Pharmacotherapy as an Augmentation to Bariatric Surgery for Obesity.

A global obesity pandemic is one of the most significant health threats worldwide owing to its close association with numerous comorbidities such as type 2 diabetes mellitus, arterial hypertension, dyslipidemia, heart failure, cancer and many others. Obesity and its comorbidities lead to a higher rate of cardiovascular complications, heart failure and increased cardiovascular and overall mortality. Bariatric surgery is at present the most potent therapy for obesity, inducing a significant weight loss in the majority of patients. In the long-term, a substantial proportion of patients after bariatric surgery experience a gradual weight regain that may, in some, reach up to a presurgical body weight. As a result, anti-obesity pharmacotherapy may be needed in some patients after bariatric surgery to prevent the weight regain or to further potentiate weight loss. This article provides an overview of the use of anti-obesity medications as an augmentation to bariatric surgery for obesity. Despite relatively limited published data, it can be concluded that anti-obesity medication can serve as an effective adjunct therapy to bariatric surgery to help boost post-bariatric weight loss or prevent weight regain.

Diabetic foot disease carries an intrinsic high risk of mortality and other severe outcomes in type 2 diabetes: a propensity score-matched retrospective population-based study.

BACKGROUND: To evaluate the association between diabetic foot disease (DFD) and the incidence of fatal and non-fatal events in individuals with type 2 diabetes (T2DM) from primary-care settings. METHODS: We built a cohort of people with a first DFD episode during 2010-2015, followed up until 2018. These subjects were 1 to 1 propensity score matched to subjects with T2DM without DFD. The incidence of all-cause mortality, the occurrence of new DFD, amputations, cardiovascular diseases, or composite outcome, including all-cause mortality and/or cardiovascular events during the follow-up period, were calculated. A Cox proportional hazard analysis was conducted to evaluate the hazard ratios (HR) for different events. RESULTS: Overall, 11,117 subjects with T2DM with a first episode of DFD were compared with subjects without DFD. We observed higher incidence rates (IRs) for composite outcome (33.9 vs. 14.5 IR per 100 person-years) and a new DFD episode event (22.2 vs. 1.1 IR per 100 person-years) in the DFD group. Compared to those without DFD, those with a first episode of DFD had a higher HR for all events, with excess rates particularly for amputation and new DFD occurrence (HR: 19.4, 95% CI: 16.7-22.6, HR: 15.1, 95% CI: 13.8-16.5, respectively) was found. CONCLUSIONS: Although DFD often coexists with other risk factors, it carries an intrinsic high risk of morbidity and mortality in individuals with T2DM. DFD should be regarded as a severe complication already at its onset, as it carries a poor clinical prognosis.

Rifampicin in the Treatment of Refractory Diabetic Foot Ulcer and Diabetic Foot Osteomyelitis-an Observational Study.

INTRODUCTION: Refractory diabetic foot ulcer (rDFU) and osteomyelitis (diabetic foot osteomyelitis [DFO]) are a major problem in people with diabetes. Often resulting from multidrug-resistant polymicrobial infection, these may result in amputation or nonhealing ulcers. In this nonrandomized open-label study, we looked at the outcome of treatment with rifampicin in patients with nonhealing diabetic foot ulcers. MATERIAL AND METHODS: Patients with DFUs (n = 67, n = 55 with DFO) unresponsive to conventional antimicrobial therapy for >3 months (rDFU) were taken as the study group. All patients received rifampicin for a minimum of 3 months (maximum 6 months if DUFs did not heal after 3 months) in addition to standard antibiotics and compared with similar kind of DFUs (n = 68, n = 55 DFO) who formed the control group, treated with conventional antimicrobial therapy. Patients were followed up for 12 months. Healing of DFU at 6 months and amputation were primary endpoints of the study. RESULTS: In total, 43 patients (64.2%) in the rifampicin group healed at 3 months and another 4 patients healed when rifampicin was continued for 6 months (n = 47, 70.1%). In the control group, 11 patients healed at 3 months (16.2%) and 25 patients healed at 6 months (36.8%). In total, 14 patients (20.9%) in the study group and 29 patients (42.6%) in the control group had to undergo minor amputation. Comparison between the rate of healing at 3 and 6 months and minor amputation between the study group and control group showed statistically significant results (P ≤ .00001, <.00001, and .008, respectively). In total, 6 and 8 patients despite healing of the primary ulcer had a subsequent recurrence of ulcer in the rifampicin and control group, respectively. CONCLUSION: Rifampicin used in conjunction with other standard poly-microbial therapy in refractory complex diabetic foot ulcer unresponsive to standard antimicrobial therapy, can significantly improve wound healing as well as decrease the need for amputation in addition to standard of care.

Charcot Foot: An Update on Diagnosis, Treatment, and Areas of Uncertainty.

BACKGROUND AND AIMS: Charcot neuroosteoarthropathy (CN) is considered a rare complication of diabetic neuropathy. Due to its insidious mode of presentation, CN may be difficult to diagnose timely and a high index of suspicion is required from both, the diabetic patient (especially those with neuropathy) and their physicians for the early diagnosis and treatment to prevent major complications. METHODS: We planned a narrative review and searched MEDLINE database to identify evidence regarding CN incidence, treatment options, and recent guidelines. As practitioners do not commonly treat CN, a characteristic clinical case is also presented. RESULTS: The available evidence for diagnosis and treatment remains of low quality. On the one hand, there is an urgent need for action to increase awareness of the disease in both practitioners and people with diabetes. On the other hand, prospective nationwide registries of patients with diabetic neuropathy will help clarify the prognostic factors that may predispose to this complication, and more randomized clinical trials are needed to identify whether medical treatment may improve CN outcomes. For the time being, offloading of the foot to stop the perpetuation of trauma, and inflammation, and importantly to arrest the progression to a deformed nonfunctional foot is the cornerstone of medical therapy of CN. Multidisciplinary assessment between diabetologists and radiologists is fundamental for prompt diagnosis. CONCLUSIONS: To avoid potentially deleterious delays in diagnosis and treatment, every physician should bear in mind that every patient with diabetic neuropathy presenting with a warm swollen foot should be treated as having CN until proven otherwise.

The effect of the different waves of COVID-19 pandemic on the outcome of diabetic foot ulcers.

AIMS: COVID-19 pandemic has massively impacted human health. We studied the effect of COVID-19 on outcome of Diabetic foot ulcers (DFUs). OBJECTIVES AND METHODS: We recruited 483 people with DFUs from June 2020 to April 2022 (pandemic) together with a matched group of 226 people with DFU from March 2019 to March 2020 (pre-pandemic). Primary endpoint was outcome of ulcers-healed or amputation (major/minor). It was sub-analysed into 3 waves of COVID-19. Secondary endpoint was healing of individual types of DFUs. Basic anthropometric data included site and type of ulcer (ischemic or neuropathic), duration, presence or absence of infection and Wagner's grading of DFUs was collected for all patients. Diagnosis of peripheral neuropathy was done by monofilament testing and peripheral arterial disease by handheld Doppler and ankle brachial index (ABI). Standardized treatment protocol was provided. All patients were monitored for 6 months. RESULTS: In the pandemic group 323 (66.9%) patients in whom ulcers healed, 70 (14.5%) underwent minor amputation, 11 (2.2%) major amputation, 29 (6%) were lost to follow up, 22 (4.6%) were not healed. Rate of healing of DFU was higher (66.9% vs 53.5%) and rate of amputation was lower (16.7% vs 23.4%) in the pandemic group than in the pre-pandemic group (P = 0.001 and 0.037 respectively). Rate of healing in first, second and third wave was 65.4%, 75.2%, 58.3% respectively (P = 0.001). Neuropathic ulcers though less prevalent (49.8% vs 57.8%) in the first two waves than in the third wave, healing was better (79.3% vs 75.6%) in the first two waves than in the third wave (P = 0.085 and 0.488 respectively). Similarly, amputation rates in ischemic and neuro-ischemic ulcers were greater in the third wave than first two waves (46.7% vs 15.7%, P = 0.049). CONCLUSION: During the COVID-19 pandemic, healing of neuropathic ulcers was better, especially in the first and second waves and travel restriction may have accounted for this. However, worsening of ischemic and neuro-ischemic ulcers was observed with more amputation in these two groups. Conversely, in the third wave withdrawal of lockdown led to worsening of DFUs resulting in less healing and more amputation.

Hypoglycaemia following the 2-hour 75g OGTT in pregnancy - Investigating maternal and foetal outcomes.

AIMS: To investigate differences in maternal and foetal outcomes in pregnancy, where patients developed hypoglycaemia following the 2-hour 75g oral glucose tolerance test (OGTT). METHOD: A retrospective cohort study of 200 pregnancies attending the Antenatal Clinic at Tameside General Hospital between 2018 and 2022. Outcomes were compared between 4 groups: normal OGTT [G1; (n = 39, 20%), diagnosis of gestational diabetes mellitus (GDM) based on OGTT [G2; BG ≥ 5.6 mmol/L or 2-h OGTT ≥7.8 (n = 41, 21%)], hypoglycaemia [G3; 2 h OGTT 3.0-3.9 mmol/L (n = 93, 47%)], or clinically significant hypoglycaemia [G4; 2 h OGTT <3.0 mmol/L (n = 27, 14%)]. Maternal BMI, foetal birth weight (FBW), neonatal complications, neo-natal intensive care unit (NICU) stay and conversion to GDM were assessed. RESULTS: Maternal BMI was lower in G3 and G4 (27.3 kg/m2 and 28.1 kg/m2 respectively) compared to G1 (30.4 kg/m2) (p = 0.02). NICU stay was more frequent in G3 (12%, n = 11) and G4 (8%, n = 2) compared to G1 (5%, n = 2). Foetal complications occurred in 27% of G3 (n = 25) and 33% of G4 (n = 9) compared to 23% in G1 (n = 9) and 17% in G2 (n = 7). FBW was similar in G1 when compared to G3 and G4 (p = 0.34). Of the 120 patients in G3 and G4, 25 patients self-monitored blood glucose for two weeks; 28% (n = 7) subsequently developed GDM. CONCLUSION: Higher rates of NICU stay and foetal complications were seen in both hypoglycaemic groups. In patients with hypoglycaemia following OGTT there is evidence to support self-monitoring blood glucose as 28% were later diagnosed with GDM.

The Association of Vitamin D Receptor Polymorphisms with COVID-19 Severity.

BACKGROUND: Association studies of vitamin D receptor (VDR) polymorphisms with COVID-19 severity have produced inconsistent results in different populations. Herein we examined VDR gene polymorphisms in a Caucasian Greek cohort of COVID-19 patients. METHODS: This was a case-control study in a tertiary university hospital in Greece including 137 COVID-19 patients with varying disease severities and 72 healthy individuals. In total 209 individuals were genotyped for the FokI (rs10735810), ApaI (rs7975232), TaqI (rs731236) and BsmI (rs1544410) single-nucleotide polymorphisms (SNP) of the VDR gene by polymerase chain reaction and restriction fragment length polymorphism analysis (PCR-RFLPs). Statistical analyses were performed to determine the association between genotype and disease severity, adjusting for various confounding factors. RESULTS: Genotype distribution of the studied VDR SNPs in the control group was in Hardy-Weinberg equilibrium. The TaqI variant was differentially distributed between controls and COVID-19 patients according to the additive model (p = 0.009), and the CC genotype was significantly associated with an increased risk for severe COVID-19 according to the recessive model [OR: 2.52, 95%CI:1.2-5.29, p = 0.01]. Multivariate analysis demonstrated a robust association of COVID-19 severity and TaqI polymorphism in the recessive model even after adjusting for multiple confounders, including age, sex and CRP levels [Adj.OR:3.23, 95%CI:1.17-8.86, p = 0.023]. The distribution of FokI, ApaI and BsmI genotypes was similar between COVID-19 patients and controls. CONCLUSIONS: The CC genotype of TaqI polymorphism is significantly associated with an increased risk for severe COVID-19 independently of age, sex or degree of inflammation.

Acute Effects of Vibrating Insoles on Dynamic Balance and Gait Quality in Individuals With Diabetic Peripheral Neuropathy: A Randomized Crossover Study.

OBJECTIVE: This study investigated the effects of vibrating insoles on dynamic balance and gait quality during level and stair walking and explored the influence of vibration type and frequency in individuals with diabetic peripheral neuropathy (DPN). RESEARCH DESIGN AND METHODS: Twenty-two men with DPN were assessed for gait quality and postural and dynamic balance during walking and stair negotiation using a motion capture system and force plates across seven vibratory insole conditions (Vcs) versus a control (Ctrl) condition (insole without vibration). Vibration was applied during standing and walking tasks, and 15-min rest-stop periods without vibration were interposed between conditions. Repeated measures test conditions were randomized. The primary outcomes were gait speed and dynamic balance. RESULTS: Gait speed during walking significantly improved in all Vcs compared with Ctrl (P < 0.005), with Vc2, Vc4, and Vc6 identified as the most effective. Gait speed increased (reflecting faster walking) during stair ascent and descent in Vc2 (Ctrl vs. Vc2 for ascent 0.447 ± 0.180 vs. 0.517 ± 0.127 m/s; P = 0.037 and descent 0.394 ± 0.170 vs. 0.487 ± 0.125 m/s; P = 0.016), Vc4 (Ctrl vs. Vc4 for ascent 0.447 ± 0.180 vs. 0.482 ± 0.197 m/s; P = 0.047 and descent 0.394 ± 0.170 vs. 0.438 ± 0.181 m/s; P = 0.017), and Vc6 (Ctrl vs. Vc6 for ascent 0.447 ± 0.180 vs. 0.506 ± 0.179 m/s; P = 0.043 and descent 0.394 ± 0.170 vs. 0.463 ± 0.159 m/s; P = 0.026). Postural balance improved during quiet standing with eyes closed in Vc2, Vc4, Vc6, and Vc7 (P < 0.005). CONCLUSIONS: Vibrating insoles are an effective acute strategy for improving postural balance and gait quality during level walking and stair descent in individuals with DPN. These benefits are particularly evident when the entire plantar foot surface is stimulated.

What is New on Diabetic Neuropathy? Insights from the 2023 ADA and EASD Conferences.

Diabetic neuropathy is a common complication of diabetes; yet its pathophysiology is still incompletely understood and until today, there is no specific treatment against it. In the two 2023 large congresses on diabetes (American Diabetes Association, ADA, European Association for the Study of Diabetes, EASD), several high-level studies have been presented. They have attempted to delineate the pathophysiology of DN, the characteristics of affected patients, and future potential treatments. We herein review the presented studies on diabetic neuropathy at these diabetes congresses and discuss the needs for future research on this topic.

Advancing type 2 diabetes therapy with iGlarLixi in older people: Pooled analysis of four randomized controlled trials.

AIM: To assess the efficacy and safety of iGlarLixi in older people (≥65 years) with type 2 diabetes (T2D) advancing or switching from oral agents, a glucagon-like peptide-1 receptor agonist (GLP-1RA), or basal insulin. MATERIALS AND METHODS: The data of participants aged <65 years and ≥65 years from four LixiLan trials (LixiLan-O, LixiLan-G, LixiLan-L, SoliMix) were evaluated over 26 or 30 weeks. RESULTS: Participants aged <65/≥65 years (n = 1039/n = 497) had a mean baseline body mass index of 31.4 and 30.7 kg/m2 and glycated haemoglobin (HbA1c) concentration of 66 mmol/mol (8.2%) and 65 mmol/mol (8.1%), respectively. Least squares mean HbA1c change from baseline to end of treatment (EOT) was -14.32 mmol/mol (-1.31%) (95% confidence interval [CI] -14.97, -13.77 [-1.37%, -1.26%]) for those aged <65 years and -13.66 mmol/mol (-1.25%) (95% CI -14.54, -12.79 [-1.33%, -1.17%]) for those aged ≥65 years. At EOT, achievement of HbA1c targets was similar between the group aged <65 years and the group aged ≥65 years: <53 mmol/mol (<7%) (59.0% and 56.5%, respectively), <59 mmol/mol (<7.5%) (75.5% and 73.0%, respectively) and <64 mmol/mol (<8%) (83.8% and 84.1%, respectively). The incidence and event rate of American Diabetes Association Level 1 hypoglycaemia during the studies were also comparable between the two groups: 26.7% and 28.2% and 1.7 and 2.1 events per patient-year for the group aged <65 years and the group aged ≥65 years, respectively. A clinically relevant reduction in HbA1c (>1% from baseline for HbA1c ≥64 mmol/mol [≥8%] or ≥0.5% from baseline for HbA1c <64 mmol/mol [<8%]) without hypoglycaemia was attained by 50.0% and 47.6% of participants aged <65 years and ≥65 years, respectively. Adverse events were similar between the two age groups. CONCLUSIONS: iGlarLixi is a simple, well-tolerated, once-daily alternative for treatment advancement in older people with T2D that provides significant improvements in glycaemic control without increasing hypoglycaemia risk, thus reducing the treatment burden.

A paradigm shift for cardiovascular outcome evaluation in diabetes: Major adverse cardiovascular events (MACE) to major adverse vascular events (MAVE).

BACKGROUND AND AIMS: Drugs for diabetes are required to demonstrate cardiovascular safety through CV outcome trials (CVOT). The pre-defined end-points for cardiovascular outcome studies may not be sufficient to capture all clinically relevant atherosclerotic cardio vascular disease (ASCVD) events particularly peripheral arterial disease (PAD). METHODS: We planned a scoping review and searched database to identify CVOT conducted in population with diabetes measuring lower limb events due to PAD as the primary outcome measure. We also searched CVOT for reported differential cardiovascular outcomes in population with PAD. RESULTS: We identified that CV outcomes are measured as 3 point major adverse cardiovascular outcomes (3P-MACE) that includes nonfatal MI and nonfatal stroke or 4P-MACE that included additional unstable angina which is further expanded to 5P-MACE by the inclusion of hospitalization for heart failure (HHF). These CV end points are captured as surrogate for CV mortality based on the biological plausibility of relation between the surrogate and final outcome from pathophysiological studies. We found the prevalence of PAD is no lesser than other CV events in people with diabetes. Moreover, PAD contributes to the significant morbidity associated with diabetes as a surrogate for mortality. However, none of the CVOT with anti-diabetic drugs include PAD events as primary outcome measure despite the inclusion of 6-25 % participants with PAD in major CVOT. PAD outcomes are objectively measurable with tibial arterial waveforms and clinical end-point as lower extremity amputation. PAD outcomes do improve with treatment including intensive glycemic control and novel oral anticoagulants. We suggest the inclusion of PAD to MACE as a pre-specified outcome for a comprehensive capture of major adverse vascular event in future studies for people with diabetes. CONCLUSIONS: MACE should be expanded to include PAD event as major adverse vascular event in cardiovascular outcome studies since PAD is clinically relevant and objectively measurable in diabetes.

Pedal acrometastasis secondary to urothelial carcinoma masquerading as Charcot arthropathy in a patient with diabetes.

A woman in her 80s with known diabetes mellitus and bladder cancer presented to her general practitioner (GP) with pain and swelling in her left foot following trauma. Initial radiographs were reported as normal, prompting a diagnosis of a simple sprain and conservative management. Three months later, the patient was referred to the orthopaedic team due to progressively increasing pain and swelling. Repeat X-rays revealed lytic lesions in both the talus and navicular bones; MRI confirmed the presence of a lytic and proliferative defect in the mid-foot, which was reported as acute Charcot arthropathy with superimposed infection. This was also considered the most likely diagnosis when imaging was reviewed in two separate multidisciplinary team) meetings. However, biopsy demonstrated that the cause of the presentation was in fact acrometastasis from urothelial carcinoma, an infrequently described entity.

Diabetes foot complications and standardized mortality rate in type 2 diabetes.

AIM: To quantify the impact of foot complications on mortality outcomes in people with type 2 diabetes (T2D), and how routinely measured factors might modulate that risk. MATERIALS AND METHODS: Data for individuals with T2D for 2010-2020, from the Salford Integrated Care Record (Salford, UK), were extracted for laboratory and clinical data, and deaths. Annual expected deaths were taken from Office of National Statistics mortality data. An index of multiple deprivation (IMD) adjusted the standardized mortality ratio (SMR_IMD). Life years lost per death (LYLD) was estimated from the difference between expected and actual deaths. RESULTS: A total of 11 806 T2D patients were included, with 5583 new diagnoses and 3921 deaths during 2010-2020. The number of expected deaths was 2135; after IMD adjustment, there were 2595 expected deaths. Therefore, excess deaths numbered 1326 (SMR_IMD 1.51). No foot complications were evident in n = 9857. This group had an SMR_IMD of 1.13 and 2.74 LYLD. In total, 2979 patients had any foot complication recorded. In this group, the SMD_IMR was 2.29; of these, 2555 (75%) had only one foot complication. Patients with a foot complication showed little difference in percentage HbA1c more than 58 mmol/mol. In multivariate analysis, for those with a foot complication and an albumin-to-creatinine ratio of more than 3 mg/mmol, the odds ratio (OR) for death was 1.93, and for an estimated glomerular filtration rate of less than 60 mL/min/1.73m2 , the OR for death was 1.92. CONCLUSIONS: Patients with T2D but without a foot complication have an SMR_IMD that is only slightly higher than that of the general population. Those diagnosed with a foot complication have a mortality risk that is double that of those without T2D.

Cell Therapy of Severe Ischemia in People with Diabetic Foot Ulcers-Do We Have Enough Evidence?

This current opinion article critically evaluates the efficacy of autologous cell therapy (ACT) for chronic limb-threatening ischemia (CLTI), especially in people with diabetes who are not candidates for standard revascularization. This treatment approach has been used in 'no-option' CLTI in the last two decades and more than 1700 patients have received ACT worldwide. Here we analyze the level of published evidence of ACT as well as our experience with this treatment method. Many studies have shown that ACT is safe and an effective method for patients with the most severe lower limb ischemia. However, some trials did not show any benefit of ACT, and there is some heterogeneity in the types of injected cells, route of administration and assessed endpoints. Nevertheless, we believe that ACT plays an important role in a comprehensive treatment of patients with diabetic foot and severe ischemia.

Endothelial Dysfunction in Diabetes Mellitus: New Insights.

Endothelial dysfunction (ED) is an important marker of future atherosclerosis and cardiovascular disease, especially in people with diabetes. This article summarizes the evidence on endothelial dysfunction in people with diabetes and adds different perspectives that can affect the presence and severity of ED and its consequences. We highlight that data on ED in type 1 diabetes are lacking and discuss the relationship between ED and arterial stiffness. Several interesting studies have been published showing that ED modulates microRNA, microvesicles, lipid levels, and the endoplasmatic reticulum. A better understanding of ED could provide important insights into the microvascular complications of diabetes, their treatment, and even their prevention.

Euvolaemic hyponatraemia as a rare first presentation of chronic hypopituitarism.

A man in his late 40s with no significant medical history presented with 2 weeks of lethargy, nausea and dizziness, alongside worsening headaches. Initial assessment revealed severe hyponatraemia and secondary hypothyroidism; urgent MRI pituitary was requested with a clinical suspicion of pituitary apoplexy. This demonstrated a likely cystic pituitary adenoma, with further testing revealing pituitary gland suppression, leading to a diagnosis of chronic secondary hypopituitarism. Initiating hormone replacement allowed substantial reported improvements in this patient's quality of life.A review of the patient's work-up revealed areas in which best practice was not followed. Cortisol measurements and paired urinary and serum osmolalities were initially not sent, nor results appropriately chased. A subsequent literature review identified that conformation with national and local guidelines on hyponatraemia management is poor. This patient's case, when combined with the literature review, provides evidence to support methods to increase educational awareness of an appropriate work-up of hyponatraemia among clinicians.

Parathyroid carcinoma presenting as severe hypercalcaemia responding to steroids.

A man in his 50s was referred with profound, symptomatic hypercalcaemia. He was diagnosed with primary hyperparathyroidism, confirmed on 99mTc-sestamibi scan. He was treated for the hypercalcaemia and referred to ear, nose and throat (ENT) surgeons for parathyroidectomy, which was delayed due to the COVID-19 pandemic. In the ensuing 18 months, he had five hospital admissions with severe hypercalcaemia requiring intravenous fluids and bisphosphonate infusions. During the last admission, hypercalcaemia was resistant to maximal medical management. Emergency parathyroidectomy was planned, but delayed due to intervening COVID-19 infection. Due to persistent severe hypercalcaemia (serum calcium: 4.23 mmol/L), he was commenced on intravenous steroids, following which serum calcium normalised. Subsequently, he underwent emergency parathyroidectomy, which normalised his serum parathyroid and calcium levels. On histopathological examination, a diagnosis of parathyroid carcinoma was made. On follow-up, patient remained well and normocalcaemic. In patients with primary hyperparathyroidism unresponsive to standard therapy, but responsive to steroids, underlying parathyroid malignancy should be considered.

The Role of Vitamin D in Health and Disease: A Narrative Review on the Mechanisms Linking Vitamin D with Disease and the Effects of Supplementation.

Vitamin D insufficiency or deficiency (VDD) is a very prevalent condition in the general population. Vitamin D is necessary for optimal bone mineralization, but apart from the bone effects, preclinical and observational studies have suggested that vitamin D may have pleiotropic actions, whereas VDD has been linked to several diseases and higher all-cause mortality. Thus, supplementing vitamin D has been considered a safe and inexpensive approach to generate better health outcomes-and especially so in frail populations. Whereas it is generally accepted that prescribing of vitamin D in VDD subjects has demonstrable health benefits, most randomized clinical trials, although with design constraints, assessing the effects of vitamin D supplementation on a variety of diseases have failed to demonstrate any positive effects of vitamin D supplementation. In this narrative review, we first describe mechanisms through which vitamin D may exert an important role in the pathophysiology of the discussed disorder, and then provide studies that have addressed the impact of VDD and of vitamin D supplementation on each disorder, focusing especially on randomized clinical trials and meta-analyses. Despite there already being vast literature on the pleiotropic actions of vitamin D, future research approaches that consider and circumvent the inherent difficulties in studying the effects of vitamin D supplementation on health outcomes are needed to assess the potential beneficial effects of vitamin D. The evaluation of the whole vitamin D endocrine system, rather than only of 25-hydroxyvitamin D levels before and after treatment, use of adequate and physiologic vitamin D dosing, grouping based on the achieved vitamin D levels rather than the amount of vitamin D supplementation subjects may receive, and sufficiently long follow-up are some of the aspects that need to be carefully considered in future studies.

Inflammatory Arthritis Associated with COVID-19 Vaccination.

COVID-19 vaccines have been shown to be highly efficacious in preventing symptomatic COVID-19 infections throughout the pandemic. There have been emerging cases of inflammatory arthritis occurring in close relation to COVID-19 vaccination. We illustrate a case of new-onset inflammatory arthritis 10 days after receiving their second Vaxzevria COVID-19 vaccine. The patient responded dramatically to prednisolone treatment but subsequently required hydroxychloroquine due to persistent inflammatory joint symptoms. Inflammatory arthritis is an increasingly recognized rare adverse effect of COVID-19 vaccination and clinicians should actively consider this in patients with new or flares of inflammatory joint disease.