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Is it time to reconsider prophylactic antimicrobial use for hematopoietic stem cell transplantation? a narrative review of antimicrobials in stem cell transplantation

Jahan D, Peile E, Sheikh MA, Islam S, Parasnath S, Sharma P, et al.

Expert Rev Anti Infect Ther, 2021 10;19(10):1259-1280.
PMID: 33711240 DOI: 10.1080/14787210.2021.1902304

INTRODUCTION: Hematopoietic Stem Cell Transplantation (HSCT) is a life-saving procedure for multiple types of hematological cancer, autoimmune diseases, and genetic-linked metabolic diseases in humans. Recipients of HSCT transplant are at high risk of microbial infections that significantly correlate with the presence of graft-versus-host disease (GVHD) and the degree of immunosuppression. Infection in HSCT patients is a leading cause of life-threatening complications and mortality.
AREAS COVERED: This review covers issues pertinent to infection in the HSCT patient, including bacterial and viral infection; strategies to reduce GVHD; infection patterns; resistance and treatment options; adverse drug reactions to antimicrobials, problems of antimicrobial resistance; perturbation of the microbiome; the role of prebiotics, probiotics, and antimicrobial peptides. We highlight potential strategies to minimize the use of antimicrobials.
EXPERT OPINION: Measures to control infection and its transmission remain significant HSCT management policy and planning issues. Transplant centers need to consider carefully prophylactic use of antimicrobials for neutropenic patients. The judicious use of appropriate antimicrobials remains a crucial part of the treatment protocol. However, antimicrobials' adverse effects cause microbiome diversity and dysbiosis and have been shown to increase morbidity and mortality.
Quorum sensing: a new prospect for the management of antimicrobial-resistant infectious diseases

Haque M, Islam S, Sheikh MA, Dhingra S, Uwambaye P, Labricciosa FM, et al.

Expert Rev Anti Infect Ther, 2021 05;19(5):571-586.
PMID: 33131352 DOI: 10.1080/14787210.2021.1843427

INTRODUCTION: Quorum-sensing (QS) is a microbial cell-to-cell communication system that utilizes small signaling molecules to mediates interactions between cross-kingdom microorganisms, including Gram-positive and -negative microbes. QS molecules include N-acyl-homoserine-lactones (AHLs), furanosyl borate, hydroxyl-palmitic acid methylester, and methyl-dodecanoic acid. These signaling molecules maintain the symbiotic relationship between a host and the healthy microbial flora and also control various microbial virulence factors. This manuscript has been developed based on published scientific papers.
AREAS COVERED: Furanones, glycosylated chemicals, heavy metals, and nanomaterials are considered QS inhibitors (QSIs) and are therefore capable of inhibiting the microbial QS system. QSIs are currently being considered as antimicrobial therapeutic options. Currently, the low speed at which new antimicrobial agents are being developed impairs the treatment of drug-resistant infections. Therefore, QSIs are currently being studied as potential interventions targeting QS-signaling molecules and quorum quenching (QQ) enzymes to reduce microbial virulence.
EXPERT OPINION: QSIs represent a novel opportunity to combat antimicrobial resistance (AMR). However, no clinical trials have been conducted thus far assessing their efficacy. With the recent advancements in technology and the development of well-designed clinical trials aimed at targeting various components of the, QS system, these agents will undoubtedly provide a useful alternative to treat infectious diseases.
Daridorexant as a novel pharmacotherapeutic approach in insomnia: a systematic review and meta-analysis

Dutta S, Singhal S, Shah R, Charan J, Dhingra S, Haque M

Expert Opin Drug Saf, 2023;22(12):1237-1251.
PMID: 37526060 DOI: 10.1080/14740338.2023.2243217

BACKGROUND: Insomnia is a multi-factorial disorder with conventional treatment options that are not satisfactory for many patients. This metaanalysis analyzed the safety and efficacy of daridorexant.
METHODS: An electronic database search for RCTs was conducted on Medline via PubMed, Cochrane, and Clinicaltrials.gov using the terms 'Daridorexant,' 'RCT,' 'Insomnia' trials evaluating the efficacy and/or safety of daridorexant for insomnia were included. The data were synthesized using Cochrane review manager version 5.4.1. Cochrane risk of bias 2.0 tool and GRADEpro-GDT were used to assess the methodological and evidence quality, respectively.
RESULTS: Of 109 searched studies, four trials were included. The risk of treatment-emergent adverse events with 25 mg daridorexant [risk ratio (RR) = 1.12 (0.88, 1.43), p = 0.36; I2 = 0%] and 50 mg daridorexant [RR = 1.25 (0.88, 1.79), p = 0.22; I2 = 28%] and serious adverse events with 25 mg [RR = 0.86 (0.23, 3.19), p = 0.82, I2 = 56%] and 50 mg [RR = 1.32 (0.29, 6.08), p = 0.72, I2 = 52%] was comparable to placebo [Moderate quality evidence]. Risk of nasopharyngitis was also comparable to placebo. The efficacy parameters like wake after sleep onset, latency to persistent sleep, and subjective total sleep time showed significant improvement with daridorexant. The risk of bias is low for three studies and some concern for one.
CONCLUSION: Daridorexant is a safer and efficacious agent for induction and maintenance of sleep for chronic insomnia.
PROSPERO: The registration number is CRD42022335233.
CLINICAL TRIAL REGISTRATION: www.clinicaltrials.gov identifiers are NCT03575104, NCT03545191, NCT03679884, and NCT02839200).
Fulltext Rays of immunity: Role of sunshine vitamin in management of COVID-19 infection and associated comorbidities

Udaya Kumar V, Pavan G, Murti K, Kumar R, Dhingra S, Haque M, et al.

Clin Nutr ESPEN, 2021 Dec;46:21-32.
PMID: 34857198 DOI: 10.1016/j.clnesp.2021.09.727

The catastrophic pandemic engendered due to the Novel coronavirus (COVID-19) outbreak which causes severe clinical afflictions on the respiratory system has severely high morbidity and mortality rates. The requirement of novel compounds is at utmost importance due to lack of targeted drug molecule to treat the afflictions and restrict the viral infection and for the usage of prophylactic treatment to avoid the spread of the infection is of utmost importance. Vitamin D is one such naturally available multifunctional molecule, which plays an eminent role in the immune system and instigation of numerous cellular pathways further promoting health benefits and enhancing the human quality of life. This article reviews the current standpoint scenario and future prevalence of vitamin D supplementation in the management of covid-19 patients. Novel findings of Vitamin D suggest that along with regulation of cell growth, neuroprotective and mood-stabilizing effects, it regulates the immune response also modulate cytokine Interleukin-6 (IL-6) by inducing progesterone-induced blocking factor (PIBF), given the IL-6 levels are considerably high in COVID-19 patients which increases the further complications. Vitamin D also have its effect on angiotensin converting enzyme (ACEII) inhibitor through which the COVID-19 virus makes cell entry. Numerous research data elucidate the play of Vitamin D, in complications of COVID-19 including the most common comorbid conditions, neurological manifestations and immunological aspects makes it an ideal molecule for adjuvant therapy. Including Vitamin D as add-on therapy in the management of COVID-19 might aid the arrest of infection and helps fight this arduous epidemic.
Fulltext Surveillance of antimicrobial resistance in low- and middle-income countries: a scattered picture

Iskandar K, Molinier L, Hallit S, Sartelli M, Hardcastle TC, Haque M, et al.

Antimicrob Resist Infect Control, 2021 03 31;10(1):63.
PMID: 33789754 DOI: 10.1186/s13756-021-00931-w

Data on comprehensive population-based surveillance of antimicrobial resistance is lacking. In low- and middle-income countries, the challenges are high due to weak laboratory capacity, poor health systems governance, lack of health information systems, and limited resources. Developing countries struggle with political and social dilemma, and bear a high health and economic burden of communicable diseases. Available data are fragmented and lack representativeness which limits their use to advice health policy makers and orientate the efficient allocation of funding and financial resources on programs to mitigate resistance. Low-quality data means soaring rates of antimicrobial resistance and the inability to track and map the spread of resistance, detect early outbreaks, and set national health policy to tackle resistance. Here, we review the barriers and limitations of conducting effective antimicrobial resistance surveillance, and we highlight multiple incremental approaches that may offer opportunities to strengthen population-based surveillance if tailored to the context of each country.
Application of Ti3 C2 MXene Quantum Dots for Immunomodulation and Regenerative Medicine

Rafieerad A, Yan W, Sequiera GL, Sareen N, Abu-El-Rub E, Moudgil M, et al.

Adv Healthc Mater, 2019 08;8(16):e1900569.
PMID: 31265217 DOI: 10.1002/adhm.201900569

Inflammation is tightly linked to tissue injury. In regenerative medicine, immune activation plays a key role in rejection of transplanted stem cells and reduces the efficacy of stem cell therapies. Next-generation smart biomaterials are reported to possess multiple biologic properties for tissue repair. Here, the first use of 0D titanium carbide (Ti3 C2 ) MXene quantum dots (MQDs) for immunomodulation is presented with the goal of enhancing material-based tissue repair after injury. MQDs possess intrinsic immunomodulatory properties and selectively reduce activation of human CD4+ IFN-γ+ T-lymphocytes (control 87.1 ± 2.0%, MQDs 68.3 ± 5.4%) while promoting expansion of immunosuppressive CD4+ CD25+ FoxP3+ regulatory T-cells (control 5.5 ± 0.7%, MQDs 8.5 ± 0.8%) in a stimulated lymphocyte population. Furthermore, MQDs are biocompatible with bone marrow-derived mesenchymal stem cells and induced pluripotent stem cell-derived fibroblasts. Finally, Ti3 C2 MQDs are incorporated into a chitosan-based hydrogel to create a 3D platform with enhanced physicochemical properties for stem cell delivery and tissue repair. This composite hydrogel demonstrates increased conductivity while maintaining injectability and thermosensitivity. These findings suggest that this new class of biomaterials may help bridge the translational gap in material and stem cell-based therapies for tissue repair and treatment of inflammatory and degenerative diseases.