreased aggression toward other monkeys, facilitating access to scarce shade critical for thermoregulation. Social tolerance predicted individual survival after the hurricane, but not before it, revealing a shift in the adaptive function of sociality.

[Therapeutic options for renal graft tumors]. / Opciones terapéuticas para tumores en el injerto renal.

Renal graft neoplasias are a rare complication,possibly due to the immunosuppressive therapy itself and increased susceptibility to potentially oncogenic viruses. Few case series have been reported in the literature on the treatment of such tumors, so far there is no clear consensus on how to deal with them. We conducted an exhaustive review of the literature to examine the treatment performed by different authors.

Ultra-fast track extubation protocol following cardiovascular surgery: Predictors of failure and outcomes.

OBJECTIVES: Identifying independent predictor factors of failure of ultra-fast track (UFT) extubation and to compare in-hospital outcomes with UFT extubation versus fast track (FT) extubation after cardiovascular surgery in adults. MATERIAL AND METHODS: Retrospective analysis of 1498 consecutive patients aged over 18 years-old undergoing cardiovascular surgery at a single institution. Between December 2014 and December 2016, FT extubation was used (N = 713) while, between December 2016 and December 2018, all patients were preoperatively considered suitable for UFT extubation (N = 785). In this instance, a standardized anaesthetic protocol was applied in all cases. The decision to not extubate in the operating room (OR) was based on intraoperative haemodynamic and ventilation. RESULTS: Extubation in the OR was possible in 699 (89%) patients. Significant independent predictors factors of UFT extubation failure were: preoperative NYHA class III-IV, myocardial infarction within two days prior to surgery, preoperative intra-aortic balloon counterpulsation, urgent/emergent surgery, intraoperative transfusion of platelets and intraoperative inotropic and vasopressor support. UFT extubation was associated with lower rates of cardiovascular complications such as congestive cardiac insufficiency (OR: 1,57; 95% CI: 1,13-2,19; p = 0,008) and new-onset postoperatory atrial fibrillation (OR: 1,40; 95% CI: 1,06-1,86; p = 0,020). Patient extubated in the OR presented lower risk of overall complications, shorter intensive care unit stay and higher short-term survival, although, no statistically significance was found when performing the multivariate adjustment. CONCLUSIONS: A routine immediate extubation in the OR following adult cardiovascular surgery is a feasible and safe practice, associated with low cardiovascular morbidity.

Epidemiology of hospitalization for acute bronchiolitis in children: differences between RSV and non-RSV bronchiolitis.

We study the clinical, management and outcome differences between respiratory syncytial virus (RSV) positive and negative bronchiolitis. A retrospective review of the medical records of children ≤ 2 years of age with acute bronchiolitis between January 1995 and December 2006 was done. There were 2,384 patients hospitalized for acute bronchiolitis, and 1,495 (62.7%) were RSV infections. Overall, hospitalization rate was 55/1,000 admissions. Mortality occurred in 0.08% of cases. Bronchiolitis due to RSV was more frequent from November to March (97%). RSV bronchiolitis had longer hospital stays (6 vs. 5 days, P<0.0001), higher risk of intensive care unit (ICU) admission (OR 2.7; 95%CI 1.87-3.9) and more oxygen use (OR 2.2; 95%CI 1.8-2.6). Infants < 2 months had longer median hospital stay (6 vs. 5 days, P <0.0001) and higher risk of ICU admission (OR 3.4; 95%CI 2.5-4.6). Prematures of < 32 gestational weeks, congenital heart disease, and atelectasis/condensation were the main risk factors for ICU admission in both RSV and non-RSV bronchiolitis. The introduction of palivizumab in prematures diminished hospitalization for RSV bronchiolitis, oxygen need, length of hospital stay and mechanical ventilation. In conclusion, this study supports that RSV bronchiolitis seems to be a more severe disease than that caused by other viruses.

[Active tuberculosis in a cohort of HIV-infected inmates in a prison in Mexico City: clinical and epidemiological characteristics]. / Tuberculosis activa en una cohorte de reclusos infectados por VIH en una cárcel de la Ciudad de México: características clínicas y epidemiológicas.

OBJECTIVE: To determine the clinical and epidemiological characteristics of prison inmates with active tuberculosis in HIV-positive prison populations. MATERIALS AND METHODS: We conducted a cohort study in HIV-infected subjects in a prison in Mexico City, with the aim of determining clinical and epidemiological characteristics of cases with active TB. RESULTS: We detected 172 HIV infected inmates and TB in 28 of them (16.3%) - 21 (12.2) with pulmonary TB--with an incidence rate of 7.7/100 persons/year for active TB and 4.7/100 persons/year for pulmonary TB. No drug resistance was found. Two clusters (4 and 2 subjects) were observed after RFLP-typing of 18 isolates, with a transmission rate of 11% by molecular and clinical analysis. CONCLUSIONS: The prevalence of active TB was found to be a thousand times greater than in the general population. Evidence of transmission inside the prison was also found.

What do we know about Q fever in Mexico?

In Mexico, Q fever is considered a rare disease among humans and animals. From March to May of 2008, three patients were referred, from the state of Hidalgo to a tertiary-care center in Mexico City, with an acute febrile illness that was diagnosed as Q fever. We decided to undertake a cross sectional pilot study to identify cases of acute disease in this particular region and to determine the seroprevalence of Coxiella burnetii among healthy individuals with known risk factors for infection with this bacteria. Q fever was defined according to the Centers for Disease Control and Prevention criteria. All subjects were interviewed for signs and symptoms of the disease, demographic and household characteristics and occupational exposure to cattle. Blood samples were taken from hospitalized and outpatients with symptoms suggestive of Q fever, as well as from asymptomatic individuals with direct and daily exposure to cattle (slaughterers, butchers, farmers, shepherds and veterinarians) in the five municipalities. We report the occurrence of 17 cases with positive antibodies against C. burnetii in a rural area of central Mexico; eight cases had clinical criteria of acute Q fever disease. Results from this pilot study underscore the need for active surveillance programs and comprehensive studies to further define the prevalence and risk factors associated with the disease in Mexico, to know more about its clinical presentation and to characterize bacterial factors involved in its pathogenesis.

Role of matrix metalloproteinase-9 (MMP-9) in striatal blood-brain barrier disruption in a 3-nitropropionic acid model of Huntington's disease.

AIMS: 3-Nitropropionic acid (3-NPA) is a natural toxin that, when administered to experimental animals, reproduces the brain lesions observed in Huntington's disease, which mainly consist of selective neurodegeneration of the striatum. The lesions also include severe alterations to the blood-brain barrier (BBB), which increase its permeability to several substances including blood components and exogenous fluorescent dyes, and the concomitant degradation of some of its constituents such as endothelial cells, tight junction proteins and the basement membrane. We studied here the role of matrix metalloproteinases (MMPs)-2 and -9, also called gelatinases A and B, in the degradation of the BBB in the striatal lesions induced by the systemic administration of 3-NPA to Sprague-Dawley rats. METHODS: 3-NPA was intraperitoneally administered at a dose of 20 mg/kg once a day for 3 days. MMPs were studied by means of immunohistochemistry and in situ zymography. RESULTS: In 3-NPA-treated rats, MMP-9 was present in most of the degraded blood vessels in the injured striatum, while it was absent in vessels from non-injured tissue. In the same animals, MMP-2 staining was barely detected close to degraded blood vessels. The combination of MMP-9 immunostaining, in situ zymography and inhibitory studies of MMP-9 confirmed that net gelatinolytic activity detected in the degraded striatal blood vessels could be attributed almost exclusively to the active form of MMP-9. CONCLUSION: Our results highlight the prominent role of MMP-9 in BBB disruption in the striatal injured areas of this experimental model of Huntington's disease.

The effects of pollination, herbivory and autonomous selfing on the maintenance of flower colour variation in Silenelittorea.

Intraspecific flower colour variation has been generally proposed to evolve as a result of selection driven by biotic or abiotic agents. In a polymorphic population of Silene littorea with pink- and white-flowered plants, we studied pollinators, analysed flower colour perception and tested for differences in pollinator visitation. We also experimentally analysed pollinator limitation in fruit and seed set, and the degree of autonomous selfing. The incidence of florivory and leaf herbivory was compared over 3-4 years. Silene littorea is mainly pollinated by bees and butterflies. Pollinators preferred pink flowers, which did not show pollinator limitation. On the contrary, white flowers showed pollinator limitation in fruit set. White-flowered plants had less floral display and higher levels of florivory than pink plants. Flower colour morphs of S. littorea can reproduce in the absence of pollinators by autonomous selfing, setting 20% and 12% of fruit and seeds in the pink morph and 27% and 20% in the white morph, respectively. Fruit set of white flowers produced by autonomous selfing did not differ from open-pollinated flowers. In conclusion, S. littorea is pollinated by insects of different orders that more frequently visit pink flowers, which is reflected in pollinator limitation of fruit set in white flowers. Moreover, this species has a mixed mating system in which both colour morphs can reproduce in the absence of pollinators by autonomous selfing, although white flowers mainly produce fruits by autogamy. We suggest that reproductive assurance by autonomous selfing helps to maintain flower colour polymorphism in this population.

HAART and the liver: friend or foe?

The overall effect of HAART on the liver is the result of the balance between hepatotoxicity and the consequences of immunoreconstitution on the evolution of HIV-associated liver diseases, particularly viral hepatitis. HAART may lead to the emergence of acute toxic hepatitis, steatosis, steatohepatitis, liver fibrosis, and noncirrhotic portal hypertension. On the other hand, HAART use has been associated with slower fibrosis progression in HIV/HCV-coinfected patients in most studies dealing with this issue. As well, an improvement of the clinical outcome of liver disease has been reported in patients taking HAART. For these reasons, the short- and mid-term effects of HAART on the liver are mostly beneficial.

Insulin resistance is associated with liver stiffness in HIV/HCV co-infected patients.

BACKGROUND: The factors that influence liver fibrosis progression in patients co-infected with human immunodeficiency virus/hepatitis C virus (HIV/HCV) are not completely understood. It is not known if insulin resistance (IR), a condition that promotes liver fibrosis in HCV mono-infected individuals, is one of these factors. OBJECTIVE: To evaluate the association between IR and liver stiffness (LS). DESIGN: Multicentre cross-sectional study. PATIENTS: 330 patients co-infected with HIV/HCV. METHODS: LS was assessed by transient elastography, which has shown a high accuracy to predict significant fibrosis in patients co-infected with HIV/HCV. The outcome variable of the study was LS. Patients with LS> or =9 kPa were considered as having significant fibrosis. IR was calculated using the HOMA method. RESULTS: LS was > or =9 kPa in 150 (45%) patients. HOMA correlated with LS (Spearman's rho correlation coefficient, 0.37; p<0.0001). The median (Q1-Q3) HOMA in patients with LS> or =9 kPa was 3.30 (2.17-5.16) while it was 2.09 (1.37-3.22) in patients with LS <9 kPa (p<0.0001). Ninety-six (39%) individuals with a HOMA <4 and 54 (63%) with a HOMA > or =4 showed LS> or =9 kPa (p<0.0001). Analyses after excluding patients with cirrhosis yielded similar results. After multivariate analyses, age > or =40 years (adjusted odds ratio (AOR), 1.85; 95% confidence interval (CI), 1.03 to 3.29; p = 0.03), CD4 cell count <200 cells/ml (AOR, 3.45; 95% CI, 1.67 to 7.11; p = 0.001), hepatitis B virus co-infection (AOR, 9.25; 95% CI, 2.42 to 35.31; p = 0.001), and HOMA > or =4 (AOR, 5.33; 95% CI, 2.70 to 10.49; p<0.0001) were the independent predictors of LS> or =9 kPa. CONCLUSION: IR is associated with LS in patients co-infected with HIV/HCV.

Alpha-methylphenylalanine, a new inducer of chronic hyperphenylalaninemia in sucling rats.

alpha-Methylphenylalanine reduces the phenylalanine hydroxylase activity of rat liver by 75 percent. Daily injections of this substance (plus phenylalanine) into rats from the 3rd to 15th day of age had no obvious toxic effects, and maintained a plasma concentration of phenylalanine comparable to that of phenylketonuric subjects.