Charting the Course: Insights into Neuroendocrine Tumor Dynamics in the United States.

OBJECTIVE: To explore changing trends and characteristics in neuroendocrine tumors (NETs) epidemiology, focusing on demographics, clinical aspects, and survival, including the impact of social determinants of health (SDOH) on outcomes. BACKGROUND: The escalating incidence and prevalence of NETs underscore the pressing need for updated epidemiologic data to reveal the evolving landscape of this condition. Access to current information is imperative for informing clinical strategies and public health initiatives targeting NETs. METHODS: A retrospective, population-based study analyzed NET patient data from 1975 to 2020, using the Surveillance, Epidemiology, and End Results (SEER 8, 12, 18) program. We calculated annual age-adjusted incidence, prevalence, and 5-year overall survival (OS) rates. Survival trends from 2000 to 2019 were examined, employing the Fine-Gray model to evaluate cancer-specific mortality. RESULTS: NETs' age-adjusted incidence rate quadrupled from 1.5 per 100,000 in 1975 to 6.0 per 100,000 in 2020. A decline in incidence occurred from 6.8 per 100,000 in 2019 to 6.0 per 100,000 in 2020. All-cause survival multivariable analysis demonstrated high grade (HR: 2.95, 95% CI: 2.63-3.09, P<0.001), single patients (HR: 1.49, 95% CI: 1.45-1.54, P<0.001), and Black patients (HR: 1.17, 95% CI:1.13-1.22, P<0.001) all had worse survival than their controls. CONCLUSION: In conclusion, our study shows a steady increase in NETs incidence until 2019, with a decline in 2020. Understanding the reasons behind this trend is vital for improved management and public health planning. Further research should focus on the factors driving these changes to enhance our understanding of NET epidemiology.

The Effects of Parathyroidectomy vs Medical Treatments for Secondary Hyperparathyroidism in Patients Undergoing Dialysis: A Meta-Analysis.

OBJECTIVE: The management of secondary hyperparathyroidism in patients undergoing dialysis is debated, with uncontrolled parathyroid hormone (PTH) levels becoming more common despite the expanded use of medical treatments like cinacalcet. This study examines the clinical benefits of parathyroidectomy vs medical treatment in reducing mortality and managing key laboratory parameters in patients undergoing dialysis. METHODS: PubMed, Embase, Cochrane, Scopus, and Web of Science databases were searched for cohort studies or randomized controlled trials published before August 18, 2023. We included studies with comparative arms, specifically medical treatment vs surgical intervention. Patients with a history of kidney transplant were excluded. Outcomes were analyzed using hazard ratios (HRs) for mortality and weighted mean differences (WMD) for laboratory parameters. RESULTS: Twenty-three studies involving 24 398 patients were analyzed. The pooled meta-analysis has shown a significant reduction in all-cause (HR, 0.47; 95% confidence interval [CI], 0.35-0.61) and cardiovascular mortality (HR, 0.58; 95% CI, 0.40-0.84) for parathyroidectomy vs medical treatments. Subgroup analysis showed that parathyroidectomy was associated with a greater reduction in mortality in patients with a PTH level over 585 pg/mL (HR, 0.37; 95% CI, 0.24-0.58). No mortality difference was found when all patients in the medical group received cinacalcet alongside standard medical treatment (HR, 1.02; 95% CI, 0.49-2.11). Parathyroidectomy also led to a larger decrease in PTH (WMD, 1078 pg/mL; 95% CI, 587-1569), calcium (WMD, 0.86 mg/dL; 95% CI, 0.43-1.28), and phosphate (WMD, 0.74 mg/dL; 95% CI, 0.32-1.16). CONCLUSION: Parathyroidectomy may offer a survival advantage compared to medical management in patients with severe secondary hyperparathyroidism.

The overtreatment of papillary thyroid microcarcinoma in the community.

INTRODUCTION: Total thyroidectomy is the traditional primary approach for papillary thyroid cancer. However, recent evidence supports conservative management for low-risk tumors like papillary thyroid microcarcinomas (PTMCs). This study explores the adoption of these practices in our community, using a cancer database to analyze treatment strategies. METHODS: A retrospective review of a 1433-patient institutional database identified 258 â€‹PTMC cases. Outcomes, including 30-day mortality, reoperation rate, postoperative hypocalcemia, and recurrent laryngeal nerve (RLN) injury, were assessed. RESULTS: Of PTMC patients, 63.4% underwent total thyroidectomy, with higher rates of RLN injury (8.8% vs. 2.3%) and hypocalcemia (12.4% vs. 0.0%) compared to lobectomy. Non-endocrine surgeons had higher postoperative radioactive iodine administration rates (28.6% vs. 6.1%). Subgroup analysis revealed a shift in total thyroidectomy rates based on tumor size and surgery period. CONCLUSION: Our community favors total thyroidectomy for PTMC, despite associated complications. Enhanced awareness and adherence to PTMC best practice guidelines are warranted.

Thoughtfully Integrating Cannabis Products Into Chronic Pain Treatment.

Cannabis products (CPs) and cannabis-based medicines (CBMs) are becoming increasingly available and are commonly used for pain management. The growing societal acceptance of cannabis and liberalization of cannabis laws allows patients to access CPs with minimal clinical oversight. While there is mechanistic plausibility that CPs and CBMs may be useful for pain management, the clinical trial literature is limited and does not refute or support the use of CBMs for pain management. Complicating matters, a large and growing body of observational literature shows that many people use CPs for pain management and in place of other medications. However, products and dosing regimens in existing trials are not generalizable to the current cannabis market, making it difficult to compare and reconcile these 2 bodies of literature. Given this complexity, clinicians need clear, pragmatic guidance on how to appropriately educate and work with patients who are using CBMs for pain management. In this review, we narratively synthesize the evidence to enable a clear view of current landscape and provide pragmatic advice for clinicians to use when working with patients. This advice revolves around 3 principles: (1) maintaining the therapeutic alliance; (2) harm reduction and benefit maximization; and (3) pragmatism, principles of patient-centered care, and use of best clinical judgment in the face of uncertainty. Despite the lack of certainty CPs and chronic pain management use, we believe that following these principles can make most of the clinical opportunity presented by discussions around CPs and also enhance the likelihood of clinical benefit from CPs.

Perioperative pain management for cleft palate surgery: a systematic review and procedure-specific postoperative pain management (PROSPECT) recommendations.

BACKGROUND/IMPORTANCE: Cleft palate surgery is associated with significant postoperative pain. Effective pain control can decrease stress and agitation in children undergoing cleft palate surgery and improve surgical outcomes. However, limited evidence often results in inadequate pain control after cleft palate surgery. OBJECTIVES: The aim of this review was to evaluate the available evidence and to develop recommendations for optimal pain management after cleft palate surgery using procedure-specific postoperative pain management (PROSPECT) methodology. EVIDENCE REVIEW: MEDLINE, Embase, and Cochrane Databases were searched for randomized controlled trials and systematic reviews assessing pain in children undergoing cleft palate repair published in English language from July 2002, through August 2023. FINDINGS: Of 1048 identified studies, 19 randomized controlled trials and 4 systematic reviews met the inclusion criteria. Interventions that improved postoperative pain, and are recommended, include suprazygomatic maxillary nerve block or palatal nerve block (if maxillary nerve block cannot be performed). Addition of dexmedetomidine to local anesthetic for suprazygomatic maxillary nerve block or, alternatively, as intravenous administration perioperatively is recommended. These interventions should be combined with a basic analgesic regimen including acetaminophen and nonsteroidal anti-inflammatory drugs. Of note, pre-incisional local anesthetic infiltration and dexamethasone were administered as a routine in several studies, however, because of limited procedure-specific evidence their contribution to pain relief after cleft palate surgery remains unknown. CONCLUSION: The present review identified an evidence-based analgesic regimen for cleft palate surgery in pediatric patients. PROSPERO REGISTRATION NUMBER: CRD42022364788.

Legal and Regulatory Aspects of Medical Cannabis in the United States.

Federal and state laws in the United States governing the use of cannabis are rapidly evolving. Under federal law, marijuana and its derivatives remain schedule I, defined as substances having no currently accepted medical use and a high potential for abuse. Hemp and its derivatives, in contrast, have been removed from schedule I. At the state level, a majority of states have passed laws legalizing cannabis in some form, although these laws vary from state to state in terms of the extent to which use is permitted, approved medical uses, and the types of regulation placed on commercial activity and quality control. This inconsistency has contributed to uncertainty among medical providers and their patients. In this review, we provide a brief account of the evolution and current state of federal and state laws and regulatory agencies involved in overseeing medical cannabis use in the United States.

Rescue of dendritic cells from glycolysis inhibition improves cancer immunotherapy in mice.

Inhibition of glycolysis in immune cells and cancer cells diminishes their activity, and thus combining immunotherapies with glycolytic inhibitors is challenging. Herein, a strategy is presented where glycolysis is inhibited in cancer cells using PFK15 (inhibitor of PFKFB3, rate-limiting step in glycolysis), while simultaneously glycolysis and function is rescued in DCs by delivery of fructose-1,6-biphosphate (F16BP, one-step downstream of PFKFB3). To demonstrate the feasibility of this strategy, vaccine formulations are generated using calcium-phosphate chemistry, that incorporate F16BP, poly(IC) as adjuvant, and phosphorylated-TRP2 peptide antigen and tested in challenging and established YUMM1.1 tumours in immunocompetent female mice. Furthermore, to test the versatility of this strategy, adoptive DC therapy is developed with formulations that incorporate F16BP, poly(IC) as adjuvant and mRNA derived from B16F10 cells as antigens in established B16F10 tumours in immunocompetent female mice. F16BP vaccine formulations rescue DCs in vitro and in vivo, significantly improve the survival of mice, and generate cytotoxic T cell (Tc) responses by elevating Tc1 and Tc17 cells within the tumour. Overall, these results demonstrate that rescuing glycolysis of DCs using metabolite-based formulations can be utilized to generate immunotherapy even in the presence of glycolytic inhibitor.

Evidence-based Perioperative Practice Utilization among Various Racial Populations-A Retrospective Cohort Trending Analysis of Lower Extremity Total Joint Arthroplasty Patients.

BACKGROUND: Various studies have demonstrated racial disparities in perioperative care and outcomes. The authors hypothesize that among lower extremity total joint arthroplasty patients, evidence-based perioperative practice utilization increased over time among all racial groups, and that standardized evidence-based perioperative practice care protocols resulted in reduction of racial disparities and improved outcomes. METHODS: The study analyzed 3,356,805 lower extremity total joint arthroplasty patients from the Premier Healthcare database (Premier Healthcare Solutions, Inc., USA). The exposure of interest was race (White, Black, Asian, other). Outcomes were evidence-based perioperative practice adherence (eight individual care components; more than 80% of these implemented was defined as "high evidence-based perioperative practice"), any major complication (including acute renal failure, delirium, myocardial infarction, pulmonary embolism, respiratory failure, stroke, or in-hospital mortality), in-hospital mortality, and prolonged length of stay. RESULTS: Evidence-based perioperative practice adherence rate has increased over time and was associated with reduced complications across all racial groups. However, utilization among Black patients was below that for White patients between 2006 and 2021 (odds ratio, 0.94 [95% CI, 0.93 to 0.95]; 45.50% vs. 47.90% on average). Independent of whether evidence-based perioperative practice components were applied, Black patients exhibited higher odds of major complications (1.61 [95% CI, 1.55 to 1.67] with high evidence-based perioperative practice; 1.43 [95% CI, 1.39 to 1.48] without high evidence-based perioperative practice), mortality (1.70 [95% CI, 1.29 to 2.25] with high evidence-based perioperative practice; 1.29 [95% CI, 1.10 to 1.51] without high evidence-based perioperative practice), and prolonged length of stay (1.45 [95% CI, 1.42 to 1.48] with high evidence-based perioperative practice; 1.38 [95% CI, 1.37 to 1.40] without high evidence-based perioperative practice) compared to White patients. CONCLUSIONS: Evidence-based perioperative practice utilization in lower extremity joint arthroplasty has been increasing during the last decade. However, racial disparities still exist with Black patients consistently having lower odds of evidence-based perioperative practice adherence. Black patients (compared to the White patients) exhibited higher odds of composite major complications, mortality, and prolonged length of stay, independent of evidence-based perioperative practice use, suggesting that evidence-based perioperative practice did not impact racial disparities regarding particularly the Black patients in this surgical cohort.

Thresholds for surgical referral in primary hyperparathyroidism: A conjoint analysis.

BACKGROUND: Primary hyperparathyroidism (PHPT) can be cured through surgery, but referral for treatment is often provider dependent. A conjoint analysis was performed to identify factors influencing referral for surgery. METHODS: Online survey assessed endocrinologists and other physicians who reviewed 10 patient scenarios. They decided whether to refer for surgery or medical management based on clinical (age, comorbidities, etc) and biochemical factors (mild or classic disease). RESULTS: Classic PHPT, age below 50, absence of comorbidities, presence of osteoporosis, and seeing a surgical provider significantly increased the likelihood of surgery referral (p < 0.001). Physician characteristics such as gender, practice duration, and setting did not have a significant influence. CONCLUSION: Despite published benefits of surgery, non-surgical physicians were less likely to refer PHPT patients for surgical treatment if patients were older (age ≥ 50), had comorbid conditions, or had mild disease. More education and advocacy are needed for improved access to surgery.

Addition of dexamethasone to prolong peripheral nerve blocks: a ChatGPT-created narrative review.

Chat Generative Pre-trained Transformer (ChatGPT), an artificial intelligence chatbot, produces detailed responses and human-like coherent answers, and has been used in the clinical and academic medicine. To evaluate its accuracy in regional anesthesia topics, we produced a ChatGPT review on the addition of dexamethasone to prolong peripheral nerve blocks. A group of experts in regional anesthesia and pain medicine were invited to help shape the topic to be studied, refine the questions entered in to the ChatGPT program, vet the manuscript for accuracy, and create a commentary on the article. Although ChatGPT produced an adequate summary of the topic for a general medical or lay audience, the review that were created appeared to be inadequate for a subspecialty audience as the expert authors. Major concerns raised by the authors included the poor search methodology, poor organization/lack of flow, inaccuracies/omissions of text or references, and lack of novelty. At this time, we do not believe ChatGPT is able to replace human experts and is extremely limited in providing original, creative solutions/ideas and interpreting data for a subspecialty medical review article.

How large language models can augment perioperative medicine: a daring discourse.

Interest in natural language processing, specifically large language models, for clinical applications has exploded in a matter of several months since the introduction of ChatGPT. Large language models are powerful and impressive. It is important that we understand the strengths and limitations of this rapidly evolving technology so that we can brainstorm its future potential in perioperative medicine. In this daring discourse, we discuss the issues with these large language models and how we should proactively think about how to leverage these models into practice to improve patient care, rather than worry that it may take over clinical decision-making. We review three potential major areas in which it may be used to benefit perioperative medicine: (1) clinical decision support and surveillance tools, (2) improved aggregation and analysis of research data related to large retrospective studies and application in predictive modeling, and (3) optimized documentation for quality measurement, monitoring and billing compliance. These large language models are here to stay and, as perioperative providers, we can either adapt to this technology or be curtailed by those who learn to use it well.

Practice Advisory for Preoperative and Intraoperative Pain Management of Cardiac Surgical Patients: Part 2.

Pain after cardiac surgery is of moderate to severe intensity, which increases postoperative distress and health care costs, and affects functional recovery. Opioids have been central agents in treating pain after cardiac surgery for decades. The use of multimodal analgesic strategies can promote effective postoperative pain control and help mitigate opioid exposure. This Practice Advisory is part of a series developed by the Society of Cardiovascular Anesthesiologists (SCA) Quality, Safety, and Leadership (QSL) Committee's Opioid Working Group. It is a systematic review of existing literature for various interventions related to the preoperative and intraoperative pain management of cardiac surgical patients. This Practice Advisory provides recommendations for providers caring for patients undergoing cardiac surgery. This entails developing customized pain management strategies for patients, including preoperative patient evaluation, pain management, and opioid use-focused education as well as perioperative use of multimodal analgesics and regional techniques for various cardiac surgical procedures. The literature related to this field is emerging, and future studies will provide additional guidance on ways to improve clinically meaningful patient outcomes.

Enhanced Recovery After Surgery (ERAS®) Society Consensus Guidelines for Emergency Laparotomy Part 3: Organizational Aspects and General Considerations for Management of the Emergency Laparotomy Patient.

BACKGROUND: This is Part 3 of the first consensus guidelines for optimal care of patients undergoing emergency laparotomy using an enhanced recovery after surgery (ERAS) approach. This paper addresses organizational aspects of care. METHODS: Experts in management of the high-risk and emergency general surgical patient were invited to contribute by the International ERAS® Society. PubMed, Cochrane, Embase, and MEDLINE database searches were performed for ERAS elements and relevant specific topics. Studies were selected with particular attention to randomized clinical trials, systematic reviews, meta-analyses and large cohort studies, and reviewed and graded using the Grading of Recommendations, Assessment, Development and Evaluation system. Recommendations were made on the best level of evidence, or extrapolation from studies on elective patients when appropriate. A modified Delphi method was used to validate final recommendations. RESULTS: Components of organizational aspects of care were considered. Consensus was reached after three rounds of a modified Delphi process. CONCLUSIONS: These guidelines are based on best current available evidence for organizational aspects of an ERAS® approach to patients undergoing emergency laparotomy and include discussion of less common aspects of care for the surgical patient, including end-of-life issues. These guidelines are not exhaustive but pull together evidence on important components of care for this high-risk patient population. As much of the evidence is extrapolated from elective surgery or emergency general surgery (not specifically laparotomy), many of the components need further evaluation in future studies.

Consensus Guidelines for Perioperative Care for Emergency Laparotomy Enhanced Recovery After Surgery (ERAS®) Society Recommendations Part 2-Emergency Laparotomy: Intra- and Postoperative Care.

BACKGROUND: This is Part 2 of the first consensus guidelines for optimal care of patients undergoing emergency laparotomy (EL) using an Enhanced Recovery After Surgery (ERAS) approach. This paper addresses intra- and postoperative aspects of care. METHODS: Experts in aspects of management of high-risk and emergency general surgical patients were invited to contribute by the International ERAS® Society. PubMed, Cochrane, Embase, and Medline database searches were performed for ERAS elements and relevant specific topics. Studies on each item were selected with particular attention to randomized clinical trials, systematic reviews, meta-analyses, and large cohort studies and reviewed and graded using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) system. Recommendations were made on the best level of evidence, or extrapolation from studies on elective patients when appropriate. A modified Delphi method was used to validate final recommendations. Some ERAS® components covered in other guideline papers are outlined only briefly, with the bulk of the text focusing on key areas pertaining specifically to EL. RESULTS: Twenty-three components of intraoperative and postoperative care were defined. Consensus was reached after three rounds of a modified Delphi Process. CONCLUSIONS: These guidelines are based on best available evidence for an ERAS® approach to patients undergoing EL. These guidelines are not exhaustive but pull together evidence on important components of care for this high-risk patient population. As much of the evidence is extrapolated from elective surgery or emergency general surgery (not specifically laparotomy), many of the components need further evaluation in future studies.