Management of Osteoporosis and Spinal Fractures: Contemporary Guidelines and Evolving Paradigms.

Physicians involved in treating spine fractures secondary to osteopenia and osteoporosis should know the pathogenesis and current guidelines on managing the underlying diminished bone mineral density, as worldwide fracture prevention campaigns are trailing behind in meeting their goals. This is a narrative review exploring the various imaging and laboratory tests used to diagnose osteoporotic fractures and a comprehensive compilation of contemporary medical and surgical management. We have incorporated salient recommendations from the Endocrine Society, the American Association of Clinical Endocrinology (AACE), and the American Society for Bone and Mineral Research (ASBMR). The use of modern scoring systems such as Fracture Risk Assessment Tool (FRAX®) for evaluating fracture risk in osteoporosis with a 10-year probability of hip fracture and major fractures in the spine, forearm, hip, or shoulder is highlighted. This osteoporosis risk assessment tool can be easily incorporated into the preoperative bone health optimization strategies, especially before elective spine surgery in osteoporotic patients. The role of primary surgical intervention for vertebral compression fracture and secondary fracture prevention with pharmacological therapy is described, with randomized clinical trial-based wisdom on its timing and dosage, drug holiday, adverse effects, and relevant evidence-based literature. We also aim to present an evidence-based clinical management algorithm for treating osteoporotic vertebral body compression fractures, tumor-induced osteoporosis, or hardware stabilization in elderly trauma patients in the setting of their impaired bone health. The recent guidelines and recommendations on surgical intervention by various medical societies are covered, along with outcome studies that reveal the efficacy of cement augmentation of vertebral compression fractures via vertebroplasty and balloon kyphoplasty versus conservative medical management in the elderly population.

Patients With Ankylosing Spondylitis Have Increased Cardiovascular and Cerebrovascular Mortality: A Population-Based Study.

BACKGROUND: Ankylosing spondylitis (AS) is a chronic inflammatory arthritis affecting the spine in young adults. It is associated with excess cardiovascular and cerebrovascular morbidity. OBJECTIVE: To determine whether patients with AS are at increased risk for cardiovascular and cerebrovascular mortality. DESIGN: Population-based retrospective cohort study using administrative health data. SETTING: Ontario, Canada. PATIENTS: 21 473 patients with AS aged 15 years or older and 86 606 comparators without AS, matched for age, sex, and location of residence. MEASUREMENTS: The primary outcome was a composite of cardiovascular and cerebrovascular death. Hazard ratios (HRs) for vascular death were calculated; adjusted for history of cancer, diabetes, dementia, inflammatory bowel disease, hypertension, chronic kidney disease, and peripheral vascular disease; and, among those aged 66 years or older, relevant drug therapies. Independent risk factors for vascular mortality were identified in patients with AS. RESULTS: The mean age of patients with AS was 46 years, and 53% were male. Patients and comparators were followed for 166 920 and 686 461 patient-years, respectively. Adjusted HRs for vascular death in AS were 1.36 (95% CI, 1.13 to 1.65) overall, 1.46 (CI, 1.13 to 1.87) in men, and 1.24 (CI, 0.92 to 1.67) in women. Significant risk factors for vascular death were age; male sex; lower income; dementia; chronic kidney disease; peripheral vascular disease; and, among patients aged 65 years or older, lack of exposure to nonsteroidal anti-inflammatory drugs and statins. LIMITATION: Diagnosis codes for AS were not validated in Ontario. CONCLUSION: Ankylosing spondylitis is associated with increased risk for vascular mortality. A comprehensive strategy to screen and treat modifiable vascular risk factors in AS is needed. PRIMARY FUNDING SOURCE: The Arthritis Program, University Health Network, Toronto; and The Arthritis Society, Canada.

Management of Metabolic-Associated Fatty Liver Disease.

Metabolic-associated fatty liver disease (MAFLD), previously known as nonalcoholic fatty liver disease (NAFLD), is the most common cause of liver disease in the world. Its prevalence is over 30% and is becoming the most common cause of liver transplants. Rates are rising along with obesity-related diseases. Risk factors for MAFLD include adverse lifestyles, genetic variations, advancing age, male sex, and alterations in the gut microbiota. Extrahepatic complications include cardiovascular disease, renal dysfunction, and colorectal cancer. As there are no currently approved medications for MAFLD, management mainly focuses on lifestyle modifications.

Role of B12 and homocysteine status in determining BMD and bone turnover in young Indians.

Vitamin B(12) (B(12)) deficiency and hyperhomocysteinemia (HHcy) are independent risk factors for low bone mineral density (BMD) and fracture risk. We studied the role of HHcy and B(12) deficiency in determining the peak bone mass in Indians. Randomly selected 151 healthy young adult subjects (females 100, mean age: 26 yr) underwent evaluation of dietary intake of calcium and B(12); sun exposure; estimation of BMD by dual-energy X-ray absorptiometry at total hip, forearm, and lumbar spine; serum 25(OH)D(3); intact parathyroid hormone; B(12); homocysteine (Hcy); and bone turnover markers (BTMs) serum crosslaps, N-mid osteocalcin, and bone-specific alkaline phosphatase. Hypovitaminosis D (serum 25OHD(3)<20 ng/mL) and serum ALP level >150 IU/L were seen in 83% and 27%, respectively. Median serum B(12) and Hcy levels were 140 pg/mL (interquartile range [IQR]: 72-230 pg/mL) and 18 µmol/L (IQR 14-32 µmol/L); B(12) deficiency (serum B(12)<200 pg/mL) and HHcy (serum Hcy>30 µmol/L) were present in 71% and 68%, respectively. Low BMD (Z-score <-2.0) was present in 17% of subjects. There was no significant correlation between serum Hcy, folate, B(12), BTM, and BMD. BMD was predicted by height, weight, and body mass index. Young Indian healthy adults have high prevalence of hypovitaminosis D, B(12) deficiency, and HHcy. There is no correlation of serum B(12), folate, and Hcy status with BTMs and BMD in young, healthy, vegetarian Indian adults. Anthropometric variables predict BMD in young Indians.

COVID-19 vaccine hesitancy among medical students: A systematic review.

BACKGROUND: Vaccine hesitancy leads to an increase in morbidity, mortality, and health-care burden. Reasons for vaccine hesitancy include anti-vax group statements, misinformation about vaccine side effects, speed of vaccine development, and general disbelief in the existence of viruses like COVID-19. Medical students are future physicians and are key influencers in the uptake of vaccines. Hence, investigating vaccine hesitancy in this population can help to overcome any barrier in vaccine acceptance. METHODS: In this paper, we review five articles on COVID-19 vaccine hesitancy in medical students and consider potential future research. All published papers relevant to the topic were obtained through extensive search using major databases. Inclusion criteria included studies that specifically investigated COVID-19 vaccine hesitancy in medical students published between 2020 and 2021. Exclusion criteria included studies that investigated vaccine hesitancy in health-care professionals, allied health, and viruses apart from COVID-19. A total of 10 studies were found from our search. RESULTS: Based on our exclusion criteria, only five studies were included in our review. The sample size ranged from 168 to 2133 medical students. The percentage of vaccine hesitancy in medical students ranged from 10.6 to 65.1%. Reasons for vaccine hesitancy included concern about serious side effects, vaccine efficacy, misinformation and insufficient information, disbelief in public health experts, financial costs, and belief that they had acquired immunity. CONCLUSION: These results suggest that vaccine hesitancy is an important cause of the incidence and prevalence of COVID-19 cases. Identifying the barriers of vaccine hesitancy in prospective physicians can help increase vaccination uptake in the general public. Further research is necessary to identify the root cause of these barriers.

COVID-19 vaccine hesitancy and influence of professional medical guidance.

BACKGROUND: Vaccine hesitancy presents a major challenge during the COVID-19 pandemic. It is crucial to address the factors contributing to vaccine hesitancy necessary to control the associated morbidity and mortality. This study aimed to investigate the impact of professional medical guidance on the likelihood of receiving the COVID-19 vaccine in immigrants of USA and Canada. MATERIALS AND METHODS: A total of 92 immigrants in the USA and Canada who predominantly spoke Malayalam were recruited using social media platforms. An online survey was administered investigating participants' confidence in receiving the COVID-19 vaccine. Following, a short webinar was conducted by a medical professional explaining the efficacy and safety of the vaccine. A postwebinar survey was immediately given assessing the confidence and likelihood of receiving the vaccine. SPSS was used to generate descriptive statistics and Pearson Chi-square analysis where appropriate. RESULTS: Results revealed that participants who attended the webinar reported greater confidence in receiving the COVID-19 vaccine. There was a statistically significant difference between pre- and postwebinar confidence scores for the COVID-19 vaccine, χ2 (12, n = 80) = 43.34, P < 0.01. CONCLUSION: Results from the current study demonstrate the successful delivery of professional medical guidance to the general public through online small-group sessions to help address the misconceptions surrounding the COVID-19 vaccine and combat vaccine hesitancy among vulnerable populations. Future studies should focus on interventions addressing vaccine hesitancy in larger and diverse populations and analyze other barriers to vaccination.

Gastroenteropancreatic neuroendocrine neoplasms: A clinical snapshot.

Our understanding about the epidemiological aspects, pathogenesis, molecular diagnosis, and targeted therapies of neuroendocrine neoplasms (NENs) have drastically advanced in the past decade. Gastroenteropancreatic (GEP) NENs originate from the enteroendocrine cells of the embryonic gut which share common endocrine and neural differentiation factors. Most NENs are well-differentiated, and slow growing. Specific neuroendocrine biomarkers that are used in the diagnosis of functional NENs include insulin, glucagon, vasoactive intestinal polypeptide, gastrin, somatostatin, adrenocorticotropin, growth hormone releasing hormone, parathyroid hormone-related peptide, serotonin, histamine, and 5-hydroxy indole acetic acid (5-HIAA). Biomarkers such as pancreatic polypeptide, human chorionic gonadotrophin subunits, neurotensin, ghrelin, and calcitonin are used in the diagnosis of non-functional NENs. 5-HIAA levels correlate with tumour burden, prognosis and development of carcinoid heart disease and mesenteric fibrosis, however several diseases, medications and edible products can falsely elevate the 5-HIAA levels. Organ-specific transcription factors are useful in the differential diagnosis of metastasis from an unknown primary of well-differentiated NENs. Emerging novel biomarkers include circulating tumour cells, circulating tumour DNA, circulating micro-RNAs, and neuroendocrine neoplasms test (NETest) (simultaneous measurement of 51 neuroendocrine-specific marker genes in the peripheral blood). NETest has high sensitivity (85%-98%) and specificity (93%-97%) for the detection of gastrointestinal NENs, and is useful for monitoring treatment response, recurrence, and prognosis. In terms of management, surgery, radiofrequency ablation, symptom control with medications, chemotherapy and molecular targeted therapies are all considered as options. Surgery is the mainstay of treatment, but depends on factors including age of the individual, location, stage, grade, functional status, and the heredity of the tumour (sporadic vs inherited). Medical management is helpful to alleviate the symptoms, manage inoperable lesions, suppress postoperative tumour growth, and manage recurrences. Several molecular-targeted therapies are considered second line to somatostatin analogues. This review is a clinical update on the pathophysiological aspects, diagnostic algorithm, and management of GEP NENs.

Efficacy and Cardiovascular Safety of GLP-1 Receptor Analogues.

Glucagon-like peptide- 1 receptor analogs (GLP-1RAs) are incretin mimetics with potent glucose-dependent insulinotropic action that translates to glycemic control in people with type- -2 diabetes mellitus (T2DM). These agents potentially have the ability to stimulate proliferation or prevent apoptosis of pancreatic ß-cells, induce weight-loss and provide vascular benefits in patients with T2DM. Newer GLP-1RA, semaglutide has shown a robust reduction in HbA1c up to 1.5 - 1.8%. However, individual differences exist between the different GLP-1RAs, in terms of efficacy, pharmacokinetics, tolerability, and vascular protection. The potential of vascular protection offered by newer anti-diabetic agents has generated a lot of excitement in the field of diabetes, and to a large extent, is now driving treatment decisions. So far, six cardiovascular outcome trials of GLP-1 RAs have been published, analyzing lixisenatide (ELIXA), liraglutide (LEADER), semaglutide (SUSTAIN-6), long-acting exenatide (EXSCEL), dulaglutide (REWIND), and oral semaglutide (PIONEER 6) with a follow-up duration of 2-4 years. LEADER, REWIND and SUSTAIN-6 trials have demonstrated a reduction in rates of major adverse cardiovascular events with active GLP-1 RA treatment, but ELIXA, PIONEER 6 and EXSCEL, have been neutral. In this review, we discuss the available evidence from randomized controlled trials (RCTs) analyzing the cardiovascular effects of various GLP-1 RAs with the aim of comparing individual drugs. We have also summarized the general aspects of GLP-1RAs that can be applied in clinical practice.

Risk of dementia in seniors with newly diagnosed diabetes: a population-based study.

OBJECTIVE: To study whether diabetes onset in late life is a risk factor for dementia. RESEARCH DESIGN AND METHODS: We conducted a population-based matched cohort study using provincial health data from Ontario, Canada. Seniors with (n = 225,045) and without newly diagnosed diabetes (n = 668,070) between April 1995 and March 2007 were followed until March 2012 for a new diagnosis of dementia. Cox proportional hazards modeling was used to compare the risk of dementia between groups after adjusting for baseline cardiovascular disease, chronic kidney disease (CKD), hypertension, and other risk factors. RESULTS: Over this period, we observed 169,114 new cases of dementia. Individuals with diabetes had a modestly higher incidence of dementia (2.68 vs. 2.62 per 100 person-years) than those without diabetes. In the fully adjusted Cox model, the risk of dementia was 16% higher among our subgroup with diabetes (hazard ratio [HR] 1.16 [95% CI 1.15-1.18]). Adjusted HRs for dementia were 1.20 (95% CI 1.17-1.22) and 1.14 (95% CI 1.12-1.16) among men and women, respectively. Among seniors with diabetes, the risk of dementia was greatest in those with prior cerebrovascular disease (HR 2.03; 95% CI 1.88-2.19), peripheral vascular disease (HR 1.47; 95% CI 1.19-1.82), and CKD (HR 1.44; 95% CI 1.38-1.51), and those with one or more hospital visits for hypoglycemia (HR 1.73; 95% CI 1.62-1.84). CONCLUSIONS: In this population-based study, newly diagnosed diabetes was associated with a 16% increase in the risk of dementia among seniors. Preexisting vascular disease and severe hypoglycemia were the greatest risk factors for dementia in seniors with diabetes.

Effect of TNF-alpha inhibitor treatment on bone mineral density in patients with ankylosing spondylitis: a systematic review and meta-analysis.

OBJECTIVES: Ankylosing spondylitis (AS) is a chronic inflammatory disease associated with an increased risk of osteoporosis and fractures. TNF inhibitors have been used to treat AS, but their effect on bone is unclear. Thus, we conducted a meta-analysis to study the effect of TNF inhibitors on spine and hip BMD in patients with AS. METHODS: Two authors independently searched MEDLINE and PubMed for longitudinal studies that had assessed the effect of TNF inhibitors on BMD in patients with AS. Studies with a minimum follow-up period of 1 year were included. RESULTS: Seven longitudinal studies and one randomized control trial were included, with a total of 568 AS patients (mean age range of 36-48 years and disease duration of 9-17 years). Lumbar spine BMD increased by 5.1% (95% CI: 4.0-6.1%, p = 0.00000) after 1 year of treatment with TNF inhibitors and by 8.6% (95% CI: 6.8-10.3%, p < 0.00001) after 2 years. Significant improvements in total hip BMD were also noted after 1 [1.8% (1.0-2.5%)] and 2 years [2.5% (1.9-3.0%)]. Compared to baseline, femoral neck BMD remained stable after 1 year [0.7% (-0.8% to 2.2%), p = 0.34]. No significant heterogeneity was noted amongst the included studies. CONCLUSIONS: TNF inhibitors can increase lumbar spine and total hip BMD and maintain femoral neck BMD for up to 2 years in patients with AS. More research is needed to assess the effect of TNF inhibitors on bone quality and fracture risk.

Juvenile granulosa cell tumor presenting as isosexual precocious puberty: A case report and review of literature.

The differential diagnosis for precocious puberty in a young female includes peripheral causes. This case report documents a rare cause of isosexual precocious puberty, a juvenile granulosa cell tumor of the ovary-and a brief literature review. A 7-year-old girl presented with rapid onset of pubertal development and elevated estradiol levels. Abdominal ultrasound revealed a mass in the right adnexa. Other causes of precocious puberty were excluded. Elective surgery was planned, but the patient presented to the emergency room with torsion of ovary. She underwent an exploratory laparotomy for tumor resection and right salpingo oophorectomy. Pathology reported a juvenile granulosa cell tumor of the ovary. Postoperatively, she experienced a cessation of vaginal bleeding and estradiol levels normalized. Early stage disease has good prognosis. Adjuvant chemotherapy is not indicated in this setting.