Citations

AbstractAimThere is increasing adoption of nonoperative management of rectal cancer; however, the extent to which trainees are proficient in nonoperative management is unclear. The aim of this work was to describe the exposure of recent colorectal resident graduates to nonoperative management, their comfort level in assessing clinical responses and their comfort in performing rectal cancer surgeries.MethodThis was an online survey of Accreditation Council for Graduate Medical Education‐certified colorectal surgery residency graduates of training programmes in 2020, 2021 and 2022 utilizing their respective WhatsApp class chat groups. Data on resident comfort in assessing complete or near complete clinical response as part of nonoperative management, adoption in practice and perceived effects on rectal cancer operative experience were collected.ResultsForty five graduates responded, with 83.3% exposed to nonoperative management in training. Eighty five per cent utilize nonoperative management in their own practices and 37.1% felt it had a negative impact on preparing them for rectal cancer surgeries. While 82.4% felt comfortable assessing a complete clinical response, only 61.8% felt comfortable assessing a near complete response. Residents who perceived a positive effect on their training felt more comfortable assessing a complete or near complete response.ConclusionMost recent graduates were exposed to nonoperative management in training and utilize it in practice, although many did not feel comfortable assessing a near complete response. A significant portion felt it had a negative impact on their experience and quantity of rectal cancer surgeries. This suggests a need to improve colorectal resident education in nonoperative management of rectal cancer while simultaneously preserving surgical experience for trainees.

ABSTRACTBackgroundRenal medullary carcinoma (RMC) is an aggressive tumor associated with sickle cell trait. Despite treatment advances for other rare renal tumors, RMC survival remains poor. We aimed to describe the contemporary management and survival of children and adults with RMC.ProcedureIn this multicenter retrospective cohort study, Pediatric Surgical Oncology Research Collaborative sites searched their databases for patients diagnosed with RMC (2000–2022). Descriptive statistics were calculated and survival analyses performed using Kaplan–Meier and Cox regression.ResultsThirty‐four patients with RMC were identified. Median age was 19 years (IQR: 15–28; range: 7–52). Most were male (24/34; 71%), Black (27/32; 84%), had sickle cell trait or disease (30/33; 91%), presented with metastatic disease (27/34; 79%), and were symptomatic at presentation (32/34; 94%). Median overall survival (OS) was 24 months from diagnosis (16 months for children, 28 months for adults, p = 0.6). Receipt of platinum‐based chemotherapy (23/34; 68%) was associated with significantly higher OS than other regimens (35 vs. 5 months, p < 0.001). Nephrectomy (24/34; 71%) was associated with significantly improved OS compared with non‐operative management (34 vs. 7 months, p = 0.001). Immunotherapy, targeted therapy, or radiation therapy were not associated with significant differences in OS, nor were age, sex, race, sickle cell status, SMARCB1/INI‐1, stage, nephrectomy approach, retroperitoneal lymph node dissection, gross residual disease, margins, or tumor size.ConclusionsRMC survival remains poor despite newer therapies. Nephrectomy and platinum‐based chemotherapy should be considered in locally advanced and metastatic disease. Coordinated international cooperative group studies are needed to meaningfully improve RMC survival.

Abstract Background Classic progressive supranuclear palsy RS syndrome (PSP‐RS) is characterized by early postural instability/falls and vertical supranuclear gaze palsy, although other signs/symptoms can occur, for example, axial rigidity, bradykinesia, and cognitive dysfunction. The Movement Disorders Society‐PSP (MDS‐PSP) criteria consider probable PSP‐RS a homogenous syndrome, but this has not been tested. Objectives We aim to investigate relationships between signs/symptoms of PSP‐RS beyond its core features and determine whether PSP‐RS is a homogeneous syndrome. Methods 118 participants who met MDS‐PSP criteria for probable PSP‐RS were analyzed. All participants received an independent clinical diagnosis based on clinical judgment. We first performed a Network Analysis using qgraph with Spearman's correlation to quantify relationships between 16 signs/symptoms followed by a k‐means clustering analysis using the same signs/symptoms to identify possible heterogeneity of the PSP‐RS designation. Results Five network clusters were identified, reflecting: (1) tremor, (2) sensitivity to bright light, (3) oculomotor function, (4) cognition, and (5) akinetic‐rigidity‐praxis. Worse akinetic‐rigidity was associated with better oculomotor function, but worse cognition. Cluster analysis revealed two clusters. Cluster I ( n = 89) had more severe clinical features than Cluster II ( n = 29). Cluster II had a higher frequency of participants (37.9%) clinically judged as not PSP‐RS: these participants were less likely to have PSP pathology on autopsy ( P = 0.03). Conclusions Some signs/symptoms of PSP‐RS strongly associate and are more likely to co‐occur. PSP‐RS, as defined by the MDS‐PSP criteria includes a subset of participants not clinically judged as PSP‐RS who are less likely to have PSP pathology.

Atopic dermatitis affects 20% to 25% of children and has significant impact on quality of life of patients and families. Recent studies of the pathogenesis of AD highlight the interplay between a defective skin barrier, immune dysfunction, and the cutaneous microbiome. Standard of care for AD treatment includes topical corticosteroids for active disease and moisturization to repair the barrier defect. Emerging treatments include dupilumab and Janus kinase (JAK) inhibitors. Reduction of triggers and proactive treatment with topical corticosteroids and/or topical calcineurin inhibitors can reduce flares. Treatment plans should be clear and as simple as possible to maximize adherence.

ABSTRACTBackgroundPrior studies have documented that patients with colorectal cancer (CRC) are at an increased risk of cardiovascular disease (CVD).ObjectivesTo examine coronary artery calcium (CAC) as a marker of subclinical atherosclerosis and its association with major adverse cardiovascular events (MACE) in patients with CRC across the cancer treatment trajectory.MethodsAdults with newly diagnosed CRC were enrolled in the prospective ColoCare study from 2017 to 2024. CAC was measured from routine diagnostic computed tomography (CT) and positron emission tomography‐CT scans at CRC diagnosis until 5 years post‐diagnosis. Atherosclerosis was defined as the presence of CAC. We used multivariable‐adjusted Fine and Gray models to assess the association between CAC and MACE risk, accounting for competing risks.ResultsAmong 300 CRC patients, the most common CVD risk factors at cancer diagnosis were hypertension (37%), hyperlipidemia (24%), and diabetes (14%). During follow‐up (median = 5.3 years), 75 (25%) individuals experienced MACE: stroke (3%), new/worsening HF (9%), HF exacerbation requiring hospitalization (2%), coronary revascularization (3%), and death (19%). Among individuals with imaging at baseline (n = 101), 37 (36.6%) had CAC, and statins were not prescribed in 11 (55.0%) patients with moderate/high CAC. For those with serial imaging (n = 61), 31.1% showed worsening CAC and 3% developed new CAC. Baseline CAC conferred a higher risk of MACE (HR = 4.79; 95% CI: 1.05–21.75, p = 0.04) after accounting for cancer‐related deaths as a competing risk.ConclusionsSubclinical atherosclerosis and MACE are common among patients with CRC. Integrating CAC from routine cancer imaging can identify patients who may benefit from cardio‐preventive treatment.

Introduction: Although primarily supplied by the vertebrobasilar system, the hippocampus is partially supplied by ipsilateral carotid artery branches through the anterior choroidal artery or a prominent posterior communicating artery. We report a patient with acute hippocampus infarction likely due to symptomatic ipsilateral tandem carotid stenosis and discuss acute vascular-mediated hippocampal injury. Case Report: An 80-year-old female with obesity, dyslipidemia, hypertension, alcohol use disorder, history of breast cancer on letrozole, and traumatic brain injury was brought into our emergency department for 24 hours of confusion. On examination, she exhibited limited registration, recall, and executive dysfunction with otherwise normal language, visuo-spatial orientation, and praxis. Brain MRI showed a small area of diffusion restriction in the anterior right hippocampus with matched FLAIR hyperintensity, consistent with acute infarction. Computed tomography angiogram head and neck showed 90% stenosis of the proximal right internal carotid artery (ICA), <50% narrowing of the proximal left ICA, and moderate bilateral narrowing of the paraclinoid ICAs, all due to calcific atheromatous plaques. The etiology of the hippocampal infarction was suspected embolism from the ipsilateral severe carotid stenosis. Planning for right cervical carotid revascularization ensued. Conclusion: This case highlights the dual hippocampal vascular supply and that hippocampal embolic infarcts could be a sign of a symptomatic severe carotid artery stenosis that may require urgent revascularization for stroke secondary prevention.

Abstract Background Preexisting diabetes (PDM) increases the risk of maternal and perinatal mortality and morbidity. Reduction of maternal hyperglycemia prior to and during pregnancy can reduce these risks. Despite compelling evidence that preconception care (PCC), which includes achieving strict glycemic goals, reduces the risk of congenital malformations and other adverse pregnancy outcomes, only a minority of individuals receive PCC. Suboptimal pregnancy outcomes demonstrated in real-world data highlight the need to further optimize prenatal glycemia. New evolving technology shows promise in helping to achieve that goal. Dysglycemia is not the only driver of poor pregnancy outcomes in PDM. The increasing impact of obesity on pregnancy outcomes underscores the importance of optimal nutrition and management of insulin sensitizing medications during prenatal care for PDM. Objective To provide recommendations for the care of individuals with PDM that lead to a reduction in maternal and neonatal adverse outcomes. Methods The Guideline Development Panel (GDP) composed of a multidisciplinary panel of clinical experts, along with experts in guideline methodology and systematic literature review, identified and prioritized 10 clinically relevant questions related to the care of individuals with diabetes before, during and after pregnancy. The GDP prioritized randomized controlled trials (RCTs) evaluating the effects of different interventions (eg, PCC, nutrition, treatment options, delivery) during the reproductive life cycle of individuals with diabetes, including type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM). Systematic reviews queried electronic databases for publications related to these 10 clinical questions. The Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) methodology was used to assess the certainty of evidence and develop recommendations. The approach incorporated perspectives from 2 patient representatives and considered patient values, costs and resources required, acceptability and feasibility, and impact on health equity of the proposed recommendations. Results In individuals with diabetes mellitus who have the possibility of becoming pregnant, we suggest asking a screening question about pregnancy intention at every reproductive, diabetes, and primary care visit. Screening for pregnancy intent is also suggested at urgent care/emergency room visits when clinically appropriate (2 | ⊕OOO). This was suggested based on indirect evidence demonstrating a strong association between PCC and both reduced glycated hemoglobin (HbA1c) at the first prenatal visit and congenital malformations. In individuals with diabetes mellitus who have the possibility of becoming pregnant, we suggest use of contraception when pregnancy is not desired (2 | ⊕⊕OO). This was suggested based on indirect evidence in women with diabetes, where PCC—including contraception as a key component—showed a clinically significant association with improvements in first-trimester HbA1c and the rate of congenital malformations, together with indirect evidence from the general population regarding the reduction of unplanned pregnancies and pregnancy terminations with the use of contraception. In individuals with T2DM, we suggest discontinuation of glucagon-like peptide-1 receptor agonist (GLP-1RA) before conception rather than discontinuation between the start of pregnancy and the end of the first trimester (2 | ⊕OOO). This was suggested based on limited data on risk of exposure to GLP-1RA receptor agonists during pregnancy. In pregnant individuals with T2DM already on insulin, we suggest against routine addition of metformin (2 | ⊕OOO). This was suggested based on the GDP judgment that the benefit of adding metformin to insulin to achieve decrease in rates of large for gestational age infants did not outweigh the potential harm of increasing the risk of small for gestational age infants or adverse childhood outcomes related to changes in body composition. In individuals with PDM, we suggest either a carbohydrate-restricted diet (&lt;175 g/day) or usual diet (&gt;175 g/day) during pregnancy (2 | ⊕OOO). This was suggested based on the GDP judgment that the available evidence was limited and very indirect, resulting in significant uncertainty about the net benefits or harms. As such, the evidence was insufficient to support a recommendation either for or against a carbohydrate intake cutoff of 175 g/day. In pregnant individuals with T2DM, we suggest either the use of a continuous glucose monitor (CGM) or self-monitoring of blood glucose (SMBG) (2 | ⊕OOO). There is lack of direct evidence supporting superiority of CGM use over SMBG for T2DM during pregnancy. There is indirect evidence supporting improved glucometrics with the use of CGM for individuals with T2DM outside of pregnancy, substantial improvements in neonatal outcomes for individuals with T1DM using CGM during pregnancy and the potential for decreasing adverse pregnancy outcomes with improved glucometrics in individuals with T2DM. In individuals with PDM using a CGM, we suggest against the use of a single 24-hour CGM target &lt;140 mg/dL (7.8 mmol/L) in place of standard-of-care pregnancy glucose targets of fasting &lt;95 mg/dL (5.3 mmol/L), 1-hour postprandial &lt;140 mg/dL (7.8 mmol/L), and 2-hour postprandial &lt; 120 mg/dL (6.7 mmol/L) (2 | ⊕OOO). This was suggested based on indirect evidence that associated adverse pregnancy outcomes with a fasting glucose &gt; 126 mg/dL (7 mmol/L). In individuals with T1DM who are pregnant, we suggest the use of a hybrid closed-loop pump (pump adjusting automatically based on CGM) rather than an insulin pump with CGM (without an algorithm) or multiple daily insulin injections with CGM (2 | ⊕OOO). This was suggested based on a meta-analysis of RCTs which demonstrated improvement in glucometrics with increased time in range (MD +3.81%; CI −4.24 to 11.86) and reduced time below range (MD −0.88%; 95% CI: −2.04 to 0.27) with the use of hybrid closed-loop pump technology. In individuals with PDM, we suggest early delivery based on risk assessment rather than expectant management (2 | ⊕OOO). This was suggested based on indirect evidence that risks may outweigh benefits of expectant management beyond 38 weeks gestation and that risk assessment criteria may be useful to inform ideal delivery timing. In individuals with PDM (including those with pregnancy loss or termination), we suggest postpartum endocrine care (diabetes management), in addition to usual obstetric care (2 | ⊕OOO). As the postpartum period frequently overlaps with preconception, this was suggested based on indirect evidence demonstrating a strong association between PCC and both reduced HbA1c at the first prenatal visit and congenital malformations. Conclusion The data supporting these recommendations were of very low to low certainty, highlighting the urgent need for research designed to provide high certainty evidence to support the care of individuals with diabetes before, during, and after pregnancy. Investment in implementation science for PCC is crucial to prevent significant mortality and morbidity for individuals with PDM and their children. RCTs to further define glycemic targets in pregnancy and refinement of emerging technology to achieve those targets can lead to significant reduction of harm and in the burden of diabetes care. Data on optimal nutrition and obesity management in pregnancy are lacking. More research on timing of delivery in women with PDM is also needed.

Background Treatment of in-stent restenosis (ISR) accounts for 10% of percutaneous coronary interventions in the USA. Paclitaxel-coated balloons (PCBs) are an alternative to uncoated balloons (UCBs) for ISR. Methods We systematically searched PubMed, Scopus, and Cochrane Central for studies comparing PCB with UCB in treating ISR. Outcomes included late lumen loss, binary restenosis, target lesion revascularization (TLR), and major adverse cardiovascular events (MACE). Results Eight trials including 1410 patients [PCB in 865 (61%), follow-up 6 months to 10 years) were identified. Angiographic outcomes of late lumen loss [mean difference: −0.50 mm; 95% confidence interval (CI): −0.66 to −0.33; P < 0.01] and binary restenosis [relative risk (RR): 0.22; 95% CI: 0.13–0.40; P < 0.01] at 6–8 months were lower with PCB. TLR at 6 months (RR: 0.16; 95% CI: 0.06–0.40; P < 0.001) and 1 year (RR: 0.45; 95% CI: 0.31–0.66; P < 0.001), MACE at 6 months (RR: 0.25; 95% CI: 0.16–0.38; P < 0.001), MACE at 3–5 years (RR: 0.54; 95% CI: 0.37–0.80; P = 0.002), and TLR at 3–5 years (RR: 0.51; 95% CI: 0.29–0.90; P = 0.021) were lower with PCB. Meta-regression revealed that ISR lesions in the left anterior descending artery were associated with lower rates of binary restenosis while the opposite was observed for left circumflex lesions. Conclusion Revascularization of coronary ISR with PCB is associated with reduced late lumen loss, binary restenosis, TLR, CCE, and MACE. PCB may be a preferred strategy for coronary ISR.

ImportanceVestibular migraine has no established treatments.ObjectiveTo test the efficacy of rizatriptan for treating vestibular migraine attacks.Design, Setting, and ParticipantsThis double-blind, randomized clinical trial of rizatriptan vs placebo was conducted from December 2014 through July 2020 (data analyses in 2021 and sensitivity analyses in 2022 and 2024) at 2 tertiary neurotologic centers. Adults with vestibular migraine were included.InterventionAll participants underwent prospective observation to confirm diagnosis and illness activity and were then randomized in a 2:1 ratio to receive rizatriptan 10 mg or placebo to treat up to 3 vestibular migraine attacks per participant.Main Outcomes and MeasuresParticipants rated symptoms as absent, mild, moderate, or severe at scheduled intervals. Primary outcomes were the percentage of attacks with reductions in vertigo and unsteadiness/dizziness from moderate or severe to absent or mild at 1 hour. Secondary outcomes were the percentage of attacks with complete resolution of vestibular symptoms at 1 hour; reductions in headache and associated symptoms at 1 hour; use of rescue medications after 1 hour; reductions in vestibular, headache, and associated symptoms at 24 hours without rescue medications; treatment satisfaction and quality of life at 48 hours; and rates of serious adverse effects and discontinuation due to adverse effects.ResultsOf 222 total participants (mean [SD] age, 42.3 [11.7] years; 70.7% were women), 134 (60.4%) with active illness treated 307 attacks. Efficacy was tested using 240 attacks with vestibular symptoms rated as moderate or severe when participants took study drug. At 1 hour, rizatriptan did not differ from placebo for reducing vertigo (73/151 [48.3%] vs 50/88 [56.8%] attacks; odds ratio [OR], 0.71 [95% CI, 0.42-1.21]), unsteadiness/dizziness (29/151 [19.2%] vs 11/89 [12.4%] attacks; OR, 1.69 [95% CI, 0.80-3.57]), or any secondary outcomes. Similar percentages of participants in rizatriptan and placebo groups (26.4% for both groups) added rescue remedies after 1 hour. At 24 hours, rizatriptan had medium effects over placebo for unsteadiness/dizziness (OR, 2.65) and motion sensitivity (OR, 3.58). Post hoc analyses of all treated attacks found a medium effect favoring rizatriptan for headache and photophobia or phonophobia at 24 hours. Treatment satisfaction was equivocal. Quality of life was mixed. No participants experienced serious adverse effects or discontinued treatment for adverse effects.Conclusions and RelevanceIn this study, rizatriptan was ineffective at 1 hour for treating vestibular migraine attacks and had limited benefit on symptoms at 24 hours. Findings do not support using rizatriptan for vestibular migraine attacks.Trial RegistrationClinicalTrials.gov Identifier: NCT02447991