Social Vulnerability and Risk of Suicide in US Adults, 2016-2020.

Importance: There were over 45 000 suicides in the US in 2020, making suicide the 12th leading cause of death. If social vulnerability is associated with suicide rates, targeted interventions for at-risk segments of the population may reduce US suicide rates. Objective: To determine the association between social vulnerability and suicide in adults. Design, Setting, and Participants: This cohort study analyzed 2 county-level social vulnerability measures (the Social Vulnerability Index [SVI] and the Social Vulnerability Metric [SVM]) and US Centers for Disease Control and Prevention-reported county-level suicides from 2016 to 2020. Data were analyzed November and December 2022. Exposures: County-level variability in social vulnerability. Main Outcomes and Measures: The primary outcome measure was number of county-level adult suicides from 2016 to 2020, offset by county adult population during those years. The association between social vulnerability (measured using the SVI and the newly created SVM for 2018) and suicide was modeled using a bayesian-censored Poisson regression model to account for the CDC's suppression of county-level suicide counts of less than 10, adjusted for age, racial and ethnic minority, and urban-rural county characteristics. Results: From 2016 to 2020, there were a total of 222 018 suicides in 3141 counties. Comparing the least socially vulnerable (0% to 10%) to the most socially vulnerable (90% to 100%) counties, there was a 56% increase in suicide rate (17.3 per 100 000 persons to 27.0 per 100 000 persons) as measured by the SVI (incidence rate ratio, 1.56; 95% credible interval, 1.51-1.60) and an 82% increase in suicide rate (13.8 per 100 000 persons to 25.1 per 100 000 persons) as measured by the SVM (incidence rate ratio, 1.82; 95% credible interval, 1.72-1.92). Conclusions and Relevance: This cohort study found that social vulnerability had a direct association with risk for adult suicide. Reducing social vulnerability may lead to life-saving reduction in the rate of suicide.

Extending the Indications of 5-Aminolevulinic Acid for Fluorescence-Guided Surgery for Different Central Nervous System Tumors: A Series of 255 Cases in Latin America

Introduction Fluorescence guidance with 5-aminolevulinic acid (5-ALA) is a safe and reliable tool in total gross resection of intracranial tumors, especially malignant gliomas and cases of metastasis. In the present retrospective study, we have analyzed 5-ALA-induced fluorescence findings in different central nervous system (CNS) lesions to expand the indications of its use in differential diagnoses. Objectives To describe the indications and results of 5-ALA fluorescence in a series of 255 cases. Methods In 255 consecutive cases, we recorded age, gender, intraoperative 5-ALA fluorescence tumor response, and 5-ALA postresection status, as well the complications related to the method. Postresection was classified as '5-ALA free' or '5-ALA residual'. The diagnosis of histopathological tumor was established according to the current classification of the World Health Organization (WHO). Results There were 195 (76.4%) 5-ALA positive cases, 124 (63.5%) of whom underwent the '5-ALA free' resection. The findings in the positive cases were: 135 gliomas of all grades; 19 meningiomas; 4 hemangioblastomas; 1 solitary fibrous tumor; 27 metastases; 2 diffuse large B cell lymphomas; 2 cases of radionecrosis; 1 inflammatory disease; 2 cases of gliosis; 1 cysticercosis; and 1 immunoglobulin G4-related disease.

Discovery of soluble epoxide hydrolase inhibitors through DNA-encoded library technology (ELT).

Inhibition of soluble epoxide hydrolase (sEH) has recently emerged as a new approach to treat cardiovascular disease and respiratory disease. Inhibitors based on 1,3,5-triazine chemotype were discovered through affinity selection against two triazine-based DNA-encoded libraries. The structure and activity relationship study led to the expansion of the original 1,4-cycloalkyl series to related aniline, piperidine, quinoline, aryl-ether and benzylic series. The 1,3-cycloalkyl chemotype led to the discovery of a clinical candidate (GSK2256294) for COPD.

Vigabatrin-associated Reversible MRI Abnormalities in an Infant with Tuberous Sclerosis.

Vigabatrin therapy is commonly used in infants diagnosed with tuberous sclerosis complex, particularly in the setting of epilepsy. Utilization of vigabatrin can result in bilateral and symmetric abnormal sequence changes within the deep brain matter and brainstem on magnetic resonance imaging. These abnormalities occur predominantly in infancy, are reversible, and can be asymptomatic or result in symptomatic clinical manifestations. We present a case with classic neuroimaging findings. Familiarity with these findings can prevent unnecessary follow up tests or studies and the cost of continuing or discontinuing vigabatrin therapy should be weighed heavily against the potential manifestation of extrapyramidal symptoms.

5-aminolevulinic Acid and Surgical Margin Analysis in Calvarial Metastasis with Pericranium or Dural Extension: Technical Note

Metastasis to the calvarium with direct pericranium or dural infiltration may be treated with radical surgical removal in selected cases. We describe microsurgical resection of calvarial metastases with fluorescence-guided technique using 5-aminolevulinic acid (5-ALA) in two female patients with breast cancer. Fluorescence findings were positive in both cases. Margins in the scalp and dural layer were 5-ALA negative at the end of surgical removal. Intraoperative pathology was performed in all cases to confirm if oncological limits were free of disease. One case was 5-ALA positive in the outer layer of the dura-mater and another in the pericranium. At the end of the removal in both cases, the surgicalmargins were 5-ALA fluorescence-free. Intraoperative pathology confirmed oncological limits of the resection. 5-aminolevulinic acid fluorescence-guided surgery for calvarial metastases with pericranium and/or dural extension seems to be a safe and reliable method to aid the surgical margins for complete removal, possibly delaying or avoiding adjuvant irradiation for progression control.

Salomón Hakim: the man behind normal pressure hydrocephalus.

The illustrious Colombian Professor Salomón Hakim provided the annals of neurology with one of the most brilliant and original bodies of research on record, developing the concept of normal pressure hydrocephalus, as well as proving that ventricular shunting is an effective treatment. Thus, Professor Hakim proved that some of the dementias, at that time considered senile, could be successfully treated. Here the authors present an historical review of his main contributions, which continue to influence the study of dementia to this day.

Salomón Hakim: the man behind normal pressure hydrocephalus / Salomón Hakim: o homem por trás da hidrocefalia de pressão normal

ABSTRACT The illustrious Colombian Professor Salomón Hakim provided the annals of neurology with one of the most brilliant and original bodies of research on record, developing the concept of normal pressure hydrocephalus, as well as proving that ventricular shunting is an effective treatment. Thus, Professor Hakim proved that some of the dementias, at that time considered senile, could be successfully treated. Here the authors present an historical review of his main contributions, which continue to influence the study of dementia to this day.

RESUMO O ilustre professor colombiano Salomón Hakim deixou como legado nos anais da neurologia uma das mais brilhantes e originais séries de pesquisa da história, desenvolvendo o conceito de hidrocefalia de pressão normal, bem como introduzindo a derivação ventricular como tratamento efetivo. Assim, Hakim provou que algumas das demências até então consideradas senis tinham possibilidade de tratamento bem-sucedido. Aqui os autores apresentarão uma revisão histórica de suas maiores contribuições, que continuam a influenciar o estudo de demências até os nossos dias.

Exercise in cirrhosis: Translating evidence and experience to practice.

Physical inactivity, sarcopenia, and frailty are highly prevalent, independent predictors of morbidity and mortality in patients with cirrhosis. Across a range of chronic diseases, exercise training is a key recommendation supported by guidelines and, for some conditions, even by governmental funding of exercise programmes. Consistent with the broader chronic disease literature, the evidence for a benefit of exercise in cirrhosis is promising. Several small trials have reported significant improvements in muscle health (mass, strength, functional capacity), quality of life, fatigue, and reductions in the hepatic venous pressure gradient, without adverse events. With strong emerging evidence surrounding the substantial risks of sarcopenia/frailty and our first-hand experiences with liver pre-transplant exercise programmes, we contend that routine patient care in cirrhosis should include an exercise prescription. Some clinicians may lack the resources and necessary background to translate the existing evidence into a practicable intervention. Our team, comprised of physiotherapists, exercise physiologists, hepatologists, transplant specialists, and knowledge translation experts from six North American centres, has distilled the essential background information, tools, and practices into a set of information ready for immediate implementation into clinics ranging from a family practice setting to specialty cirrhosis clinics. Augmenting the rationale and evidence are supplementary materials including video and downloadable materials for both patients and the physician. Supporting the exercising patient is a section regarding information about nutrition, providing practical tips suitable for all patients with cirrhosis.

Surgical Treatment of Cavernous Angiomas in the Pineal Gland ­ Case Report

Pineal cavernous angioma is a vascular malformation that has a prevalence lower than 1%. The etiology is debated. It is believed that it is originated from an autosomal dominant inheritance or from radiotherapeutic treatment. Complete resection enables the cure and prevents complications of the natural evolution of the lesion, mainly hemorrhagic events. A female patient, with 67 years of age, presented mental confusion and visual acuity deficit, which evolved to periods of psychomotor agitation. A magnetic resonance imaging (MRI) scan of the head showed a lobulated mass lesion in the pineal region with hypersignal on T1 and hyposignal on the susceptibility weighted imaging (SWI) sequence. Hydrocephalus was also noticed. The patient underwent a microsurgery for complete lesion resection though a supracerebellar/ supratentorial access. The anatomopathology revealed an arteriovenous malformation compatible with cavernous angioma. The pineal cavernous angioma is a rare malformation that should be considered in the differential diagnosis of expansive lesions of the pineal gland.

Treatment of Refractory Postural Tachycardia Syndrome with Subcutaneous Octreotide Delivered Using an Insulin Pump.

Postural Tachycardia Syndrome (PoTS) represents a disorder of the autonomic nervous system that results in symptoms of orthostatic intolerance. Despite having a severe impact on the patient's quality of life, the current treatment options for PoTS are based on limited evidence. Subsequently, this results in clinicians having to utilise a variety of treatment regimens in the hope of successfully providing symptomatic relief. However, the options available for PoTS are not without significant side effects that can worsen an already debilitating condition. Our cases provide a further novel treatment option for clinicians to consider in PoTS refractory to established treatments.

Determining predictors of early response to exenatide in patients with type 2 diabetes mellitus.

Exenatide is a GLP-1 analogue used in the management of T2DM yet within a subset of patients fails due to adverse side effects or from failure to attain the end goal. This retrospective observational study aimed to determine whether we could predict response to exenatide in patients with T2DM. 112 patients on exenatide were included with patient age, gender, duration of T2DM, medications alongside exenatide and weight, BMI, and HbA1c at baseline and 3 and 6 months of exenatide use being recorded. 63 responded with 11 mmol/mol reduction from baseline HbA1c after six months and 49 did not respond to exenatide. HbA1c solely differed significantly between cohorts at baseline, 3 months, and 6 months (P < 0.05). Regression analyses identified a negative linear relationship with higher baseline HbA1c correlating to greater reductions in HbA1c by 6 months (P < 0.0001). HbA1c was the sole predictor of exenatide response with higher baseline HbA1c increasing the odds of response by 5% (P = 0.004). Patients with HbA1c reductions ≥15-20% by 3 months were more likely to be responders by 6 months (P = 0.033). Our study identified that baseline HbA1c acted as the sole predictor of exenatide response and that response may be determined after 3 months of exenatide administration.

System accuracy evaluation of the GlucoRx nexus voice TD-4280 blood glucose monitoring system.

Use of blood glucose (BG) meters in the self-monitoring of blood glucose (SMBG) significantly lowers the risk of diabetic complications. With several BG meters now commercially available, the International Organization for Standardization (ISO) ensures that each BG meter conforms to a set degree of accuracy. Although adherence to ISO guidelines is a prerequisite for commercialization in Europe, several BG meters claim to meet the ISO guidelines yet fail to do so on internal validation. We conducted a study to determine whether the accuracy of the GlucoRx Nexus TD-4280 meter, utilized by our department for its cost-effectiveness, complied with ISO guidelines. 105 patients requiring laboratory blood glucose analysis were randomly selected and reference measurements were determined by the UniCel DxC 800 clinical system. Overall the BG meter failed to adhere to the ≥95% accuracy criterion required by both the 15197:2003 (overall accuracy 92.4%) and 15197:2013 protocol (overall accuracy 86.7%). Inaccurate meters have an inherent risk of over- and/or underestimating the true BG concentration, thereby risking patients to incorrect therapeutic interventions. Our study demonstrates the importance of internally validating the accuracy of BG meters to ensure that its accuracy is accepted by standardized guidelines.

Standing-based office work shows encouraging signs of attenuating post-prandial glycaemic excursion.

OBJECTIVES: The main aim of this study was to compare two days of continuous monitored capillary blood glucose (CGM) responses to sitting and standing in normally desk-based workers. DESIGN, SETTING AND PARTICIPANTS: This open repeated-measures study took place in a real office environment, during normal working hours and subsequent CGM overnight measures in 10 participants aged 21-61 years (8 female). MAIN OUTCOMES: Postprandial (lunch) measures of: CGM, accelerometer movement counts (MC) heart rate, energy expenditure (EE) and overnight CGM following one afternoon of normal sitting work compared with one afternoon of the same work performed at a standing desk. RESULTS: Area-under-the-curve analysis revealed an attenuated blood glucose excursion by 43% (p=0.022) following 185 min of standing (143, 95% CI 5.09 to 281.46 mmol/L min) compared to sitting work (326; 95% CI 228 to 425 mmol/L min). Compared to sitting, EE during an afternoon of standing work was 174 kcals greater (0.83 kcals/min; p=0.028). The accelerometer MC showed no differences between the afternoons of seated versus standing work; reported differences were thus a function of the standing work and not from additional physical movements around the office. CONCLUSIONS: This is the first known 'office-based' study to provide CGM measures that add some of the needed mechanistic information to the existing evidence-base on why avoiding sedentary behaviour at work could lead to a reduced risk of cardiometabolic diseases.

Hepatic steatosis, GH deficiency and the effects of GH replacement: a Liverpool magnetic resonance spectroscopy study.

OBJECTIVE: Non-alcoholic fatty liver disease (NAFLD) is reported to be more common in patients with GH deficiency (GHD) than in the general population. we aimed to determine: i) liver fat in patients with GHD compared with age and body mass index (BMI)-matched controls; and ii) effect of 6 months of GH replacement (GHR) on liver fat. PARTICIPANTS AND METHODS: The study included 28 GHD patients and 24 controls. 12 patients were studied before and after 6 months of GHR. Anthropometry, liver enzymes and lipid profiles were measured, and body composition and intrahepatocellular lipid (IHCL) were determined by magnetic resonance imaging and spectroscopy. RESULTS: Age and BMI (median (inter-quartile range)) of patients and controls were 52.6 (14) vs 52.6 (12) years (P=0.9) and 27.8 (24.7, 34.7) vs 27.9 (25.1, 32.1) kg/m(2) (P=0.9). IGF1 was lower in the patients (11.5 vs 16.0 nmol/l, P=0.002). There was no difference in liver transaminases, lipids or IHCL between patients and controls (2.8 (1.3, 8.6) vs 5.0 (1.5, 12.7), P=0.72), despite significantly higher visceral fat in GHD patients. Thirty-two percent of patients and 50% of controls had NAFLD (defined as IHCL >5.6%), and the relationship between IHCL and BMI was the same in each group. GHR significantly reduced abdominal subcutaneous and visceral fat in all patients; however, GHR did not reduce liver fat. CONCLUSIONS: NAFLD is equally common in patients with GHD and matched controls. GHR is associated with a hierarchical reduction in fat deposition (fat loss: visceral > subcutaneous > liver). Further studies involving GHD patients with NAFLD are required to conclude the role of GHR in treating NAFLD.

Isolated thyroxine malabsorption treated with intramuscular thyroxine injections.

An 18-year-old girl with multiple autoimmune endocrinopathies was referred to the endocrinology clinic for management of hypothyroidism. She required increasing doses of thyroxine but remained hypothyroid. Daily and weekly supervised thyroxine administration strategies were unsuccessful. She was extensively investigated for malabsorption; however, all the results were normal. She was subsequently commenced on weekly intramuscular thyroxine injections and became biochemically and clinically euthyroid. Subsequent elective hospital admission and administration of thyroxine via nasogastric tube resulted in recurrence of her hypothyroidism. This case demonstrates apparent isolated true levothyroxine malabsorption existing in isolation and suggests that intramuscular thyroxine injections may be a useful therapeutic modality in these patients.

Starvation-induced true diabetic euglycemic ketoacidosis in severe depression.

True euglycemic diabetic ketoacidosis [blood glucose <200 mg/dl (11.1 mmol/l)] is relatively uncommon and in type 1 diabetes can be caused by starvation of any cause in conjunction with an intercurrent illness. We report a case of euglycemic diabetic ketoacidosis precipitated by starvation resulting from severe depression in a patient with type 1 diabetes. He was acidotic with ketonuria, but his blood glucose was only 105 mg/dl (5.8 mmol/l). He was rehydrated, the acidosis was corrected, and his depression was later treated. This case involves the complex interplay among type 1 diabetes, depression, ketoacidosis, and starvation physiology resulting in glucose concentrations in keeping with euglycemic diabetic ketoacidosis. The case also highlights that even in the absence of hyperglycemia, acid/base status should be assessed in an ill patient with diabetes, and in cases of euglycemic diabetic ketoacidosis, the diagnosis of depression should be considered as a cause for suppressed appetite and anorexia.

Effects of growth hormone administration on bone mineral metabolism, PTH sensitivity and PTH secretory rhythm in postmenopausal women with established osteoporosis.

INTRODUCTION: Growth hormone (GH) replacement improves target organ sensitivity to PTH, PTH circadian rhythm, calcium and phosphate metabolism, bone turnover, and BMD in adult GH-deficient (AGHD) patients. In postmenopausal women with established osteoporosis, GH and insulin like growth factor-1 (IGF-1) concentrations are low, and administration of GH has been shown to increase bone turnover and BMD, but the mechanisms remain unclear. We studied the effects of GH administration on PTH sensitivity, PTH circadian rhythm, and bone mineral metabolism in postmenopausal women with established osteoporosis. MATERIALS AND METHODS: Fourteen postmenopausal women with osteoporosis were compared with 14 healthy premenopausal controls at baseline that then received GH for a period of 12 mo. Patients were hospitalized for 24 h before and 1, 3, 6, and 12 mo after GH administration and half-hourly blood and 3-h urine samples were collected. PTH, calcium (Ca), phosphate (PO(4)), nephrogenous cyclic AMP (NcAMP), beta C-telopeptide of type 1 collagen (betaCTX), procollagen type I amino-terminal propeptide (PINP), and 1,25-dihydroxyvitamin D [1,25(OH)(2)D] were measured. Circadian rhythm analysis was performed using Chronolab 3.0 and Student's t-test and general linear model ANOVAs for repeated measures were used where appropriate. RESULTS: IGF-1 concentration was significantly lower in the women with established osteoporosis compared with controls (101.5 +/- 8.9 versus 140.9 +/- 10.8 mug/liter; p < 0.05) and increased significantly after 1, 3, 6, and 12 mo of GH administration (p < 0.001). Twenty-four-hour mean PTH concentration was higher in the osteoporotic women (5.4 +/- 0.1 pM) than in healthy controls (4.4 +/- 0.1 pM, p < 0.001) and decreased after 1 (5.2 +/- 0.1 pM, p < 0.001), 3 (5.0 +/- 0.1 pM, p < 0.001), 6 (4.7 +/- 0.1 pM, p < 0.001), and 12 mo (4.9 +/- 0.1 pM, p < 0.05) of GH administration compared with baseline. NcAMP was significantly lower in osteoporotic women (17.2 +/- 1.2 nM glomerular filtration rate [GFR]) compared with controls (21.4 +/- 1.4 nM GFR, p < 0.05) and increased after 1 (24.2 +/- 2.5 nM GFR, p < 0.05), 3 (27.3 +/- 1.5 nM GFR, p < 0.001), and 6 mo (32.4 +/- 2.5 nM GFR, p < 0.001) compared with baseline. PTH secretion was characterized by two peaks in premenopausal women and was altered in postmenopausal women with a sustained increase in PTH concentration. GH administration also restored a normal PTH secretory pattern in the osteoporotic women. The 24-h mean adjusted serum calcium (ACa) concentration increased at 1 and 3 mo (p < 0.001) and PO(4) at 1, 3, 6, and 12 mo (p < 0.001). 1,25(OH)(2)D concentration increased after 3, 6, and 12 mo of GH (p < 0.05). An increase in urine Ca excretion was observed at 3 and 6 mo (p < 0.05), and the renal threshold for maximum tubular phosphate reabsorption rate (TmPO4/GFR) increased after 1, 3, 6, and 12 mo (p < 0.05). betaCTX concentration increased progressively from 0.74 +/- 0.07 mug/liter at baseline to 0.83 +/- 0.07 mug/liter (p < 0.05) at 1 mo and 1.07 +/- 0.09 mug/liter (p < 0.01) at 3 mo, with no further increase at 6 or 12 mo. PINP concentration increased progressively from baseline (60 +/- 5 mug/liter) to 6 mo (126 +/- 11 mug/liter, p < 0.001), with no further increase at 12 mo. The percentage increase in PINP concentration was significantly higher than betaCTX (p < 0.05). CONCLUSIONS: Our study shows that GH has a regulatory role in bone mineral metabolism. GH administration to postmenopausal osteoporotic women improves target organ sensitivity to PTH and bone mineral metabolism and alters PTH secretory pattern with greater increases in bone formation than resorption. These changes, resulting in a net positive bone balance, may partly explain the mechanism causing the increase in BMD after long-term administration of GH in postmenopausal women with osteoporosis shown in previous studies and proposes a further component in the development of age-related postmenopausal osteoporosis.