PTSD increases risk for major adverse cardiovascular events through neural and cardio-inflammatory pathways.

While posttraumatic stress disorder (PTSD) is known to associate with an elevated risk for major adverse cardiovascular events (MACE), few studies have examined mechanisms underlying this link. Recent studies have demonstrated that neuro-immune mechanisms, (manifested by heightened stress-associated neural activity (SNA), autonomic nervous system activity, and inflammation), link common stress syndromes to MACE. However, it is unknown if neuro-immune mechanisms similarly link PTSD to MACE. The current study aimed to test the hypothesis that upregulated neuro-immune mechanisms increase MACE risk among individuals with PTSD. This study included N = 118,827 participants from a large hospital-based biobank. Demographic, diagnostic, and medical history data collected from the biobank. SNA (n = 1,520), heart rate variability (HRV; [n = 11,463]), and high sensitivity C-reactive protein (hs-CRP; [n = 15,164]) were obtained for a subset of participants. PTSD predicted MACE after adjusting for traditional MACE risk factors (hazard ratio (HR) [95 % confidence interval (CI)] = 1.317 [1.098, 1.580], ß = 0.276, p = 0.003). The PTSD-to-MACE association was mediated by SNA (CI = 0.005, 0.133, p < 0.05), HRV (CI = 0.024, 0.056, p < 0.05), and hs-CRP (CI = 0.010, 0.040, p < 0.05). This study provides evidence that neuro-immune pathways may play important roles in the mechanisms linking PTSD to MACE. Future studies are needed to determine if these markers are relevant targets for PTSD treatment and if improvements in SNA, HRV, and hs-CRP associate with reduced MACE risk in this patient population.

Variable exposure to echocardiography core competencies when applying minimum recommended procedural numbers for cardiology fellows in training.

BACKGROUND: The American College of Cardiology Core Cardiovascular Training Statement (COCATS) defined echocardiography core competencies and set the minimum recommend number of echocardiograms to perform (150) and interpret (300) for independent practice in echocardiography (level 2 training). Fellows may lack exposure to key pathologies that are relatively infrequent, however, even when achieving an adequate number of studies performed and interpreted. We hypothesized that cardiology fellows would lack exposure to 1 or more cardiac pathologies related to core competencies in COCATS when performing and interpreting the minimum recommend number of studies for level 2 training. METHODS: We retrospectively reviewed 11,250 reports from consecutive echocardiograms interpreted (7,500) and performed (3,750) by 25 cardiology fellows at a University tertiary referral hospital who graduated between 2015 and 2019. The first 300 echocardiograms interpreted and the first 150 echocardiograms performed by each fellow were included in the analysis. Echocardiography reports were reviewed for cardiac pathologies relating to core competencies defined in COCATS. RESULTS: All 25 fellows lacked exposure to 1 or more cardiac pathologies related to echocardiography core competencies despite meeting COCATS minimum recommended numbers for echocardiograms performed and interpreted. Pathologies for which 1 or more fellows encountered 0 cases despite meeting the minimum recommended numbers for both echocardiograms performed and interpreted included: pericardial constriction (16/25 fellows), aortic dissection (15/25 fellows), pericardial tamponade (4/25 fellows), valvular mass/thrombus (2/25 fellows), prosthetic valve dysfunction (1/25 fellows), and cardiac chamber mass/thrombus (1/25 fellows). CONCLUSIONS: Cardiology fellows who completed the minimum recommend number of echocardiograms performed and interpreted for COCATS level 2 training frequently lacked exposure to cardiac pathologies, even in a University tertiary referral hospital setting. These data suggest that fellowship programs should monitor pathology case counts for each fellow in training, in addition to the minimum recommend number of echocardiograms defined by COCATS, to ensure competency for independent practice in echocardiography.

Risks of adverse events in patients with orthostatic intolerance undergoing surgery with general anesthesia.

INTRODUCTION: Orthostatic intolerance (OI) is a group of disorders characterized by symptoms that occur upon standing and resolve with recumbence. Although well established but not widely recognized, these diagnoses may create uncertainty for clinicians dealing with a patient affected by OI and requiring a surgical procedure. OBJECTIVES: To determine the rate of intra- and postoperative major adverse events in patients with OI undergoing surgery with general anesthesia. METHODS: The study was a retrospective study of patients with orthostatic intolerance who underwent surgery requiring general anesthesia from 1 January 2000 to 31 December 2018. RESULTS: A total 171 patients with OI underwent 190 surgeries. In patients with POTS and orthostatic-induced VVS, there were no major significant adverse events. There was one episode of AVNRT in a patient with POTS and one episode of bradycardia secondary to vasovagal reflex in a patient with orthostatic-induced VVS. Moreover, there were 13 (6.8%) episodes of postoperative hypotension. However, the majority of these episodes were related to bleeding, volume depletion or sepsis. All cases of hypotension responded well to appropriate therapy. In patients with OH, the rate of postoperative major adverse cardiac events was 4.7%, and the 30-day mortality rate was 6.1%. This is not significantly different from the calculated risk for patients without OH. There were no myocardial infarctions or deaths at 30 days in patients with POTS or orthostatic-induced VVS. CONCLUSION: Patients with OI may not experience higher rates of perioperative complications compared with patients without OI syndromes.

Hypertonic saline for bronchiolitis in infants.

QUESTION: Recently, a 1-year-old patient returned from admission in the hospital for bronchiolitis, and the report I received indicated that he was treated with inhaled hypertonic saline, among other treatments. Is this therapy recommended for children in the acute care setting? ANSWER: Bronchiolitis, caused mostly by respiratory syncytial virus, is very common in the winter. It is the most frequent cause of hospitalization in infancy. Several good studies have been conducted in the past decade on the use of nebulized hypertonic saline for bronchiolitis management; however, they offer conflicting results. While there might be a role for the use of nebulized hypertonic saline in children who are hospitalized with bronchiolitis for more than 3 days, treatment in other settings does not confer enough benefit to recommend its use.

Pediatric Pain Management in the Emergency Department: The Triage Nurses' Perspective.

UNLABELLED: Understanding triage nurses' perspectives of pain management is essential for timely pain care for children in the emergency department. Objectives of this study were to describe the triage pain treatment protocols used, knowledge of pain management modalities, and barriers and attitudes towards implementation of pain treatment protocols. METHODS: A paper-based survey was administered to all triage nurses at three Canadian pediatric emergency departments, between December 2011 and January 2012. RESULTS: The response rate was 86% (n=126/147). The mean respondent age was 40 years (standard deviation [SD] 9.3) with 8.6 years (SD 7.7) of triage experience. General triage emergency department (GTED) nurses rated adequacy of triage pain treatment lower than pediatric-only triage emergency department (PTED) nurses (P < .001). GTED nurses reported a longer acceptable delay between triage time and administration of analgesia than PTED nurses (P < .002). Most nurses rated more comfort with a protocol involving administration of acetaminophen (97 mm, interquartile range [IQR] 92, 99) or ibuprofen (97 mm, IQR 93, 100) than for oral morphine (67 mm, IQR 35, 94) or oxycodone (57 mm, IQR 15, 81). The top three reported barriers to triage-initiated pain protocols were monitoring capability, time, and access to medications. Willingness to implement a triage-initiated pain protocol was rated as 81 mm (IQR 71, 96). DISCUSSION: Triage nurses are willing to implement pain protocols for children in the emergency department, but differences in comfort and experience exist between PTED and GTED nurses. Provision of triage initiated pain protocols and associated education may empower nurses to improve care for children in pain in the emergency department.

Practical Considerations of Remote Care in Thoracic Aortopathy in India.

Background: Thoracic aortopathy includes conditions like aortic aneurysms and dissections, posing significant management challenges. In India, care delivery is complicated by geographic vastness, financial constraints, and healthcare resource disparities. Telemedicine and digital health technologies offer promising solutions. Methods: A comprehensive review of literature and clinical experiences was conducted to explore the implementation of remote care strategies for thoracic aortopathy in India. The review included studies from 2000 to 2023 and insights from cardiothoracic specialists. Results: Remote care benefits include improved access to specialized expertise, enhanced patient engagement, and optimized resource utilization. Telemedicine enables consultations without travel, and remote monitoring facilitates early intervention. However, challenges like technology integration, digital literacy, patient engagement, privacy concerns, and regulatory compliance need addressing. Discussion: Telemedicine offers significant advantages but requires overcoming challenges to ensure effective, secure care. Careful planning for technology integration, patient education, robust privacy measures, and supportive regulatory policies are essential. Addressing these issues can bridge the healthcare access gap and improve outcomes in India's diverse landscape.

Association of Angiotensin II Receptor Type 1 and Endothelin-1 Receptor Type A Agonistic Autoantibodies With Adverse Remodeling and Cardiovascular Events After Acute Myocardial Infarction.

BACKGROUND: The left ventricular remodeling (LVR) process has limited the effectiveness of therapies after myocardial infarction. The relationship between autoantibodies activating AT1R-AAs (angiotensin II receptor type 1-AAs) and ETAR-AAs (autoantibodies activating endothelin-1 receptor type A) with myocardial infarction has been described. Among patients with ST-segment-elevation myocardial infarction, we investigated the relationship between these autoantibodies with LVR and subsequent major adverse cardiac events. METHODS AND RESULTS: In this prospective observational study, we included 131 patients with ST-segment-elevation myocardial infarction (61±11 years of age, 112 men) treated with primary percutaneous coronary intervention. Within 48 hours of admission, 2-dimensional transthoracic echocardiography was performed, and blood samples were obtained. The seropositive threshold for AT1R-AAs and ETAR-AAs was >10 U/mL. Patients were followed up at 6 months, when repeat transthoracic echocardiography was performed. The primary end points were LVR, defined as a 20% increase in left ventricular end-diastolic volume index, and major adverse cardiac event occurrence at follow-up, defined as cardiac death, nonfatal re-myocardial infarction, and hospitalization for heart failure. Forty-one (31%) patients experienced LVR. The prevalence of AT1R-AAs and ETAR-AAs seropositivity was higher in patients with versus without LVR (39% versus 11%, P<0.001 and 37% versus 12%, P=0.001, respectively). In multivariable analysis, AT1R-AAs seropositivity was significantly associated with LVR (odds ratio [OR], 4.66; P=0.002) and represented a risk factor for subsequent major adverse cardiac events (OR, 19.6; P=0.002). CONCLUSIONS: AT1R-AAs and ETAR-AAs are associated with LVR in patients with ST-segment-elevation myocardial infarction. AT1R-AAs are also significantly associated with recurrent major adverse cardiac events. These initial observations may set the stage for a better pathophysiological understanding of the mechanisms contributing to LVR and ST-segment-elevation myocardial infarction prognosis.

Effect of Stress-Related Neural Pathways on the Cardiovascular Benefit of Physical Activity.

BACKGROUND: The mechanisms underlying the psychological and cardiovascular disease (CVD) benefits of physical activity (PA) are not fully understood. OBJECTIVES: This study tested whether PA: 1) attenuates stress-related neural activity, which is known to potentiate CVD and for its role in anxiety/depression; 2) decreases CVD in part through this neural effect; and 3) has a greater impact on CVD risk among individuals with depression. METHODS: Participants from the Mass General Brigham Biobank who completed a PA survey were studied. A subset underwent 18F-fluorodeoxyglucose positron emission tomography/computed tomographic imaging. Stress-related neural activity was measured as the ratio of resting amygdalar-to-cortical activity (AmygAC). CVD events were ascertained from electronic health records. RESULTS: A total of 50,359 adults were included (median age 60 years [Q1-Q3: 45-70 years]; 40.1% male). Greater PA was associated with both lower AmygAC (standardized ß: -0.245; 95% CI: -0.444 to -0.046; P = 0.016) and CVD events (HR: 0.802; 95% CI: 0.719-0.896; P < 0.001) in multivariable models. AmygAC reductions partially mediated PA's CVD benefit (OR: 0.96; 95% CI: 0.92-0.99; P < 0.05). Moreover, PA's benefit on incident CVD events was greater among those with (vs without) preexisting depression (HR: 0.860; 95% CI: 0.810-0.915; vs HR: 0.929; 95% CI: 0.910-0.949; P interaction = 0.011). Additionally, PA above guideline recommendations further reduced CVD events, but only among those with preexisting depression (P interaction = 0.023). CONCLUSIONS: PA appears to reduce CVD risk in part by acting through the brain's stress-related activity; this may explain the novel observation that PA reduces CVD risk to a greater extent among individuals with depression.

Are wait times and length of stay in Alberta emergency departments for children's mental health meeting national benchmarks? Trends from 2002 to 2008.

OBJECTIVE: To describe wait times, treatment times and length of stay (LOS) for pediatric mental health visits to emergency departments (EDs). METHODS: The present study was a retrospective cohort analysis of mental health visits (n=30,656) made by children <18 years of age between April 2002 and March 2008 to EDs in Alberta using administrative data. Wait time (time from triage to physician assessment), treatment time (time from physician assessment to end of visit) and LOS (time from start to end of visit) were examined for each visit. Wait time and treatment time data were available for 2006 to 2008, and LOS data were available for all study years. Wait times and LOS were compared with national benchmarks for the Canadian Triage and Acuity Scale (CTAS; levels 1 [resuscitative] through 5 [nonurgent]). All times are presented in h and min. RESULTS: Median wait times for visits triaged as CTAS 1, 2, 3 and 4 exceeded national recommendations. The longest wait times were for visits triaged as urgent (CTAS 3; 1 h 46 min) and less urgent (CTAS 4; 1 h 45 min). Lower-acuity visits had wait times that exceeded treatment times (CTAS 4: 1 h 45 min versus 1 h 8 min; CTAS 5: 1 h 5 min versus 52 min). Across all CTAS levels, the LOS in the ED increased during the study period, but met national benchmarks. CONCLUSIONS: Most median ED wait times for pediatric mental health visits exceeded national recommendations, while the median LOS for all visits met recommendations. Lower-acuity visits had wait times that exceeded treatment times. Future research should explore whether longer wait times are associated with adverse outcomes, and whether current wait/treatment times are warranted to ensure that ED throughput is optimized.

OBJECTIF: Décrire les temps d'attente, la durée du traitement et la durée de séjour (DdS) lors de visites au département d'urgence (DU) en raison de problèmes de santé mentale en pédiatrie. MÉTHODOLOGIE: La présente étude était une analyse rétrospective de cohorte des visites effectuées par des enfants de moins de 18 ans pour des problèmes de santé mentale (n=30 656) entre avril 2002 et mars 2008 aux DU de l'Alberta, extrapolées selon les données administratives. Pour chaque visite, les chercheurs ont examiné le temps d'attente (délai entre le triage et l'évaluation du médecin), la durée du traitement (délai entre l'évaluation du médecin et la fin de la visite) et la DdS (délai entre le début et la fin de la visite). Les données sur le temps d'attente et la durée du traitement étaient disponibles de 2006 à 2008, tandis que celles sur la DdS l'étaient pour toutes les années de l'étude. Les chercheurs ont comparé les temps d'attente et la DdS avec les normes nationales d'après l'Échelle canadienne de triage et de gravité (ÉCTG; niveaux 1 [réanimation] à 5 [non urgent]). Les temps et les durées sont présentés en heures et en minutes. RÉSULTATS: Le temps d'attente médian des visites dont le triage correspondait à une ÉCTG de 1, 2, 3 et 4 était supérieur aux recommandations nationales. Les temps d'attente les plus longs s'associaient aux visites classées comme urgentes (ÉCGT 3; 1 h 46 min) et moins urgentes (ÉCGT 4; 1 h 45 min) lors du triage. Le temps d'attente des visites moins aiguës était plus long que la durée de traitement (ÉCGT 4 : 1 h 45 min par rapport à 1 h 8 min; ÉCGT 5 : 1 h 5 min par rapport à 52 min). Dans tous les niveaux d'ÉCGT, la DdS au DU a augmenté pendant la période de l'étude, mais respectait les normes nationales. CONCLUSION: La plupart des temps d'attente médians des visites au DU pour des problèmes de santé mentale en pédiatrie étaient plus longs que les recommandations nationales, tandis que la DdS médiane de toutes les visites respectait les recommandations. Les visites moins aiguës s'associaient à des temps d'attente plus longs que la durée de traitement. Les prochaines recherches devraient viser à déterminer si les temps d'attente plus longs s'associent à des effets indésirables et si le temps d'attente et la durée de traitement actuels se justifient pour assurer l'optimisation du cheminement au DU.

Radionuclide Imaging of Heart-Brain Connections.

The heart and brain have a complex interplay wherein disease or injury to either organ may adversely affect the other. The mechanisms underlying this connection remain incompletely characterized. However, nuclear molecular imaging is uniquely suited to investigate these pathways by facilitating the simultaneous assessment of both organs using targeted radiotracers. Research within this paradigm has demonstrated important roles for inflammation, autonomic nervous system and neurohormonal activity, metabolism, and perfusion in the heart-brain connection. Further mechanistic clarification may facilitate greater clinical awareness and the development of targeted therapies to alleviate the burden of disease in both organs.

Reduced Stress-Related Neural Network Activity Mediates the Effect of Alcohol on Cardiovascular Risk.

BACKGROUND: Chronic stress associates with major adverse cardiovascular events (MACE) via increased stress-related neural network activity (SNA). Light/moderate alcohol consumption (ACl/m) has been linked to lower MACE risk, but the mechanisms are unclear. OBJECTIVES: The purpose of this study was to evaluate whether the association between ACl/m and MACE is mediated by decreased SNA. METHODS: Individuals enrolled in the Mass General Brigham Biobank who completed a health behavior survey were studied. A subset underwent 18F-fluorodeoxyglucose positron emission tomography, enabling assessment of SNA. Alcohol consumption was classified as none/minimal, light/moderate, or high (<1, 1-14, or >14 drinks/week, respectively). RESULTS: Of 53,064 participants (median age 60 years, 60% women), 23,920 had no/minimal alcohol consumption and 27,053 ACl/m. Over a median follow-up of 3.4 years, 1,914 experienced MACE. ACl/m (vs none/minimal) associated with lower MACE risk (HR: 0.786; 95% CI: 0.717-0.862; P < 0.0001) after adjusting for cardiovascular risk factors. In 713 participants with brain imaging, ACl/m (vs none/minimal) associated with decreased SNA (standardized beta -0.192; 95% CI: -0.338 to -0.046; P = 0.01). Lower SNA partially mediated the beneficial effect of ACl/m on MACE (log OR: -0.040; 95% CI: -0.097 to -0.003; P < 0.05). Further, ACl/m associated with larger decreases in MACE risk among individuals with (vs without) prior anxiety (HR: 0.60 [95% CI: 0.50-0.72] vs 0.78 [95% CI: 0.73-0.80]; P interaction = 0.003). CONCLUSIONS: ACl/m associates with reduced MACE risk, in part, by lowering activity of a stress-related brain network known for its association with cardiovascular disease. Given alcohol's potential health detriments, new interventions with similar effects on SNA are needed.

Surgery-induced reactive oxygen species enhance colon carcinoma cell binding by disrupting the liver endothelial cell lining.

OBJECTIVE: Resection of primary colorectal cancer is associated with enhanced risk of development of liver metastases. It was previously demonstrated that surgery initiated an early inflammatory response resulting in elevated tumour cell adhesion in the liver. Because reactive oxygen species (ROS) are shown to be produced and released during surgery, the effects of ROS on the liver vascular lining and tumour cell adhesion were investigated. METHODS: Human endothelial cell monolayers (human umbilical vein endothelial cells (HUVECs) and human microvascular endothelial cells of the lung (HMEC-1s)) were exposed to ROS production, after which electrical impedance, cellular integrity and tumour cell adhesion were investigated. Furthermore, surgery-induced tumour cell adhesion as well as the role of ROS and liver macrophages (Kupffer cells) in this process were studied in vivo. RESULTS: Production of ROS decreased cellular impedance of endothelial monolayers dramatically. Moreover, formation of intercellular gaps in endothelial monolayers was observed, exposing subendothelial extracellular matrix (ECM) on which colon carcinoma cells adhered via integrin molecules. Endothelial damage was, however, prevented in the presence of ROS-scavenging enzymes. Additionally, surgery induced downregulation of both rat and human liver tight junction molecules. Treatment of rats with the ROS scavenger edaravone prevented surgery-induced tumour cell adhesion and downregulation of tight junction proteins in the liver. Interestingly, depletion of Kupffer cells prior to surgery significantly reduced the numbers of adhered tumour cells and prevented disruption of expression of tight junction proteins. CONCLUSIONS: In this study it is shown that surgery-induced ROS production by macrophages damages the vascular lining by downregulating tight junction proteins. This leads to exposure of ECM, to which circulating tumour cells bind. In light of this, perioperative therapeutic intervention, preventing surgery-induced inflammatory reactions, may reduce the risk of developing liver metastases, thereby improving the clinical outcome of patients with colorectal cancer.

Treatment of a Recalcitrant Non-union of the Clavicle.

Background: Plate fixation is the treatment of choice for a midshaft clavicle non-union. Those non-unions that require >1 surgical procedure to heal are termed recalcitrant non-union. Regardless of the number of previously failed procedures, our surgical strategy is aimed at achieving an optimal mechanical and biological environment to facilitate healing. Materials and methods: We performed a retrospective analysis of 14 patients with a recalcitrant clavicle non-union treated with open reduction and plate fixation combined with graft augmentation when indicated. Healing rates after index surgery were analysed. All patients were observed for at least 12 months. Results: All patients healed at a mean time of 193.2 days (range 90-390). Five of the 14 patients had at least one positive surprise culture, for which they received antibiotic treatment. At the latest follow-up, no patient reported pain or discomfort. Mean disability of the arm, shoulder and hand (DASH) score was 16.3 points (range 0-40), indicating only mild residual impairment. A possible link was found between the time between injury and definitive surgery and the time to healing [Pearson correlation 0.527, sig. (two-tailed) 0.000]. Conclusion: This study shows 100% bone healing and good functional outcomes after surgical revision for a recalcitrant clavicle non-union. How to cite this article: Grewal S, Baltes TPA, Wiegerinck E, et al. Treatment of a Recalcitrant Non-union of the Clavicle. Strategies Trauma Limb Reconstr 2022;17(1):1-6.

How safe are paediatric emergency departments? A national prospective cohort study.

BACKGROUND: Despite the high number of children treated in emergency departments, patient safety risks in this setting are not well quantified. Our objective was to estimate the risk and type of adverse events, as well as their preventability and severity, for children treated in a paediatric emergency department. METHODS: Our prospective, multicentre cohort study enrolled children presenting for care during one of 168 8-hour study shifts across nine paediatric emergency departments. Our primary outcome was an adverse event within 21 days of enrolment which was related to care provided at the enrolment visit. We identified 'flagged outcomes' (such as hospital visits, worsening symptoms) through structured telephone interviews with patients and families over the 21 days following enrolment. We screened admitted patients' health records with a validated trigger tool. For patients with flags or triggers, three reviewers independently determined whether an adverse event occurred. RESULTS: We enrolled 6376 children; 6015 (94%) had follow-up data. Enrolled children had a median age of 4.3 years (IQR 1.6-9.8 years). One hundred and seventy-nine children (3.0%, 95% CI 2.6% to 3.5%) had at least one adverse event. There were 187 adverse events in total; 143 (76.5%, 95% CI 68.9% to 82.7%) were deemed preventable. Management (n=98, 52.4%) and diagnostic issues (n=36, 19.3%) were the most common types of adverse events. Seventy-nine (42.2%) events resulted in a return emergency department visit; 24 (12.8%) resulted in hospital admission; and 3 (1.6%) resulted in transfer to a critical care unit. CONCLUSION: In this large-scale study, 1 in 33 children treated in a paediatric emergency department experienced an adverse event related to the care they received there. The majority of events were preventable; most were related to management and diagnostic issues. Specific patient populations were at higher risk of adverse events. We identify opportunities for improvement in care.

Surgery for Colorectal Cancer: A Trigger for Liver Metastases Development? New Insights into the Underlying Mechanisms.

Surgery is a crucial intervention and provides the best chance of cure for patients with colorectal cancer. Experimental and clinical evidence, however, suggests that paradoxically surgery itself may precipitate or accelerate tumor recurrence and/or liver metastasis development. This review addresses the various aspects of surgery-induced metastasis formation and sheds light on the role of inflammation as potential trigger for metastasis development. Understanding these mechanisms may provide potential new perioperative interventions to improve treatment outcomes, and as such could transform the perioperative timeframe from a facilitator of metastatic progression to a window of opportunity to reduce the risk of liver metastasis development. Ultimately, this can potentially improve long-term survival rates and quality of life in patients with colorectal cancer.

Usefulness of Glucagon-Like Peptide-1 Receptor Agonists to Reduce Adverse Cardiovascular Disease Events in Patients with Type 2 Diabetes Mellitus.

Evidence suggests glucagon-like peptide-1 receptor agonists (GLP-1 RA) reduce cardiovascular disease (CVD) events. The objective of this study was to analyze randomized controlled trials (RCT) testing GLP-1 RA's effect on CVD events among participants with type 2 diabetes (T2DM). RCTs comparing GLP-1 RA versus placebo were identified using the PubMed and Cochrane databases. The endpoints in this study included major adverse cardiovascular events (MACE; a composite of cardiovascular death, nonfatal myocardial infarction (MI), and nonfatal stroke), and the individual components of MACE. The primary analysis calculated risk ratios (RR) and 95% confidence intervals (CI) for each endpoint. Heterogeneity for each endpoint was calculated using Chi2 and I2 tests. For any endpoint with significant heterogeneity, a meta-regression was performed using mean baseline hemoglobin A1C (A1C) as the moderator and a R2 value was calculated. Seven RCTs (N = 56,004) were identified with 174,163 patient-years of follow-up. GLP-1 RA reduced MACE [RR 0.89, 95% CI 0.83 to 0.95], cardiovascular death [RR 0.88, 95% CI 0.81 to 0.95], and nonfatal stroke [RR 0.85, 95% CI 0.77 to 0.95]. There was no statistically significant heterogeneity among these RCTs. GLP-1 RA did not reduce nonfatal MI [RR 0.91, 95% CI 0.81 to 1.02]. However, there was significant heterogeneity among these RCTs (Chi2 = 12.68, p = 0.05, I2 = 53%). When accounting for baseline A1C in the regression model, there was no longer significant heterogeneity for this endpoint (p = 0.23, I2 = 27%). A potential linear relationship between baseline A1C and GLP-1 RA's effect on nonfatal MI (R2 = 0.64) was observed. In conclusion, GLP-1 RA reduced MACE, cardiovascular death, and nonfatal stroke; GLP-1 RA did not reduce nonfatal MI, however there may be a linear association between baseline A1C and GLP-1 RA's effect on nonfatal MI.

Oral Antibiotic Prophylaxis Reduces Surgical Site Infection and Anastomotic Leakage in Patients Undergoing Colorectal Cancer Surgery.

BACKGROUND: Surgical-site infection (SSI) and anastomotic leakage (AL) are major complications following surgical resection of colorectal carcinoma (CRC). The beneficial effect of prophylactic oral antibiotics (OABs) on AL in particular is inconsistent. We investigated the impact of OABs on AL rates and on SSI. METHODS: A systematic review and meta-analysis of recent RCTs and cohort studies was performed including patients undergoing elective CRC surgery, receiving OABs with or without mechanical bowel preparation (MBP). Primary outcomes were rates of SSI and AL. Secondarily, rates of SSI and AL were compared in broad-spectrum OABs and selective OABs (selective decontamination of the digestive tract (SDD)) subgroups. RESULTS: Eight studies (seven RCTs and one cohort study) with a total of 2497 patients were included. Oral antibiotics combined with MBP was associated with a significant reduction in SSI (RR = 0.46, 95% confidence interval (CI) 0.31-0.69), I2 = 1.03%) and AL rates (RR = 0.58, 95% CI 0.37-0.91, I2 = 0.00%), compared to MBP alone. A subgroup analysis demonstrated that SDD resulted in a significant reduction in AL rates compared to broad-spectrum OABs (RR = 0.52, 95% CI 0.30 to 0.91), I2 = 0.00%). CONCLUSION: OABs in addition to MBP reduces SSI and AL rates in patients undergoing elective CRC surgery and, more specifically, SDD appears to be more effective compared to broad-spectrum OABs in reducing AL.

Disturbed remodeling and delayed fracture healing in pediatric pycnodysostosis patients.

Pycnodysostosis is an autosomal recessive disease caused by a gene mutation leading cathepsin K deficiency. Pathological fractures of the long bones are common, but guidelines on fracture treatment in these patients are still lacking. We have treated 5 fractures in 2 pediatric pycnodysostosis patients. We hypothesize that pycnodysostosis patients have an incomplete remodeling process in fracture healing because of cathepsin K deficiency. Therefore, to minimize the role of endochondral bone formation (indirect) after a fracture, it seems prudent to strive for direct bone healing (intramembranous) instead of indirect bone healing. Open reduction with internal fixation should be the goal.