Hypovitaminosis D and hyperparathyroidism: a 5-year postoperative follow-up of 30,458 gastric bypass and sleeve gastrectomy patients.

BACKGROUND: Bariatric procedures are associated with nutrient deficiencies. Studies show an association between gastric bypass (Roux-en-Y gastric bypass [RYGB]) and hypovitaminosis D as well as hyperparathyroidism, yet few compare RYGB to sleeve gastrectomy (SG), and large long-term analyses are scarce. OBJECTIVE: Evaluate trends of vitamin D and parathyroid hormone (PTH) levels in RYGB and SG. SETTING: National quality register. METHOD: The Scandinavian Obesity Surgery Registry records all bariatric surgeries in Sweden. Data from 2008 to 2021 on primary RYGB or SG with reported 25-hydroxy vitamin D (25-OH-D) and/or PTH levels were included. Individuals with an estimated glomerular filtration rate of <60 mL/min/1.73 m2 were excluded, leaving a study population of 25,385 RYGB and 5073 SG patients. RESULTS: A decrease in 25-OH-D, mirrored by an increase in PTH, was observed after the first year for both procedures, but more pronounced in RYGB. At 5 years, 25-OH-D levels were still higher than at baseline. Regular supplementation resulted in better 25-OH-D and PTH levels. Linear regression found that procedure type (RYGB versus SG), 25-OH-D levels, and time since surgery were significant factors in predicting PTH levels. The risk of pathologic PTH levels (>7 pmol/L) at 2 and 5 years postoperatively was roughly three times higher in RYGB (odds ratios = 3.41 and 2.84, respectively). CONCLUSIONS: Previous studies alongside these results suggest that RYGB, more so than SG, may cause hypovitaminosis D and thereby hyperparathyroidism, which could lead to osteopenia. The threshold for 25-OH-D should be >75 nmol/L, and despite higher levels, current vitamin D supplementation may not be sufficient. Follow-up should include screening for hyperparathyroidism and hypovitaminosis D.

Calcium-based phosphate binders and bone mineral density in patients undergoing hemodialysis: a retrospective cohort study.

BACKGROUND: Calcium supplements are commonly prescribed to prevent fractures in patients with osteoporosis. Nonetheless, they are generally eschewed in hemodialysis patients because they increase vascular calcification and induce cardiovascular disease. This retrospective cohort study aimed to investigate the effect of calcium-based phosphate binders (CBPB) on bone mineral density (BMD) in hemodialysis patients. METHODS: Outpatients on dialysis who underwent BMD measurement from January to December 2017, whose data on BMD trends and CBPB administration were recorded over the next 4 years, were enrolled. Patients receiving anti-osteoporotic medications were excluded. The association between the presence and duration of CBPB administration and changes in BMD was evaluated. RESULTS: The femoral neck's BMD decreased from 0.836 g/cm2 (0.702-0.952) to 0.764 g/cm2 (0.636-0.896) (P < 0.001) in the non-CBPB group (patients who never received CBPB over 4 years, n = 32). The CBPB group (n = 56) exhibited only a minute decrease from 0.833 g/cm2 (0.736-0.965) to 0.824 g/cm2 (0.706-0.939) (P = 0.004). Multivariate linear regression analysis revealed better BMD maintenance in the CBPB group [ß-coefficient (95% CI): 0.033 (0.001-0.065); P = 0.046] than in the non-CBPB group. Additionally, the prolonged-CBPB administration group showed superior BMD preservation [ß-coefficient (95% CI): 0.038 (0.001-0.076); P = 0.042]. CONCLUSION: CBPB administration may be associated with BMD maintenance.

[Iron supplementation in patients with chronic inflammatory bowel disease: recommendations for a practical approach]. / Eisensupplementation bei Patienten mit chronisch-entzündlicher Darmerkrankung: Empfehlungen zur praxisnahen Vorgehensweise.

Iron deficiency is the predominant cause of anemia. Iron deficiency anemia plays a major role, especially in patients with inflammatory bowel disease (IBD), and is the most common extraintestinal manifestation and IBD-associated systemic complication. The presence of anemia leads to a reduction in quality of life in patients with IBD associated with limitations in physical, emotional, and cognitive function. In addition, it is associated with an increased hospitalization rate. For this reason, iron supplementation is of particular importance. Oral and intravenous iron supplements are used to treat iron deficiency. Due to the lack of absorption and gastrointestinal side effects of oral substitution, intravenous supplementation is becoming increasingly important. However, there are still certain concerns about intravenous administration.With the help of this review, we want to address the topic of iron substitution in patients with IBD, summarize current guideline recommendations, and provide a practical approach.

Safety and Efficacy of HL301 In Radiation Pneumonitis in Patients With Unresectable Non-Small Cell Lung Cancer Receiving Curative Concurrent Chemoradiotherapy: A Multicenter, Randomized, Double-Blinded, Placebo-Controlled, Phase 2a Clinical Trial.

PURPOSE: We aimed to investigate the safety and efficacy of HL301, a standardized combination product of 7 medicinal plants, in radiation pneumonitis in patients with unresectable non-small cell lung cancer undergoing curative concurrent chemoradiotherapy. METHODS AND MATERIALS: The target accrual was 87 and a total of 63 patients were enrolled due to poor accrual rate. We randomly assigned the 63 patients to receive a placebo (arm A), or 1200 mg HL301 (arm B), or 1800 mg HL301 (arm C). Patients received weekly paclitaxel and carboplatin concurrently with intensity-modulated radiation therapy at 60 to 66 Gy in conventional fractionation. Durvalumab was administered as a maintenance treatment according to standard clinical practice. HL301 was administered orally, daily for 12 weeks. The primary endpoint was incidence of grade ≥2 radiation pneumonitis at 24 weeks postchemoradiotherapy. RESULTS: The baseline characteristics of the patients were well balanced. The drug was tolerable with a compliance rate of 86.6%, 86.2%, and 88.8% in arms A, B, and C, respectively (P = .874). None of the patients experienced severe drug-related adverse events. No significant difference in the rate of adverse events were observed between the treatment arms. The incidence of grade ≥2 radiation pneumonitis at 24 weeks postchemoradiotherapy was 37.5% (95% CI, 18.5%-61.4%), 55.6% (95% CI, 33.7%-75.4%), and 52.4% (95% CI, 32.4%-71.7%) in arms A, B, and C, respectively (P = .535). CONCLUSIONS: This is the first exploratory clinical trial to test the safety and efficacy of HL301 in patients with non-small cell lung cancer. Safety and feasibility of HL301 were established but no signals of efficacy in reducing radiation pneumonitis was observed in this dose level.

Beneficial Effects of Echinacoside on Cognitive Impairment and Diabetes in Type 2 Diabetic db/db Mice.

INTRODUCTION: Cognitive dysfunction is an important comorbidity of diabetes. Insulin resistance may play a critical role in diabetes-related cognitive impairment. Echinacoside (ECH), a natural phenylethanoid glycoside, is the active component of anti-diabetes prescriptions in traditional Chinese medicine. Its effect on modulating insulin resistance has been confirmed but modulating neurodegenerative disease remains unclear. METHODS: Db/db mice, a spontaneous type 2 diabetes mode, were intragastrically administered ECH by 300 mg/kg or an equivalent volume of saline. Weight, blood glucose, and insulin resistance index were measured. Morris water maze test was performed to observe the compound effects on cognition. Hippocampal lesions were observed by histochemical analysis. RESULTS: In db/db mice, ECH alleviated diabetes symptoms, memory loss, and hippocampal neuronal damage. Next, the expression of CD44 and phosphorylated tau was upregulated in diabetic mice. In addition, the insulin receptor substrate-1/phosphatidylinositol 3-kinase /protein kinase B signaling pathway was dysregulated in diabetic mice. All these dysregulations could be reversed by ECH. DISCUSSION: This study provides theoretical support and experimental evidence for the future application of ECH in diabetic cognition dysfunction treatment, promoting the development of traditional medicines.

Oral iron supplementation: new formulations, old questions.

Iron-deficiency anemia and pre-anemic iron deficiency are the most frequent pathologies. The first line of treatment involves oral iron supplementation. The simplest, least expensive, and most commonly prescribed drug is ferrous sulfate, while other ferrous salts and ferric complexes with polysaccharides or succinylated milk proteins are also widely used. In recent years, novel iron formulations have been developed, such as the lipophilic iron donor ferric maltol, or nanoparticle encapsulated sucrosomial® iron. Oral iron supplementation is usually efficacious in correcting iron-deficiency anemia and replenishing iron stores but causes gastrointestinal side effects that reduce compliance. When oral iron supplementation is contraindicated, intravenous iron therapy can rapidly achieve therapeutic targets without gastrointestinal complications. Herein, we critically review literature on relative efficacy and tolerability of currently available oral iron supplements, and summarize recent data on optimal dosage and frequency.

Combination therapy for kidney disease in people with diabetes mellitus.

Diabetic kidney disease (DKD), defined as co-existing diabetes and chronic kidney disease in the absence of other clear causes of kidney injury, occurs in approximately 20-40% of patients with diabetes mellitus. As the global prevalence of diabetes has increased, DKD has become highly prevalent and a leading cause of kidney failure, accelerated cardiovascular disease, premature mortality and global health care expenditure. Multiple pathophysiological mechanisms contribute to DKD, and single lifestyle or pharmacological interventions have shown limited efficacy at preserving kidney function. For nearly two decades, renin-angiotensin system inhibitors were the only available kidney-protective drugs. However, several new drug classes, including sodium glucose cotransporter-2 inhibitors, a non-steroidal mineralocorticoid antagonist and a selective endothelin receptor antagonist, have now been demonstrated to improve kidney outcomes in people with type 2 diabetes mellitus. In addition, emerging preclinical and clinical evidence of the kidney-protective effects of glucagon-like-peptide-1 receptor agonists has led to the prospective testing of these agents for DKD. Research and clinical efforts are geared towards using therapies with potentially complementary efficacy in combination to safely halt kidney disease progression. As more kidney-protective drugs become available, the outlook for people living with DKD should improve in the next few decades.

Chronic Low Back Pain in Adults: Evaluation and Management.

Chronic low back pain, defined as lumbar pain persisting for 12 weeks or more, occurs in about 13% of U.S. adults. Patients with chronic low back pain should have a history and physical examination to identify red flags that may indicate serious conditions that warrant immediate intervention or yellow flags (i.e., psychological, environmental, and social factors) that indicate risk of disability. The examination should include an evaluation for radicular symptoms. Routine imaging is not recommended but is indicated when red flags are present, there is a neuromuscular deficit, or if pain does not resolve with conservative therapy. Patients should avoid bed rest. Nonpharmacologic treatment is first-line management and may include therapies with varying evidence of support, such as counseling, exercise therapy, spinal manipulation, massage, heat, dry needling, acupuncture, transcutaneous electrical nerve stimulation, and physical therapy. Pharmacologic interventions are second-line treatment. Nonsteroidal anti-inflammatory drugs are the initial medication of choice; duloxetine may also be beneficial. Evidence is inconclusive to recommend the use of benzodiazepines, muscle relaxants, antidepressants, corticosteroids, insomnia agents, anticonvulsants, cannabis, acetaminophen, or long-term opioids. Epidural corticosteroid injections are not recommended except for short-term symptom relief in patients with radicular pain. Most patients with chronic low back pain will not require surgery; evaluation for surgery may be considered in those with persistent functional disabilities and pain from progressive spinal stenosis, worsening spondylolisthesis, or herniated disk. Physicians should consider prevention of chronic low back pain when patients present with acute back pain. Screening tools are available to predict the progression from acute to chronic low back pain, and targeted treatment strategies are beneficial for preventing progression.

5-EPIFAT trial protocol: a multi-center, randomized, placebo-controlled trial of the efficacy of pharmacotherapy for fatigue using methylphenidate, bupropion, ginseng, and amantadine in advanced cancer patients on active treatment.

BACKGROUND: Cancer-related fatigue (CRF) is still undertreated in most patients, as evidence for pharmacological treatments is limited and conflicting. Also, the efficacy of the pharmacological agents relative to each other is still unclear. Therefore, medications that may potentially contribute to improving CRF will be investigated in this head-to-head trial. Our main objective is to compare the efficacy of methylphenidate vs. bupropion vs. ginseng vs. amantadine vs. placebo in patients with advanced cancer. METHODS: The 5-EPIFAT study is a 5-arm, randomized, multi-blind, placebo-controlled, multicenter trial that will use a parallel-group design with an equal allocation ratio comparing the efficacy and safety of four medications (Methylphenidate vs. Bupropion vs. Ginseng vs. Amantadine) versus placebo for management of CRF. We will recruit 255 adult patients with advanced cancer who experience fatigue intensity ≥ 4 based on a 0-10 scale. The study period includes a 4-week intervention and a 4-week follow-up with repeated measurements over time. The primary outcome is the cancer-related fatigue level over time, which will be measured by the functional assessment of chronic illness therapy-fatigue (FACIT-F) scale. To evaluate safety, the secondary outcome is the symptomatic adverse events, which will be assessed using the Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events in cancer clinical trials (PRO-CTCAE). Also, a subgroup analysis based on a decision tree-based machine learning algorithm will be employed for the clinical prediction of different agents in homogeneous subgroups. DISCUSSION: The findings of the 5-EPIFAT trial could be helpful to guide clinical decision-making, personalization treatment approach, design of future trials, as well as the development of CRF management guidelines. TRIAL REGISTRATION: IRCT.ir IRCT20150302021307N6. Registered on 13 May 2023.

ß-Estradiol Supplementation Regulates Cholesterol Synthesis Independent of Unsaturated Fat Consumption in Adult Zebrafish.

Obesity is a public health concern resulting in a variety of health complications, including heart disease and insulin resistance. Estrogens have been associated with a reduced risk of obesity, but this relationship remains incompletely understood. We assessed the role of 17ß-estradiol (E2) in mitigating complications associated with obesity by supplementing E2 in the diets of overfed zebrafish. We report that dietary E2 supplementation protects against weight gain and modulates de novo cholesterol synthesis in a sex-specific manner. Our studies lead us to propose a model in which E2 regulates hmgcr expression independently of unsaturated fat consumption. These data can be used to develop sex-specific treatments for obesity-related health conditions.

Effect of transcutaneous electrical acupoint stimulation on postoperative urinary function in elderly patients undergoing total hip arthroplasty. / ç»çš®ç©´ä½ç”µåˆºæ¿€å¯¹è€å¹´æ‚£è€ å ¨é«‹å ³èŠ‚ç½®æ¢æœ¯åŽæŽ’å°¿åŠŸèƒ½çš„å½±å“.

OBJECTIVES: To observe the effect of transcutaneous electrical acupoint stimulation (TEAS) on postoperative urinary function in elderly patients undergoing total hip arthroplasty (THA). METHODS: One hundred and eighty elderly patients undergoing unilateral THA without indwelling urinary catheters were randomly assigned to a TEAS group (90 cases, 3 cases dropped out, 4 cases were eliminated) and a sham TEAS group (90 cases, 1 case dropped out, 4 cases were eliminated). Both groups received fascia iliac block and subarachnoid block anesthesia under ultrasound guidance. The patients in the TEAS group were treated with TEAS at Zhongji (CV 3), Guanyuan (CV 4), and bilateral Huiyang (BL 35), Ciliao (BL 32) 30 minutes before anesthesia initiation, with dissperse-dense wave, frequency of 2 Hz/100 Hz, until 30 minutes after surgery. The patients in the sham TEAS group underwent the same procedure with the device applied at the same acupoints but without electrical stimulation. The incidence of postoperative urinary retention (POUR), time to first void, voiding threshold, urinary adenosine triphosphate (ATP) level, postoperative abnormal voiding status (bladder residual volume, re-catheterization rate, nocturia occurrence), and postoperative incidence of urinary tract infection (UTI) and prosthetic joint infection (PJI) were observed in both groups. RESULTS: The incidence of POUR in the TEAS group was lower than that in the sham TEAS group (P<0.05); the time to first void in the TEAS group was shorter than that in the sham TEAS group (P<0.05); the voiding threshold in the TEAS group was lower than that in the sham TEAS group (P<0.05); the urinary ATP level in the TEAS group was higher than that in the sham TEAS group (P<0.05); the bladder residual volume in the TEAS group was lower than that in the sham TEAS group (P<0.05); the nocturia occurrence in the TEAS group was lower than that in the sham TEAS group (P<0.05). However, there was no statistically significant difference in re-catheterization rate, incidence of UTI, and incidence of PJI between the two groups (P>0.05). CONCLUSIONS: TEAS could effectively reduce the occurrence of postoperative urinary retention and improve the postoperative urinary function in elderly patients undergoing THA, which might be related with increasing the urinary ATP level.

Protocol for a phase II study to evaluate the efficacy and safety of nivolumab as a postoperative adjuvant therapy for patients with esophageal cancer treated with preoperative docetaxel, cisplatin plus 5-fluorouracil treatment (PENTAGON trial).

BACKGROUND: In Japan, preoperative adjuvant chemotherapy followed by surgical resection is the standard treatment for patients with locally advanced esophageal squamous cell carcinoma. However, the risk of recurrence after surgical resection remains high. Although a randomized controlled trial evaluating the efficacy of nivolumab, a fully human monoclonal anti-programmed death 1 antibody, as postoperative adjuvant therapy after neoadjuvant chemoradiotherapy and surgery established its superior efficacy as adjuvant therapy, the efficacy for patients who received preoperative adjuvant chemotherapy has not been demonstrated. This study aims to elucidate the efficacy and safety of nivolumab as postoperative adjuvant therapy for patients with esophageal squamous cell carcinoma after preoperative adjuvant chemotherapy with docetaxel and cisplatin plus 5-fluorouracil followed by surgical resection. METHODS: This study is a multi-institutional, single-arm, Phase II trial. We plan to recruit 130 esophageal squamous cell carcinoma patients, who have undergone preoperative adjuvant chemotherapy with docetaxel and cisplatin plus 5-fluorouracil followed by surgical resection. If the patient did not have a pathological complete response, nivolumab is started as a postoperative adjuvant therapy within 4-16 weeks after surgery. The nivolumab dose is 480 mg/day every four weeks. Nivolumab is administered for up to 12 months. The primary endpoint is disease-free survival; the secondary endpoints are overall survival, distant metastasis-free survival, and incidence of adverse events. DISCUSSION: To our knowledge this study is the first trial establishing the efficacy of nivolumab as postoperative adjuvant therapy for patients with esophageal squamous cell carcinoma after preoperative adjuvant chemotherapy with docetaxel and cisplatin plus 5-fluorouracil followed by surgical resection. In Japan, preoperative adjuvant chemotherapy followed by surgery is a well-established standard treatment for resectable, locally advanced esophageal squamous cell carcinoma. Therefore, developing an effective postoperative adjuvant therapy has been essential for improving oncological outcomes.

Implementation of a light therapy team to administer photobiomodulation therapy: A standardized protocol to prevent and treat oral mucositis in the pediatric hematopoietic stem cell transplant population.

BACKGROUND: Oral mucositis (OM) is a painful and common complication of hematopoietic stem cell transplant (HSCT). The Children's Oncology Group recently published guidelines recommending photobiomodulation (PBM) for preventing and treating OM in pediatric HSCT patients. However, this is a rarely used intervention in pediatric hospitals. PROCEDURE: Patients undergoing allogeneic HSCT, or autologous HSCT for a neuroblastoma diagnosis, had PBM administered from the first day of conditioning to transplant Day +20. We successfully developed a standardized treatment protocol and workflow to ensure consistent and uniform delivery of PBM. In addition, clinical patient data were compared before and after PBM implementation. RESULTS: The administration of PBM at our center was feasible, but required dedicated staff. A registered nurse (RN) was determined to be the best fit to deliver PBM. Sixty-two patients received PBM from October 2022 to September 2023; patients from 2021 before PBM implementation were used for comparison. Patients receiving PBM were more likely (p = .03) to engage in teeth brushing (56/62 = 90%) compared to baseline (61/81 = 75%). Mean days of OM decreased from 11.3 to 9 days; patients who received PBM were less likely (p < .001) to be discharged on total parental nutrition (TPN) (11/62 = 18%) compared to baseline (50/82 = 61%). OM-related supportive care costs (TPN and patient-controlled anesthesia [PCA]) were lower (p = .02) for those who received PBM (median cost = $31,229.87 vs. $37,370.66). CONCLUSION: PBM, as the standard of care in the pediatric HSCT population, is safe, feasible, and well-tolerated. At our center, a dedicated RN was critical to providing standardized treatment and ensuring sustainability.

Non-Pharmacological Interventions for Depression and Anxiety in Parkinson's Disease.

Non-pharmacological interventions, including cognitive-behavioral therapy (CBT), non-invasive brain stimulation (NIBS), electroconvulsive therapy (ECT), light therapy (LT), and physical rehabilitation/exercise, have shown promise as effective approaches to treat symptoms of depression and anxiety in individuals with Parkinson's disease (PD). In this narrative literature overview, we discuss the state-of-the-art regarding these treatment options and address future perspectives for clinical practice and research. Non-pharmacological interventions hold promise to treat depression and anxiety in PD. There is meta-analytic evidence for the efficacy of CBT, NIBS, ECT, LT, and exercise on improving depressive symptoms. For the treatment of anxiety symptoms, CBT shows large effects but scientific evidence of other non-pharmacological interventions is limited. Importantly, these treatments are safe interventions with no or mild side-effects. More research is needed to tailor treatment to the individuals' needs and combined interventions may provide synergistic effects.We conclude that non-pharmacological interventions should be considered as alternative or augmentative treatments to pharmacological and neurosurgical approaches for the treatment of depression and anxiety in individuals with PD.

Small bowel intramural hematoma caused by warfarin: case report and literature review.

BACKGROUND: Intramural hematoma of the small bowel is a rare yet acute gastrointestinal condition typically linked with impaired coagulation function, often posing diagnostic challenges. It is principally encountered in patients undergoing prolonged anticoagulant therapy, specifically warfarin. CASE PRESENTATION: We reported a case of intramural hematoma associated with warfarin use. The patient was admitted to hospital with abdominal pain and had received anticoagulant therapy with warfarin 2.5 mg/day for 4 years. Laboratory examination showed decreased coagulation function, abdominal CT showed obvious thickening and swelling of part of the jejunal wall, and abdominal puncture found no gastroenteric fluid or purulent fluid. We treated the patient with vitamin K and fresh frozen plasma. The patient was discharged after the recovery of coagulation function. Then we undertaook a comprehensive review of relevant case reports to extract shared clinical features and effective therapeutic strategies. CONCLUSION: Our analysis highlights that hematoma in the small intestinal wall caused by warfarin overdose often presents as sudden and intense abdominal pain, laboratory tests suggest reduced coagulation capacity, and imaging often shows thickening of the intestinal wall. Intravenous vitamin K and plasma supplementation are effective non-surgical strategies. Nevertheless, in instances of severe obstruction and unresponsive hemostasis, surgical resection of necrotic intestinal segments may be necessary. In the cases we reported, we avoided surgery by closely monitoring the coagulation function. Therefore, we suggest that identifying and correcting the impaired coagulation status of patient is essential for timely and appropriate treatment.

Shifts in Diagnostic Testing for Headache in the Emergency Department, 2015 to 2021.

Importance: Subarachnoid hemorrhage is typically diagnosed by noncontrast head computed tomography (CT); lumbar puncture is recommended if computed tomography is nondiagnostic, although CT cerebral angiography has been promoted as an alternative to lumbar puncture in this diagnostic pathway. The outcomes of this debate in practice have not been studied. Objective: To determine whether CT cerebral angiography use has increased in lieu of lumbar puncture among emergency department (ED) patients with headache, with an increase in unruptured intracranial aneurysm detection. Design, Setting, and Participants: This retrospective cohort study took place in 21 community EDs of an integrated health care system in Northern California between 2015 and 2021. Participants were adult (aged >17 years) health plan members with a chief concern of headache. Exclusions were prior diagnoses of subarachnoid hemorrhage, unruptured intracranial aneurysm, cerebral arteriovenous malformation, or cerebrospinal fluid shunt. Data were analyzed from October to November 2023. Exposures: CT cerebral angiography and/or lumbar puncture during the ED encounter. Main Outcomes and Measures: Primary and secondary outcomes were 14-day and 90-day unruptured intracranial aneurysm detection, respectively. Safety outcomes were missed diagnoses of subarachnoid hemorrhage or bacterial meningitis. The annual incidence of unruptured intracranial aneurysm detection was normalized to the incidence of subarachnoid hemorrhage (UIA:SAH ratio). Average annualized percentage changes were quantified using joinpoint regression analysis. Results: Among 198 109 included ED encounters, the mean (SD) age was 47.5 (18.4) years; 140 001 patients (70.7%) were female; 29 035 (14.7%) were Black or African American, 59 896 (30.2%) were Hispanic or Latino, and 75 602 (38.2%) were White. Per year, CT cerebral angiography use increased (18.8%; 95% CI, 17.7% to 20.3%) and lumbar punctures decreased (-11.1%; 95% CI, -12.0% to -10.4%), with a corresponding increase in the 14-day UIA:SAH ratio (3.5%; 95% CI, 0.9% to 7.4%). Overall, computed tomography cerebral angiography use increased 6-fold relative to lumbar puncture, with a 33% increase in the detection of UIA. Results were similar at 90 days and robust to sensitivity analyses. Subarachnoid hemorrhage (1004 cases) and bacterial meningitis (118 cases) were misdiagnosed in 5% and 18% of cases, respectively, with no annual trends (P = .34; z1003 = .95 and P = .74; z117 = -.34, respectively). Conclusions and Relevance: In this cohort study of ED patients with headache, increases in CT cerebral angiography use were associated with fewer lumbar punctures and higher detection of unruptured intracranial aneurysms, with no significant change in missed diagnoses of subarachnoid hemorrhage or bacterial meningitis. While this shift in diagnostic strategy appeared safe in the short-term, the long-term consequences remain unclear.

The complementary roles of iron and estrogen in menopausal differences in cardiometabolic outcomes.

Biological hormonal changes are frequently cited as an explanatory factor of sex and menopause differences in cardiometabolic diseases (CMD) and its associated risk factors. However, iron metabolism which varies between sexes and among women of different reproductive stages could also play a role. Recent evidence suggest that iron may contribute to CMD risk by modulating oxidative stress pathways and inflammatory responses, offering insights into the mechanistic interplay between iron and CMD development. In the current review, we provide a critical appraisal of the existing evidence on sex and menopausal differences in CMD, discuss the pitfall of current estrogen hypothesis as sole explanation, and the emerging role of iron in CMD as complementary pathway. Prior to menopause, body iron stores are lower in females as compared to males, but the increase during and after menopause, is tandem with an increased CMD risk. Importantly, basic science experiments show that an increased iron status is related to the development of type 2 diabetes (T2D), and different cardiovascular diseases (CVD). While epidemiological studies have consistently reported associations between heme iron intake and some iron biomarkers such as ferritin and transferrin saturation with the risk of T2D, the evidence regarding their connection to CVD remains controversial. We delve into the factors contributing to this inconsistency, and the limitation of relying on observational evidence, as it does not necessarily imply causation. In conclusion, we provide recommendations for future studies on evaluating the potential role of iron in elucidating the sex and menopausal differences observed in CMD.

TaoHe ChengQi decoction ameliorates sepsis-induced cardiac dysfunction through anti-ferroptosis via the Nrf2 pathway.

BACKGROUND: Sepsis-induced cardiac dysfunction (SICD) is a serious complication of sepsis that is associated with increased mortality. Ferroptosis has been reported in the SICD. TaoHe ChengQi decoction (THCQD), a classical traditional Chinese medicinal formula, has multiple beneficial pharmacological effects. The potential effects of THCQD on the SICD remain unknown. PURPOSE: To investigate the effect of THCQD on SICD and explore whether this effect is related to the regulation of myocardial ferroptosis through nuclear factor erythroid 2-related factor 2 (Nrf2) activation. METHODS: We induced sepsis in a mouse model using cecal ligation and puncture (CLP) and administered THCQD (2 and 4 g/kg) and dexamethasone (40 mg/kg). Mice mortality was recorded and survival curves were plotted. Echocardiography, hematoxylin and eosin staining, and analysis of serum myocardial injury markers and inflammatory factors were used to evaluate cardiac pathology. Myocardial ferroptosis was detected by quantifying specific biomarker content and protein levels. Through HPLC-Q-Exactive-MS analysis, we identified the components of the THCQD. Network pharmacology analysis and Cellular Thermal Shift Assay (CETSA) were utilized to predict the targets of THCQD for treating SICD. We detected the expression of Nrf2 using Western blotting or immunofluorescence. An RSL3-induced ferroptosis model was established using neonatal rat cardiomyocytes (NRCMs) to further explore the pharmacological mechanism of THCQD. In addition to measuring cell viability, we observed changes in NRCM mitochondria using electron microscopy and JC-1 staining. NRF2 inhibitor ML385 and Nrf2 knockout mice were used to validate whether THCQD exerted protective effects against SICD through Nrf2-mediated ferroptosis signaling. RESULTS: THCQD reduced mortality in septic mice, protected against CLP-induced myocardial injury, decreased systemic inflammatory response, and prevented myocardial ferroptosis. Network pharmacology analysis and CETSA experiments predicted that THCQD may protect against SICD by activating the Nrf2 signaling pathway. Western blotting and immunofluorescence showed that THCQD activated Nrf2 in cardiac tissue. THCQDs consistently mitigated RSL3-induced ferroptosis in NRCM, which is related to Nrf2. Furthermore, the pharmacological inhibition of Nrf2 and genetic Nrf2 knockout partially reversed the protective effects of THCQD on SICD and ferroptosis. CONCLUSION: The effect of THCQD on SICD was achieved by activating Nrf2 and its downstream pathways.

High-dose Vitamin C injection ameliorates against sepsis-induced myocardial injury by anti-apoptosis, anti-inflammatory and pro-autophagy through regulating MAPK, NF-κB and PI3K/AKT/mTOR signaling pathways in rats.

AIMS: This study aimed to evaluate the effects of VC on SIMI in rats. METHODS: In this study, the survival rate of high dose VC for SIMI was evaluated within 7 days. Rats were randomly assigned to three groups: Sham group, CLP group, and high dose VC (500 mg/kg i.v.) group. The animals in each group were treated with drugs for 1 day, 3 days or 5 days, respectively. Echocardiography, myocardial enzymes and HE were used to detect cardiac function. IL-1ß, IL-6, IL-10 and TNF-α) in serum were measured using ELISA kits. Western blot was used to detect proteins related to apoptosis, inflammation, autophagy, MAPK, NF-κB and PI3K/Akt/mTOR signaling pathways. RESULTS: High dose VC improved the survival rate of SIMI within 7 days. Echocardiography, HE staining and myocardial enzymes showed that high-dose VC relieved SIMI in rats in a time-dependent manner. And compared with CLP group, high-dose VC decreased the expressions of pro-apoptotic proteins, while increased the expression of anti-apoptotic protein. And compared with CLP group, high dose VC decreased phosphorylation levels of Erk1/2, P38, JNK, NF-κB and IKK α/ß in SIMI rats. High dose VC increased the expression of the protein Beclin-1 and LC3-II/LC3-I ratio, whereas decreased the expression of P62 in SIMI rats. Finally, high dose VC attenuated phosphorylation of PI3K, AKT and mTOR compared with the CLP group. SIGNIFICANCE: Our results showed that high dose VC has a good protective effect on SIMI after continuous treatment, which may be mediated by inhibiting apoptosis and inflammatory, and promoting autophagy through regulating MAPK, NF-κB and PI3K/AKT/mTOR pathway.