Cholecalciferol Exhibits no Antibacterial Effect on Staphylococcus aureus and Escherichia coli: an in-vitro Study.

BACKGROUND: The pleiotropic effect of cholecalciferol (vitamin D3) has gained significant momentum and has been explored widely. OBJECTIVES: The study aimed to investigate the antimicrobial effect of cholecalciferol against S. aureus and E. coli. METHODS: An in-vitro study was performed for the antimicrobial effect of cholecalciferol against S. aureus and E. coli. The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) were determined following the broth microdilution method. RESULTS: The MIC value of cholecalciferol against both S. aureus and E. coli was 0.312 mg/ml, and the MBC for both organisms was 1.25 mg/ml. However, we also observed a significant antimicrobial effect in the dimethyl sulfoxide (DMSO) control at 12.5% (v/v). Therefore, the observed antimicrobial effect may be attributed to DMSO, indicating cholecalciferol does not directly inhibit S. aureus and E. coli. CONCLUSION: This study indicates that cholecalciferol does not directly inhibit S. aureus and E. coli. Hence, we suggest exploring the antibacterial properties of other vitamin D analogs, such as calcitriol or its synergetic effect with other antimicrobial agents.

The association between micronutrient levels and diabetic foot ulcer: A systematic review with meta-analysis.

Background: Diabetic foot ulcers (DFU) are a major complication of diabetes mellitus (DM). Nutrient deficiencies are among the major risk factors in DFU development and healing. In this context, we aimed to investigate the possible association between micronutrient status and risk of DFU. Methods: A systematic review (Prospero registration: CRD42021259817) of articles, published in PubMed, Web of Science, Scopus, CINAHL Complete, and Embase, that measured the status of micronutrients in DFU patients was performed. Results: Thirty-seven studies were considered, of which thirty were included for meta-analysis. These studies reported levels of 11 micronutrients: vitamins B9, B12, C, D, E, calcium, magnesium, iron, selenium, copper, and zinc. DFU, compared to healthy controls (HC) had significantly lower vitamin D (MD: -10.82 14 ng/ml, 95% CI: -20.47, -1.16), magnesium (MD: -0.45 mg/dL, 95% CI: -0.78, -0.12) and selenium (MD: -0.33 µmol/L, 95% CI: -0.34, -0.32) levels. DFU, compared to DM patients without DFU, had significantly lower vitamin D (MD: -5.41 ng/ml, 95% CI: -8.06, -2.76), and magnesium (MD: -0.20 mg/dL, 95% CI: -0.25, -0.15) levels. The overall analysis showed lower levels of vitamin D [15.55ng/ml (95% CI:13.44, 17.65)], vitamin C [4.99µmol/L (95% CI:3.16, 6.83)], magnesium [1.53mg/dL (95% CI:1.28, 1.78)] and selenium [0.54µmol/L (95% CI:0.45, 0.64)]. Conclusion: This review provides evidence that micronutrient levels significantly differ in DFU patients, suggesting an association between micronutrient status and risk of DFU. Therefore, routine monitoring and supplementations are warranted in DFU patients. We suggest that personalized nutrition therapy may be considered in the DFU management guidelines. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=259817, identifier CRD42021259817.

Association of serum ferritin with severity and clinical outcome in COVID-19 patients: An observational study in a tertiary healthcare facility.

Background: Ferritin, an intracellular protein, has a pivotal role in immune dysregulation. Hyperferritinemia has been associated with higher disease severity and adverse clinical outcomes in COVID-19, including mortality. We aimed to study the association of serum ferritin levels with disease severity and clinical outcomes and its severity prediction potential in COVID-19 patients. Methods: This retrospective study included 870 adult patients with symptomatic COVID-19 infection hospitalized between July 1, 2020 to December 21, 2020. All the patients had a positive polymerase chain reaction test result of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Results: The median age was 55 (IQR:40, 65) years with a male predominance [66.32% (n = 577)], among 870 COVID-19. Of these, 413 (47.47%) had mild COVID-19, and 457 (52.53%) had moderate plus severe COVID-19 disease. Median ferritin levels were significantly high in moderate to severe COVID-19 infection compared to mild [545.8 (326.0, 1046.0) vs 97.3 (52.65-155.5) (p = 0.001)], and in patients who developed a complication compared to without complications [380 (177.05, 863.15) vs 290 (110.9, 635) (p = 0.002). A slight elevation in median ferritin levels was observed in patients who had an ICU stay than non-ICU [326 (129.8, 655) vs 309 (119.1, 684) (p = 0.872)]. The cut-off for ferritin was identified at >287.4 ng/ml for mild versus moderate plus severe COVID-19 infections. Conclusion: Moderate to severe COVID-19 patients have elevated ferritin levels. Patients with more than 287.4 ng/ml ferritin value would have greater chances of developing moderate to severe COVID-19 infections.

Impact of tuberculosis disease on human gut microbiota: a systematic review.

INTRODUCTION: This systematic review evaluates the gut microbiota (GM) status in tuberculosis (TB) patients compared to healthy volunteers due to the disease or its treatment. AREAS COVERED: We conducted a systematic review of all articles published in PubMed, Web of Science, and Embase that assessed the impact of TB disease and anti-tubercular therapy (ATT) on GM from inception till January 2022 (Protocol registration number in PROSPERO: CRD42021261884). Regarding the microbial diversity indices and taxonomy, we found a significant difference in GM status between the TB and healthy control (HC) groups. We found an overabundance of Phylum Proteobacteria and depletion of some short-chain fatty acid-producing bacteria genera like Bifidobacteria, Roseburia, and Ruminococcus in the TB group. We found that ATT exacerbates the degree of dysbiosis caused by Mycobacteria tuberculosis disease. EXPERT OPINION: The modulation of GM in TB patients in clinical practice may serve as a promising target to reverse the dysbiosis caused. Moreover, this can optimistically change the TB treatment outcome. We expect that appropriate probiotic supplementation with antimycobacterial treatment during tuberculosis disease will help stabilize the GM throughout the treatment phase and protect the GM from dysbiosis.

Vitamin D attenuates biofilm-associated infections via immunomodulation and cathelicidin expression: a narrative review.

INTRODUCTION: Infections are becoming more difficult to treat, at least partly on account of microbes that produce biofilms. Reports suggest that decreased levels of antimicrobial peptides like cathelicidin, elevated levels of inflammatory cytokines, and biofilm formation are all associated with vitamin D deficiency, making vitamin D - deficient individuals more susceptible to infection. Infections attributable to biofilm-producing microbes can be managed by adjuvant therapy with vitamin D because of its immunomodulatory role, particularly because of the ability of vitamin D-pathway to induce the antimicrobial peptides like cathelicidin and decrease proinflammatory cytokines. AREAS COVERED: This narrative review covers biofilm formation, infections associated with biofilm due to vitamin D deficiency, putative role of vitamin D in host protection and the effect of vitamin D supplementation in biofilm-associated infections. A comprehensive literature search in PubMed and Google Scholar utilizing suitable keywords at multiple time points extracted relevant articles. EXPERT OPINION: Although vitamin D deficiency has been associated with infections by biofilm producing microbes, comprehensive clinical trials in various ethnicities are required to understand the likely relationships between vitamin D receptor gene expression, cathelicidin levels, and infection outcome. Current evidence hypothesizes that maintaining normal vitamin D level can help prevent and treat these infections.

Cefepime-induced Neurotoxicity: A Retrospective Cohort Study in a South-Indian Tertiary Healthcare Facility.

BACKGROUND: Cefepime is a fourth-generation cephalosporin with a broad spectrum coverage and anti-pseudomonal activity. The safety profile of cefepime was relatively favourable until neurotoxicity was first reported in 1999. Despite cefepime-induced neurotoxicity (CIN), it continues to be a principal part of parenteral treatment for various infections. OBJECTIVE: The study aimed to determine the incidence and risk factors for CIN compared to other antibiotics. METHODS: A retrospective cohort study was conducted involving 738 patients over eight months in Kasturba Medical College and Hospital, Manipal, India. Patients with cefepime were selected as study cohort (SC; n= 496), and other antibiotics were included in the reference cohort (RC; n=242). RESULTS: The results showed that 53 (10.7%) patients developed neurotoxicity in the SC, whereas 12 (5%) patients in the RC. A significant association was found between neurotoxicity and cefepime use (X2 =6.641; p=0.01). SC has a 2.29 times increased risk of neurotoxicity than RC (OR: 2.29; 95% CI: 1.2-4.38). Risk estimation showed that renal failure patients had a 5.5 times higher risk for CIN than non-renal failure patients (OR: 5.5; 95% CI: 2.98 - 10.17). CIN symptoms were disorientation (38.5%), loss of consciousness (23.1%), drowsiness (18.5%), etc. The calculated number needed to harm (NNH) for cefepime was 17.2. CONCLUSION: The study found a higher incidence of CIN compared to other antibiotics-induced neurotoxicity and a harmful association between cefepime use and CIN development. Besides, renal failure is a risk factor for CIN. Therefore, the study warrants the use of cefepime, where no other alternatives are available.

Phytotherapy in Diabetic Foot Ulcers: A Promising Strategy for Effective Wound Healing.

Despite the advancement in wound care, the effective therapy of chronic diabetic ulcers continues to be a challenge. Wound healing is a highly controlled process, which involves a sequence of complex overlapping steps. This healing pathway comprises of hemostasis, inflammation, proliferative, and remodeling phases. Recent evidence suggests that phytomedicines can prevent or repair different kinds of destructive cellular damage, including chronic wounds. Several phytochemicals such as polyphenols, alkaloids, flavonoids, terpenoids, and glycosides have pleiotropic effects, including stimulation of fibroblast proliferation, the main step in wound healing. Besides, the mechanism involves induction of collagen synthesis, migration, and reepithelization and their antimicrobial, antioxidant, anti-inflammatory, and immunomodulatory actions. Similarly, the use of phytochemicals alone or as an adjuvant with standard therapy has demonstrated promising results in managing complications in the diabetic foot. For instance, the extract of Carica papaya has been shown antioxidant, antimicrobial, and anti-inflammatory, and immunomodulatory effects, which, together with proteolytic enzymatic activity, contributes to its wound healing property. It is generally believed that phytotherapy has no or minimal toxicity than synthetic therapeutic agents, favoring its use in diabetic foot ulcer management. The current review highlights the selected phytochemicals and their sources; and potential application in diabetic foot ulcer management.Key teaching points and nutritional relevanceCurrently, phytochemicals have been shown wide potential in disease. management including alleviating clinical manifestations, preventing degenerative disease, and curing illness.Increased evidence of phytochemical as anti-infective and anti-inflammatory suggests its role in the management of diabetic foot ulcer(DFU).Potential benefit along with minimal adverse effect favors its application as adjuvant therapy.Further research is needed to standardize its dose and formulation to enhance its clinical application in DFU management.

Vitamin D receptor gene polymorphism and vitamin D supplementation on clinical/ treatment outcome in tuberculosis: current and future perspectives.

INTRODUCTION: Tuberculosis (TB) is a transnational public health concern, which requires more precise treatment strategies than the existing approaches. Vitamin D modulates the inflammatory and immune response to the disease. Robust evidence shows that vitamin D deficiency and its receptor gene polymorphism influence the susceptibility to TB and the outcome of the anti-tubercular treatment (ATT). However, in the different populations, these findings were inconsistent and even contradictory. AREAS COVERED: The current review focuses on the association between vitamin D receptor (VDR) gene polymorphism with the risk of development of TB disease and response to the ATT. Additionally, it reviews various systematic reviews and meta-analyses on the impact of vitamin D supplements on both clinical and treatment outcomes in TB patients. EXPERT OPINION: Although the majority of the findings rule out the benefits of the supplementation, sufficient evidence is available to warrant larger epidemiological research that should be aimed to generate possible interaction among the VDR polymorphism, vitamin D status, and the outcome in TB. We conclude that establishing such an association in different ethnic populations will help design nutrigenomics- or pharmacogenomics-based vitamin D supplementation to develop a personalized medicine approach to flatten the curve of TB disease.

Effect of Vitamin D Supplementation in Type 2 Diabetes Patients with Tuberculosis: A Systematic Review.

BACKGROUND: Diabetes mellitus (DM) and tuberculosis (TB) have been recognized as reemerging epidemics, especially in developing countries. Among all the risk factors, diabetes causes immunosuppression, increasing the risk of active TB three times. Vitamin D has been found as a link between DM-TB co-morbidity. OBJECTIVE: Vitamin D affects the immune response, suppresses Mycobacterium tuberculosis (Mtb) growth, and affects insulin secretion. The present systematic review determines the effect of vitamin D supplementation on clinical and therapeutic outcomes of DM-TB patients. METHOD: A comprehensive literature search was carried out in PubMed, Cochrane, Web of Science, and Scopus database to determine eligible studies from inception to January 2021. Out of the 639 articles retrieved, three randomized controlled trials (RCTs) were included in the systematic review. RESULT: The effect of vitamin D3 or oral cholecalciferol supplementation was assessed on outcomes, such as duration to sputum smear conversion, TB scores improvement, change in glycemic parameters, including HbA1c, FBS, and PLBS, and laboratory parameters, such as Hb, ESR, and CRP. Duration of sputum smear conversion was decreased by two weeks in the vitamin D3 supplemented group in two studies. TB score improvement and changes in glycemic parameters were inclined towards supplemented group; however, they were not significant. CONCLUSION: The overall effect of vitamin D3 supplementation on TB patients with DM was not significant. Further studies are required in the future examining the effect of supplementation on outcomes in this population.

Pharmacogenomics and Personalized Medicine in Type 2 Diabetes Mellitus: Potential Implications for Clinical Practice.

Type 2 diabetes mellitus (T2DM) is the most common form of diabetes, and is rising in incidence with widespread prevalence. Multiple gene variants are associated with glucose homeostasis, complex T2DM pathogenesis, and its complications. Exploring more effective therapeutic strategies for patients with diabetes is crucial. Pharmacogenomics has made precision medicine possible by allowing for individualized drug therapy based on a patient's genetic and genomic information. T2DM is treated with various classes of oral hypoglycemic agents, such as biguanides, sulfonylureas, thiazolidinediones, meglitinides, DPP4 inhibitors, SGLT2 inhibitors, α-glucosidase inhibitors, and GLP1 analogues, which exhibit various pharmacogenetic variants. Although genomic interventions in monogenic diabetes have been implemented in clinical practice, they are still in the early stages for complex polygenic disorders, such as T2DM. Precision DM medicine has the potential to be effective in personalized therapy for those suffering from various forms of DM, such as T2DM. With recent developments in genetic techniques, the application of candidate-gene studies, large-scale genotyping investigations, genome-wide association studies, and "multiomics" studies has begun to produce results that may lead to changes in clinical practice. Enhanced knowledge of the genetic architecture of T2DM presents a bigger translational potential. This review summarizes the genetics and pathophysiology of T2DM, candidate-gene approaches, genome-wide association studies, personalized medicine, clinical relevance of pharmacogenetic variants associated with oral hypoglycemic agents, and paths toward personalized diabetology.

Probiotics in Prevention and Treatment of COVID-19: Current Perspective and Future Prospects.

Saving lives and flattening the curve are the foremost priorities during the ongoing pandemic spread of SARS-CoV-2. Developing cutting-edge technology and collating available evidence would support frontline health teams. Nutritional adequacy improves general health and immunity to prevent and assuage infections. This review aims to outline the potential role of probiotics in fighting the COVID-19 by covering recent evidence on the association between microbiota, probiotics, and COVID-19, the role of probiotics as an immune-modulator and antiviral agent. The high basic reproduction number (R0) of SARS-CoV-2, absence of conclusive remedies, and the pleiotropic effect of probiotics in fighting influenza and other coronaviruses together favour probiotics supplements. However, further support from preclinical and clinical studies and reviews outlining the role of probiotics in COVID-19 are critical. Results are awaited from many ongoing clinical trials investigating the benefits of probiotics in COVID-19.

Vitamin D in Prevention and Treatment of COVID-19: Current Perspective and Future Prospects.

Vitamin D deficiency (VDD) partly explains geographical differences in COVID-19 susceptibility, severity, and mortality. VDD among African-Americans, diabetics, hypertensive, and aged populations possibly explain the higher death rate, aggravated by cocooning. Vitamin D is pleiotropic, mediating bone metabolism, calcium homeostasis, and immune functions, whereas VDD is associated with inflammatory reactions and immune dysfunction, predisposing individuals to severe infections. Vitamin D modulates innate and adaptive immunity via the expression of genes that code antimicrobial peptides (AMPs). And the expression of cluster of differentiation (CD)14, the co-receptor for epidermal toll-like receptor (TLR)4. AMPs stimulate TLR2 in macrophages, increasing the conversion of vitamin D into its active form by cytochrome P450 27B1. Antiviral properties of vitamin D-induced AMPs can shift the polarization of the adaptive immune response from helper T cells (Th)1 to the more regulatory Th2 responses that suppress immune over-reactivity by preventing cytokine storm, which is already demonstrated during the Spanish flu episode. Vitamin D induces antiviral effects by both direct and indirect mechanisms via AMPs, immunomodulation, the interplay between major cellular and viral elements, induction of autophagy and apoptosis, variation of genetic and epigenetic factors. The crosstalk between vitamin D and intracellular signaling pathways may operate as a primary regulatory action on viral gene transcription. VDD may increase the likelihood of infection with enveloped viruses, including retrovirus, hepatitis, and dengue. Global data correlates severe VDD with COVID-19 associated coagulopathy, disrupted immune response and mortality, reduced platelet count, and prolonged prothrombin time, suggesting benefits from supplementation.Key teaching pointsVitamin D induces antiviral effects by direct and indirect mechanisms via AMPs, immunomodulation, induction of autophagy, etc.Epidemiology of VDD partly explains geographical differences in COVID-19 susceptibility, severity, and mortality.Global data correlates severe VDD with COVID-19 associated coagulopathy, disrupted immune response and mortality, reduced platelet count, and prolonged prothrombin time, together suggesting benefits from supplementation.Many clinical trials are underway globally to delineate the role of vitamin D in both prevention and treatment of COVID-19.

Vitamin D Supplementation in Diabetic Foot Ulcers: A Current Perspective.

INTRODUCTION: Diabetic foot ulcer (DFU) is a major complication of diabetes mellitus, as it can physically and emotionally impact the person. Its management can be challenging and expensive, depending on the severity of the wound and the presence of infection. BACKGROUND: The fat-soluble molecule, vitamin D, has gained great importance ever since its pleiotropism has been recognized. Its efficacy could be attributed to the presence of vitamin D receptors in most of the body tissues. Vitamin D plays a significant role in cell proliferation, differentiation, and immune modulation. It modulates the T and B cells resulting in the suppression of the immunoglobulins, autoimmunity, and inflammation. METHODS: We performed a literature search with the objective to highlight the role of vitamin D in peripheral vascular disease and peripheral neuropathy, which are the major risk factors for DFU, as well as evidences of its role in wound healing and management of DFU. RESULTS: Preclinical and clinical studies have shown that vitamin D influences multiple phases of wound healing and thereby accelerates the process. It modulates various cells involved in proliferation and remodelling phases. Vitamin D also enhances the expression of antimicrobial peptides that help to eliminate the microbes, as well as suppress the proinflammatory responses while enhancing the anti-inflammatory responses. CONCLUSION: This review concludes vitamin D to have a protective role in the immune and vascular system, improve glycaemic outcomes, and wound healing. Therefore, vitamin D could be a preferred adjuvant in the management of DFU.

A prospective observational study on psychotropic drug use in non psychiatric wards.

BACKGROUND: Psychotropic medications are the first line for the management of psychiatric illnesses; in addition, they are also being used in an off-labeled manner. Inappropriate prescribing of psychotropic medications either can cause serious harm or may be of no benefit to the patients. However, there is a dearth of information on the pattern of psychotropic drug use in the nonpsychiatry wards. AIM: The aim of this study is to assess the use of psychotropic drugs in general medicine and surgical wards of a teaching hospital. MATERIALS AND METHODS: An observational study was conducted in the general medicine and surgical wards of a university teaching hospital over 6 months. Patients admitted to the medicine and surgical ward were observed for a prescription of psychotropic medications. Once they were prescribed with a psychotropic medication, the patients were included in the study and were followed until discharge. All the necessary information such as dose, route, class of psychotropic and prescriber's status were documented and analyzed. RESULTS: A total of 322 patients were prescribed with 452 psychotropic medications. The average number of psychotropic per patient was 1.40 ± 0.76 (range: 1-4). The rate of psychotropic medications prescription in the nonpsychiatric ward is 10.73%. Alcohol dependence syndrome (n = 90 [26.71%]) and pain (n = 43 [43.87%]) were the observed psychiatric and nonpsychiatric indications. The frequently prescribed psychotropic classes were benzodiazepines (n = 165 [36.50%]) and antidepressants (n = 144 [31.86%]). Nonpsychiatrists (n = 250 [55.3%]) were the common prescribers and benzodiazepines (n = 124 [27.43%]) were the preferred class for nonpsychiatrist, whereas psychiatrist prescribed different class of psychotropic drugs. CONCLUSION: This study emphasizes that nonpsychiatrist irrespective of their specialty prescribed psychotropic medication for psychiatric and nonpsychiatric indications.