Inflammatory bowel disease (IBD), which includes Crohn’s disease and ulcerative colitis, is a nonspecific chronic inflammation of the gastrointestinal tract. Despite recent advances in therapeutics and newer management strategies, IBD largely remains untreatable. Helminth therapy is a promising alternative therapeutic for IBD that has gained some attention in the last two decades. Helminths have immunomodulatory effects and can alter the gut microbiota. The immunomodulatory effects include a strong Th2 immune response, T-regulatory cell response, and the production of regulatory cytokines. Although concrete evidence regarding the efficacy of helminth therapy in IBD is lacking, clinical studies and studies done in animal models have shown some promise. Most clinical studies have shown that helminth therapy is safe and easily tolerable. Extensive work has been done on the whipworm Trichuris, but other helminths, including Schistosoma, Trichinella, Heligmosomoides, and Ancylostoma, have also been explored for pre-clinical and animal studies. This review article summarizes the potential of helminth therapy as an alternative therapeutic or an adjuvant to the existing therapeutic procedures for IBD treatment.

Inflammatory bowel disease (IBD), which includes Crohn’s disease and ulcerative colitis, is a nonspecific chronic inflammation of the gastrointestinal tract. Despite recent advances in therapeutics and newer management strategies, IBD largely remains untreatable. Helminth therapy is a promising alternative therapeutic for IBD that has gained some attention in the last two decades. Helminths have immunomodulatory effects and can alter the gut microbiota. The immunomodulatory effects include a strong Th2 immune response, T-regulatory cell response, and the production of regulatory cytokines. Although concrete evidence regarding the efficacy of helminth therapy in IBD is lacking, clinical studies and studies done in animal models have shown some promise. Most clinical studies have shown that helminth therapy is safe and easily tolerable. Extensive work has been done on the whipworm Trichuris, but other helminths, including Schistosoma, Trichinella, Heligmosomoides, and Ancylostoma, have also been explored for pre-clinical and animal studies. This review article summarizes the potential of helminth therapy as an alternative therapeutic or an adjuvant to the existing therapeutic procedures for IBD treatment.

Inflammatory bowel disease (IBD), which includes Crohn’s disease and ulcerative colitis, is a nonspecific chronic inflammation of the gastrointestinal tract. Despite recent advances in therapeutics and newer management strategies, IBD largely remains untreatable. Helminth therapy is a promising alternative therapeutic for IBD that has gained some attention in the last two decades. Helminths have immunomodulatory effects and can alter the gut microbiota. The immunomodulatory effects include a strong Th2 immune response, T-regulatory cell response, and the production of regulatory cytokines. Although concrete evidence regarding the efficacy of helminth therapy in IBD is lacking, clinical studies and studies done in animal models have shown some promise. Most clinical studies have shown that helminth therapy is safe and easily tolerable. Extensive work has been done on the whipworm Trichuris, but other helminths, including Schistosoma, Trichinella, Heligmosomoides, and Ancylostoma, have also been explored for pre-clinical and animal studies. This review article summarizes the potential of helminth therapy as an alternative therapeutic or an adjuvant to the existing therapeutic procedures for IBD treatment.

The disease burden of chronic kidney disease (CKD) and its impact on healthcare systems has been poorly studied in Asia, a socioeconomically diverse region with wide variations in availability, access, and quality of CKD care. The high CKD burden in this region is predominantly driven by an increased prevalence of risk factors including diabetes mellitus, hypertension, obesity, and use of traditional medicines and is further aggravated by challenges associated with effective implementation of population-based screening and surveillance systems in early detection and intervention of CKD. The Asian continent mostly comprised of low- and middle-income countries with resource restraints lacks robust population-based CKD registries resulting in a paucity of data on CKD incidence and prevalence, various treatment modalities, uptake of current guidelines, and the overall impact of implementation of developmental programs. There is an urgent need for a collaborative action plan between the healthcare community and governments in this region to detect CKD in its early stages and prevent its complications including kidney failure, cardiovascular disease, and death. Research- based evidence on the impact of early detection, sustainable treatment options, quality of life, delay or avoidance of dialysis, and related cost analysis is the need of the hour. We highlight successful implementation of strategic and policy-sharing programs adopted in a few countries; also, consolidate available region-specific data, quantify estimates of CKD burden and propose strategies with a multidisciplinary approach involving patients, the healthcare community and governmental bodies to combat CKD and its complications.

Inflammatory bowel disease (IBD) is a multifactorial disease, which is thought to be an interplay between genetic, environment, microbiota, and immune-mediated factors. Dysbiosis in the gut microbial composition, caused by antibiotics and diet, is closely related to the initiation and progression of IBD. Differences in gut microbiota composition between IBD patients and healthy individuals have been found, with reduced biodiversity of commensal microbes and colonization of opportunistic microbes in IBD patients. Gut microbiota can, therefore, potentially be used for diagnosing and prognosticating IBD, and predicting its treatment response. Currently, there are no curative therapies for IBD. Microbiota-based interventions, including probiotics, prebiotics, synbiotics, and fecal microbiota transplantation, have been recognized as promising therapeutic strategies. Clinical studies and studies done in animal models have provided sufficient evidence that microbiota-based interventions may improve inflammation, the remission rate, and microscopic aspects of IBD. Further studies are required to better understand the mechanisms of action of such interventions. This will help in enhancing their effectiveness and developing personalized therapies. The present review summarizes the relationship between gut microbiota and IBD immunopathogenesis. It also discusses the use of gut microbiota as a noninvasive biomarker and potential therapeutic option.

Venous thromboembolism (VTE) is a complication in children with acute lymphoblastic leukemia (ALL). The Chinese Children's Cancer Group-ALL-2015 protocol was carried out in China, and epidemiology, clinical characteristics, and risk factors associated with VTE were analyzed. We collected data on VTE in a multi-institutional clinical study of 7640 patients with ALL diagnosed in 20 hospitals from January 2015 to December 2019. First, VTE occurred in 159 (2.08%) patients, including 90 (56.6%) during induction therapy and 108 (67.92%) in the upper extremities. T-ALL had a 1.74-fold increased risk of VTE (95% CI 1.08-2.8, P = 0.022). Septicemia, as an adverse event of ALL treatment, can significantly promote the occurrence of VTE (P < 0.001). Catheter-related thrombosis (CRT) accounted for 75.47% (n = 120); and, symptomatic VTE, 58.49% (n = 93), which was more common in patients aged 12-18 years (P = 0.023), non-CRT patients (P < 0.001), or patients with cerebral thrombosis (P < 0.001). Of the patients with VTE treated with anticoagulation therapy (n = 147), 4.08% (n = 6) had bleeding. The VTE recurrence rate was 5.03% (n = 8). Patients with VTE treated by non-ultrasound-guided venous cannulation (P = 0.02), with residual thrombus (P = 0.006), or with short anticoagulation period (P = 0.026) had high recurrence rates. Thus, preventing repeated venous puncture and appropriately prolonged anticoagulation time can reduce the risk of VTE recurrence.
Humans ; Child ; Venous Thromboembolism/etiology* ; East Asian People ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/epidemiology* ; Risk Factors ; Thrombosis/chemically induced* ; China/epidemiology* ; Anticoagulants/adverse effects* ; Recurrence

Humans ; Amyotrophic Lateral Sclerosis/drug therapy* ; Neurons ; Phosphatidylinositol 3-Kinases

The cofactor nicotinamide adenine dinucleotide (NAD⁺) plays a key role in a wide range of physiological processes and maintaining or enhancing NAD⁺ levels is an established approach to enhancing healthy aging. Recently, several classes of nicotinamide phosphoribosyl transferase (NAMPT) activators have been shown to increase NAD⁺ levels in vitro and in vivo and to demonstrate beneficial effects in animal models. The best validated of these compounds are structurally related to known urea-type NAMPT inhibitors, however the basis for the switch from inhibitory activity to activation is not well understood. Here we report an evaluation of the structure activity relationships of NAMPT activators by designing, synthesising and testing compounds from other NAMPT ligand chemotypes and mimetics of putative phosphoribosylated adducts of known activators. The results of these studies led us to hypothesise that these activators act via a through-water interaction in the NAMPT active site, resulting in the design of the first known urea-class NAMPT activator that does not utilise a pyridine-like warhead, which shows similar or greater activity as a NAMPT activator in biochemical and cellular assays relative to known analogues.

Purpose: Mortality rates following hip fracture surgery have been well-studied. This study was conducted to examine mortality rates in asymptomatic patients presenting for treatment of acute hip fractures with concurrent positive COVID-19(+) tests compared to those with negative COVID-19(–) tests. Materials and Methods: A total of 149 consecutive patients undergoing hip fracture surgery during the COVID-19 pandemic at two academic medical centers were reviewed retrospectively. Patients were divided into two groups for comparative analysis: one group included asymptomatic patients with COVID-19+ tests versus COVID-19– tests. The primary outcome was mortality at 30-days and 90-days. Results: COVID-19+ patients had a higher mortality rate than COVID-19– patients at 30-days (26.7% vs 6.0%, P=0.005) and 90-days (41.7% vs 17.2%, P=0.046) and trended towards an increased length of hospital stay (10.1 ±6.2 vs 6.8±3.8 days, P=0.06). COVID-19+ patients had more pre-existing respiratory disease (46.7% vs 11.2%,P=0.0002). Results of a Cox regression analysis showed an increased risk of mortality at 30-days and 90-days from COVID-19+ status alone without an increased risk of death in patients with pre-existing chronic respiratory disease. Conclusion Factors including time to surgery, age, preexisting comorbidities, and postoperative ambulatory status have been proven to affect mortality and complications in hip fracture patients; however, a positive COVID-19 test result adds another variable to this process. Implementation of protocols that will promote prompt orthogeriatric assessments, expedite patient transfer, limit operating room traffic, and optimize anesthesia time can preserve the standard of care in this unique patient population.

Progress in the treatment of diabetic kidney disease (DKD) has been modest since the early trials on renin-angiotensin-aldosterone system inhibitors (RAASis). Although sodium-glucose co-transporter 2 inhibitors (SGLT2is) have revolutionized the management of DKD by lowering proteinuria and protecting organs, other novel treatment approaches with good evidence and efficacy that can be used in conjunction with a RAASi or SGLT2i in managing DKD have emerged in the past few years. This review discusses the evidence for glucagon-like peptide-1 receptor agonist, selective mineralocorticoid receptor antagonist, and selective endothelin A receptor antagonist, emerging treatment options for DKD beyond SGLT2 inhibition.