Sentinel lymph node biopsy before and after neoadjuvant chemotherapy in cN0 breast cancer patients: impact on axillary morbidity and survival-a propensity score cohort study.

PURPOSE: In patients with clinically lymph node-negative (cN0) breast cancer, performing sentinel lymph node biopsy (SLNB) after neoadjuvant chemotherapy (NACT) has been preferentially embraced in comparison to before NACT. However, survival outcomes associated with both strategies remain understudied. We aimed to compare the axillary lymphadenectomy (ALND) rate, disease-free survival (DFS), and overall survival (OS), between two strategies. METHODS: We included 310 patients in a retrospective observational study. SNLB was performed before NACT from December 2006 to April 2014 (107 cases) and after NACT from May 2014 to May 2020 (203 patients). An inverse probability of treatment weighting (IPTW) method was applied to homogenize both groups. Hazard ratios (HR) and odd ratios (OR) are reported with 95% confidence intervals (95%CI). RESULTS: The lymphadenectomy rate was 29.9% before NACT and 7.4% after NACT (p < 0.001), with an OR of 5.35 95%CI (2.7-10.4); p = .002. After 4 years of follow-up, SLNB after NACT was associated with lower risk for DFS, HR 0.42 95%CI (0.17-1.06); p = 0.066 and better OS, HR 0.21 CI 95% (0.07-0.67); p = 0.009 than SLNB before NACT. After multivariate analysis, independent adverse prognostic factors for OS included SLNB before NACT, HR 3.095 95%CI (2.323-4.123), clinical nonresponse to NACT, HR 1.702 95% CI (1.012-2.861), and small tumors (cT1) with high proliferation index, HR 1.889 95% (1.195-2.985). CONCLUSION: Performing SLNB before NACT results in more ALND and has no benefit for patient survival. These findings support discontinuing the practice of SLNB before NACT in patients with cN0 breast cancer.

The effect of omitting axillary dissection and the impact of radiotherapy on patients with breast cancer sentinel node macrometastases: a cohort study following the ACOSOG Z0011 and AMAROS trials.

PURPOSE: To report the outcomes of implementing the ACOSOG Z0011 and AMAROS trials relevant to clinical practice, and to define target groups in whom to avoid or recommend axillary radiotherapy (ART). We also aimed to analyse the reduction in morbidity when axillary lymph node dissection (ALND) was omitted. METHODS: A retrospective cohort study of T1-T2 patients with macrometastases at sentinel lymph node (SLN) who were treated between 2011 and 2020. Breast surgery included either lumpectomy or mastectomy. Patients with ≤ 2 positive SLN were divided into two cohorts by whether they received ART or not. Survival outcomes and morbidity were analysed by Kaplan-Meyer curves and Cox-regression, respectively. RESULTS: 260 pN1a patients were included and ALND was avoided in 167 (64.2%). According the Z0011 results, 72 (43.1%) received no further ART; and based on AMAROS criteria 95 (56.9%) received ART. Median follow-up was 54 months. The 5-year overall survival was 96.8% in the non-RT cohort and 93.4% in the RT cohort (p = 0.19), while the respective 5-year disease-free survivals were 100% and 92.3% (p = 1.06). Lymphedema developed in 3.6% of patients after SLNB versus 43% after ALND (OR 20.25; 95%CI 8.13-50.43). Decreased upper-extremity range of motion appeared in 8.4% of patients after SLNB versus 31.2% after ALND (OR 4.95; 95%CI 2.45-9.98%). CONCLUSIONS: Our study confirms that omitting ALND is safe and has high survival rates in patients with T1-T2 tumours and ≤ 2 positive SLNs. Adding ART could be a treatment option for patients who present other risk factors. Avoiding ALND with or without ART was associated with significantly less arm morbidity.

Can we avoid axillary lymph node dissection in N2 breast cancer patients with chemo-sensitive tumours such as HER2 and TNBC?

PURPOSE: To find a group of cN2 patients or patients with high axillary burden who become ypN0 after neoadjuvant chemotherapy (NACT) and who may benefit from avoiding a lymphadenectomy. METHODS: A retrospective observational cohort study was conducted with 221 clinically staged N2 patients or patients with at least 3 suspicious lymph nodes found by ultrasound at diagnosis. The predictive factors for ypN0 analysed were age, MRI-determined tumour size, histological subtype, the Nottingham histologic grade, surrogate molecular subtype, ki-67 and vascular invasion when present. Clinical and radiological responses after NACT were also evaluated. Univariate and multivariate analyses by logistic regression were performed. Distant disease-free survival (DDFS) was calculated in relation to the status of the axillary lymph nodes after NACT. RESULTS: After NACT, 89 patients (40.3%) had axillary pathologic complete response (pCR) (ypN0) and 132 (59.7%) had residual axillary disease (ypN+). Molecular surrogate subtype, Ki-67 expression, and the clinical and radiological responses to NACT were the only independent factors associated with ypN0. Axillary pCR was observed more often in HER2-positive and triple-negative tumours than in luminal ones (OR 7.5 and 3.6, respectively). DDFS was 88.7% (95% CI 80.7-96.7%) for ypN0 and 56.2% (95% CI 32.1-80.3%) for ypN+ (p = 0.09). CONCLUSIONS: In HER2-positive and triple-negative breast cancer patients staged as cN2 or with high axillary burden before NACT, a sentinel lymph node biopsy after NACT could be recommended if there is a clinical and radiological response.

Trends, seasonality and the association between outpatient antibiotic use and antimicrobial resistance among urinary bacteria in the Netherlands.

OBJECTIVES: To determine trends, seasonality and the association between community antibiotic use and antimicrobial resistance (AMR) in Escherichia coli and Klebsiella pneumoniae in urinary tract infections. METHODS: We analysed Dutch national databases from January 2008 to December 2016 regarding antibiotic use and AMR for nitrofurantoin, trimethoprim, fosfomycin and ciprofloxacin. Antibiotic use was expressed as DDD/1000 inhabitant-days (DID) and AMR was expressed as the percentage of resistance from total tested isolates. Temporal trends and seasonality were analysed with autoregressive integrated moving average (ARIMA) models. Each antibiotic use-resistance combination was cross-correlated with a linear regression of the ARIMA residuals. RESULTS: The trends of DID increased for ciprofloxacin, fosfomycin and nitrofurantoin, but decreased for trimethoprim. Similar trends were found in E. coli and K. pneumoniae resistance to the same antibiotics, except for K. pneumoniae resistance to ciprofloxacin, which decreased. Resistance levels peaked in winter/spring, whereas antibiotic use peaked in summer/autumn. In univariate analysis, the strongest and most significant cross-correlations were approximately 0.20, and had a time delay of 3-6 months between changes in antibiotic use and changes in resistance. In multivariate analysis, significant effects of nitrofurantoin use and ciprofloxacin use on resistance to these antibiotics were found in E. coli and K. pneumoniae, respectively. There was a significant association of nitrofurantoin use with trimethoprim resistance in K. pneumoniae after adjusting for trimethoprim use. CONCLUSIONS: We found a relatively low use of antibiotics and resistance levels over a 9 year period. Although the correlations were weak, variations in antibiotic use for these four antibiotics were associated with subsequent variations in AMR in urinary pathogens.

Association between EBRT dose volume histograms and quality of life in prostate cancer patients.

AIM: To evaluate the association between dose-volume histogram (DVH) values in organs at risk (OAR) and patient-reported HRQoL outcomes. BACKGROUND: Data on the association between DVHs and health-related quality of life (HRQoL) in prostate cancer (PCa) patients are limited. MATERIALS AND METHODS: Five-year follow-up study of 154 patients with organ-confined (stage T1/T2) PCa treated with EBRT between January 2003 and November 2005. HRQoL was evaluated with the Expanded Prostate Cancer Index (EPIC). DVH for OARs (penile bulb, rectum and bladder) were created for all patients for whom data were available (119/154; 77%). The functional data analysis (FDA) statistical method was used. HRQoL data was collected prospectively and data analysis was performed retrospectively. RESULTS: Worsening of urinary incontinence and obstructive symptoms correlated with higher DVH dose distributions at 24 months. Increased rectal bleeding at months 24 and 60 correlated with higher DVH dose distributions in the 40-70 Gy range. Patients with deterioration in rectal incontinence presented a higher DVH distribution range than patients without rectal incontinence. Penile bulb DVH values and erectile dysfunction were not significantly associated. CONCLUSIONS: DVH parameters and post-radiotherapy HRQoL appear to be closely correlated, underscoring the importance of assessing DVH values prior to initiating EBRT to determine the risk of developing HRQoL related adverse effects. Advanced treatment modalities may be appropriate in high risk cases to minimize treatment-related toxicity and to improve treatment outcomes and HRQoL. Future studies are needed to better elucidate the association between pre-treatment DVH parameters in organs at risk and subsequent HRQoL.

Localized prostate cancer treated with external beam radiation therapy: Long-term outcomes at a European comprehensive cancer centre.

AIMS AND BACKGROUND: To present survival and toxicity outcomes in patients with clinically localized, non-metastatic prostate cancer (PCa) treated with external beam radiotherapy (EBRT) combined with androgen deprivation therapy (ADT). MATERIALS AND METHODS: Retrospective study of 849 PCa patients (pts) treated from 1996 to 2005. Until August 2000, all patients (281) were treated with conventional dose EBRT (<76 Gy); subsequent pts received ≥76 Gy (565 pts). Median age was 70 years (range, 39-82). Most pts were intermediate (353; 42.8%) or high-risk (344; 41.7%). Mean PSA was 10.1 ng/ml. Median dose to the prostate was 75 Gy. Complete ADT was administered to 525 pts (61.8%). RESULTS: Median follow-up was 109.6 months (range, 68.3-193.4). Overall survival (OS) was 92.5% and 81.1% at 5 and 10 years; by risk group (low, intermediate, high), 5- and 10-year OS rates were 94.3% and 85.9%, 92.3% and 79.2%, and 91.9% and 80.2% (p = 0.728). Five- and 10-year BRFS was 94.1% and 80.6% (low risk), 86.4% and 70.9% (intermediate), and 85.2% and 71.4% (high) (p = 0.0666). Toxicity included rectitis: grade 1 (G1) (277 pts; 32.6%), G2 (108; 12.7%), and G3 (20; 2.6%) and urethritis: G1 (294; 34.6%); G2 (223; 26.2%), and G3 (11; 1.3%). By dose rate (<76 Gy vs. ≥76 Gy), 5 and 10-year BRFS rates were 83.1% and 68.3% vs. 88.4% and 74.8% (p = 0.038). CONCLUSIONS: Our results are comparable to other published series in terms of disease control and toxicity. These findings confirm the need for dose escalation to achieve better biochemical control and the benefits of ADT in high-risk PCa patients.

SNAP-Ed Programming for College Students Experiencing Food Insecurity: A Qualitative Process-Focused Evaluation.

BACKGROUND: Growing recognition of food insecurity experienced by college students has led to efforts on college campuses to provide students with food assistance benefits and related nutrition education. A Supplemental Nutrition Assistance Program-Education (SNAP-Ed) program was developed for college students as one of these efforts. OBJECTIVE: To explore program content, recruitment, and implementation through experiences of program implementers in a novel SNAP-Ed intervention among college students. DESIGN: This qualitative study used focus groups and a case study approach to elicit program implementers' experiences delivering SNAP-Ed to college students. PARTICIPANTS/SETTING: Students, staff, and faculty (n = 26) implementing SNAP-Ed with college students experiencing food insecurity across eight campuses in the California State University system participated in 8 focus groups in 2021-2022. MAIN OUTCOME MEASURES: A process evaluation framework was used to evaluate content fit and orientation; recruitment, retention, and reach; and structure and capacity for implementation. ANALYSES PERFORMED: Focus groups were recorded, transcribed, and coded via thematic analysis using NVivo (QSR International, Burlington, MA). RESULTS: Five themes were identified: (1) need for this work to extend college-based basic needs services; (2) importance of aligning programming with college student context/needs; (3) common factors important for attracting/engaging the audience; (4) program barriers; and (5) training/team sharing for extending ideas. CONCLUSIONS: Study findings suggest tailoring SNAP-Ed programming to the needs of college students experiencing food insecurity, such as integrating student-relevant cooking skills, recipes, and topics of interest. Additional intervention and research efforts may lead to a new model for serving college students with SNAP-Ed.

Rheumatoid Arthritis and Its Implications on Inflammatory Bowel Disease.

Background: The association between inflammatory bowel disease (IBD) and arthritis has long been known, but it was not until the 1950s that IBD-associated arthritis was recognized as a distinct pathology independent from rheumatoid arthritis (RA). There is evidence that RA and other autoimmune conditions exist at higher rates in patients with IBD compared to the general population. We aimed to determine if the presence of RA in IBD patients is a factor for mortality and IBD-related surgery in this population. Methods: Using Epic's Slicer Dicer function, we queried the International Classification of Diseases, 10th Revision (ICD-10) codes K50 and K51 to identify patients with IBD. Duplicates and those with incomplete information were excluded, leaving a total of 3,613 patients. Data collected included basic demographic information, surgical history, and the presence of RA. We used Student's t-test to analyze between group differences for the continuous variables. When it was determined that variances for the comparisons of continuous data were unequal, Welch-Satterthwaite t-test statistics were used. We used the Chi-square test to analyze between group differences for the categorical variables. The Fisher's exact test was employed when any of the expected frequencies was 5 or less. All tests were two-sided with criterion for statistical significance at a P value less than 0.05. All the analyses were done by SAS 9.4 (SAS Institute, Cary, NC). Results: Of the approximately 2.7 million adults in Slicer Dicer, there were 3,613 patients (0.13%) identified with IBD. Patients with ulcerative colitis (UC) accounted for 37% of the total group (n = 1,343) and 2,270 patients (62.8%) had Crohn's disease (CD). From the total, 2,084 were women (57.68%) and 1,529 (42.32%) were men. More than 90% of the patients were white (n = 3,321). The mean age was 53.3 ± 18.5. Eight hundred forty-eight patients (23.47%) had documented RA. Mortality was higher in patients with IBD and RA than those with IBD alone (7.31% vs. 3.98%, P value ≤ 0.0001). Conclusions: IBD patients with RA have higher mortality rates and need for IBD-related surgery than patients with IBD alone.

Association of Elevated Glycated Hemoglobin (HbA1c) in COVID-19 Patients Admitted to the Intensive Care Unit and Their Clinical Outcomes.

Aim The study aimed to collect retrospective data to investigate the association between elevated glycated hemoglobin (HbA1c) levels and clinical outcomes in COVID-19 patients admitted to the ICU, including in-hospital mortality and 90-day mortality.  Methods This is an observational retrospective study using electronic health records of patients with diabetes admitted to the ICU with COVID-19 across the University of Pittsburgh Medical Center (UPMC) in Central PA Hospitals. Our retrospective analysis was performed on patients admitted to the ICU between May 1st, 2021, to May 1st, 2022. The HbA1c level obtained within three months before their admission was evaluated and stratified to show their association with clinical outcomes, including in-hospital mortality and 90-day mortality. Additionally, the need for insulin drip and ICU and hospital length of stay were compared among these patients.  Results We analyzed 384 patients, which were distributed in three groups. The majority of the patients (183 patients or 47.66%) had an HbA1c below 7%, 113 patients (29.43%) had an HbA1c between 7-9%, and 88 patients (22.92%) had an HbA1c above 9%. The group with an HbA1c<7% had a mortality rate of 54.1% during the hospital stay, with a median stay of 13 days. The patients with an HbA1c between 7-9% had a higher mortality rate of 65.49% with a median stay of 12 days. The patients with HbA1c>9% had a mortality rate of 43.18% with a median stay of 11.5 days.  Conclusion This retrospective study found that there was no linear association between higher HbA1c levels and a higher risk of mortality during hospitalization. The 90-day mortality rate was not statistically different among the three HbA1c groups. The need for insulin drip was higher in patients with higher HbA1c levels. The majority of patients in all three groups were classified as low-risk based on their BMI, and there were no significant differences in the distribution of patients across BMI categories in the HbA1c groups.

Pseudo-Progression of Melanoma Treated with Nivolumab/Ipilimumab: A Case Report.

BACKGROUND Melanoma is an aggressive skin cancer that can be difficult to manage. Its treatment has been transformed by immunotherapy. Melanoma cells frequently have mutations that make them vulnerable to attack by the immune system, and this is how immunotherapy can fight this cancer. Immunotherapy with checkpoint inhibitors targets mechanisms that malignant cells use to evade immune system detection, blocking proteins produced by the tumor, and allowing the immune system to identify and attack cancerous cells. CASE REPORT A 74-year-old woman presented with a lump on the right side of her chest. Tests revealed a metastatic malignant tumor with melanocytic differentiation. Stage IV melanoma was diagnosed, and the patient started therapy with nivolumab/ipilimumab for palliative intent, which she tolerated without adverse effects. However, she was hospitalized for Clostridioides difficile colitis after 3 treatment cycles, and computed tomography (CT) scan findings suggested disease progression. Positron emission tomography (PET)-CT obtained after her discharge from the hospital showed a complete metabolic response at all disease sites, indicating the initial progression was most likely a pseudo-progression from the use of immunotherapy. The patient continued with nivolumab as a single agent and has been doing well. CONCLUSIONS This case highlights the importance of careful evaluation of immunotherapy response in patients with melanoma. The initial progression noted in this patient was most likely pseudo-progression, which resolved with further immunotherapy. Clinicians should consider PET-CT imaging in cases of suspected pseudo-progression to avoid unnecessary changes in therapy. Patient response to immunotherapy demonstrates the effectiveness of immunotherapy in treating advanced melanoma.

Antibiotic prescription patterns and non-clinical factors influencing antibiotic use by Ecuadorian veterinarians working on cattle and poultry farms: A cross-sectional study.

Understanding antibiotic prescription patterns and non-clinical factors influencing antibiotic use is essential for implementing strategies to promote appropriate antibiotic use. There is, however, limited research exploring these issues with Ecuadorian veterinarians. Therefore, a questionnaire was developed and applied cross-sectionally to veterinarians (n = 173) from two professional organizations to explore the antibiotic prescription patterns and non-clinical factors (e.g., attitudes and perceptions) influencing antibiotic use, and to identify strategies to reduce antibiotic use. The response rate was 78.4%. Responses were compared between veterinarians working mainly on cattle and poultry farms using Mann-Whitney U tests. The most important attitudes, beliefs and perceptions towards antimicrobial resistance (AMR) and antibiotic use were identified with the Relative Importance Index (RII). Veterinarians showed high awareness of AMR and its implications for public health, as well as the necessity of reducing antibiotic use. However, some veterinarians appear to underestimate the potential contribution of veterinary antibiotic use on AMR in humans. Veterinarians self-reported high prescription (> 20%) of antibiotics for cattle and poultry that are critically important for human medicine, such as 3rd and 4th generation cephalosporins, polymyxins and quinolones. Further, antibiotic therapy was not tailored to disease type. Cattle and poultry veterinarians perceived similar barriers to increasing antibiotic stewardship including: poor biosecurity measures, animal confinement, low feed quality, farmers' behaviors (such as stopping antibiotic treatment, storing antibiotics on farms, buying antibiotics in veterinary supply stores), and sales agents' roles as non-professional prescribers of antibiotics. Overall, veterinarians were broadly supportive (>90%) of most strategies to promote appropriate antibiotic use. They saw more merit in improving biosecurity of farms and implementing educational programs for farmers and veterinarians. This study provides insight into the complexity of antibiotic use on Ecuadorian farms and the need for holistic strategies in a One Health context, to achieve antibiotic stewardship.

Seasonality of antimicrobial use in Dutch food-producing animals.

Due to globally increasing antimicrobial resistance (AMR), it is pivotal to understand factors contributing to antimicrobial use (AMU) to enable development and implementation of AMR-reducing interventions. Therefore, we explored seasonal variations of systemic AMU in food-producing animals in the Netherlands. Dutch surveillance data from January 2013 to December 2018 from cattle, pig, and broiler farms were used. AMU was expressed as the number of Defined Daily Dosages Animal per month (DDDA/animal-month) per farm by animal sector, antimicrobial line (first, second, and third), antimicrobial class, and farm type. Seasonality of AMU was analyzed using Generalized Additive Models (GAMs) with DDDA/animal-month as outcome variable, and year and month as independent variables. Year and month were modelled as smooth terms represented with penalized regression splines.Significant seasonality of AMU was found in the cattle and pig sectors, but not in broilers. Significant seasonality of AMU was found mainly for first-line antimicrobials. In the cattle sector, a significant increase during winter was found for the use of amphenicols (an increase of 23.8%) and long-acting macrolides (an increase of 3.4%). In the pig sector, seasonality of AMU was found for pleuromutilins (p < 0.001) with an increase of 20% in October-November. The seasonality of pleuromutilins was stronger in sows/piglets (an increase of 47%) than in fattening pigs (16% increase). Only in fattening pigs, the use of amphenicols showed a significant seasonality with an increase of 11% during winter (P < 0.001). AMU in cattle and pig sectors shows seasonal variations likely caused by seasonality of diseases. In broilers, no AMU seasonality was observed, possibly due to the controlled environment in Dutch farms. In the context of the one health concept, future studies are necessary to explore whether this seasonality is present in other populations and whether it has implications for antimicrobial resistance in humans through the food chain.

Chronic Oral Amiodarone as a Cause of Acute Liver Failure.

Acute liver failure (ALF) is a rare condition that can have a variable clinical course and potentially fatal outcomes. Medication toxicity is a known etiology, however liver failure induced by amiodarone is rare and has been reported mostly in the setting of intravenous (IV) infusion. We present an 84-year-old patient who developed ALF after chronic use of oral amiodarone. The patient received supportive care and her symptoms improved.

Ten-year experience of bone SBRT in breast cancer: analysis of predictive factors of effectiveness.

PURPOSE: Data on the benefit of stereotactic body radiation therapy (SBRT) in patients with breast cancer (BC) and bone metastases remain limited. The purpose of this study is to report our 10-year experience of bone SBRT, analyzing toxicity and prognostic factors for local control (LC); progression-free survival, and overall survival (OS). METHODS/PATIENTS: We analyzed all spine and non-spine bone SBRT performed in patients with BC during the 2012-2022 period at our institution. Treatments carried out with ablative intent in stereotactic conditions with dose/fraction ≥ 5 Gy in 5 or fewer sessions were considered. Demographic, treatment, and toxicity data were recorded according to CTCAEv4. Risk factors were assessed through univariate and multivariate analysis by Cox regression. RESULTS: 60 bone SBRT treatments were performed during the study period. 75% were spine SBRT and 25% were non-spine SBRT (median BED4Gy was 80 Gy4). The median age was 52.5 years (34-79). The median tumor volume was 2.9 cm3 (0.5-39.4). The median follow-up was 32.4 months (1.2-101.7). 1 and 2 years LC were 92.9 and 86.6%, respectively. 1 and 2 years OS were 100 and 90.6%, respectively. Multivariate analysis (MVA) associated volume of the treated lesion ≥ 13 cm3 with worse LC (p = 0.046; HR 12.1, 95%CI = 1.1-140.3). In addition, deferring SBRT > 3 months after lesion diagnosis to prioritize systemic treatment showed a significant benefit, improving the 2 years LC up to 96.8% vs. 67.5% for SBRT performed before this period (p = 0.031; HR 0.1, 95%CI = 0.01-0.8). Hormonal receptors, the total number of metastases, and CA15-3 value were significantly associated with OS in MVA. During follow-up, three non-spine fractures (5%) were observed. CONCLUSIONS: According to our data, bone SBRT is a safe and effective technique for BC. Upfront systemic treatment before SBRT offers a benefit in LC. Therefore, SBRT should be considered after prior systemic treatment in this population.

Prognostic Scores and Survival Rates by Etiology of Hepatocellular Carcinoma: A Review.

Hepatocellular carcinoma (HCC) is a common cancer and ranks sixth among all malignancies worldwide. Risk factors for HCC can be classified as infectious or behavioral. Viral hepatitis and alcohol abuse are currently the most common risk factors for HCC; however, nonalcoholic liver disease is expected to become the most common cause of HCC in upcoming years. HCC survival rates vary according to the causative risk factors. As in any malignancy, staging is crucial in making therapeutic decisions. The selection of a specific score should be individualized according to patient characteristics. In this review, we summarize the current data on epidemiology, risk factors, prognostic scores, and survival in HCC.

Bruton's tyrosine kinase inhibition reduces disease severity in a model of secondary progressive autoimmune demyelination.

Bruton's tyrosine kinase (BTK) is an emerging target in multiple sclerosis (MS). Alongside its role in B cell receptor signaling and B cell development, BTK regulates myeloid cell activation and inflammatory responses. Here we demonstrate efficacy of BTK inhibition in a model of secondary progressive autoimmune demyelination in Biozzi mice with experimental autoimmune encephalomyelitis (EAE). We show that late in the course of disease, EAE severity could not be reduced with a potent relapse inhibitor, FTY720 (fingolimod), indicating that disease was relapse-independent. During this same phase of disease, treatment with a BTK inhibitor reduced both EAE severity and demyelination compared to vehicle treatment. Compared to vehicle treatment, late therapeutic BTK inhibition resulted in fewer spinal cord-infiltrating myeloid cells, with lower expression of CD86, pro-IL-1ß, CD206, and Iba1, and higher expression of Arg1, in both tissue-resident and infiltrating myeloid cells, suggesting a less inflammatory myeloid cell milieu. These changes were accompanied by decreased spinal cord axonal damage. We show similar efficacy with two small molecule inhibitors, including a novel, highly selective, central nervous system-penetrant BTK inhibitor, GB7208. These results suggest that through lymphoid and myeloid cell regulation, BTK inhibition reduced neurodegeneration and disease progression during secondary progressive EAE.

Developing Cardio-Oncology Programs in the New Era: Beyond Ventricular Dysfunction Due to Cancer Treatments.

Cardiovascular disease is a common problem in cancer patients that is becoming more widely recognized. This may be a consequence of prior cardiovascular risk factors but could also be secondary to the anticancer treatments. With the goal of offering a multidisciplinary approach to guaranteeing optimal cancer therapy and the early detection of related cardiac diseases, and in light of the recent ESC Cardio-Oncology Guideline recommendations, we developed a Cardio-Oncology unit devoted to the prevention and management of these specific complications. This document brings together important aspects to consider for the development and organization of a Cardio-Oncology program through our own experience and the current evidence.

Evidence-based guidelines for hypofractionated radiation in breast cancer: conclusions of the Catalan expert working group.

INTRODUCTION: Daily, moderate hypofractionation has become standard treatment for breast cancer following breast-conserving surgery, although substantial variation exists in its use. This paper describes the generation of consensus-based recommendations for the utilisation of this therapy at the healthcare system level and compares these to American Society for Radiation Oncology (ASTRO) guidelines. MATERIALS AND METHODS: Consensus-based guidelines were developed in three steps, including a systematic literature review and involvement of radiation oncologists specialising in breast cancer in Catalonia: (a) creation of a working group and evidence review; (b) consideration of the levels of evidence and agreement on the formulation of survey questions; and (c) performance of survey and development of consensus-based recommendations. Results were compared to the ASTRO recommendations. RESULTS: Consensus was above 80% for 10 of the 14 survey items. Experts supported hypofractionated radiotherapy for all breast cancer patients aged 40 years or more; with invasive carcinoma and breast-conserving surgery; without radiation of lymph nodes; and regardless of the tumour size, histological grade, molecular subtype, breast size, laterality, other treatment characteristics, or need for a boost. Over half favoured its use in all situations, even where available scientific evidence is insufficient. The resulting recommendations and the quality of the evidence are comparable to those from ASTRO, despite some differences in the degree of consensus. CONCLUSION: Specialists agree that hypofractionation is the standard treatment for breast cancer following breast-conserving surgery, but some specific areas require a higher level of evidence before unequivocally extending indications.

Gastric Antral Gastrointestinal Stromal Tumor Presenting With Severe Anemia.

Gastrointestinal stromal tumors are rare gastrointestinal tract growths associated with high rates of malignant transformation. Most cases are asymptomatic and can be identified by computed tomography scan. We present the case of a 50-year-old male with melena and fatigue. Endoscopy showed an ulcerated submucosal tumor diagnosed as a gastrointestinal stromal tumor after surgical resection; it did not present with metastasis and was successfully treated surgically without relapse.

Association between animal welfare indicators and microbiological quality of beef carcasses, including Salmonella spp., from a slaughterhouse in Ecuador.

BACKGROUND AND AIM: Pre-slaughter management and slaughter operations are considered critical factors for animal welfare and meat quality. Previous studies have found poor animal welfare management at municipal slaughterhouses in Ecuador, and little is known about how this affects the microbiological quality of the meat. Therefore, the aim of the study was to analyze the association of the microbiological quality of beef carcasses and animal welfare indicators in a municipal slaughterhouse in Ecuador. MATERIALS AND METHODS: Data for 6 months were collected from a municipal slaughterhouse in Ecuador. Five trained researchers were strategically located along the slaughter process. A total of 351 animals were observed with regard to welfare indicators, and their carcasses were sampled to evaluate microbiological quality. Antemortem (slipping, falling, and vocalization) and postmortem animal welfare indicators (bleed interval, pH, temperature, and bruises) were measured. To determine the total aerobic bacteria (TAB) and Escherichia coli counts and the presence of Salmonella spp., we collected samples by swabbing four different points of each carcass. The association between microbiological quality and animal welfare indicators was studied using univariate and multivariate logistic regressions. RESULTS: The mean TAB count was 5.3 log CFU/cm2, and the mean total count of E. coli was 2.4 log CFU/cm2. Salmonella spp. were isolated in 3.1% of the carcasses. An electric goad was used in all animals, 19.1% slipped at least once, and 19.9% vocalized. The mean pH of the carcasses was 7.2, and 79.2% of carcasses had bruises. Multivariate analysis showed that Salmonella spp. and the TAB count were associated with pH and the number of bruises (p = 0.01 in both cases). CONCLUSION: Although there was non-significant association between the majority of animal welfare indicators and microbiological quality, the poor management affecting animal welfare and carcass hygiene are worrisome.