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.

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.

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.

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

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.

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.

Objective: From the economic point of view, this study was to systematically assess the status quo on lung cancer screening in the world and to provide reference for further research and implementation of the programs, in China. Methods: PubMed, EMbase, The Cochrane Library,CNKI and Wanfang Data were searched to gather papers on studies related to economic evaluation regarding lung cancer screening worldwide, from the inception of studies to June 30(th), 2018. Basic characteristics, methods and main results were extracted. Quality of studies was assessed. Cost were converted to Chinese Yuan under the exchange rates from the World Bank. The ratio of incremental cost-effectiveness ratio (ICER) to local GDP per capita were calculated. Results: A total of 23 studies (only 1 randomized controlled trial) were included and the overall quality was accepted. 22 studies were from the developed countries. Nearly half of the studies (11 studies) took 55 years old as the starting age of the screening program. Smoking history was widely applied for the selection of criteria on target populations (18). Low-dose computed tomography (LDCT) was involved in every study used to evaluate the economic effectiveness. Annual (17) and once-life time (7) screening were more common frequencies. 22 studies reported ICERs for LDCT screening, compared to no screening, of which 17 were less than 3 times local GDP per capita, and were considered as cost-effectiveness, according to the WHO's recommendation. 15 and 7 studies reported ICERs for annual and once-life time screening, of which 12 and 7 studies were in favor the results of their cost-effectiveness, respectively. Additionally, the cost-effectiveness of once-lifetime screening was likely to be superior to the annual screening. Differences of cost-effectiveness among the subgroups, by starting age or by the smoking history, might exist. Conclusions: Based on the studies, evidence from the developed countries demonstrated that LDCT screening programs on lung cancer, implemented among populations selected by age and smoking history, generally appeared more cost-effective. Combined with the local situation of health resource, the findings could provide direction for less developed regions/countries lacking of local evidence. Low frequency of LDCT screening for lung cancer could be adopted when budget was limited. Data on starting ages, smoking history and other important components related to the strategy of screening programs, needs to be precisely evaluated under the situation of local population.
China ; Cost-Benefit Analysis ; Early Detection of Cancer/methods* ; Humans ; Lung Neoplasms/prevention & control* ; Middle Aged ; Quality-Adjusted Life Years ; Randomized Controlled Trials as Topic