Aortic Arch Plaques and the Long-Term Risk of Stroke and Cardiovascular Events in the Statin Era.

BACKGROUND: Aortic arch plaques are associated with an increased risk of ischemic stroke in patients with cryptogenic stroke or prior embolic events. However, this relationship is unclear in the community. We investigated (1) the long-term risk of stroke and cardiovascular events associated with arch plaques and (2) whether statin therapy prescribed for any indication modified the association. METHODS: A total of 934 stroke-free participants (72±9 years; 37% men) from the CABL study (Cardiovascular Abnormalities and Brain Lesion) were evaluated. Arch plaques were assessed by suprasternal transthoracic echocardiography; plaques ≥4 mm in thickness were classified as large plaques. The primary outcome was ischemic stroke; the secondary outcome was combined cardiovascular events (ischemic stroke, myocardial infarction, and cardiovascular death). The plaque-related risk of outcomes was also analyzed according to the presence of statin treatment. No plaque was used as a reference. RESULTS: Aortic arch plaques were present in 645 participants (69.1%), with large plaques in 114 (12.2%). During a mean follow-up of 11.3±3.6 years, 236 (25.3%) cardiovascular events occurred (76 ischemic strokes, 27 myocardial infarctions, and 133 cardiovascular deaths). Large arch plaques were independently associated with combined events (adjusted hazard ratio, 2.19 [95% CI, 1.40-3.43]) but not stroke alone (adjusted hazard ratio, 1.09 [95% CI, 0.50-2.38]). The association between large plaques and cardiovascular events was significant in participants receiving statins (adjusted hazard ratio, 2.57 [95% CI, 1.52-4.37]) but not in others; however, participants on statin treatment also had a worse risk profile (higher body mass index, greater frequencies of hypertension, diabetes, and coronary artery disease). CONCLUSIONS: Aortic arch plaques may be a marker of cardiovascular risk rather than a direct embolic stroke source in older adults without prior stroke. The efficacy of broader cardiovascular risk factors control, beyond cholesterol levels alone, for primary prevention of cardiovascular events in individuals with aortic arch plaques may require further investigation.

Stable iron (58Fe) isotopic measurements in Kenyan toddlers during 3 months of iron supplementation demonstrate that half of the iron absorbed is lost.

Increased iron loss may reduce the effectiveness of iron supplementation. The objective of this study was to determine if daily oral iron supplementation increases iron loss, measured using a stable isotope of iron (58Fe). We enrolled and dewormed 24 iron-depleted Kenyan children, 24-27 months of age, whose body iron was enriched and equilibrated with 58Fe given at least 1 year earlier. Over 3 months of supplementation (6 mg iron/kg body weight [BW]/day), mean (±SD) iron absorption was 1.10 (±0.28) mg/day. During supplementation, 0.55 (±0.36) mg iron/day was lost, equal to half of the amount of absorbed iron. Supplementation did not increase faecal haem/porphyrin or biomarkers of enterocyte damage and gut or systemic inflammation. Using individual patient data, we examined iron dose, absorption and loss among all available long-term iron isotopic studies of supplementation. Expressed in terms of body weight, daily iron loss was correlated significantly with iron absorption (Pearson's r = 0.66 [95% confidence interval 0.48-0.78]) but not with iron dose (r = 0.16 [95% CI -0.10-0.40]). The results of this study indicate that iron loss is increased with daily oral iron supplementation and may blunt the efficacy of iron supplements in children. This study was registered at ClinicalTrials.gov as NCT04721964.

Pediatric oncology provider perspectives and patient/family perceptions of chemotherapy-induced nausea and vomiting management: Experiences at an academic medical center.

BACKGROUND: Chemotherapy-induced nausea and vomiting (CINV) is common in children undergoing cancer treatment, and significantly impacts quality of life. Clinical practice guidelines (CPGs) have been developed to guide CINV management, though many patients do not receive guideline-concordant care. Few studies have examined provider perspectives on CINV management or preferred improvement approaches, or pediatric patient perception of CINV control. METHODS: A cross-sectional study of pediatric oncology providers was conducted at a large freestanding children's hospital. Providers completed an anonymous online survey about CINV control in patients admitted for scheduled chemotherapy, and their knowledge and utilization of CINV CPGs. A survey of English and Spanish-speaking pediatric oncology patients admitted for scheduled chemotherapy was conducted to assess CINV management, with key demographics used to understand association with perceptions and adherence to antiemetic guidelines. RESULTS: For providers, 75% of respondents felt CINV management could be moderately or extremely improved, significantly more so by chemotherapy prescribers and pediatric medical residents than nurses. Over half of respondents did not have awareness of CINV CPGs, particularly pediatric medical residents. For patients, nausea was reported to be extremely well controlled in 44% of cases, and vomiting extremely well controlled in 50% of cases. There were no significant differences in patient-reported CINV across demographics, when considering emetogenicity of chemotherapy received, or concordance to guidelines. CONCLUSIONS: Implementing education in this area may help to improve provider comfort, and ultimately, the patient experience. Future studies will expand upon this novel patient perception, and develop and evaluate CINV management interventions.

Evaluation of ChatGPT-generated medical responses: A systematic review and meta-analysis.

OBJECTIVE: Large language models (LLMs) such as ChatGPT are increasingly explored in medical domains. However, the absence of standard guidelines for performance evaluation has led to methodological inconsistencies. This study aims to summarize the available evidence on evaluating ChatGPT's performance in answering medical questions and provide direction for future research. METHODS: An extensive literature search was conducted on June 15, 2023, across ten medical databases. The keyword used was "ChatGPT," without restrictions on publication type, language, or date. Studies evaluating ChatGPT's performance in answering medical questions were included. Exclusions comprised review articles, comments, patents, non-medical evaluations of ChatGPT, and preprint studies. Data was extracted on general study characteristics, question sources, conversation processes, assessment metrics, and performance of ChatGPT. An evaluation framework for LLM in medical inquiries was proposed by integrating insights from selected literature. This study is registered with PROSPERO, CRD42023456327. RESULTS: A total of 3520 articles were identified, of which 60 were reviewed and summarized in this paper and 17 were included in the meta-analysis. ChatGPT displayed an overall integrated accuracy of 56 % (95 % CI: 51 %-60 %, I2 = 87 %) in addressing medical queries. However, the studies varied in question resource, question-asking process, and evaluation metrics. As per our proposed evaluation framework, many studies failed to report methodological details, such as the date of inquiry, version of ChatGPT, and inter-rater consistency. CONCLUSION: This review reveals ChatGPT's potential in addressing medical inquiries, but the heterogeneity of the study design and insufficient reporting might affect the results' reliability. Our proposed evaluation framework provides insights for the future study design and transparent reporting of LLM in responding to medical questions.

Iron Deficiency in Chronic Pediatric Heart Failure: Overall Assessment and Outcomes in Dilated Cardiomyopathy.

OBJECTIVE: To evaluate the frequency of iron status assessment in pediatric heart failure and the prevalence and adverse effects of absolute iron deficiency in dilated cardiomyopathy-induced heart failure. STUDY DESIGN: We retrospectively reviewed records of children with chronic heart failure at our center between 2010 and 2020. In children with dilated cardiomyopathy, we analyzed baseline cardiac function, hemoglobin level, and subsequent risk of composite adverse events (CAE), including death, heart transplant, ventricular assist device (VAD) placement, and transplant registry listing. Absolute iron deficiency and iron sufficiency were defined as transferrin saturations <20% and ≥30%, respectively; and indeterminant iron status as 20%-29%. RESULTS: Of 799 patients with chronic heart failure, 471 (59%) had no iron-related laboratory measurements. Of 68 children with dilated cardiomyopathy, baseline transferrin saturation, and quantitative left ventricular ejection fraction (LVEF), 33 (49%) and 14 (21%) were iron deficient and sufficient, respectively, and 21 (31%) indeterminant. LVEF was reduced to 23.6 ± 12.1% from 32.9 ± 16.8% in iron deficiency and sufficiency, respectively (P = .04), without a significant difference in hemoglobin. After stratification by New York Heart Association classification, in advanced class IV, hemoglobin was reduced to 10.9 ± 1.3 g/dL vs 12.7 ± 2.0 g/dL in iron deficiency and sufficiency, respectively (P = .01), without a significant difference in LVEF. CONCLUSIONS: In this single-center study, iron deficiency was not monitored in most children with chronic heart failure. In pediatric dilated cardiomyopathy-induced heart failure, absolute iron deficiency was prevalent and associated with clinically consequential and possibly correctable decreases in cardiac function and hemoglobin concentration.

Body mass index and additional risk factors for cancer in adults with cystic fibrosis.

BACKGROUND: Adults with cystic fibrosis (CF) have an increased risk of a variety of cancers, notably gastrointestinal cancers. In CF higher body mass index (BMI) is associated with improved long-term outcomes, yet in the general population high BMI is associated with increased cancer risk. We aimed to delineate associations between BMI and other factors with cancer risk in adults with CF. METHODS: This was a retrospective cohort study using CF Foundation Patient Registry data from 1992 to 2015. Data were collected on age, sex, CFTR mutation class, pancreatic insufficiency, and annualized data on BMI and FEV1. The primary analysis was the association between BMI and cancer, with secondary analyses focused on BMI trajectory. Multivariable logistic regression was performed, with analyses stratified by history of transplant. RESULTS: Of 26,199 adults with CF, 446 (1.7%) had cancer diagnosed by histology at a mean age of 40.0 years (SD 12.2), with a higher proportion of transplanted patients developing cancer (137 (3.8%) v 309(1.4%), p < 0.001). Among non-transplanted patients, there was no association between BMI and cancer (p for trend = 0.43). Pancreatic insufficiency (p < 0.01) and higher FEV1 (p < 0.01) were associated with increased cancer risk. In transplanted patients, higher BMI was associated with reduced risk of cancer (p for trend = 0.04). Older age was associated with increased risk in both groups (p < 0.001). BMI trajectories were not associated with cancer risk in either group. CONCLUSION: Higher BMI is associated with a reduced risk of cancer in transplanted adults with CF. Pancreatic insufficiency is a risk factor for cancer in non-transplanted CF patients.

Pediatric hematology providers' contraceptive practices for female adolescents and young adults with sickle cell disease: A national survey.

BACKGROUND: Adolescent and young adult (AYA) women with sickle cell disease (SCD) have increased pregnancy-related health risks and are prescribed potentially teratogenic medications, yet limited data are available regarding pediatric SCD provider contraceptive practices. We aimed to assess pediatric hematology providers' beliefs, practices, motivators, and barriers for providing contraceptive care to female AYAs with SCD. METHODS: Guided by the Health Belief Model (HBM), we developed a 25-question, web-based survey to assess practices. Survey links were distributed nationwide to pediatric SCD and/or general hematology providers through their publicly available emails and by request to directors of U.S.-accredited Pediatric Hematology-Oncology fellowship programs for distribution to their SCD providers. Data analysis included descriptive statistics, chi-square analysis, and logistic regression. RESULTS: Of 177 respondents, 160 surveys meeting inclusion criteria were analyzed. Most providers reported counseling (77.5%) and referring female AYA patients for contraception (90.8%), but fewer reported prescribing contraception (41.8%). Proportionally fewer trainees provided counseling compared with established providers (54% vs. 85%, p < .001), with a similar trend for prescribing (p = .05). Prescription practices did not differ significantly by provider beliefs regarding potential teratogenicity of hydroxyurea. Key motivators included patient request and disclosure of sexual activity. Key barriers included inadequate provider training, limited visit time, and perceived patient/parent interest. CONCLUSION: Provider contraceptive practices for female AYAs with SCD varied, especially by provider status. Health beliefs regarding teratogenic potential of hydroxyurea did not correlate with contraceptive practices. Clinical guidelines, provider training, and patient/parent decision-making tools may be tested to assess whether provider contraceptive practices could be improved.

Provider and staff crisis well-being associated with trust in leadership and baseline burnout.

BACKGROUND: The impact of the coronavirus 2019 (COVID-19) pandemic on the emotional health of health care workers continues to be an area of active research. However, few studies have focused on those working in pediatrics and its subspecialties, as well as ancillary and non-patient-facing staff. The purpose of this study was to determine the prevalence and associated predictors of burnout and emotional well-being of providers and staff. METHODS: An anonymous electronic survey was developed evaluating demographics, pandemic experiences, possible predictor variables, and three main outcomes of burnout, psychological distress, and perceived stress. Pediatric hematology oncology (PHO) chiefs and program directors across the country were invited to participate and disseminate the survey to their programs. RESULTS: A total of 682/1950 (35% of invited) individuals responded to all predictor and outcome variables. Over half reported high levels of burnout and some reported moderate/high levels of distress. Prepandemic burnout and decreased trust in leadership were associated with all three outcomes. Additional predictors included having a child ≤18 years at home, hospital role, and worrying about patient care or relationship with their patients. The majority (n = 444/682, 65.5%) reported that their institution had made COVID-19-related mental health resources available. However, only 6.5% (n = 44/682) reported utilizing these resources. CONCLUSIONS: While the majority of PHO providers and staff were resilient during the early stages of the COVID-19 pandemic, many reported high levels of burnout, yet few are utilizing institutional resources. This study has highlighted several actionable areas to help identify and address factors that are wearing down the emotional well-being of providers and staff.

Bacteremia in Febrile, Non-neutropenic, and Well-appearing Children With Cancer.

Fever in a neutropenic pediatric oncology patient requires prompt assessment due to the risk of infectious complications. The appropriate management of fever in non-neutropenic patients, however, is not well-established. We describe the rate of bacteremia in a cohort of non-neutropenic pediatric oncology patients with fever at a large institution. Patients were included if they presented to the emergency department or outpatient clinic between 2009 and 2014 with fever, had a central venous catheter (CVC), and were not neutropenic. Three hundred eighty-six episodes of fever occurring in 159 patients were included in the data analysis. Fifty-nine percent of patients were male, 41% had a diagnosis of acute lymphoblastic leukemia, and 90% had a port-a-cath as CVC. The rate of bacteremia was 3.4%; presence of a port-a-cath was protective against bacteremia whereas a white blood cell count >20,000/mm3 was associated with a higher likelihood of bacteremia. Gram-positive microorganisms were most commonly isolated (64.3%) and frequently resistant to cephalosporins. In summary, in our study, the rate of bacteremia was low among non-neutropenic, well-appearing pediatric cancer patients with a CVC and was not associated with any serious medical complications. Prospective research is needed to determine the most appropriate management of these patients.

Modeling risks of cardiovascular and cancer mortality following a diagnosis of loco-regional breast cancer.

BACKGROUND: Many women with breast cancer also have a high likelihood of cardiovascular mortality, and while there are several cardiovascular risk prediction models, none have been validated in a cohort of breast cancer patients. We first compared the performance of commonly-used cardiovascular models, and then derived a new model where breast cancer and cardiovascular mortality were modeled simultaneously, to account for the competing risk endpoints and commonality of risk factors between the two events. METHODS: We included 20,462 women diagnosed with stage I-III breast cancer between 2000 and 2010 in Kaiser Permanente Northern California (KPNC) with follow-up through April 30, 2015, and examined the performance of the Framingham, CORE and SCOREOP cardiovascular risk models by area under the receiver operating characteristic curve (AUC), and observed-to -expected (O/E) ratio. We developed a multi-state model based on cause-specific hazards (CSH) to jointly model the causes of mortality. RESULTS: The extended models including breast cancer characteristics (grade, tumor size, nodal involvement) with CVD risk factors had better discrimination at 5-years with AUCs of 0.85 (95% CI 0.83, 0.86) for cardiovascular death and 0.80 (95% CI 0.78, 0.87) for breast cancer death compared with the existing cardiovascular models evaluated at 5 years AUCs ranging 0.71-0.78. Five-year calibration for breast and cardiovascular mortality from our multi-state model was also excellent (O/E = 1.01, 95% CI 0.91-1.11). CONCLUSION: A model incorporating cardiovascular risk factors, breast cancer characteristics, and competing events, outperformed traditional models of cardiovascular disease by simultaneously estimating cancer and cardiovascular mortality risks.

Notch Signaling Mediates Differentiation in Barrett's Esophagus and Promotes Progression to Adenocarcinoma.

BACKGROUND & AIMS: Studies are needed to determine the mechanism by which Barrett's esophagus (BE) progresses to esophageal adenocarcinoma (EAC). Notch signaling maintains stem cells in the gastrointestinal tract and is dysregulated during carcinogenesis. We explored the relationship between Notch signaling and goblet cell maturation, a feature of BE, during EAC pathogenesis. METHODS: We measured goblet cell density and levels of Notch messenger RNAs in BE tissues from 164 patients, with and without dysplasia or EAC, enrolled in a multicenter study. We analyzed the effects of conditional expression of an activated form of NOTCH2 (pL2.Lgr5.N2IC), conditional deletion of NOTCH2 (pL2.Lgr5.N2fl/fl), or loss of nuclear factor κB (NF-κB) (pL2.Lgr5.p65fl/fl), in Lgr5+ (progenitor) cells in L2-IL1B mice (which overexpress interleukin 1 beta in esophagus and squamous forestomach and are used as a model of BE). We collected esophageal and stomach tissues and performed histology, immunohistochemistry, flow cytometry, transcriptome, and real-time polymerase chain reaction analyses. Cardia and forestomach tissues from mice were cultured as organoids and incubated with inhibitors of Notch or NF-kB. RESULTS: Progression of BE to EAC was associated with a significant reduction in goblet cell density comparing nondysplastic regions of tissues from patients; there was an inverse correlation between goblet cell density and levels of NOTCH3 and JAG2 messenger RNA. In mice, expression of the activated intracellular form of NOTCH2 in Lgr5+ cells reduced goblet-like cell maturation, increased crypt fission, and accelerated the development of tumors in the squamocolumnar junction. Mice with deletion of NOTCH2 from Lgr5+ cells had increased maturation of goblet-like cells, reduced crypt fission, and developed fewer tumors. Esophageal tissues from in pL2.Lgr5.N2IC mice had increased levels of RelA (which encodes the p65 unit of NF-κB) compared to tissues from L2-IL1B mice, and we found evidence of increased NF-κB activity in Lgr5+ cells. Esophageal tissues from pL2.Lgr5.p65fl/fl mice had lower inflammation and metaplasia scores than pL2.Lgr5.N2IC mice. In organoids derived from pL2-IL1B mice, the NF-κB inhibitor JSH-23 reduced cell survival and proliferation. CONCLUSIONS: Notch signaling contributes to activation of NF-κB and regulates differentiation of gastric cardia progenitor cells in a mouse model of BE. In human esophageal tissues, progression of BE to EAC was associated with reduced goblet cell density and increased levels of Notch expression. Strategies to block this pathway might be developed to prevent EAC in patients with BE.

Clinical significance of recurrent gastroesophageal junction intestinal metaplasia after endoscopic eradication of Barrett's esophagus.

BACKGROUND AND AIMS: After endoscopic eradication of Barrett's esophagus (BE), recurrence of intestinal metaplasia at the gastroesophageal junction (GEJIM) is common. The clinical significance of this finding is unclear. We assessed whether recurrent GEJIM is associated with increased risk of subsequent dysplasia and whether endoscopic treatment lowers this risk. METHODS: A retrospective, multicenter, cohort study was performed of treated BE patients who achieved complete eradication of intestinal metaplasia (IM). Postablation follow-up was performed at standard intervals. Recurrent GEJIM was defined as nondysplastic IM on gastroesophageal junction biopsy specimens without endoscopic evidence of BE. Patients were categorized as "never-GEJIM," "GEJIM-observed," or "GEJIM-treated." Endoscopic treatment for recurrent GEJIM was at the endoscopists' discretion. The primary outcome was dysplasia recurrence. Analyses were performed using log-rank tests and Cox proportional hazards modeling. RESULTS: Six hundred thirty-three patients were analyzed; median follow-up was 47 months (interquartile range, 24-69). Most patients (81%) had high-grade dysplasia or intramucosal adenocarcinoma before treatment. Dysplasia recurrence was 2.2% per year. GEJIM-observed patients had the lowest rate of recurrence (.6%/y) followed by GEJIM-treated (2.2%/y) and never-GEJIM (2.6%/y) (log-rank P = .07). In multivariate analyses, compared with never-GEJIM, the risk of dysplasia recurrence was significantly lower in GEJIM-observed patients (adjusted hazard ratio, .19; 95% confidence interval, .05-.81) and not different in GEJIM-treated patients (adjusted hazard ratio, .81; 95% confidence interval, .39-1.67). Older age and longer initial BE length were independently associated with recurrence. CONCLUSIONS: Recurrent GEJIM after endoscopic eradication of BE was not associated with an increased risk of subsequent dysplasia. Future studies are warranted to determine if observation is appropriate for this finding.

A bilingual dietary intervention early in treatment is feasible and prevents weight gain in childhood acute lymphoblastic leukemia.

BACKGROUND: Childhood acute lymphoblastic leukemia (ALL) is the most common pediatric malignancy. The onset of obesity during childhood ALL has been well established and is associated with inferior survival rates and increased treatment-related toxicities. This pilot study sought to determine if a dietary intervention is feasible and minimizes weight gain during the initial phases of treatment for ALL. METHODS: Participants were recruited from four institutions, fluent in English or Spanish, between 5 and 21 years old, and enrolled within 3 days of starting induction therapy. Participants were counseled for 6 months to follow a low glycemic diet. Dietary and anthropometric data were collected at diagnosis, end of induction, and end of month 6 (NCT03157323). RESULTS: Twenty-three of 28 participants (82.1%) were evaluable and included in the analysis. Dietary changes targeted by the nutrition intervention were successful; sugar intake declined (P = .003), whereas vegetable intake increased (P = .033). The majority of participants were able to adhere to the dietary principles prescribed: ≥70.0% reduced glycemic load and ≥60.0% increased fiber intake and decreased sugar intake. Importantly, we did not observe an increase in body mass index z-score during induction or over the 6-month intervention period. Most families found the nutrition intervention easy to follow (60%) and affordable (95%) despite simultaneous initiation of treatment for ALL. CONCLUSIONS: A 6-month nutrition intervention initiated during the initial phase of treatment for childhood ALL is feasible and may prevent weight gain. Our preliminary findings need to be confirmed in a larger clinical trial.

Low CD4 count may be a risk factor for non-tuberculous mycobacteria infection in pediatric hematopoietic cell transplant recipients.

BACKGROUND: HCT leaves patients in a relative state of immune deficiency both during their initial transplant admission and for several years following discharge. NTM are generally harmless colonizers of the outside environment, but for immunocompromised patients, they can cause significant disease due to a paucity of T-cell defense. While routine prophylaxis against NTM is recommended for patients with low CD4 counts in certain clinical settings (eg, AIDS), this is not yet established for HCT patients despite their higher risk. METHODS: Here we build upon our prior work to determine risk factors for NTM in pediatric HCT patients by comparing NTM patient characteristics to matched HCT controls. RESULTS: We followed 272 patients across a 13-year time period, with 11 cases of NTM. Patients with NTM had a significantly lower CD4 count at Day 365 than matched HCT controls (105.5 ± 97.0 cells/µl vs. 856.2 ± 446.1 cells/µl, respectively; p = .001). No other potential risk factors (eg, CMV, GvHD, disease type) were found to be statistically significant, including use of T-cell depleting agents. This is consistent with an average diagnosis of NTM at Day +323 (ie, outside immediate post-transplant period). All-cause mortality was similar between NTM and control HCT groups, with an NTM attributable mortality of <10%. CONCLUSION: Since reduced CD4 counts are associated with NTM, and cost and morbidity are high, azithromycin prophylaxis for CD4 count <200 cells/µl in high-risk patients should be considered.

Validation of a Questionnaire to Identify Respiratory Tract Infections in Children With Sickle Cell Disease.

BACKGROUND: No validated questionnaires have been published that are specific for identifying respiratory infections in children with sickle cell disease (SCD). METHODS: A questionnaire was developed that included 6 respiratory symptoms (difficulty breathing, wheezing, fever, cough, runny or stuffy nose, and sore throat) to identify respiratory events for a clinical trial. The questionnaire results were compared with identification of viral respiratory pathogens from nasal samples by reverse transcriptase polymerase chain reaction. RESULTS: Eighty questionnaire responses (40 with symptom/s and 40 without) paired with isolation of viral respiratory pathogen from nasal samples were obtained from 53 children with SCD, ages 4 to 18 years over 2 separate periods in different seasons. The questionnaire yielded a sensitivity of 82%, specificity of 72% with an overall accuracy of 76%. The kappa value was 0.53, indicating moderate agreement, and the Fleiss' kappa test statistic was 4.77 with P<0.001, indicating that agreement between the 2 methods was not by chance. CONCLUSION: These results provide evidence for validity of this 6-symptom respiratory questionnaire in identification of respiratory viral infections for use in SCD-related research.

Prognostic value of nadir GH levels for long-term biochemical remission or recurrence in surgically treated acromegaly.

CONTEXT: Outcome of acromegaly surgery is assessed by IGF-1 and glucose-suppressed GH, but whether the latter provides additional clinically relevant information when IGF-1 is normal is unclear. The role of GH suppression testing after surgery requires clarification. METHODS: We studied 97 acromegaly patients with normal IGF-1 after surgery by measuring GH after oral glucose longitudinally, initially at ≥ 3 months after surgery and repeated one or more times ≥ 1 year later. Nadir GH was categorized as normal or abnormal relative to the 97.5th percentile of nadir GH in 100 healthy subjects, which were ≤ 0.14 µg/L (DSL IRMA) or ≤ 0.15 µg/L(IDS iSYS). Signs and symptoms scores and insulin resistance were followed longitudinally. RESULTS: Of 68 patients with initial normal GH suppression 63 (93%) remained in remission and of 29 with initial abnormal GH suppression, 9 (31%) recurred. Recurrence was more common in patients with abnormal suppression (P < 0.001). A total of 14 patients recurred, including 5 with normal GH suppression progressing to abnormal and then recurrence. Overall, serial signs and symptoms and insulin resistance assessments did not identify patients with abnormal suppression or recurrence. CONCLUSION: Risk of recurrence after surgery is increased for patients with a normal IGF-1 level, but abnormal GH suppression. We newly find, using both our and others' cut-offs, that while normal suppression predicts long-term remission in most patients, some can progress from normal to abnormal suppression and then recurrence after many years of follow up. Nadir GH levels are of prognostic value in acromegaly patients with normal IGF-1 levels after surgery.

Where Have All the Emergencies Gone? The Impact of the COVID-19 Pandemic on Obstetric and Gynecologic Procedures and Consults at a New York City Hospital.

STUDY OBJECTIVE: The purpose of this study was to assess the impact of the coronavirus disease 2019 (COVID-19) pandemic on surgical volume and emergency department (ED) consults across obstetrics-gynecology (OB-GYN) services at a New York City hospital. DESIGN: Retrospective cohort study. SETTING: Tertiary care academic medical center in New York City. PATIENTS: Women undergoing OB-GYN ED consults or surgeries between February 1, 2020 and April 15, 2020. INTERVENTIONS: March 16 institutional moratorium on elective surgeries. MEASUREMENTS AND MAIN RESULTS: The volume and types of surgeries and ED consults were compared before and after the COVID-19 moratorium. During the pandemic, the average weekly volume of ED consults and gynecology (GYN) surgeries decreased, whereas obstetric (OB) surgeries remained stable. The proportions of OB-GYN ED consults, GYN surgeries, and OB surgeries relative to all ED consults, all surgeries, and all labor and delivery patients were 1.87%, 13.8%, 54.6% in the pre-COVID-19 time frame (February 1-March 15) vs 1.53%, 21.3%, 79.7% in the COVID-19 time frame (March 16-April 15), representing no significant difference in proportions of OB-GYN ED consults (p = .464) and GYN surgeries (p = .310) before and during COVID-19, with a proportionate increase in OB surgeries (p <.002). The distribution of GYN surgical case types changed significantly during the pandemic with higher proportions of emergent surgeries for ectopic pregnancies, miscarriages, and concern for cancer (p <.001). Alternatively, the OB surgery distribution of case types remained relatively constant. CONCLUSION: This study highlights how the pandemic has affected the ways that patients in OB-GYN access and receive care. Institutional policies suspending elective surgeries during the pandemic decreased GYN surgical volume and affected the types of cases performed. This decrease was not appreciated for OB surgical volume, reflecting the nonelective and time-sensitive nature of obstetric care. A decrease in ED consults was noted during the pandemic begging the question "Where have all the emergencies gone?" Although the moratorium on elective procedures was necessary, "elective" GYN surgeries remain medically indicated to address symptoms such as pain and bleeding and to prevent serious medical sequelae such as severe anemia requiring transfusion. As we continue to battle COVID-19, we must not lose sight of those patients whose care has been deferred.

Major Variation across Local Transplant Centers in Probability of Kidney Transplant for Wait-Listed Patients.

BACKGROUND: Geographic disparities in access to deceased donor kidney transplantation persist in the United States under the Kidney Allocation System (KAS) introduced in 2014, and the effect of transplant center practices on the probability of transplantation for wait-listed patients remains unclear. METHODS: To compare probability of transplantation across centers nationally and within donation service areas (DSAs), we conducted a registry study that included all United States incident adult kidney transplant candidates wait listed in 2011 and 2015 (pre-KAS and post-KAS cohorts comprising 32,745 and 34,728 individuals, respectively). For each center, we calculated the probability of deceased donor kidney transplantation within 3 years of wait listing using competing risk regression, with living donor transplantation, death, and waiting list removal as competing events. We examined associations between center-level and DSA-level characteristics and the adjusted probability of transplant. RESULTS: Candidates received deceased donor kidney transplants within 3 years of wait listing more frequently post-KAS (22%) than pre-KAS (19%). Nationally, the probability of transplant varied 16-fold between centers, ranging from 4.0% to 64.2% in the post-KAS era. Within DSAs, we observed a median 2.3-fold variation between centers, with up to ten-fold and 57.4 percentage point differences. Probability of transplantation was correlated in the post-KAS cohort with center willingness to accept hard-to-place kidneys (r=0.55, P<0.001) and local organ supply (r=0.44, P<0.001). CONCLUSIONS: Large differences in the adjusted probability of deceased donor kidney transplantation persist under KAS, even between centers working with the same local organ supply. Probability of transplantation is significantly associated with organ offer acceptance patterns at transplant centers, underscoring the need for greater understanding of how centers make decisions about organs offered to wait-listed patients and how they relate to disparities in access to transplantation.

Validation and demonstration of a new comprehensive model of Alzheimer's disease progression.

INTRODUCTION: Identifying the course of Alzheimer's disease (AD) for individual patients is important for numerous clinical applications. Ideally, prognostic models should provide information about a range of clinical features across the entire disease process. Previously, we published a new comprehensive longitudinal model of AD progression with inputs/outputs covering 11 interconnected clinical measurement domains. METHODS: Here, we (1) validate the model on an independent cohort; and (2) demonstrate the model's utility in clinical applications by projecting changes in 6 of the 11 domains. RESULTS: Survival and prevalence curves for two representative outcomes-mortality and dependency-generated by the model accurately reproduced the observed curves both overall and for patients subdivided according to risk levels using an independent Cox model. DISCUSSION: The new model, validated here, effectively reproduces the observed course of AD from an initial visit assessment, allowing users to project coordinated developments for individual patients of multiple disease features.

Extrapyramidal signs and Alzheimer's disease prognosis in a multiethnic, community-based sample of demented elders.

INTRODUCTION: Extrapyramidal signs (EPS) are a common feature of Alzheimer's disease associated with worse outcomes in observational studies of dementia. Less research has been conducted on ethnic minority and non-clinic-based populations. METHODS: One hundred and forty-two multiethnic community-dwelling participants with dementia were selected. Adjusted Cox models were fitted for mortality, cognitive (Mini Mental State Examination ≤10), functional (Blessed Dementia Rating Scale ≥10), and dependency (needs full-time care) endpoints with baseline EPS as predictor. RESULTS: Thirty-seven participants (26.06%) had EPS at baseline. EPS predicted more rapid time to death (hazard ratio [HR] = 2.76, 95% confidence interval [CI] = 1.49, 5.42), and functional endpoint (HR = 3.88, 95% CI = 1.75, 8.62) but not cognitive and dependency endpoints. No evidence of interaction by ethnicity, age, sex, education, or apolipoprotein E ε4 polymorphism was found. DISCUSSION: Our results partially confirm previous studies on predominantly White, clinic-based samples. Further research is needed to better understand the etiological role of EPS in AD.