Irritable Bowel Syndrome Is Not Associated with an Increased Risk of Polyps and Colorectal Cancer: A Systematic Review and Meta-Analysis.

OBJECTIVES: Colorectal cancer (CRC) is the third most common malignancy in the US. Several factors are associated with increased/decreased CRC risk and often linked to adenomatous colorectal polyps (CRP). Recent studies suggest a lower risk of neoplastic lesions among irritable bowel syndrome (IBS) patients. We aimed to systematically assess the occurrence of CRC and CRP in IBS patients. METHODS: Searches of the Medline, Cochrane, and EMBASE databases were performed, blindly and independently, by two investigators. Studies of CRC or CRP incidence in IBS patients (diagnosed by Rome or other symptom-based criteria) were eligible for inclusion. CRC and CRP effect estimates were pooled in meta-analyses using random models. RESULTS: Of 4941 non-duplicate studies, 14 were included, comprising 654,764 IBS patients and 2,277,195 controls in 8 cohort studies, and 26,641 IBS patients and 87,803 controls in 6 cross-sectional studies. Pooled analysis revealed a significantly decreased prevalence of CRP in IBS subjects vs. controls, with a pooled odds ratio (OR) of 0.29 (95% CI (0.15, 0.54)). There was significant heterogeneity between studies (I2 = 96%, p < 0.01). This finding persisted when studies which did not report pre-cancerous polyps separately were excluded (OR 0.23, 95% CI (0.15, 0.35), I2 = 85%, p < 0.01). CRC prevalence was lower in IBS subjects, but this did not reach statistical significance (OR 0.40, 95% CI (0.09, 1.77]). CONCLUSION: Our analyses reveal a decreased incidence of colorectal polyps in IBS, although CRC did not reach significance. Mechanistic studies with detailed genotypic analysis and clinical phenotyping are needed to better elucidate the potentially protective effect of IBS on CRC development.

CaMK4 controls follicular helper T cell expansion and function during normal and autoimmune T-dependent B cell responses.

Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by dysregulated B cell compartment responsible for the production of autoantibodies. Here, we show that T cell-specific expression of calcium/calmodulin-dependent protein kinase IV (CaMK4) leads to T follicular helper (Tfh) cells expansion in models of T-dependent immunization and autoimmunity. Mechanistically, CaMK4 controls the Tfh-specific transcription factor B cell lymphoma 6 (Bcl6) at the transcriptional level through the cAMP responsive element modulator α (CREMα). In the absence of CaMK4 in T cells, germinal center formation and humoral immunity is impaired in immunized mice, resulting in reduced anti-dsDNA titres, as well as IgG and complement kidney deposition in the lupus-prone B6.lpr mouse. In human Tfh cells, CaMK4 inhibition reduced BCL6 expression and IL-21 secretion ex vivo, resulting in impaired plasmablast formation and IgG production. In patients with SLE, CAMK4 mRNA levels in Tfh cells correlated with those of BCL6. In conclusion, we identify CaMK4/CREMα as a driver of T cell-dependent B cell dysregulation in autoimmunity.

Gender-affirming hormone treatment and cognitive function in transgender young adults: a systematic review and meta-analysis.

BACKGROUND: Previous studies have examined whether steroid hormone treatment in transgender individuals may affect cognitive function; yet, their limited power does not allow firm conclusions to be drawn. We leveraged data from to-date literature aiming to explore the effect of gender-affirming hormone administration on cognitive function in transgender individuals. METHODS: A search strategy of MEDLINE was developed (through June 1, 2019) using the key terms transgender, hormone therapy and cognitive function. Eligible were (i) cohort studies examining the longitudinal effect of hormone therapy on cognition, and (ii) cross-sectional studies comparing the cognitive function between treated and non-treated individuals. Standardized mean differences (Hedges' g) were pooled using random-effects models. Study quality was evaluated using the Newcastle-Ottawa Scale. OUTCOMES: Ten studies (seven cohort and three cross-sectional) were eligible representing 234 birth-assigned males (aM) and 150 birth-assigned females (aF). The synthesis of cohort studies (n = 5) for visuospatial ability following hormone treatment showed a statistically significant enhancement among aF (g = 0.55, 95% confidence intervals [CI]: 0.29, 0.82) and an improvement with a trend towards statistical significance among aM (g = 0.28, 95%CI: -0.01, 0.58). By contrast, no adverse effects of hormone administration were shown. No heterogeneity was evident in most meta-analyses. INTERPRETATION: Current evidence does not support an adverse impact of hormone therapy on cognitive function, whereas a statistically significant enhancing effect on visuospatial ability was shown in aF. New longitudinal studies with longer follow-up should explore the long-term effects of hormone therapy, especially the effects on younger individuals, where there is greater scarcity of data.

Survival and mortality rates of Wilms tumour in Southern and Eastern European countries: Socioeconomic differentials compared with the United States of America.

BACKGROUND: Despite recent therapeutic advancements, Wilms tumour (WT) presents remarkable survival variations. We explored mortality and survival patterns for children (0-14 years) with WT in 12 Southern and Eastern European (SEE) countries in comparison with the United States of America (USA). METHODS: A total of 3966 WT cases (0-14 years) were registered by a network of SEE childhood cancer registries (N:1723) during available registration periods circa 1990-2016 and surveillance, epidemiology, and end results program (SEER) (N:2243; 1990-2012); mortality data were provided by the respective national statistical services. Kaplan-Meier curves and Cox proportional hazards models were used to assess the role of age, sex, year of diagnosis, urbanisation and Human Development Index (HDI) on overall survival (OS). RESULTS: Persisting regional variations shape an overall 78% 5-year OS in the participating SEE countries, lagging behind the USA figure (92%, p=0.001) and also reflected by higher SEE mortality rates. Worth mentioning is the gradually escalating OS in SEE (hazard ratio [HR]5-year increment:0.67, 95% confidence interval [CI]:0.60, 0.75) vs. a non-significant 10% improvement in the SEER data, which had a high starting value. OS differentials [two-fold less favourable among children aged 10-14 years, boys and those living in rural SEE areas (HR:1.37; CI:1.10-1.71) or countries with inferior HDI (2-3-fold)] were minimal in the USA. CONCLUSIONS: Children with WT residing in SEE countries do not equally enjoy the substantial survival gains, especially for those living in rural areas and in lower HDI countries. Noteworthy are steep and sizeable survival gains in SEE along with the newly presented Greek data pointing to achievable survival goals in SEE despite the financial crisis.

Perioperative Complications of Cesarean Delivery Myomectomy: A Meta-analysis.

OBJECTIVE: To assess the association of myomectomy during cesarean delivery with intraoperative and perioperative maternal morbidity. DATA SOURCES: We searched MEDLINE (1966-2017), Scopus (2004-2017), ClinicalTrials.gov (2008-2017), EMBASE (1980-2017), and Cochrane Central Register of Controlled Trials CENTRAL (1999-2017) databases. METHODS OF STUDY SELECTION: We selected all observational studies that reported outcomes on patients undergoing myomectomy at the time of cesarean delivery. Statistical meta-analysis was performed with RevMan 5.3. RESULTS: Nineteen studies were included in our systematic review with a total number of 3,900 women. Among them, 2,301 women had myomectomy during cesarean delivery and 1,599 had cesarean delivery only. Women undergoing concomitant myomectomy had a mild decline in hemoglobin compared with those who had cesarean delivery only (mean difference 0.25 mg/dL, 95% CI 0.06-0.45). Myomectomy at the time of cesarean delivery is associated with longer surgical time compared with cesarean delivery alone (mean difference 13.87 minutes, 95% CI 4.78-22.95). Blood transfusion (odds ratio [OR] 1.41, 95% CI 0.96-2.07) and postoperative fever (OR 1.12, 95% CI 0.80-1.56) rates did not differ between the two groups (myomectomy compared with no myomectomy). A statistically, but not clinically, significant increase in postoperative hospitalization was evident in the myomectomy group (mean difference 0.35 days, 95% CI 0.25-0.46). CONCLUSION: This systematic review and meta-analysis of observational studies demonstrated an association with increased operative time and hemoglobin drop in patients who underwent cesarean myomectomy compared with cesarean delivery alone. No increased rate of major hemorrhage or need for transfusion was identified. Cesarean myomectomy may be considered in cases of isolated myomas, although randomized trials are needed.