Changes in neurocognitive assessment scores after initiating dolutegravir- versus elvitegravir-based antiretroviral therapy.

This prospective cohort study enrolled people living with HIV initiating antiretroviral therapy (ART) containing the integrase inhibitors, dolutegravir (DTG) or elvitegravir (EVG) and administered the Montreal Cognitive Assessment (MoCA) at baseline and again after approximately six months to compare changes in MoCA scores. The proportion of patients found to have cognitive impairment, as indicated by a MoCA score <26/30, on each agent were also compared and comparisons were made between changes in each domain assessed by the MoCA (visuospatial/executive, naming, attention, language, abstraction, delayed recall, and orientation). Thirty-five evaluable participants were enrolled, 18 on DTG and 17 on EVG. The median [interquartile range(IQR)] age was 44 (32 to 54) years, 63% were male, 57% were African American. The median (IQR) MoCA score at baseline was 25 (23 to 27) with no difference between groups (p=0.249). The median (IQR) change in MoCA score was 0 (-1 to 2) for DTG and 1 (0 to 3) for EVG (p = 0.183). Of those on DTG, 8 (44%) had MoCA scores <26 on follow-up compared to 11 (65%) on EVG (p = 0.229). There were no significant differences in changes in any of the individual MoCA domains.

Decreased liver triglyceride content in adult rats exposed to protein restriction during gestation and lactation: roles of hepatic lipogenesis and lipid utilization in muscle and adipose tissue.

Protein restriction throughout pregnancy and lactation reduces liver triglyceride (TG) content in adult male rat offspring. The study determined the contribution of hepatic lipogenesis to the reduction in liver TG content. Rats received either control or protein-restricted diets throughout pregnancy and lactation. Offspring were sacrificed on day 65. Hepatic fatty acid uptake and de novo fatty acid and TG biosynthesis were similar between control and low-protein (LP) offspring. These results indicate that hepatic lipogenesis cannot mediate the decrease in liver TG content in LP offspring. We then determined whether increased lipid utilization in adipose tissue and muscle was responsible for the decrease in liver TG content. There was suggestive evidence of increased sympathetic nervous system tone in epididymal adipose tissue of LP offspring that increased fatty acid uptake, TG lipolysis, and utilization of fatty acids in mitochondrial thermogenesis. Measurement of similar parameters demonstrated that such alterations do not occur in gastrocnemius muscle, another major lipid-utilizing tissue. Our results suggest that the decrease in liver TG content in LP offspring is likely due to increased diversion of fatty acids to white and brown adipose tissue depots and their enhanced utilization to fuel mitochondrial thermogenesis.

Impact of an interprofessional transition of care service on 30-day hospital reutilizations.

The objective of this study was to evaluate the impact of an interprofessional Transitions of Care (TOC) service on 30-day hospital reutilization inclusive of hospital readmissions and ED visits. This was a retrospective cohort study including patients discharged from an academic medical center between September 2013 and October 2014. Patients scheduled for a hospital follow-up visit in the post-acute care clinic (PACC) were included in the intervention group and patients without a post-discharge interprofessional TOC service were included in the comparison group. The intervention included a hospital follow-up visit with an interprofessional healthcare team. The primary composite outcome was hospital reutilization, defined as a hospital readmission or ED visit within 30 days of the discharge date. Overall, 330 patients were included in each group. In the intention-to-treat analysis, the primary composite outcome was not significantly different between groups (16.97% vs. 19.39%, P = 0.4195) whereas in the per-protocol analysis (all patients who showed to their PACC appointment), the primary outcome was significantly different in favor of the intervention group (9.28% vs. 19.39%, P = 0.0009). When components were analyzed separately, there was a statistically significant difference in favor of intervention group for hospital readmissions, but there was no difference for ED visits. This study demonstrates that an outpatient interprofessional TOC service with patient engagement from a team of nurses, pharmacists, physicians, and social workers may reduce 30-day hospital readmissions but may not impact 30-day ED visits.

Impact of Delayed Oral Vancomycin for Severe Clostridium difficile Infection.

Background: Treatment of severe Clostridium difficile infection (CDI) with oral vancomycin (VAN) is known to be superior to treatment with metronidazole (MDZ). However, previous studies have not evaluated the impact on patients when oral VAN therapy is delayed after diagnosis of severe CDI. Materials and Methods: This was a single-center, retrospective study of adult patients who were diagnosed with severe CDI. The objective was to compare clinical outcomes for patients treated initially with oral VAN versus patients receiving delayed oral VAN after at least 48 hours of initial treatment with MDZ. The primary outcome was all-cause in-hospital mortality. Results: There were 101 patients who comprised the initial oral VAN group, while 20 patients comprised the delayed oral VAN group. There was no significant difference in all-cause in-hospital mortality for patients in the initial oral VAN treatment group compared to those who had delayed oral VAN therapy (4.95% vs 15.00%, P = 0.13). Patients who were initially treated with oral VAN experienced a significantly higher rate of clinical cure (49.50% vs 20.00%, P = 0.02), shorter median postinfection length of hospitalization (7.0 days vs 13.0 days, P < 0.001), shorter median time to resolution of leukocytosis (3.9 days vs 10.4 days, P = 0.01), and were less likely to have an end of treatment serum creatinine greater than 1.5 times their baseline (8.7% vs 29.4%, P = 0.03). Conclusion: Patients who receive oral VAN as their initial treatment for severe CDI experience improved clinical outcomes compared to patients receiving delayed oral VAN after being initially treated with MDZ.

Intravenous Vancomycin Associated With the Development of Nephrotoxicity in Patients With Class III Obesity.

BACKGROUND: A consensus statement recommends initial intravenous (IV) vancomycin dosing of 15-20 mg/kg every 8- 24 hours, with an optional 25- to 30-mg/kg loading dose. Although some studies have shown an association between weight and the development of vancomycin-associated nephrotoxicity, results have been inconsistent. OBJECTIVE: To evaluate the correlation between incidence of nephrotoxicity associated with weight-based IV vancomycin dosing strategies in nonobese and obese patients. METHODS: This retrospective cohort study evaluated hospitalized adult patients admitted who received IV vancomycin. Patients were stratified into nonobese (body mass index [BMI] <25 kg/m2), obesity class I and II (BMI 30-39.9kg/m2), and obesity class III (BMI≥40 kg/m2) groups; patients who were overweight but not obese were excluded. Incidence of nephrotoxicity and serum vancomycin trough concentrations were evaluated. RESULTS: Of a total of 62 documented cases of nephrotoxicity (15.1%), 13 (8.7%), 23 (14.3%), and 26 (26.3%) cases were observed in nonobese, obesity class I and II, and obesity class III groups, respectively ( P=0.002). Longer durations of therapy ( P<0.0001), higher initial maintenance doses in both total milligrams/day ( P=0.0137) and milligrams/kilogram ( P=0.0307), and any trough level >20 mg/L ( P<0.0001) were identified as predictors of development of nephrotoxicity. Concomitant administration of piperacillin/tazobactam, diuretics, and IV contrast were associated with development of nephrotoxicity ( P<0.005, all). Patients with class III obesity were 3-times as likely to develop nephrotoxicity when compared with nonobese patients (odds ratio [OR]=2.99; CI=1.12-7.94) and obesity class I and II patients (OR=3.14; CI=1.27-7.75). CONCLUSIONS: Obesity and other factors are associated with a higher risk of vancomycin-associated nephrotoxicity.

Maternal protein restriction during pregnancy and lactation alters central leptin signalling, increases food intake, and decreases bone mass in 1 year old rat offspring.

The effects of perinatal nutrition on offspring physiology have mostly been examined in young adult animals. Aging constitutes a risk factor for the progressive loss of metabolic flexibility and development of disease. Few studies have examined whether the phenotype programmed by perinatal nutrition persists in aging offspring. Persistence of detrimental phenotypes and their accumulative metabolic effects are important for disease causality. This study determined the effects of maternal protein restriction during pregnancy and lactation on food consumption, central leptin sensitivity, bone health, and susceptibility to high fat diet-induced adiposity in 1-year-old male offspring. Sprague-Dawley rats received either a control or a protein restricted diet throughout pregnancy and lactation and pups were weaned onto laboratory chow. One-year-old low protein (LP) offspring exhibited hyperphagia. The inability of an intraperitoneal (i.p.) leptin injection to reduce food intake indicated that the hyperphagia was mediated by decreased central leptin sensitivity. Hyperphagia was accompanied by lower body weight suggesting increased energy expenditure in LP offspring. Bone density and bone mineral content that are negatively regulated by leptin acting via the sympathetic nervous system (SNS), were decreased in LP offspring. LP offspring did not exhibit increased susceptibility to high fat diet induced metabolic effects or adiposity. The results presented here indicate that the programming effects of perinatal protein restriction are mediated by specific decreases in central leptin signalling to pathways involved in the regulation of food intake along with possible enhancement of different CNS leptin signalling pathways acting via the SNS to regulate bone mass and energy expenditure.

Life Course Factors Associated with Initiation and Continuation of Exclusive Breastfeeding.

INTRODUCTION: Exclusive breastfeeding (EBF) benefits the life course health development of infants, families, and society. Professional health associations recommend EBF for 4 months, and many now recommend EBF for 6 months. Yet only 18.8 % of US infants born in 2011 were exclusively breastfed. Numerous studies on breastfeeding are published, but few describe EBF. This study describes characteristics of women who initiated EBF and examines the associations of those factors with EBF lasting ≥4 months. The Life Course Health Development (LCHD)framework was used to structure the analysis and interpret results. METHODS: Data collected through the Infant Feeding Practices Study II survey (2005-2007) were used to identify a cohort of women (n = 1226) practicing EBF at the time of hospital discharge and their sociodemographic, health, work, and child care characteristics. Associations of these characteristics with EBF lasting ≥4 months were studied by bivariate and logistic regression analyses. RESULTS: College education [odds ratio (OR) 2.14, 95 %confidence interval (CI) 1.58-2.89] and marriage (OR2.19, 95 % CI 1.43-3.37) were associated with greater odds of EBF lasting ≥4 months, whereas the plan to return to work after birth (OR 0.57, 95 % CI 0.43-0.74), living in the south (OR 0.67, 95 % CI 0.47-0.95), and postpartum depression risk (OR 0.43, 95 % CI 0.28­0.66)were associated with lower odds of EBF lasting ≥ 4 months. DISCUSSION: Several factors associated with disparities in continued EBF were identified. The application of the LCHD framework furthers understanding of the multiple and interacting risks associated with early discontinuation of EBF.

Decreased liver triglyceride content in adult rats exposed to protein restriction during gestation and lactation: role of hepatic triglyceride utilization.

We have previously demonstrated that protein restriction throughout gestation and lactation reduces liver triglyceride content in adult rat offspring. However, the mechanisms mediating the decrease in liver triglyceride content are not understood. The aim of the current study was to use a new group of pregnant animals and their offspring and determine the contribution of increased triglyceride utilization via the hepatic fatty-acid oxidation and triglyceride secretory pathways to the reduction in liver triglyceride content. Pregnant Sprague-Dawley rats received either a control or a low protein diet throughout pregnancy and lactation. Pups were weaned onto laboratory chow on day 28 and killed on day 65. Liver triglyceride content was reduced in male, but not female, low-protein offspring, both in the fed and fasted states. The reduction was accompanied by a trend towards higher liver carnitine palmitoyltransferase-1a activity, suggesting increased fatty-acid transport into the mitochondrial matrix. However, medium-chain acyl coenzyme A dehydrogenase activity within the mitochondrial matrix, expression of nuclear peroxisome proliferator activated receptor-α, and plasma levels of ß-hydroxybutyrate were similar between low protein and control offspring, indicating a lack of change in fatty-acid oxidation. Hepatic triglyceride secretion, assessed by blocking peripheral triglyceride utilization and measuring serum triglyceride accumulation rate, and the activity of microsomal transfer protein, were similar between low protein and control offspring. Because enhanced triglyceride utilization is not a significant contributor, the decrease in liver triglyceride content in male low-protein offspring is likely due to alterations in liver fatty-acid transport or triglyceride biosynthesis.

Impact of a logistics management program on admitted patient boarders within an emergency department.

INTRODUCTION: ED crowding is a public health issue, and hospitals across the country must pursue aggressive strategies to improve patient flow to help solve this growing problem. The logistics management program (LMP) is an expansion of the bed management process to include a systematic approach to patient flow management throughout the facility and a clinical liaison or field agent to drive throughput at all points of care. The purpose of this study was to examine the effects of an LMP on ED length of stay (ED evaluation times and ED placement times), as well as inpatient length of stay (IPLOS). METHODS: This is a quasi-experimental study of 28,684 ED admissions in a suburban, tertiary medical center before and after implementing an LMP (2008 vs 2009). RESULTS: The median ED evaluation time was 219 minutes (interquartile range [IQR], 178 minutes) in 2008 versus 207 minutes (IQR, 171 minutes) in 2009 (P < .001). The median ED placement time was 219 minutes (IQR, 259 minutes) in 2008 versus 193 minutes (IQR, 158 minutes) in 2009 (P < .001). The median IPLOS was 3.93 days (IQR, 4.9 days) in 2008 versus 3.83 days (IQR, 4.7 days) in 2009 (P < .001), which represents a reduction of 1,483 inpatient days in 2009. DISCUSSION: The results provide strong evidence to support the impact of an LMP on decreasing ED evaluation times, ED placement times, and IPLOS. Further exploration is needed to examine the program as a best practice, as well as its applicability for other facilities.

Prevalence and Value of Board Certification Among Pharmacy Practice Faculty in the United States.

OBJECTIVE: To determine the prevalence of board certification among pharmacy practice faculty in the United States, motivators and barriers to certification, and association between board certification and professional achievements and accomplishments that may support career advancement. METHODS: In phase I, the prevalence of board-certified pharmacy practice faculty in the United States was determined by cross-referencing lists of faculty and board-certified pharmacists. In phase II, faculty were stratified by rank and invited to participate in a survey regarding professional characteristics, motivators and barriers to board certification, and professional achievements and accomplishments that may support career advancement for pharmacy practice faculty. RESULTS: The prevalence of board certification among the 3276 pharmacy practice faculty was 56%. The prevalence was the highest among assistant professors (61%). A total of 746 faculty completed the survey (33% response rate). Of those respondents, 73% reported being currently certified, 23% never certified, and 4% previously certified. Overall, to be recognized as an expert in the field was identified as the most commonly perceived reason faculty obtain board certification (44%). Currently and previously certified faculty ranked the desire to be recognized as an expert in the field as the most common reason they obtained board certification (61%). There was a positive correlation between board certification and certain professional accomplishments. CONCLUSION: The prevalence of board-certified pharmacy practice faculty has increased since 2011, but motivators and barriers for board certification remain similar. Board certification may support career advancement for pharmacy practice faculty.

Impact of Student Pharmacist State Anxiety on Vasopressor Calculation Accuracy in Advanced Cardiac Life Support Simulations.

OBJECTIVE: To assess the impact of student pharmacist state anxiety on vasopressor calculation accuracy in advanced cardiac life support (ACLS) simulations. METHODS: Third-year professional students participated in 2 ACLS-related simulation laboratory sessions. In week 1, students completed 3 calculations at their workstation with no stressors. Students were then randomized into teams for a bedside simulation where they independently completed 3 additional calculations either with or without stressors. Team assignments were maintained for week 2 where all participants completed a high-fidelity ACLS simulation that included a team vasopressor calculation. At both encounters, calculation accuracy was assessed as well as pre- and post-state anxiety using the Spielberger State-Trait Anxiety Inventory (STAI) survey tool. RESULTS: Students' (N = 145) trait anxiety aligned with normative data for similarly aged professional students. Post-simulation state anxiety in week 1 was found to be higher for those completing the activity with stressors than without (STAI score 44.7 vs 36.9) paired with lower bedside calculation accuracy, despite similar initial workstation calculation accuracy. In week 2, pre-simulation state anxiety score and calculation accuracy were not significantly different between the 2 groups. However, the state anxiety score significantly increased post-simulation for those exposed to stress in the previous week. CONCLUSION: Stress negatively impacted student pharmacist vasopressor calculation accuracy. However, the repeated exposure to a stressed simulation did not result in a significant difference in pre- or post-simulation state anxiety score or calculation accuracy when compared to a non-stressed control. Consideration should be made whether to include more "real-life" simulations in student pharmacist education.

Optimal energy provision early in ICU stay for critically ill patients receiving parenteral nutrition.

BACKGROUND: Literature on optimal energy provision via parenteral nutrition (PN) is limited and the evidence quality is low. The purpose of this study is to determine if there is a difference in outcomes in adult critically ill patients when receiving lower vs higher calorie provision via PN early in intensive care unit (ICU) stay. METHODS: Adult patients initiated on PN within the first 10 days of ICU stay from May 2014 to June 2021 were included in this retrospective study. The primary outcome was to determine the impact of lower (<20 kcal/kg/day) vs higher (>25 kcal/kg/day) calorie provision on all-cause, in-hospital mortality. Secondary outcomes were to determine the impact of calorie provision on hospital or ICU length of stay and incidence of complications. RESULTS: This study included 133 patients: a lower calorie provision group (n = 77) and a higher calorie provision group (n = 56). There was a significant difference in all-cause, in-hospital mortality between the lower and the higher calorie provision groups (36.36% and 17.86%, respectively; P = 0.02). However, upon a multivariate analysis of death at discharge, the specific calorie provision group did not affect the probability of death at hospital discharge. The secondary outcomes were not significantly different between groups. CONCLUSION: When comparing lower calorie provision with higher calorie provision in adult critically ill patients receiving PN early within their ICU stay, there were no differences in outcomes after controlling for significant confounders. Future larger prospective studies should further evaluate optimal caloric provision via PN in this population.

A transitions of care (TOC) PharmD elective and its impact on students' perceptions on their TOC knowledge, skills, and attitudes.

INTRODUCTION: Transitions of care (TOC) continue to evolve as a problem within our health care system and is a direct driver to worsened patient outcomes. Currently information of in-depth instruction and application of TOC content within health care education, especially pharmacy, is limited. In 2012, a small team of faculty members created a specialized TOC pharmacy elective for third year doctor of pharmacy students. The purpose of this paper is to describe the impact of this TOC course on students' perceptions on their TOC knowledge, skills, and attitudes over the four years course span. METHODS: A pre-/post-paper anonymous survey was distributed to the students. Descriptive statistics captured the analyzed survey questions into four main themes. Within each respective theme, quantitative data were provided for pre- and post-survey responses to illustrate the difference in the scores with corresponding P values to showcase if significance was present. RESULTS: The response rate of the survey was 100%. Within all of the respective themes, all of the survey questions, pre- to post-responses, had a significant shift toward a higher degree of agreement. CONCLUSIONS: This study illustrates the impact a course dedicated to TOC has on student's learning.

Continuous glucose monitoring metrics for earlier identification of pre-diabetes: protocol for a systematic review and meta-analysis.

INTRODUCTION: Glycaemic variability and other metrics are not well characterised in subjects without diabetes. More comprehensive sampling as obtained with continuous glucose monitoring (CGM) may improve diagnostic accuracy of the transition from health to pre-diabetes. Our goal is to investigate the glycaemic system as it shifts from health to pre-disease in adult patients without diabetes using CGM metrics. New insights may offer therapeutic promise for reversing dysglycaemia more successfully with dietary, nutritional and lifestyle change before progression occurs to pre-diabetes and diabetes. METHODS AND ANALYSIS: This systematic review will include comprehensive searches of the PubMed, Scopus, Cochrane Library and ClinicalTrials.gov databases, with restrictions set to studies published in the last 10 years in English and planned search date 10 March 2022. Reference lists of studies that meet eligibility criteria in the screening process will subsequently be screened for the potential inclusion of additional studies. We will include studies that examine CGM use and report diagnostic criteria such as fasting glucose and/or haemoglobin A1c such that we can assess correlation between CGM metrics and established diagnostic criteria and describe how CGM metrics are altered in the transition from health to pre-diabetes. The screening and data extraction will be conducted by two independent reviewers using Covidence. All included papers will also be evaluated for quality and publication bias using Cochrane Collaboration risk of bias tools. If there are two or more studies with quantitative estimates that can be combined, we will conduct a meta-analysis after assessing heterogeneity. ETHICS AND DISSEMINATION: The systematic review methodology does not require formal ethical review due to the nature of the study design. Study findings will be publicly available and published in a peer-reviewed journal. PROSPERO REGISTRATION NUMBER: CRD42022308222.

When Eating Becomes Torturous: Understanding Nutrition-Related Cancer Treatment Side Effects among Individuals with Cancer and Their Caregivers.

Individuals living with cancer often experience multiple nutrition-related side effects from cancer treatment, including changes in taste and smell, nausea, diarrhea, loss of appetite, and pain during eating. These side effects can profoundly impact nutritional status and quality of life. The purpose of this study was to explore experiences with nutrition-related cancer treatment side effects among cancer patients and their family caregivers, the way they manage such side effects, and the resulting changes in food preferences and behaviors. Structured surveys and in-depth interviews were conducted. Interviews focused on the presence and management of treatment side effects, how those changes influenced food preferences, and the extent to which they interfered with quality of life. Most patients (72%) reported treatment side effects; 61% reported that these side effects impacted their eating and drinking. Common side effects included fatigue (58%), dry mouth (30%), nausea (24%), constipation (20%) and diarrhea (20%). Six overarching qualitative themes were identified: Spiral of side effects; Pain of eating; Burden of eating; Loss of taste/change in taste; Symptom management; and Solutions. The authors conclude with implications for food and nutrition practice-moving beyond traditional recommendations of what to eat or avoid-to consider the overall patient and caregiver experience.

Refining interprofessional, outpatient transitions of care services to reduce hospital readmissions.

RATIONALE, AIMS AND OBJECTIVES: Transitions of care between healthcare facilities are associated with increased risk of adverse events and hospital readmissions. Previous studies employing pharmacists in transitions of care showed reduced 30-day readmissions, however, many were without an active comparator. There is no standardized approach to pharmacist involvement in transitions of care services, making it difficult to ascertain where pharmacist expertise is most meaningful. This paper aims to compare the 30-day hospital readmissions between an interprofessional hospital discharge visit (iHDV) with physician and pharmacist involvement to a non-interprofessional HDV (PHDV) without pharmacist involvement. METHOD: This was a retrospective quality improvement initiative examining patients of two outpatient clinical practices within a large, academic medical centre. The primary analysis compared 30-day hospital readmission rates for patients with a scheduled PHDV or iHDV within 30-days of index hospital discharge date, regardless of attendance at the HDV. The secondary outcome compared 30-day hospital readmission rates for patients who completed a PHDV or iHDV. Primary and secondary outcomes were evaluated using bivariate analysis and multivariate analysis by stepwise logistic regression, for both intention-to-treat (ITT) and per protocol (PP). RESULTS: This study found significantly lower 30-day hospital readmissions for patients scheduled for a PHDV compared to an iHDV (16.7% vs 21.5%, P = .0230) in an unadjusted analysis, but no significant difference in adjusted analyses (P = .4856). Per-protocol analysis found no significant difference in 30-day hospital readmission rates between groups in unadjusted and adjusted analyses. Visit completion rates were significantly different between groups, with approximately twice as many PHDV group patients completing visits as compared to the iHDV group (74.1% vs 61.5%, P < .0001). CONCLUSION: This study demonstrates an interprofessional clinic visit employing a clinical pharmacist in the post-hospital discharge visit did not significantly reduce 30-day hospital readmission rates compared to a post-hospital discharge visit without pharmacist involvement.

Optimal vancomycin dose in the treatment of Clostridium difficile infection, antimicrobial stewardship initiative.

C. difficile infections (CDI) are increasingly recognized as a leading cause of infectious diarrhea, with increasing morbidity and mortality. Treatment primarily centers around oral vancomycin treatment. A wide range of dosing regimens exist in clinical practice, with little evidence to help distinguish the therapeutic benefit between them. This is a retrospective cohort study conducted at an academic medical center that enrolled adult patients admitted with CDI. The primary outcome was a composite of complete or partial cure at the end of treatment and was assessed using a test of equivalency with a 20% equivalency limit. Subjects were divided into low dose (125 mg) or high dose (250 mg or 500 mg) of oral vancomycin dosed every 6 hours. Overall, 78 patients were included who received low dose vancomycin and 33 who received high dose. Generally, the two groups were similar, except the low dose group had significantly more leukocytosis and less ICU admission or hypotension compared to the high dose group. Equivalency between the two treatment groups was demonstrated (Absolute Risk Difference -0.022, 90% confidence interval: -0.13 to 0.18, p = 0.03). A stepwise logistic regression identified gender, baseline albumin, and ICU admission as significant predictors of the chance for complete or partial cure. No differences between groups for the secondary outcomes of 90-day readmission/recurrence, 30-day all-cause mortality, or time to resolution of diarrhea were demonstrated. Low dose oral vancomycin was demonstrated to result in equivalent outcomes compared to high dose vancomycin for the treatment of CDI.

Risk Factors for Recurrence of Clostridioides difficile in Hospitalized Patients.

BACKGROUND: Diarrhea and pseudomembranous colitis associated with Clostridioides difficile - a spore-forming anaerobic Gram-positive bacillus - is a major infection in hospitalized patients with a profound impact on clinical and economic outcomes. Recurrence (rCDI) is common and predisposes to further episodes with poor outcomes. METHOD: We aimed to identify a wide range of risk factors for recurrence to guide stewardship initiatives. After ethical approval, we commenced collecting demographic and clinical data of patients older than 18 years with clinically and microbiologically confirmed C. difficile infection. Data were statistically analyzed using R software. RESULTS: Of 204 patients included in the analysis, 36 (18%) suffered 90-day recurrence, rCDI was higher among females (23%) compared to males (13%), overall age median (IQR) was 66 (51-77), and for rCDI cases 81 (69-86) years. Among 26 variables analyzed to evaluate their association with rCDI, prior clindamycin exposure, concurrent use of aztreonam, patients >76 years, total hospital length of stay, and LOS before diagnosis ≤7 days, WBC ≤ 9.85 × 103 at discharge were more likely to experience rCDI. CONCLUSION: As identified in this analysis, patients with risk factors for rCDI could be candidates for close monitoring, a high index of suspicion, and risk mitigation interventions to avoid rCDI and improve clinical outcomes.

Phosphorylated STAT3 (Tyr705) as a biomarker of response to pimozide treatment in triple-negative breast cancer.

Triple-negative breast cancer (TNBC) displays an aggressive clinical course, heightened metastatic potential, and is linked to poor survival rates. Through its lack of expression of the estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2), this subtype remains unresponsive to traditional targeted therapies. Undesirable and sometimes life-threatening side effects associated with current chemotherapeutic agents warrant the development of more targeted treatment options. Targeting signal transducer and activator of transcription 3 (STAT3), a transcription factor implicated in breast cancer (BCa) progression, has proven to be an efficient approach to halt cancer growth in vitro and in vivo. Currently, there are no FDA-approved STAT3 inhibitors for TNBC. Although pimozide, a FDA-approved antipsychotic drug, has been attributed a role as a STAT3 inhibitor in several cancers, its role on this pathway remains unexplored in TNBC. As a "one size fits all" approach cannot be applied to TNBC therapies due to the heterogeneous nature of this aggressive cancer, we hypothesized that STAT3 could be a novel biomarker of response to guide pimozide therapy. Using human cell lines representative of four TNBC subtypes (basal-like 1, basal-like 2, mesenchymal-like, mesenchymal stem-like), our current report demonstrates that pimozide significantly reduced their invasion and migration, an effect that was predicted by STAT3 phosphorylation on tyrosine residue 705 (Tyr705). Mechanistically, phosphorylated STAT3 (Tyr705) inhibition resulting from pimozide treatment caused a downregulation of downstream transcriptional targets such as matrix metalloproteinase-9 (MMP-9) and vimentin, both implicated in invasion and migration. The identification of biomarkers of response to TNBC treatments is an active area of research in the field of precision medicine and our results propose phosphorylated STAT3 (Tyr705) as a novel biomarker to guide pimozide treatment as an inhibitor of invasion and migration.

Essential role of STAT5a in DCIS formation and invasion following estrogen treatment.

Ductal carcinoma in situ (DCIS) is one of the earliest stages of breast cancer (BCa). The mechanisms by which DCIS lesions progress to an invasive state while others remain indolent are yet to be fully characterized and both diagnosis and treatment of this pre-invasive disease could benefit from better understanding the pathways involved. While a decreased expression of Caveolin-1 (Cav-1) in the tumor microenvironment of patients with DCIS breast cancer was linked to progression to invasive breast cancer (IBC), the downstream effector(s) contributing to this process remain elusive. The current report shows elevated expression of Signal Transducer and Activator of Transcription 5a (STAT5a) within the DCIS-like lesions in Cav-1 KO mice following estrogen treatment and inhibition of STAT5a expression prevented the formation of these mammary lesions. In addition, STAT5a overexpression in a human DCIS cell line (MCF10DCIS.com) promoted their invasion, a process accelerated by estrogen treatment and associated with increased levels of the matrix metalloproteinase-9 (MMP-9) precursor. In sum, our results demonstrate a novel regulatory axis (Cav-1♦STAT5a♦MMP-9) in DCIS that is fully activated by the presence of estrogen. Our sudies suggest to further study phosphorylated STAT5a (Y694) as a potential biomarker to guide and predict outcome of DCIS patient population.