Phosphatidylinositol 3-kinase signaling pathway and inflammatory bowel disease: Current status and future prospects

Inflammatory bowel disease (IBD) is a chronic life-limiting disease of gastrointestinal tract characterized by widespread enteric inflammation. IBD is a multifactorial disease, and different environmental, microbial, and immune-related factors give rise to the development of disease. Among several factors, the preponderance of pro-inflammatory T helper 17 cells over the anti-inflammatory regulatory T cells augments inflammation in the intestinal mucosa. Prevailing evidence accentuates that PI3K signaling pathway plays a central role in the pathophysiology of the condition by regulating the inflammatory process in the gut mucosa. By recognizing the implications of PI3K in the pathogenesis of IBD, agents that could modulate this pathway have recently been at the focus of research, yielding encouraging results mainly in the experimental IBD models. In this review, we have summarized the recent advances, which may hold the keys to identify novel therapeutic strategies for IBD.     

Obesity and weight change during the COVID-19 pandemic in children and adults: A systematic review and meta-analysis

Many obesity risk factors have increased during the COVID-19 pandemic, including physical inactivity, poor diet, stress, and poverty. The aim of this systematic review was to evaluate the impact of the COVID-19 pandemic, as well as associated lockdowns or restrictions, on weight change in children and adults. We searched five databases from January 2020 to November 2021. We included only longitudinal studies with measures from before and during the pandemic that evaluated the change in weight, body mass index (BMI) (or BMI z-scores for children), waist circumference, or the prevalence of obesity. Random effects meta-analyses were conducted to obtain pooled estimates of the mean difference in outcomes. Subgroups were evaluated for age groups and diabetes or obesity at baseline. The risk of bias was assessed using a modified version of the Newcastle-Ottawa Scale, and the certainty of the evidence was assessed using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach. A total of 74 studies were included (3,213,776 total participants): 31 studies of children, 41 studies of adults, and 2 studies of children and adults. In children, the pooled mean difference was 1.65 kg (95% confidence interval [CI]: 0.40, 2.90; 9 studies) for weight and 0.13 (95% CI 0.10, 0.17; 20 studies) for BMI z-scores, and the prevalence of obesity increased by 2% (95% CI 1%, 3%; 12 studies). In adults, the pooled mean difference was 0.93 kg (95% CI 0.54, 1.33; 27 studies) for weight and 0.38 kg/m² (95% CI 0.21, 0.55; 25 studies) for BMI, and the prevalence of obesity increased by 1% (95% CI 0%, 3%; 11 studies). In children and adults, the pooled mean difference for waist circumference was 1.03 cm (95% CI −0.08, 2.15; 4 studies). There was considerable heterogeneity observed for all outcomes in both children and adults, and the certainty of evidence assessed using GRADE was very low for all outcomes. During the first year of the COVID-19 pandemic, small but potentially clinically significant increases in weight gain, BMI, and increased prevalence of obesity in both children and adults were observed. Increases were greater in children, and targeted prevention interventions may be warranted.     

Bronchopleural fistula causing persistent pneumothorax in COVID‐19 pneumonia patient with no risk factors

Although pneumothorax is a well‐known complication of COVID‐19 pneumonia especially in patients requiring mechanical ventilation, bronchopleural fistula causing persistent pneumothorax in sole COVID‐19 pneumonia is extremely rare. In this case, we illustrate that bronchopleural fistula can be found in COVID‐19 pneumonia, even with no risk factors nor mechanical ventilation administration.     

Post-initiation predictors of discontinuation of the sodium-glucose cotransporter-2 inhibitors: A comparative cohort study from the United Kingdom

Aims

To assess post-initiation predictors of discontinuation of sodium-glucose cotransporter-2 (SGLT2) inhibitors compared to dipeptidyl-peptidase-4 (DPP-4) inhibitors in the United Kingdom.

Materials and Methods

We conducted a comparative population-based retrospective cohort study using primary care data from the UK Clinical Practice Research Datalink (CPRD) with linked data to hospital and death records. We included new metformin users who initiated either SGLT2 inhibitors or DPP-4 inhibitors between January 2013 and October 2019. The main outcome was treatment discontinuation, defined as the first 90-day gap after the estimated treatment end date. We used a series of extended Cox models to assess which time-dependent predictors were associated with treatment discontinuation. To test if the hazard ratio of discontinuation for each predictor was statistically different between SGLT2 and DPP-4 inhibitors, an exposure-predictor interaction term was added to each model.

Results

There were 2550 new users of SGLT2 inhibitors and 8195 new users of DPP-4 inhibitors. Approximately 69% of SGLT2 inhibitor and 74% of DPP-4 inhibitor users had discontinued treatment by the end of follow-up. Occurrence of fractures after treatment initiation was a significant predictor of discontinuation of SGLT2 inhibitors (hazard ratio [HR] 4.13, 95% confidence interval [CI] 2.12-8.06) but not DPP-4 inhibitors (HR 0.93, 95% CI 0.79-1.11). The rate of treatment discontinuation was significantly higher for those with low estimated glomerular filtration rate and minimal contact with the healthcare system. Efficacy endpoints, such as heart failure and glycated haemoglobin level, were not associated with treatment discontinuation.

Conclusions

Our findings reflect some discrepancy between the available evidence and prescribing behaviour for SGLT2 inhibitors.     

Sister Marie Joseph nodule and Krükenberg's tumor: rare association revealing a gastric adenocarcinoma

It was about a 61-year-old patient who presented an indurated and painless umbilical swelling surrounded by ulcerated plaque and an abdominal arch progressing for 8 months. Abdomino-pelvic ultrasound and abdominal-pelvic CT scan revealed in right ovarian the presence of a mass with a cystic''s tissue, a thickness with a subcutaneous infiltration of the umbilical region and the diffuse infiltration of gastric parietal mesenteric fat. Histology of the ovarian mass confirmed Krükenberg''s tumor and that of the Sister Marie-Joseph''s nodule confirmed umbilical skin metastasis. The primary was a well differentiated gastric adenocarcinoma. The death occurred after the first chemotherapy treatment. The association of Krükenberg''s tumor with Sister Marie-Joseph''s nodule, rare and unusual, has been revealing of a gastric adenocarcinoma which up to now was unknown and asymptomatic.     

Apigenin in cancer therapy: Prevention of genomic instability and anticancer mechanisms

The incidence of cancer has been growing worldwide. Better survival rates following the administration of novel drugs and new combination therapies may concomitantly cause concern regarding the long-term adverse effects of cancer therapy, for example, second primary malignancies. Moreover, overcoming tumour resistance to anticancer agents has been long considered as a critical challenge in cancer research. Some low toxic adjuvants such as herb-derived molecules may be of interest for chemoprevention and overcoming the resistance of malignancies to cancer therapy. Apigenin is a plant-derived molecule with attractive properties for chemoprevention, for instance, promising anti-tumour effects, which may make it a desirable adjuvant to reduce genomic instability and the risks of second malignancies among normal tissues. Moreover, it may improve the efficiency of anticancer modalities. This paper aims to review various effects of apigenin in both normal tissues and malignancies. In addition, we explain how apigenin may have the ability to protect usual cells against the genotoxic repercussions following radiotherapy and chemotherapy. Furthermore, the inhibitory effects of apigenin on tumours will be discussed.     

Outcome of trabeculectomy in hospital Melaka, Malaysia

AIM: To study the success and outcome of trabeculectomy in Hospital Melaka. METHODS: Medical records of all patients who underwent trabeculectomy between January 1, 2007 and October 31, 2010 whom were followed up for at least 6 months postoperatively in Hospital Melaka were retrospectively reviewed. RESULTS: A total number of 117 eyes of 91 patients with the age range between 12 to 84 years underwent primary trabeculectomy (n=20, 17.1%), combine trabeculectomy with cataract surgery (n=90, 76.9%), repeat trabeculectomy (n=5, 4.3%), and combine repeat trabeculectomy with cataract surgery (n=2, 1.7%). The disease spectrum includes primary open-angle glaucoma (POAG) (54 patients, 59.3%), priamry angle-closure glaucoma (PACG) (14 patients, 15.4%), secondary glaucomas (19 patients, 20.9%) and juvenile glaucomas (4 patients, 4.4%). Preoperative mean intraocular pressure (IOP) was (24.69±8.67)mmHg as compared to postoperative mean IOP of (15.81±6.66)mmHg, (15.07±4.72)mmHg and (15.68 ±3.65)mmHg at 6-month, 12-month and 24-month respectively. Eighty-two point one percent of eyes (n=96) achieved complete success (CS), 12.8% (n=15) with qualified success (QS) and only 5.1% (n=6) failed at 6 month with two of them warrant other filtering surgery. At twelve months, trabeculectomy with CS was 71.6% (n=63), QS in 22.7% (n=20) and failure in 5.7% (n=5). Sixty-seven point five percent (n=27) attained CS, 20.0% (n=8) with QS while 12.5% (n=5) failed at 24 month postoperative. CONCLUSION: As the understanding of the lower the IOP, the better the patients retaining the visual function, trabeculectomy is significantly a choice of treatment in uncontrolled glaucoma. This study concluded that trabeculectomy performed in Hospital Melaka has produced significant success as compared to other studies.