Cylindrospermopsin exposure promotes redox unbalance and tissue damage in the liver of Poecilia reticulata, a neotropical fish species.

There is a growing concern regarding the adverse risks exposure to cylindrospermopsin (CYN) might exert on animals and humans. However, data regarding the toxicity of this cyanotoxin to neotropical fish species are scarce. Using the fish species Poecilia reticulata, the influence of CYN concentrations equal to and above the tolerable for drinking water may produce on liver was determined by assessing biomarkers of antioxidant defense mechanisms and correlated to qualitative and semiquantitative histopathological observations. Adult females were exposed to 0.0 (Control); 0.5, 1 and 1.5 µg/L pure CYN for 24 or 96 hr, in triplicate. Subsequently the livers were extracted for biochemical assays and histopathological evaluation. Catalase (CAT) activity was significantly increased only by 1.5 µg/L CYN-treatment, at both exposure times. Glutathione -S-transferase (GST) activity presented a biphasic response for both exposure times. It was markedly decreased after exposure by 0.5 µg/L CYN treatment but significantly elevated by 1.5 µg/L CYN treatment. All CYN treatments produced histopathological alterations, as evidenced by hepatocyte cords degeneration, steatosis, inflammatory infiltration, melanomacrophage centers, vessel congestion, and areas with necrosis. Further, an IORG >35 was achieved for all treatments, indicative of the presence of severe histological alterations in P. reticulata hepatic parenchyma and stroma. Taken together, data demonstrated evidence that CYN-induced hepatotoxicity in P. reticulata appears to be associated with an imbalance of antioxidant defense mechanisms accompanied by histopathological liver alterations. It is worthy to note that exposure to low environmentally-relevant CYN concentrations might constitute a significant risk to health of aquatic organisms.

Susceptibility of AutoML mortality prediction algorithms to model drift caused by the COVID pandemic.

BACKGROUND: Concept drift and covariate shift lead to a degradation of machine learning (ML) models. The objective of our study was to characterize sudden data drift as caused by the COVID pandemic. Furthermore, we investigated the suitability of certain methods in model training to prevent model degradation caused by data drift. METHODS: We trained different ML models with the H2O AutoML method on a dataset comprising 102,666 cases of surgical patients collected in the years 2014-2019 to predict postoperative mortality using preoperatively available data. Models applied were Generalized Linear Model with regularization, Default Random Forest, Gradient Boosting Machine, eXtreme Gradient Boosting, Deep Learning and Stacked Ensembles comprising all base models. Further, we modified the original models by applying three different methods when training on the original pre-pandemic dataset: (Rahmani K, et al, Int J Med Inform 173:104930, 2023) we weighted older data weaker, (Morger A, et al, Sci Rep 12:7244, 2022) used only the most recent data for model training and (Dilmegani C, 2023) performed a z-transformation of the numerical input parameters. Afterwards, we tested model performance on a pre-pandemic and an in-pandemic data set not used in the training process, and analysed common features. RESULTS: The models produced showed excellent areas under receiver-operating characteristic and acceptable precision-recall curves when tested on a dataset from January-March 2020, but significant degradation when tested on a dataset collected in the first wave of the COVID pandemic from April-May 2020. When comparing the probability distributions of the input parameters, significant differences between pre-pandemic and in-pandemic data were found. The endpoint of our models, in-hospital mortality after surgery, did not differ significantly between pre- and in-pandemic data and was about 1% in each case. However, the models varied considerably in the composition of their input parameters. None of our applied modifications prevented a loss of performance, although very different models emerged from it, using a large variety of parameters. CONCLUSIONS: Our results show that none of our tested easy-to-implement measures in model training can prevent deterioration in the case of sudden external events. Therefore, we conclude that, in the presence of concept drift and covariate shift, close monitoring and critical review of model predictions are necessary.

Clinical Course of Very Early-Onset Inflammatory Bowel Disease.

OBJECTIVES: Data on the phenotypes and disease outcomes of very early-onset inflammatory bowel disease (VEO-IBD) are limited. The aims of this study were to describe the clinical features, outcomes, and treatment response of VEO-IBD patients and to compare them with later-onset pediatric inflammatory bowel disease (P-IBD) patients. METHODS: All consecutive patients aged 0-6 years who were diagnosed with Crohn disease (CD), ulcerative colitis, or IBD unclassified (IBD-U) at 2 academic hospitals from 2010 to March 2021 were included. They were compared to sex-matched IBD patients aged 6-17 years. RESULTS: Two hundred thirty-two patients were included, 78 (34%) with VEO-IBD and 154 (66%) with P-IBD. IBD-U was the most common diagnosis in the VEO-IBD group compared to P-IBD (28% vs 3%, P < 0.001), while CD was predominant in older children (27% vs 52%, P < 0.001). The VEO-IBD group showed lower rates of clinical remission after induction with steroids compared to older children (82% vs 93%, P = 0.01), higher rates of steroid resistance (14% vs 5%, P = 0.02), and steroid dependence (27% vs 8%, P < 0.001). The number of patients who started anti-tumor necrosis factor (TNF)-α agents was similar between the groups. Anti-TNF-α retention was lower in the VEO-IBD group at 1 and 2 years (59% vs 85%, P = 0.003; 16% vs 55%, P < 0.001, respectively). Surgical risk appeared to be higher for VEO-IBD (32% vs 14%, P < 0.001). CONCLUSIONS: When compared to P-IBD patients, patients with VEO-IBD may have a more severe disease course, a poorer response to steroids and anti-TNF-α agents, and require more frequent surgical procedures.

Long term results of video-assisted anal fistula treatment for complex anal fistula: another shattered dream?

AIM: Complex anal fistula represents a burden for patients, and its management is a challenge for surgeons. Video-assisted anal fistula treatment (VAAFT) is one sphincter-sparing technique. However, data on its long-term effectiveness are scant. We aimed to explore the outcomes of VAAFT in a retrospective cohort of patients referred to a tertiary centre. METHOD: Consecutive adult patients with a minimum of 2 years' follow-up after VAAFT were reviewed. Patients were followed up to 5 years postoperatively. Failure was defined as incomplete healing of the external orifice(s) during the first 6 months. Recurrence was defined as new radiologically and/or clinically confirmed onset of the fistula after primary healing. A generalized linear model was fitted to evaluate the association between failure and sociodemographic characteristics. Predictors of recurrence were determined in a subgroup analysis of patients found to be free from disease at 6 months postoperatively. RESULTS: Overall, 106 patients (70% male; mean age 41 years) were reviewed. Of these 86% had a previous seton placement. Fistulas were either high trans-sphincteric (74%), suprasphincteric (12%) or extrasphincteric (13%). Eight (7%) patients experienced postoperative complications, none of which required reintervention. Mean follow-up was 53 ± 13.2 months. VAAFT failed in 14 (13%) patients. The overall recurrence rate ranged from 29% at 1 year to 63% at 5 years. Multiple external orifices, suprasphincteric fistula, younger age, previous surgery and higher complexity of the fistulous tract were independent risk factors for recurrence. CONCLUSION: VAAFT is a safe sphincter-sparing technique. The initially high success rate decreases over time and relates to a higher degree of complexity.

Targeting early stages of cardiotoxicity from anti-PD1 immune checkpoint inhibitor therapy.

AIMS: Cardiac immune-related adverse events (irAEs) from immune checkpoint inhibition (ICI) targeting programmed death 1 (PD1) are of growing concern. Once cardiac irAEs become clinically manifest, fatality rates are high. Cardio-oncology aims to prevent detrimental effects before manifestation of severe complications by targeting early pathological changes. We therefore aimed to investigate early consequences of PD1 inhibition for cardiac integrity to prevent the development of overt cardiac disease. METHODS AND RESULTS: We investigated cardiac-specific consequences from anti-PD1 therapy in a combined biochemical and in vivo phenotyping approach. Mouse hearts showed broad expression of the ligand PDL1 on cardiac endothelial cells as a main mediator of immune-crosstalk. Using a novel melanoma mouse model, we assessed that anti-PD1 therapy promoted myocardial infiltration with CD4+ and CD8+ T cells, the latter being markedly activated. Left ventricular (LV) function was impaired during pharmacological stress, as shown by pressure-volume catheterization. This was associated with a dysregulated myocardial metabolism, including the proteome and the lipidome. Analogous to the experimental approach, in patients with metastatic melanoma (n = 7) receiving anti-PD1 therapy, LV function in response to stress was impaired under therapy. Finally, we identified that blockade of tumour necrosis factor alpha (TNFα) preserved LV function without attenuating the anti-cancer efficacy of anti-PD1 therapy. CONCLUSIONS: Anti-PD1 therapy induces a disruption of cardiac immune homeostasis leading to early impairment of myocardial functional integrity, with potential prognostic effects on the growing number of treated patients. Blockade of TNFα may serve as an approach to prevent the manifestation of ICI-related cardiotoxicity.

Trans-anal minimally invasive surgery (TAMIS) versus trans-anal endoscopic microsurgery (TEM): a comparative case-control matched-pairs analysis.

AIM: Since its introduction, transanal endoscopic microsurgery (TEM) has become the treatment of choice for rectal benign lesions not amenable to flexible endoscopic excision and for early rectal cancer. Disposable soft devices as the Trans-anal Minimally Invasive Surgery (TAMIS) are a valid alternative to non-disposable rigid trans-anal endoscopic microsurgery (TEM) platforms. The aim of the present study is to compare TEM and TAMIS in terms of incidence of R1 resection and lesion fragmentation which were combined in a composite outcome called quality resection. Perioperative complication and operative time were also investigated. METHODS: A total of 132 patients were eligible for this study of whom 63 (47.7%) underwent TAMIS and 69 (52.3%) underwent TEM. Patients were extracted for from a prospective maintained database and groups resulted homogenous after matching using propensity score in terms of size of the lesion, height from the anal verge, position within the rectal lumen, preoperative histology, neoadjuvant treatment. A multivariate logistic and linear regression analysis was carried out using those variables that have significant independent relationship with the quality of surgical resection and operative time. RESULTS: The incidence of R0 resection and lesion fragmentation was similar between groups. No differences were found in terms of perioperative complication. TAMIS was associated with less setup time and less operative time compared with TEM. Variables influencing quality resection at the multivariate analysis were larger lesion (> 5 cm) and ≥ T2 stage. Variables influencing operative time were surgical procedure (TEM vs TAMIS), height from the anal verge and size of the lesion. CONCLUSION: The present study shows that TEM and TAMIS are equally effective in terms of quality of local excision and perioperative complication. TAMIS resulted less operative time consuming compared to TEM.

Understanding how and under what circumstances decision coaching works for people making healthcare decisions: a realist review.

BACKGROUND: Decision coaching is non-directive support delivered by a trained healthcare provider to help people prepare to actively participate in making healthcare decisions. This study aimed to understand how and under what circumstances decision coaching works for people making healthcare decisions. METHODS: We followed the realist review methodology for this study. This study was built on a Cochrane systematic review of the effectiveness of decision coaching interventions for people facing healthcare decisions. It involved six iterative steps: (1) develop the initial program theory; (2) search for evidence; (3) select, appraise, and prioritize studies; (4) extract and organize data; (5) synthesize evidence; and (6) consult stakeholders and draw conclusions. RESULTS: We developed an initial program theory based on decision coaching theories and stakeholder feedback. Of the 2594 citations screened, we prioritized 27 papers for synthesis based on their relevance rating. To refine the program theory, we identified 12 context-mechanism-outcome (CMO) configurations. Essential mechanisms for decision coaching to be initiated include decision coaches', patients', and clinicians' commitments to patients' involvement in decision making and decision coaches' knowledge and skills (four CMOs). CMOs during decision coaching are related to the patient (i.e., willing to confide, perceiving their decisional needs are recognized, acquiring knowledge, feeling supported), and the patient-decision coach interaction (i.e., exchanging information, sharing a common understanding of patient's values) (five CMOs). After decision coaching, the patient's progress in making or implementing a values-based preferred decision can be facilitated by the decision coach's advocacy for the patient, and the patient's deliberation upon options (two CMOs). Leadership support enables decision coaches to have access to essential resources to fulfill their role (one CMOs). DISCUSSION: In the refined program theory, decision coaching works when there is strong leadership support and commitment from decision coaches, clinicians, and patients. Decision coaches need to be capable in coaching, encourage patients' participation, build a trusting relationship with patients, and act as a liaison between patients and clinicians to facilitate patients' progress in making or implementing an informed values-based preferred option. More empirical studies, especially qualitative and process evaluation studies, are needed to further refine the program theory.

Co-exposure of iron oxide nanoparticles and glyphosate-based herbicide promote liver toxicity in guppy (Poecilia reticulata): A histochemical and ultrastructural approach.

Citrate functionalized iron oxide nanoparticles (IONPs) are employed for various purposes-including environmental remediation but the interaction of IONPs with aquatic contaminants is poorly understood. Among those, glyphosate-based herbicides are toxic and affect target organs such as the liver. Evaluations of livers of female Poecilia reticulata by exposures to IONPs at a concentration of 0.3 mg/L were performed with association to: (1) 0.65 mg of glyphosate per litter and (2) 1.3 mg of glyphosate per litter of Roundup Original, and (3) glyphosate P.A at 0.65 mg/L. These associations were carried out progressively, after 7, 14, and 21 days. We detected circulatory disturbances, inflammatory responses, activation of the immune system, regressive changes, and progressive responses with changes in the connective tissue and decreased glycogen reserve from days 14 to 21. Ultrastructural changes in the Disse space and microvilli of hepatocytes indicated decreased contact surface area. In general, the damage was time and concentration dependent, increasing from 7 to 14 days and tending to stabilize from 14 to 21 days. Therefore, herbicide-associated IONPs functioned as xenobiotics inducing intense cellular detoxification processes and activation of hepatic immune responses.

A Lack of Practice Effects on Memory Tasks Predicts Conversion to Alzheimer Disease in Patients With Amnestic Mild Cognitive Impairment.

The aim of the current study was to test the accuracy of practice effects, that is, improvement in test performance due to repeated neuropsychological evaluations, in identifying patients with amnestic mild cognitive impairment (a-MCI) at greater risk of conversion to Alzheimer disease (AD). For this purpose, we conducted a longitudinal study of 54 patients diagnosed with a-MCI at the first assessment and followed-up for 4 years. During this time, 18 patients converted to AD. Baseline and 6- to 12-month follow-up performances on a large set of neuropsychological tests were analyzed to determine their diagnostic ability to predict later conversion to dementia. Results demonstrate that a lack of practice effects on episodic memory tests is an accurate prognostic indicator of late conversion to AD in a-MCI patients. In fact, even though the performance of both groups was substantially comparable at the baseline evaluation, stable a-MCI patients greatly improved their memory performance at retest after 6 to 12 months; instead, scores of converter a-MCI remained stable or decreased passing from baseline to follow-up. Standardized z-change scores on memory tasks, which were computed as a reliable measure of performance change, classified group membership with very good overall accuracy, which was higher than the classification of converter and stable a-MCIs provided by baseline or follow-up scores. We hypothesize that the lack of practice effects on memory tasks mirrors the early involvement of medial temporal lobe areas in converter a-MCI that are fundamental for the consolidation of new memory traces.

Verbal and spatial memory spans in mild cognitive impairment.

OBJECTIVES: Working memory (WM) for verbal and visual material may be affected early in individuals with mild cognitive impairment (MCI). Verbal and visuospatial span tasks, that is neuropsychological procedures commonly used for the clinical assessment of WM, have been scarcely investigated in these patients. Therefore, this study was aimed at evaluating whether performance on tests of verbal and visual-spatial span (which rely to different extents on distinct components of the WM system) is differently sensitive to the presence of MCI and, in particular, of a preclinical AD condition in patients with MCI. MATERIALS & METHODS: 99 patients with amnesic MCI were given the Digit Span Forward (DSF) and Digit Span Backward (DSB) tests and the Corsi span task (CS) at baseline and were followed up for two years. 32 MCI patients converted to Alzheimer's disease (MCIc), but 67 patients did not deteriorate to meet the criteria for AD (MCIs). RESULTS: Results showed that although performance on DSF did not differ between groups, performance on DSB and CS and ratio indexes indicative of a performance decline passing from DSF to DSB and from DSF to CS significantly discriminated between a group of matched healthy controls and the overall group of MCI patients. Moreover, the ratio indexes significantly discriminated between MCIc and MCIs individuals. CONCLUSIONS: These data are consistent with the hypothesis that individuals with MCI, particularly those destined to convert to AD, are affected by reduced central executive resources even though the phonological loop is still functioning normally.

Decision coaching for people making healthcare decisions.

BACKGROUND: Decision coaching is non-directive support delivered by a healthcare provider to help patients prepare to actively participate in making a health decision. 'Healthcare providers' are considered to be all people who are engaged in actions whose primary intent is to protect and improve health (e.g. nurses, doctors, pharmacists, social workers, health support workers such as peer health workers). Little is known about the effectiveness of decision coaching. OBJECTIVES: To determine the effects of decision coaching (I) for people facing healthcare decisions for themselves or a family member (P) compared to (C) usual care or evidence-based intervention only, on outcomes (O) related to preparation for decision making, decisional needs and potential adverse effects. SEARCH METHODS: We searched the Cochrane Library (Wiley), Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (Ovid), Embase (Ovid), PsycINFO (Ovid), CINAHL (Ebsco), Nursing and Allied Health Source (ProQuest), and Web of Science from database inception to June 2021. SELECTION CRITERIA: We included randomised controlled trials (RCTs) where the intervention was provided to adults or children preparing to make a treatment or screening healthcare decision for themselves or a family member. Decision coaching was defined as: a) delivered individually by a healthcare provider who is trained or using a protocol; and b) providing non-directive support and preparing an adult or child to participate in a healthcare decision. Comparisons included usual care or an alternate intervention. There were no language restrictions. DATA COLLECTION AND ANALYSIS: Two authors independently screened citations, assessed risk of bias, and extracted data on characteristics of the intervention(s) and outcomes. Any disagreements were resolved by discussion to reach consensus. We used the standardised mean difference (SMD) with 95% confidence intervals (CI) as the measures of treatment effect and, where possible, synthesised results using a random-effects model. If more than one study measured the same outcome using different tools, we used a random-effects model to calculate the standardised mean difference (SMD) and 95% CI. We presented outcomes in summary of findings tables and applied GRADE methods to rate the certainty of the evidence. MAIN RESULTS: Out of 12,984 citations screened, we included 28 studies of decision coaching interventions alone or in combination with evidence-based information, involving 5509 adult participants (aged 18 to 85 years; 64% female, 52% white, 33% African-American/Black; 68% post-secondary education). The studies evaluated decision coaching used for a range of healthcare decisions (e.g. treatment decisions for cancer, menopause, mental illness, advancing kidney disease; screening decisions for cancer, genetic testing). Four of the 28 studies included three comparator arms.  For decision coaching compared with usual care (n = 4 studies), we are uncertain if decision coaching compared with usual care improves any outcomes (i.e. preparation for decision making, decision self-confidence, knowledge, decision regret, anxiety) as the certainty of the evidence was very low.  For decision coaching compared with evidence-based information only (n = 4 studies), there is low certainty-evidence that participants exposed to decision coaching may have little or no change in knowledge (SMD -0.23, 95% CI: -0.50 to 0.04; 3 studies, 406 participants). There is low certainty-evidence that participants exposed to decision coaching may have little or no change in anxiety, compared with evidence-based information. We are uncertain if decision coaching compared with evidence-based information improves other outcomes (i.e. decision self-confidence, feeling uninformed) as the certainty of the evidence was very low. For decision coaching plus evidence-based information compared with usual care (n = 17 studies), there is low certainty-evidence that participants may have improved knowledge (SMD 9.3, 95% CI: 6.6 to 12.1; 5 studies, 1073 participants). We are uncertain if decision coaching plus evidence-based information compared with usual care improves other outcomes (i.e. preparation for decision making, decision self-confidence, feeling uninformed, unclear values, feeling unsupported, decision regret, anxiety) as the certainty of the evidence was very low. For decision coaching plus evidence-based information compared with evidence-based information only (n = 7 studies), we are uncertain if decision coaching plus evidence-based information compared with evidence-based information only improves any outcomes (i.e. feeling uninformed, unclear values, feeling unsupported, knowledge, anxiety) as the certainty of the evidence was very low. AUTHORS' CONCLUSIONS: Decision coaching may improve participants' knowledge when used with evidence-based information. Our findings do not indicate any significant adverse effects (e.g. decision regret, anxiety) with the use of decision coaching. It is not possible to establish strong conclusions for other outcomes. It is unclear if decision coaching always needs to be paired with evidence-informed information. Further research is needed to establish the effectiveness of decision coaching for a broader range of outcomes.

Adepamycin: design, synthesis and biological properties of a new peptide with antimicrobial properties.

Antimicrobial peptides (AMP) are molecules with a broad spectrum of activities that have been identified in most living organisms. In addition, synthetic AMPs designed from natural polypeptides have been largely investigated. Here, we designed a novel AMP using the amino acid sequence of a plant trypsin inhibitor from Adenanthera pavonina seeds (ApTI) as a template. The 176 amino acid residues ApTI sequence was cleaved in silico using the Collection of Antimicrobial Peptides (CAMPR3), through the sliding-window method. Further improvements in AMP structure were carried out, resulting in adepamycin, an AMP designed from ApTI. Adepamycin showed antimicrobial activity from 0.9 to 3.6 µM against Escherichia coli, Klebsiella oxytoca, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Staphylococcus aureus strains. Moreover, this peptide also displayed activity against Candida albicans and Candida tropicalis. No toxic effects were observed on healthy human cells. Studies on the mechanism of action of adepamycin were carried out using an E. coli and C. tropicalis. Adepamycin triggers membrane disturbances, leading to intracellular nucleic acids release in E. coli. For C. tropicalis, an initial interference with the plasma membrane integrity is followed by the formation of intracellular reactive oxygen species (ROS), leading to apoptosis. Structurally, adepamycin was submitted to circular dichroism spectroscopy, molecular modeling and molecular dynamics simulations, revealing an environment-dependent α-helical structure in the presence of 2,2,2- trifluoroethanol (TFE) and in contact with mimetic vesicles/membranes. Therefore, adepamycin represents a novel lytic AMP with dual antibacterial and antifungal properties.

Secondary aortoenteric fistula successfully treated with staged endovascular repair and duodenal resection without graft removal.

Secondary aorto-enteric fistulae (SAEF) are rare life-threatening complications that occur after abdominal aortic graft implant to treat aortic aneurysm or occlusive disease. Conventional treatments such as extra-anatomic bypass grafting with aortic ligation and subsequent graft removal with bowel repair are associated with a 25% to 90% operative mortality rate. In the emergency setting, patients unsuitable for major arterial surgery may benefit from a staged, less invasive approach. We present a case of SAEF treated with endoluminal deployment of a stent graft followed by duodenojejunal resection and anastomosis without further aortic reconstruction and graft removal.

Gender-specific histopathological response in guppies Poecilia reticulata exposed to glyphosate or its metabolite aminomethylphosphonic acid.

Ecotoxicity of glyphosate (GLY) and its metabolite aminomethylphosphonic acid (AMPA) was investigated in guppies, Poecilia reticulata. We tested the effects of these chemicals on the gills and liver of both male and female guppies using qualitative and quantitative histopathological analyses associated with histopathological condition indexes. Both genders showed similar median lethal concentration (LC50 ) at 96 h for GLY (68.78 and 70.87 mg l-1 ) and AMPA (180 and 164.32 mg l-1 ). However, the histopathological assessment of both fish organs exposed to sublethal concentrations of GLY (35 mg l-1 ) and AMPA (82 mg l-1 ) for 96 h showed a tissue- and gender-specific histopathological response. In both exposure assays, fish presented mainly progressive changes, such as proliferation of the interlamellar epithelium, partial and total fusion of secondary lamellae. The liver showed mainly regressive changes, such as steatosis, pyknotic nuclei and high distribution of collagen fibers. Unusually large hepatocytes as degenerated cells were also detected. Histopathological changes in gills were similar for the males and females, but the liver response was different between the genders. The hepatic inflammatory changes were more common in males. The increase in the area of hepatocyte vacuoles is gender dependent with higher values in the male compared to the female guppies exposed to GLY and AMPA. Multiparametric analysis indicated that the male guppies are more sensitive than females, particularly in the presence of AMPA. Our study shows that the histopathological assessment associated with gender-specific response can be successfully used in ecotoxicological assessment of GLY and the metabolite AMPA. Copyright © 2017 John Wiley & Sons, Ltd.

Lack of association between rrl and erm(41) mutations and clarithromycin resistance in Mycobacterium abscessus complex.

BACKGROUND: Mycobacterium abscessus complex (MABC) includes species with high resistance rates among mycobacterial pathogens. In fact, MABC infections may not respond to clarithromycin treatment, which has historically been very effective against MABC infection. Molecular markers have been proposed to detect both acquired (rrl polymorphisms) and inducible (erm(41) polymorphisms) clarithromycin resistance in MABC isolates. OBJECTIVES: This study aimed to evaluate the susceptibility profile and molecular markers of clarithromycin resistance in MABC. METHODS: The clarithromycin susceptibility profile was determined by broth microdilution with reads on days 3, 5, 7 and 14. Mutations in the rrl and erm(41) genes were evaluated by polymerase chain reaction (PCR) using specific primers, followed by sequencing. FINDINGS: A total of 14 M. abscessus subsp. abscessus isolates and 28 M. abscessus subsp. massiliense isolates were evaluated, and clarithromycin resistance was observed in all isolates for up to three days of incubation. None of the 42 isolates exhibited a point mutation in the rrl gene, while all the isolates had a T28 polymorphism in the erm(41) gene. Moreover, all 28 M. abscessus subsp. massiliense isolates had a deletion in the erm(41) gene. MAIN CONCLUSIONS: While all the MABC isolates exhibited acquired clarithromycin resistance, no isolates exhibited a point mutation in the rrl gene in this study. The M. abscessus subsp. massiliense isolates demonstrated clarithromycin resistance, which is an uncommon phenotype. The molecular data for the rrl and erm(41) genes were not consistent with the phenotypic test results of clarithromycin susceptibility, indicating a lack of correlation between molecular clarithromycin resistance markers for both acquired and inducible resistance.

Tumor-Stroma Ratio is an independent predictor for overall survival and disease free survival in gastric cancer patients.

BACKGROUND: Despite different prognostic factors have been already studied, patients undergoing potentially curative resection for gastric cancer, still have a poor outcome. There is therefore the need to identify novel prognostic factors. Recently, Tumor-Stroma Ratio (TSR) was proven to be associated with prognosis in different types of cancers. Aim of this study was to evaluate the prognostic value of TSR in gastric cancer patients. METHODS: 106 patients underwent gastrectomy between January 2004 and December 2015. Demographics and histopathological characteristics were collected. We considered a 50% TSR cutoff value to divide patients in Stroma-Rich (≥50%) and Stroma-Poor (<50%) groups. RESULTS: Forty-one (38.7%) patients were classified as Stroma-Poor while 65 (61.3%) as Stroma-Rich (61.3%). The Stroma-Rich patients had a higher number of positive lymph-nodes, lymph node ratio (LNR), a higher percentage of T3/T4 local invasion and N2/N3, and a more advanced TNM. Moreover, these patients showed a higher percentage of lymphovascular and perineural invasion. With a median FU of 38 months Stroma-Rich patients had a significantly worse 5-years actuarial overall survival (OS) and disease free survival (DFS) compared to Stroma-Poor patients. Moreover, the multivariate analysis showed that Stroma-Rich was the only independent factor associated with OS and DFS together with TNM-Stage. CONCLUSIONS: TSR is an independent marker of poor prognosis in patients with gastric cancer that should be readily incorporated into routine clinical pathology reporting. Identification of sensitive markers for patients who had undergone curative gastrectomy and who are at high risk of recurrence could provide useful information for planning follow-up after surgery or intensive and or/targeting adjuvant chemotherapy.

Association of social and clinical conditions to the quality of life of patients with heart failure. / Associação das condições sociais e clínicas à qualidade de vida de pacientes com insuficiência cardíaca.

OBJECTIVE: To analyze the association between sociodemographic and clinical conditions with the quality of life related to health of heart failure patients. METHOD: Cross-sectional study with a non-random sample of 84 outpatients with heart failure, performed in the city of João Pessoa, PB, Brazil, in the period from January to July 2015. The questionnaire by name Minnesota Living with Heart Questionnaire was used The following tests were applied in data analysis: t-Student, ANOVA and Pearson's Correlation, com a 5% significance level. RESULTS: The average scores of the Minnesota Living with Heart Failure Questionnaire showed a good quality of life in the group under study. There was a significant negative association between quality of life and age: thus the lower the age, the worse the quality of life. CONCLUSION: Health promotion actions become necessary to improve the coping capacity of this disease, especially for younger patients.

Single-incision laparoscopic cholecystectomy: does it work? A systematic review.

BACKGROUND: Single-incision laparoscopic cholecystectomy (SILC) has been widely introduced into the clinical practice, but the real clinical benefits for patients still remain a matter of debate. We conducted a systematic review, according to the PRISMA guidelines comparing clinical and peri-operative outcomes of SILC and conventional laparoscopic cholecystectomy (CLC). METHOD: A literature search, including only randomised controlled trials (RCTs), was performed via PubMed, Google Scholar, Cochrane Library and Embase database. The reviewers extracted data from the manuscripts of selected articles including patient demographics, operative time, morbidity rate, post-operative length of stay, conversion rate, cost data, pain and satisfaction with cosmetic results. RESULT: Seventeen RCTs matching the inclusion criteria were finally selected for the analysis. A total of 1293 patients were involved in the review, including 663 (51.3 %) patients who have undergone SILC and 630 (48.7 %) patients who have undergone CLC. Post-operative pain was significantly worse in SILC patients in four studies, in CLC patients in four studies, while in the remnants seven studies, no differences in pain scores were found. Data on satisfaction for post-operative cosmetics were significantly better for SILC patients in all studies but two. Operating time was significantly longer in SILC group while there is no statistically significant difference in conversion rate. Morbidity rate was similar in both groups, as was the incidence of bile duct injuries. Costs were significantly higher in SILC group. SILC was considered a more challenging procedure in all studies. CONCLUSION: The role of SILC is still controversial. Until now, no real significant benefit has been proven: overall satisfaction is the only clear advantage of SILC, and this is mainly related to cosmetic results. Indications to SILC are mainly limited to patients with uncomplicated disease, with BMI ≤ 30 kg/m(2), whose surgery is unlikely to be converted to an open or multiport approach.