Citations

Postoperative pancreatic fistula (POPF) is a critical complication following pancreatic surgeries, marked by leakage of pancreatic fluid due to anastomotic or pancreatic duct failure. Recent advancements have refined its definition, risk classification and management strategies. This review emphasises discussing new definitions, classification updates, predictive factors (both pancreatic and non-pancreatic), comparisons of surgical techniques and therapeutic advancements. Emerging trials and innovations, such as robotic-assisted surgery and personalised stents, are also addressed. The evolving understanding of POPF underscores the need for holistic and patient-centred surgical strategies.

Although CNP (C‐type natriuretic peptide) was first identified in brain tissue, its systemic expression and release is mainly located to the endothelial lining of the vasculature. As such, CNP should not be viewed as a classic blood‐borne hormone but rather as a local factor that supports the integrity of vascular function. Albeit CNP is structurally related to both ANP and BNP (A‐ and B‐type natriuretic peptide), the main signaling pathway is through a specific membrane‐bound receptor without crosstalk from endocrine ANP and BNP. CNP expression and CNP‐mediated effects can thus be uniquely targeted without interference from the related cardiac NPs. In this perspective, we present the CNP system as a largely overlooked target for potential intervention in cardiometabolic disease, hypertension, and diabetes before onset of complications and overt heart failure. To fully unleash this potential, with this perspective, we hope to fuel renewed interest with a focus on use of human in vitro and ex vivo systems as well as experimental medical approaches and human cohort data.

Background To compare the effectiveness of glucagon‐like peptide‐1 receptor agonists (GLP‐1 RAs) versus bariatric surgery on cardiovascular outcomes in patients with heart failure (HF) with preserved ejection fraction and obesity. Methods Using the TriNetX research network, we conducted a retrospective cohort study of adults (aged ≥18 years) with HF with preserved ejection fraction and obesity (body mass index >30 kg/m 2 ) from 2017 to 2022. Patients were categorized into 2 cohorts: those receiving GLP‐1 RAs (semaglutide or tirzepatide) and those who underwent bariatric surgery. Propensity score matching (1:1) was used to balance baseline characteristics. Primary outcomes included acute HF events and all‐cause hospitalizations. Secondary outcomes included all‐cause death, myocardial infarction, stroke, and follow‐up body mass index. Cox proportional hazard models were used to estimate hazard ratios (HRs). Results A total of 2747 patients were included per cohort (mean age, 68 years). GLP‐1 RA therapy was associated with lower incidence of acute HF events (38.9% versus 44.6%; HR, 0.78 [95% CI, 0.72–0.85]), all‐cause death (11.1% versus 14.8%; HR, 0.71 [95% CI, 0.61–0.82]), and all‐cause hospitalizations (66.4% versus 77.3%; HR, 0.62 [95% CI, 0.58–0.66]). Rates of myocardial infarction (13.8% versus 13.4%; HR 0.99 [0.86–1.14]) and stroke (9.7% versus 10.7%; HR, 0.87 [0.74–1.02]) were similar between groups. Mean body mass index at follow‐up was 38.0 in the GLP‐1 RA cohort versus 37.7 after bariatric surgery ( P =0.34). Hemoglobin A 1c at follow‐up was higher in the GLP‐1 RA group (7.4 versus 6.8; P <0.001). Conclusions In patients with HF with preserved ejection fraction and obesity, GLP‐1 RA therapy was associated with improved outcomes compared with bariatric surgery, supporting the need for prospective trials to evaluate GLP‐1 RAs as a therapeutic alternative.

Background Cardiovascular disease (CVD) is a leading cause of death in cancer survivors. Predicting CVD risk in this population remains challenging. Risk prediction models that use machine learning algorithms could provide an objective method for accurate risk prediction to facilitate the prevention and management of CVD in cancer survivors. We evaluated previously tested machine learning algorithms and logistic regression (regularized by machine learning methods), in addition to testing and validating newer, more complex machine learning algorithms, for CVD prediction in cancer survivors. Methods This multicenter study used a database of 3835 multiracial cancer survivors with 89 clinical, laboratory, and echocardiographic features over 20 years. Models were trained using repeated random and time‐split samples and tested on a separate cohort of 329 patients. Model performance was assessed using the area under the receiver operating characteristic curve. Results Regularized logistic regression achieved an area under the receiver operating characteristic curve of 0.845 (heart failure), 0.783 (atrial fibrillation), 0.792 (coronary artery disease), and 0.806 (composite CVD). These are comparable to 0.837 and 0.848 for heart failure, using Bayesian additive regression tree and random forest as more advanced machine learning models, respectively. De novo composite CVD (post‐cancer diagnosis) was also predicted with an area under the receiver operating characteristic curve of 0.826 using regularized logistic regression, compared with 0.735 and 0.802 using decision tree and random forest, respectively. Conclusions Regularized logistic regression and advanced machine learning models demonstrated similar predictive performance, with institutional transferability. These tools may support risk stratification and prevention strategies in cardio‐oncology using longitudinal data. Registration URL: https://www.clinicaltrials.gov ; Unique identifier: NCT05377320.

Background: The use of spinal cord stimulation (SCS) for managing severe refractory chronic pain has expanded considerably due to positive statistical evidence regarding its use; however, the statistical robustness of the underlying randomized controlled trials (RCTs) requires further scrutiny. One such tool that can be used for this purpose is the fragility index, which quantifies how many individual outcome events must be altered for an outcome to lose statistical significance. Thus the index can be used quantitatively to assess the stability and robustness of an RCT’s conclusions, with higher values indicating increased trial stability. This study assesses the fragility of pain outcomes across RCTs investigating SCS for chronic pain to better understand the quality and robustness of evidence. Methods: A systematic search was conducted for RCTs assessing SCS for any chronic pain indication. The primary outcome was an evaluation of the trial-specific fragility index for the prespecified pain primary outcomes of RCTs. Secondary outcomes included an evaluation of fragility for (1) specified indications for SCS therapy, (2) reported pain outcomes appearing in three or more RCTs, (3) the presence/absence of a conflict of interest, and (4) comparisons of SCS to conservative management or different SCS waveform modalities. Results: A total of 30 RCTs were included. The median (interquartile range [IQR]) fragility index across the primary outcome of all trials was 5.45 (3.00 to 11.45). There was no statistical difference between the (1) types of outcomes (dichotomous vs. continuous; P = 0.710), (2) primary versus secondary pain outcomes ( P = 0.771), or (3) presence versus absence of trial conflict of interest ( P = 0.753). Indications with a median (IQR) fragility score greater than three included persistent spinal pain syndrome type 2 with a score of 8.00 (2.80 to 12.60), painful diabetic neuropathy with a score of 6.00 (3.00 to 11.80), complex regional pain syndrome with a score of 7.20 (4.62 to 81.50), mixed etiologies with a score of 9.00 (3.00 to 38.00), and other etiologies with a score of 3.00 (1.00 to 8.55). Conclusions: This study suggests that the majority of RCTs investigating primary pain outcomes after SCS therapy are robust with relatively high fragility scores. Reporting the fragility of outcomes in trials can provide a more comprehensive assessment of trial robustness and can further aid clinicians in interpreting trial results and making informed treatment decisions.

Advances in cancer therapies have transformed many malignancies into chronic or manageable conditions, but have been linked to adverse, including cardiovascular, events. Vascular toxicities associated with cancer treatment range from abnormal vasoreactivity to accelerated atherosclerosis, arterial thrombotic events, vasculitis, and arterial aneurysms or dissections. 5-fluorouracil and VEGF (vascular endothelial growth factor) inhibitors are the agents most commonly linked to abnormal vasoreactivity, whereas BCR-ABL (breakpoint cluster region–Abelson murine leukemia viral oncogene homolog) inhibitors and immune checkpoint inhibitors have been associated with accelerated atherosclerosis. Arterial thrombotic events are seen with VEGF and BCR-ABL inhibitors as well as platinum drugs. Vasculitis emerged with the use of immune checkpoint inhibitors, and arterial aneurysms and dissections with VEGF inhibitors. Radiation therapy can lead to several of the outlined vascular toxicities. This review comprehensively explores the mechanisms of vascular complications associated with chemotherapy, targeted therapies, immunotherapies, and radiation therapy. Key contributors include endothelial injury and dysfunction, oxidative stress, and inflammation. An understanding of the mechanisms of vascular toxicities may facilitate optimal treatment and preventive strategies in patients with cancer.

Background: Accurate characterization of tumor stiffness and adhesion is crucial when surgically resecting meningiomas. Currently, such determinations are difficult to ascertain through standard preoperative imaging diagnostics and clinical experience. Herein, we explored magnetic resonance elastography (MRE) as a means of assessing these parameters and thereby improving neurosurgical resections. Methods: This prospective study of 193 patients with meningiomas involved three distinct patient subsets (cohort 1, 88 [2017–2021]; cohort 2, 55 [2022–2023]; cohort 3, 50 [2023–2024]. We analyzed preoperatively obtained MRE data on meningioma stiffness (cohorts 1 and 2) and adhesion (cohort 2) for accuracy, while matching subjects with or without MRE studies (cohort 3, 1:1 ratio) to define the role of preoperative MRE in improving operative outcomes. Results: Areas under the curve (AUCs) for MRE in gauging meningioma stiffness and adhesion were 0.87 and 0.89, respectively. Both parameters significantly surpassed empiric predictions of stiffness and adhesion rendered by surgeons and radiologists, based on routine magnetic resonance imaging (MRI). MRE-determined stiffness measures independently correlated with prolonged resection duration, whereas MRE-assessed adhesion showed independent associations with increased blood loss, longer duration of tumor resection, and higher risk of pial injury. Ultimately, results based on cohort 3 demonstrated that MRE has great potential in this setting to improve neurosurgical procedures by significantly reducing intraoperative bleeding, resection duration, and risks of pial injury. Conclusion: MRE is a promising, noninvasive tool for accurately assessing meningioma stiffness and adhesion, standing to improve the precision and safety of needed surgical intervention.

Abstract Objectives The aim of this work was to develop an American Headache Society position statement addressing diagnostic screening for migraine among girls and women. Background Despite its high prevalence and substantial negative impacts, migraine is underdiagnosed and undertreated. Diagnostic screening for migraine enables more patients to receive timely, appropriate, and effective management. Methods Development of this position statement followed the rules established by the American Headache Society Guidelines Committee. The published literature was reviewed to determine if migraine meets criteria for when disease screening is justified, to guide recommendations for screening tools, and to determine subpopulation(s) for which migraine screening is indicated. After author consensus was reached, the position statement was reviewed and approved by the American Headache Society Board of Directors. Results Migraine fulfills established criteria for conditions in which screening is appropriate since it is highly prevalent, results in significant morbidity, and exerts substantial economic and social costs. Migraine incidence and prevalence are exceptionally high among girls and women during adolescence and through menopause. Furthermore, there are valid and reliable diagnostic screening methods (e.g., ID Migraine) and effective treatments that reduce migraine symptoms and disease impact. Conclusion Yearly diagnostic screening for migraine should be included as part of women's preventive healthcare services, particularly from adolescence to menopause.

Background: Clozapine is the preferred medication for treatment-resistant schizophrenia with therapeutic drug monitoring (TDM) suggested to mediate its safe and effective use. However, clozapine TDM is not a ubiquitous element of care in clinical practice. Understanding the current state of clinicians' perceptions of and barriers to clozapine TDM is a crucial step in improving its use. Methods: A survey related to the use, perceptions, and barriers of clozapine TDM was distributed across multiple national organizations in the United States, representing several disciplines. Results: Most of the 190 respondents were consultants or attending physicians (42.5%) or pharmacists (52.3%). Nearly 80% of respondents had ordered clozapine level measurements in the year before completing the survey but identified slow turnaround time (TaT) as an important barrier; 73.5% of respondents noted that level measurements were performed at an offsite laboratory. Although 86.8% agreed that clozapine levels should be checked once an initial target dose was reached, less than half would subsequently order clozapine level measurements routinely, unless clinical factors such as nonadherence (96.5% agreement), new interaction (94.5% agreement), or change in smoking status (94.5% agreement) occurred. More pharmacists than prescribers indicated confidence in interpreting and clinically applying clozapine TDM results (84.6% versus 70.1%, P = 0.024), with a similar finding between the groups regarding faster clozapine TDM TaT, resulting in improved patient safety (89.0% versus 68.7% agreement, P = 0.003). In addition, more pharmacists would also conduct clozapine TDM in the setting of an acute inflammatory or infectious process (84.9% versus 61.2%, P = 0.002). Conclusions: These data provide insights into clozapine TDM perception, availability, TaT, and barriers. Further research is required to assess whether a faster TaT and more frequent clozapine TDM positively influence patient outcomes from a safety and effectiveness perspective.

PURPOSE Venetoclax, an oral BCL-2 inhibitor, has efficacy in t(11;14)-positive relapsed/refractory multiple myeloma (RRMM), which is enhanced by dexamethasone, which promotes BCL-2 dependency. METHODS The randomized, open-label, phase III CANOVA study (ClinicalTrials.gov identifier: NCT03539744 ) enrolled adults with t(11;14)-positive RRMM who had received ≥2 previous lines of therapy. Patients were randomly assigned (1:1) to venetoclax-dexamethasone or pomalidomide-dexamethasone until progression or intolerable toxicity. The primary end point was independent review committee assessed–progression-free survival (PFS) in the intention-to-treat population analyzed by stratified log-rank test (two-sided type I error rate, α = .05), with hazard ratio (HR) and 95% CI estimated by stratified Cox proportional hazard model. Secondary end points included response rates, overall survival (OS), minimal residual disease (MRD) negativity rate (<10 –5 ), and safety. RESULTS Overall, 263 patients were randomly assigned (venetoclax-dexamethasone, n = 133; pomalidomide-dexamethasone, n = 130). Median PFS was 9.9 months (95% CI, 6.9 to 12.6) with venetoclax-dexamethasone versus 5.8 months (95% CI, 3.8 to 9.2) with pomalidomide-dexamethasone (HR, 0.823 [95% CI, 0.596 to 1.136]; P = .24). Overall response and very good partial response or better rates were 62% and 39%, respectively, with venetoclax-dexamethasone versus 35% and 14% with pomalidomide-dexamethasone. MRD negativity rate was 8% with venetoclax-dexamethasone and 0% with pomalidomide-dexamethasone. Median OS was 32.4 months (95% CI, 26.4 to 40.7) with venetoclax-dexamethasone and 26.9 months (95% CI, 20.4 to 38.9) with pomalidomide-dexamethasone (HR, 0.856 [95% CI, 0.612 to 1.197]). Grade ≥3 treatment-emergent adverse event rates were 67% with venetoclax-dexamethasone versus 83% with pomalidomide-dexamethasone. There were 16 (12%) treatment-emergent deaths with venetoclax-dexamethasone versus 8 (6%) with pomalidomide-dexamethasone. CONCLUSION The primary end point of PFS was not met. PFS and OS were numerically longer with venetoclax-dexamethasone versus pomalidomide-dexamethasone in t(11;14)-positive RRMM. Consistent with previous studies, infections were associated with venetoclax-dexamethasone; no new safety signals were observed.