A Minority of Childhood Disorders of Gut-Brain Interaction Persist Into Adulthood: A Risk-Factor Analysis.

INTRODUCTION: Disorders of gut-brain interaction (DGBIs) may originate in childhood. There are currently limited data on persistence of DGBI into adulthood and risk factors for persistence. Furthermore, there are no data on this question from general practice, where the majority of DGBIs are diagnosed and managed. This study documents the proportion of childhood-diagnosed DGBIs that persisted into adulthood and what factors were associated with persistence. METHODS: General practice records were obtained for more than 60,000 patients whose medical record spanned both childhood and adulthood years. Patients with diagnosed organic gastrointestinal disorder were excluded. Medical records were also interrogated for potential risk factors. RESULTS: Eleven percent of patients with irritable bowel syndrome (IBS) and 20% of patients with functional dyspepsia (FD) diagnosed in childhood had repeat diagnoses of the same condition in adulthood. Female sex (odds ratio [OR] 2.02) was associated with persistence for IBS, while a childhood diagnosis of gastritis (OR 0.46) was risk-protective. Childhood non-steroidal anti-inflammatory drug use (OR 1.31, 95% confidence interval [CI] 1.09-1.56) was a risk factor for persistence in IBS. For FD, a childhood diagnosis of asthma (OR 1.30, 95% CI 1.00-1.70) was a risk factor, as was anxiety for both IBS (OR 1.24, 95% CI 1.00-1.54) and FD (OR 1.48 95% CI 1.11-1.97) with a similar finding for depression for IBS (OR 1.34, 95% CI 1.11-1.62) and FD (OR 1.88 95% CI 1.47-2.42). DISCUSSION: Childhood DGBIs persist into adulthood in 10%-20% of patients, suggesting that management monitoring should continue into adulthood. Those diagnosed with anxiety or mood disorders in childhood should receive particular attention, and prescription of non-steroidal anti-inflammatory drugs in children should be made judiciously.

Quark Mass Dependence of Heavy Quark Diffusion Coefficient from Lattice QCD.

We present the first study of the quark mass dependence of the heavy quark momentum and spatial diffusion coefficients using lattice QCD with light dynamical quarks corresponding to a pion mass of 320 MeV. We find that, for the temperature range 195 MeV

Kleine-Levin syndrome is associated with birth difficulties and genetic variants in the TRANK1 gene loci.

Kleine-Levin syndrome (KLS) is a rare disorder characterized by severe episodic hypersomnia, with cognitive impairment accompanied by apathy or disinhibition. Pathophysiology is unknown, although imaging studies indicate decreased activity in hypothalamic/thalamic areas during episodes. Familial occurrence is increased, and risk is associated with reports of a difficult birth. We conducted a worldwide case-control genome-wide association study in 673 KLS cases collected over 14 y, and ethnically matched 15,341 control individuals. We found a strong genome-wide significant association (rs71947865, Odds Ratio [OR] = 1.48, P = 8.6 × 10-9) within the 3'region of TRANK1 gene locus, previously associated with bipolar disorder and schizophrenia. Strikingly, KLS cases with rs71947865 variant had significantly increased reports of a difficult birth. As perinatal outcomes have dramatically improved over the last 40 y, we further stratified our sample by birth years and found that recent cases had a significantly reduced rs71947865 association. While the rs71947865 association did not replicate in the entire follow-up sample of 171 KLS cases, rs71947865 was significantly associated with KLS in the subset follow-up sample of 59 KLS cases who reported birth difficulties (OR = 1.54, P = 0.01). Genetic liability of KLS as explained by polygenic risk scores was increased (pseudo R2 = 0.15; P < 2.0 × 10-22 at P = 0.5 threshold) in the follow-up sample. Pathway analysis of genetic associations identified enrichment of circadian regulation pathway genes in KLS cases. Our results suggest links between KLS, circadian regulation, and bipolar disorder, and indicate that the TRANK1 polymorphisms in conjunction with reported birth difficulties may predispose to KLS.

Cardiovascular Outcomes of Differentiated Thyroid Cancer Patients on Long Term TSH Suppression: A Systematic Review and Meta-Analysis.

We performed a systematic review and meta-analysis of the literature regarding cardiovascular outcomes of differentiated thyroid cancer (DTC) patients who are on long term thyroid stimulating hormone suppression. Searches were carried out using Prisma guidelines in Medline, Embase, CENTRAL, CINAHL and Scopus databases. Eligible papers were those which investigated discrete cardiovascular clinical outcomes in TSH suppressed patients and meta-analysis of selected studies was performed using Revman 5.4.1. We found a total of 195 879 DTC patients with median length to follow up of 8.6 years (range 5-18.8 years). Analysis showed DTC patients to be at higher risk of atrial fibrillation (HR 1.58, 95% CI 1.40, 1.77), stroke (HR 1.14, 95% CI 1.09, 1.20) and all-cause mortality (HR 2.04, 95% CI 1.02, 4.07). However, there was no difference in risk of heart failure, ischemic heart disease or cardiovascular mortality. These findings suggest that degree of TSH suppression must be titrated to accommodate risk of cancer recurrence and cardiovascular morbidity.

Does the microbiome play a role in the pathogenesis of colonic diverticular disease? A systematic review.

BACKGROUND AND AIMS: The role of the microbiota in diverticulosis and diverticular disease is underexplored. This systematic review aimed to assess all literature pertaining to the microbiota and metabolome associations in asymptomatic diverticulosis, symptomatic uncomplicated diverticular disease (SUDD), and diverticulitis pathophysiology. METHODS: Seven databases were searched for relevant studies published up to September 28, 2022. Data were screened in Covidence and extracted to Excel. Critical appraisal was undertaken using the Newcastle Ottawa Scale for case/control studies. RESULTS: Of the 413 papers screened by title and abstract, 48 full-text papers were reviewed in detail with 12 studies meeting the inclusion criteria. Overall, alpha and beta diversity were unchanged in diverticulosis; however, significant changes in alpha diversity were evident in diverticulitis. A similar Bacteroidetes to Firmicutes ratio compared with controls was reported across studies. The genus-level comparisons showed no relationship with diverticular disease. Butyrate-producing microbial species were decreased in abundance, suggesting a possible contribution to the pathogenesis of diverticular disease. Comamonas species was significantly increased in asymptomatic diverticulosis patients who later developed diverticulitis. Metabolome analysis reported significant differences in diverticulosis and SUDD, with upregulated uracil being the most consistent outcome in both. No significant differences were reported in the mycobiome. CONCLUSION: Overall, there is no convincing evidence of microbial dysbiosis in colonic diverticula to suggest that the microbiota contributes to the pathogenesis of asymptomatic diverticulosis, SUDD, or diverticular disease. Future research investigating microbiota involvement in colonic diverticula should consider an investigation of mucosa-associated microbial changes within the colonic diverticulum itself.

Increased mucosal eosinophils in colonic diverticulosis and diverticular disease.

AIMS: Eosinophils contribute to tissue homeostasis, damage, and repair. The mucosa of colonic diverticula has not been evaluated for eosinophils by quantitative histology. We aimed to investigate whether mucosal eosinophils and other immune cells are increased in colonic diverticula. METHODS: Hematoxylin and eosin stained sections from colonic surgical resections (n = 82) containing diverticula were examined. Eosinophils, neutrophils, and lymphocytes, in five high power fields in the lamina propria were counted at the base, neck, and ostia of the diverticulum and counts compared to non-diverticula mucosa. The cohort was further subgrouped by elective and emergency surgical indications. RESULTS: Following an initial review of 10 surgical resections from patients with diverticulosis, a total of 82 patients with colonic resections containing diverticula from the descending colon were evaluated (median age 71.5, 42 M/40F). Eosinophil counts for the entire cohort were increased in the base and neck (median 99 and 42, both P = <0.001) compared with the control location (median 16). Eosinophil counts remained significantly increased in the diverticula base (both P = <0.001) and neck (P = 0.01 and <0.001, respectively) in both elective and emergency cases. Lymphocytes were also significantly increased at the diverticula base compared to controls in both elective and emergency subgroups. CONCLUSION: Eosinophils are significantly and most strikingly increased within the diverticulum in resected colonic diverticula. While these observations are novel, the role of eosinophil and chronic inflammation is as yet unclear in the pathophysiology of colonic diverticulosis and diverticular disease.

Toppling television injuries in children and adolescents: a systematic review and meta-analysis.

CONTEXT: Toppling televisions (TVs) are a source of childhood injury but meta-analysis has not assessed the likelihood of TV injuries in children. OBJECTIVE: To present pooled results for injuries, following a systematic review. DATA SOURCES: MEDLINE, Scopus, Google Scholar and EMBASE databases were searched to 5 December 2022. STUDY SELECTION: Included studies met the following criteria: (1) assessed toppling TV injuries in paediatric populations; (2) reported point estimates as an OR or enabled its calculation and (3) used a comparison group. DATA EXTRACTION: A standardised form was used to include information on publication year, study design, population type, country, sample size, mean age, risk factors, point estimates or data used to calculate ORs. RESULTS: A total of 12 803 TV injuries were identified (five studies). Head and neck injuries (OR: 2.13, 95% CI: 1.21 to 3.75) and hospital admission (OR: 2.28, 95% CI: 1.80 to 2.90) were more likely in children aged under 6 years than over 6 years. Conversely, torso injuries were less likely in younger children (OR: 0.60, 95% CI: 0.51 to 0.70). Children under 6 were two and a half times more likely to die or be admitted to an intensive care unit (ICU) as a result of toppling TVs, although this was not statistically significant. Males did not sustain more TV injuries than females. CONCLUSIONS: Children aged under 6 years are more likely to die, sustain head injuries and require hospital treatment from toppling TVs. Strategies for injury prevention must go beyond warning labels to include community education, promotion and use of tip restraint devices, mandatory safety standards and a commitment from manufacturers to improve TV sets stability.

TSH receptor autoantibody levels post-total thyroidectomy in Graves' ophthalmopathy: a meta-analysis.

BACKGROUND: TSH receptor autoantibodies (TRAbs) are pathognomonic for Graves' disease and are thought to also underly the pathogenesis of Graves' ophthalmopathy (GO). A decline in TRAb levels has been documented post-total thyroidectomy (TTx) in GO, however with conflicting correlations with disease outcomes. The aim of the study was to compare the effectiveness of TTx to other treatment modalities of Graves' disease and examine whether the lowering of TRAbs is associated with GO improvements. METHOD: We searched electronic databases including Medline, Embase, Scopus, and Web of Science until 31 September 2022 using a broad range of keywords. Patients with GO undergoing TTx with measurements of both TRAbs and progression of the disease using a validated GO scoring system were included. Fourteen studies encompassing data from 1047 patients with GO met our eligibility criteria. The PRISMA guidelines were followed, and five studies had comparable data that were suitable for a meta-analysis. RESULTS: The Cochrane Risk of Bias tool for RCTs showed low risk of bias across most domains. The pooled odds ratio showed that more patients significantly had normalized TRAb levels post-TTx as compared to other interventions (OR: 1.36, 95% CI: 1.02-1.81, p = 0.035). But, there was no significant difference in GO improvement post-TTx as compared with other intervention groups. CONCLUSIONS: This meta-analysis shows that TRAb levels may decline largely post-TTx, but may not predict added improvements to the progression of GO. Thus, future studies with uniform designs are required to assess the minimal significant GO improvements.

Public understanding of sustainable diets and changes towards sustainability: A qualitative study in a UK population sample.

Dietary consumption contributes significantly to the environmental impacts of daily life. Changes to consumption are required, but limited work investigates the reasoning underlying relevant dietary choices. This study aimed to explore public understanding of sustainable diets and any willingness or attempts to make changes towards sustainability in a sample of the UK population. A qualitative approach was used. Twenty-one participants (10 males; predominantly young adults; with a range of living circumstances and cooking responsibilities) were interviewed. Interviews were analysed using inductive thematic analysis. Four themes were identified that related to understanding sustainable diets: 'Consistent with the definition by the Food and Agriculture Organisation of the United Nations (FAO)', 'Multiple benefits', 'Unsure' and 'Competing Interests'. Four themes related to making changes: 'Willing, but unsure', 'Small easy changes', 'Enablers' and 'Barriers'. An additional theme 'COVID-19 pandemic' reflected the period when the work was done (February-May 2021). Within these themes, participants were able to define sustainable eating in a manner that was consistent with and incorporated aspects of the definition by the FAO, could identify sustainable actions that they were undertaking or could undertake, and considered these to be beneficial, but there was a lot of uncertainty, and alternative or competing definitions and actions were also given. Participants were also willing to make changes to make their diet more sustainable, and preferences were expressed for small easy changes of high impact, but there was again considerable uncertainty as to what changes to make. Caution due to the small and select sample is required, but suggestions from this work include increasing awareness and knowledge of the environmental impacts of dietary choices, focusing on small easy changes of likely impact and personal benefit, and increasing availability and accessibility to sustainable diets.

Revision total knee arthroplasty for arthrofibrosis improves range of motion.

PURPOSE: Arthrofibrosis after primary total knee arthroplasty (TKA) is a significant contributor to patient dissatisfaction. While treatment algorithms involve early physical therapy and manipulation under anaesthesia (MUA), some patients ultimately require revision TKA. It is unclear whether revision TKA can consistently improve these patient's range of motion (ROM). The purpose of this study was to evaluate ROM when revision TKA was performed for arthrofibrosis. METHODS: A retrospective study of 42 TKA's diagnosed with arthrofibrosis from 2013 to 2019 at a single institution with a minimum 2-year follow-up was performed. The primary outcome was ROM (flexion, extension, and total arc of motion) before and after revision TKA, and secondary outcomes included patient reported outcomes information system (PROMIS) scores. Categorical data were compared using chi-squared analysis, and paired samples t tests were performed to compare ROM at three different times: pre-primary TKA, pre-revision TKA, and post-revision TKA. A multivariable linear regression analysis was performed to assess for effect modification on total ROM. RESULTS: The patient's pre-revision mean flexion was 85.6 degrees, and mean extension was 10.1 degrees. At the time of the revision, the mean age of the cohort was 64.7 years, the average body mass index (BMI) was 29.8, and 62% were female. At a mean follow-up of 4.5 years, revision TKA significantly improved terminal flexion by 18.4 degrees (p < 0.001), terminal extension by 6.8 degrees (p = 0.007), and total arc of motion by 25.2 degrees (p < 0.001). The final ROM after revision TKA was not significantly different from the patient's pre-primary TKA ROM (p = 0.759). PROMIS physical function, depression, and pain interference scores were 39 (SD = 7.72), 49 (SD = 8.39), and 62 (SD = 7.25), respectively. CONCLUSION: Revision TKA for arthrofibrosis significantly improved ROM at a mean follow-up of 4.5 years with over 25 degrees of improvement in the total arc of motion, resulting in final ROM similar to pre-primary TKA ROM. PROMIS physical function and pain scores showed moderate dysfunction, while depression scores were within normal limits. While physical therapy and MUA remain the gold standard for the early treatment of stiffness after TKA, revision TKA can improve ROM. LEVEL OF EVIDENCE: IV.

Duodenal Eosinophils and Mast Cells in Functional Dyspepsia: A Systematic Review and Meta-Analysis of Case-Control Studies.

BACKGROUND & AIMS: This study explored the link between duodenal eosinophils and mast cells in patients with functional dyspepsia (FD). METHODS: MEDLINE (PubMed) and Embase electronic databases were searched until June 2021 for case-control studies reporting duodenal eosinophils and mast cells in FD. Pooled standardized mean difference (SMD), odds ratio, and 95% CIs of duodenal eosinophils and mast cells in FD patients and controls were calculated, using a random-effects model. RESULTS: Twenty-two case-control studies with 1108 FD patients and 893 controls were identified. Duodenal eosinophils (SMD, 1.29; 95% CI, 0.85-1.73; P = .0001) and mast cells (SMD, 2.11; 95% CI, 1.14-3.07; P = .0001) were increased in FD patients compared with controls. Substantial heterogeneity was found (I2 = 93.61, P = .0001; and I2 = 96.69, P = .0001, respectively) and visual inspection of funnel plots confirmed publication bias. Degranulation of duodenal eosinophils was significantly higher in FD patients compared with controls (odds ratio, 3.78; 95% CI, 6.76-4.48; P = .0001), without statistically significant heterogeneity. We conducted a sensitivity analysis for duodenal eosinophils, by including only high-quality studies, and the results remained unchanged (SMD, 1.73; 95% CI, 1.06-2.40; P = .0001), with substantial heterogeneity. Postinfectious FD patients had increased duodenal eosinophils compared with controls (SMD, 3.91; 95% CI, 1.32-6.51; P = .001) and FD patients without any history of infection (SMD, 1.42; 95% CI, 0.88-1.96; P = .001). Helicobacter pylori-negative FD patients had significantly higher duodenal eosinophils compared with controls (SMD, 3.98; 95% CI, 2.13-5.84; P = .0001), with substantial heterogeneity. No significant difference in duodenal eosinophils was seen according to FD subtypes. CONCLUSIONS: This meta-analysis suggests a link between duodenal microinflammation and FD. However, the quality of evidence is very low, largely owing to the unexplained heterogeneity and serious risk of publication bias in all comparative analyses. Thus, causality remains uncertain and further studies are required.

Human intestinal spirochetosis, irritable bowel syndrome, and colonic polyps: A systematic review and meta-analysis.

Human colonic spirochetosis (CS) is usually due toBrachyspira pilosicolior Brachyspira aalborgiinfection. While traditionally considered to be commensal bacteria, there are scattered case reports and case series of gastrointestinal (GI) symptoms in CS and reports of colonic polyps with adherent spirochetes. We performed a systematic review and meta-analysis investigating the association between CS and GI symptoms and conditions including the irritable bowel syndrome (IBS) and colonic polyps. Following PRISMA 2020 guidelines, a systematic search of Medline, CINAHL, EMBASE, and Web of Science was performed using specific keywords for CS and GI disease. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using a random-effects model. Of 75 studies identified in the search, 8 case-control studies met the inclusion criteria for meta-analysis and 67 case series studies met the inclusion criteria for pooled prevalence analysis. CS was significantly associated with diarrhea (n = 141/127, cases/controls, OR: 4.19, 95% CI: 1.72-10.21, P = 0.002) and abdominal pain (n = 64/65, OR: 3.66, 95% CI: 1.43-9.35, P = 0.007). CS cases were significantly more likely to have Rome III-diagnosed IBS (n = 79/48, OR: 3.84, 95% CI: 1.44-10.20, P = 0.007), but not colonic polyps (n = 127/843, OR: 8.78, 95% CI: 0.75-103.36, P = 0.084). In conclusion, we found evidence of associations between CS and both diarrhea and IBS, but not colonic polyps. CS is likely underestimated due to suboptimal diagnostic methods and may be an overlooked risk factor for a subset of IBS patients with diarrhea.

Trampoline centre injuries in children and adolescents: a systematic review and meta-analysis.

CONTEXT: No evidence-based review has compared injury risks sustained on trampolines at home and in trampoline centres. OBJECTIVE: To present pooled results for injury type, site and treatment from studies reporting injuries that occurred on trampolines at home and in trampoline centres. DATA SOURCES: MEDLINE, Scopus, Google Scholar and Embase databases were searched to 31 December 2021. STUDY SELECTION: Inclusion criteria: (1) assessment of trampoline injuries (home and trampoline centres); (2) children and adolescents; (3) the point estimate was reported as an odds ratio (OR); and (4) an internal comparison was used. DATA EXTRACTION: Data were reported according to Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines. A random-effects model was used to estimate effect. RESULTS: There were 1 386 843 injuries (n=11 studies). There was an increased likelihood of musculoskeletal and/or orthopaedic injuries (OR 2.45, 95% CI 1.66 to 3.61, p<0.001), lower extremity injury (OR 2.81, 95% CI 1.99 to 3.97, p<0.001), sprains (OR 1.64, 95% CI 1.36 to 1.97, p<0.001) and a need for surgery (OR 1.89, 95% CI 1.37 to 2.60, p<0.001) at trampoline centres compared with home trampolines. Conversely, upper extremity injury (OR 0.49, 95% CI 0.25 to 0.95, p=0.03), concussion (OR 0.48, 95% CI 0.35 to 0.65, p<0.001) and lacerations (OR 0.46, 95% CI 0.35 to 0.59, p<0.001) were less likely to occur at trampoline centres than at home. CONCLUSIONS: Children using trampoline centres are more likely to suffer severe trauma and require surgical intervention than children using home trampolines. Development and implementation of preventative strategies, public awareness, and mandatory safety standards are urgently required for trampoline centres.

Health-related out-of-pocket expenses for children living with rare diseases - tuberous sclerosis and mitochondrial disorders: A prospective pilot study in Australian families.

AIM: We aimed to describe health-related out-of-pocket (OOP) expenses incurred by Australian families living with children with chronic and complex diseases. METHODS: A prospective pilot study of OOP expenses in families with children with tuberous sclerosis (TS) or mitochondrial disorders (MD) in 2016-2017. An initial survey assessed the family's financial situation, child's health functioning and estimated previous 6 months' and lifetime OOP expenses. Thereafter, families completed a survey each month for 6 months, prospectively tracking OOP expenses. RESULTS: Initial surveys were completed by 13 families with 15 children; median age 7 years (range: 1-12); 5 with MD, 10 with TS. All families reported OOP expenses: 38% paid $2000 per annum, more than double the annual per-capita OOP costs reported for Australia by the Organisation for Economic Co-operation and Development. Eight families estimated $5000-$25 000 in OOP expenses over their child's lifetime and 62% of mothers reduced or stopped work due to caring responsibilities. Eleven families paid annual private health insurance premiums of $2000-$5122, but 72% said this was poor value-for-money. Prospective tracking by eight families (9 children) identified the median OOP expenditure was $863 (range $55-$1398) per family for 6 months. OOP spending was associated with visits to allied health professionals, non-prescription medicines, special foods, supplements and disposable items. Eight families paid for 91 prescription medications over 6 months. CONCLUSION: All families caring for children with TS or MD reported OOP expenses. A larger study is needed to explore the affordability of health care for children living with a broader range of chronic diseases.

Primary biliary cholangitis in pregnancy: A systematic review with meta-analysis.

BACKGROUND: The outcomes and disease associations in pregnant women with primary biliary cholangitis (PBC) have not been largely explored. This study aimed to determine the level of evidence associated with maternal and fetal outcomes and other disease associations in female patients with PBC. DATA SOURCES: A comprehensive literature search was conducted. Maternal and fetal outcomes were obtained from patients with a previous, current or subsequent diagnosis of PBC. A random-effects model was employed, using odds ratios (ORs) with 95% confidence intervals (CIs). RESULTS: Eleven studies, with 2179 female PBC patients were included. Pregnant women with PBC were significantly more likely to have a miscarriage (OR = 1.27, 95% CI: 1.02-1.58; P = 0.03), and a history of abortion (OR = 1.50, 95% CI: 1.09-2.07; P = 0.01), with absent heterogeneity (I2 = 0%). PBC pregnant women were significantly more likely to deliver via vaginal birth (OR = 1.69, 95% CI: 1.33-2.14; P < 0.001) with low level heterogeneity (I2 < 0.001%). Patients had a statistically significant increased likelihood of lifetime smoking (OR = 1.95, 95% CI: 1.17-3.23; P = 0.01). Egger's regression revealed no evidence of publication bias. CONCLUSIONS: This meta-analysis provides pooled evidence that a PBC pregnancy is associated with fetal morbidity and maternal lifestyle associations that may influence pregnancy outcomes. More studies are needed to establish disease associations that may directly affect pregnancy outcomes. These data are essential for clinicians managing these patients before, during or after pregnancy.

DIFFERENTIAL IMPACT OF PERIODONTAL TREATMENT STRATEGIES DURING PREGNANCY ON PERINATAL OUTCOMES: A SYSTEMATIC REVIEW AND META-ANALYSIS.

OBJECTIVES: This study aimed to evaluate the impact of different periodontal treatment strategies during pregnancy on perinatal outcomes. STUDY SELECTION: This systematic review and meta-analysis of clinical trials was conducted according to PRISMA guidelines to assess the effect of mouthwash in addition to scaling and root planning (SRPM) on pregnancy outcomes, including preterm birth, low birth weight, gestational age, and birth weight. Pooled risk ratios (RR), mean differences (MD), and 95% confidence intervals (CI) were calculated using the random effect model. RESULTS: Twenty trials involving 5938 participants, including thirteen trials comparing scaling and root planning (SRP) and seven trials comparing SRPM with control groups. SRPM was associated with reduced risk of preterm birth (RR = 0.37; 95%CI = 0.16-0.84; P = .017; I2=93.26%; P < .001; number needed to treat (NNT): 3), low birth weight (RR = 0.54; 95%CI = 0.40-0.74; P < .0001; I2 = 0%; P = .46; NNT: 13), increased gestational age (MD = 0.78; 95%CI: 0.19-1.37; P = .009; I2 = 87.15%; P < .001), and birth weight (MD = 121.77; 95%CI = 3.19-240.34; P = .044; I2 = 80.68%; P < .001). There were no statistically significant differences in the analysis of SRP group, except for the increased birth weight (MD = 93.85; 95% CI = 3.27-184.42; P = .042; I2 = 84.11%; P < .001). CONCLUSION: Using mouthwash in addition to scaling and root planning (SRPM) for the treatment of periodontal disease during pregnancy significantly improves perinatal outcomes.

Cyclic alternating pattern in obstructive sleep apnea: A preliminary study.

Obstructive sleep apnea is linked to cardiovascular disease, metabolic disorders and dementia. The precise nature of the association between respiratory events in obstructive sleep apnea, cortical or subcortical arousals, and cognitive, autonomic and oxidative stress consequences remains incompletely elucidated. Previous studies have aimed to understand the relationship between obstructive sleep apnea and arousal patterns, as defined by the cyclic alternating pattern, but results have been inconsistent, in part likely due to the presence of associated comorbidities. To better define this relationship, we analysed cyclic alternating patterns in patients with obstructive sleep apnea without any additional comorbidities. We identified 18 adult male, non-obese subjects with obstructive sleep apnea and no other comorbidities or medication history, who underwent whole-night electroencephalography and polysomnography. Cyclic alternating pattern analysis was performed and verified by certified somnologists. Pairwise linear regression analysis demonstrated an inverse relationship between obstructive sleep apnea severity and cyclic alternating pattern subtype A1, and a direct correlation with cyclic alternating pattern subtype A3. Cyclic alternating pattern subtypes A1 prevail in milder obstructive sleep apnea phenotype, whilst cyclic alternating pattern subtypes A2 and A3 overcome among moderate-to-severe obstructive sleep apnea patients. The milder obstructive sleep apnea group also presented higher sleep efficiency, and increased percentages of non-rapid eye movement stage 3 and rapid eye movement sleep, as well as longer cyclic alternating pattern sequences in N3, while severe obstructive sleep apnea patients spent more time in lighter sleep stages. These results imply/suggest a balance between cyclic alternating pattern's adaptive and maladaptive arousal processes in obstructive sleep apnea of differing severities. In milder obstructive sleep apnea (apnea-hypopnea index < 20), sleep continuity may be reinforced by cyclic alternating pattern subtype A1, whereas in more severe obstructive sleep apnea, decompensation of these sleep-stabilizing mechanisms may occur and more intrusive cyclic alternating pattern fluctuations disrupt sleep circuitry.

Systematic review with meta-analysis: autoimmune hepatitis in pregnancy.

BACKGROUND: Maternal and fetal outcomes in pregnant patients with autoimmune hepatitis (AIH) has been largely unexplored. AIM: This meta-analysis aims to determine the level of evidence associated with both maternal and fetal outcomes in patients with AIH. METHODS: We conducted a comprehensive literature search. The studies included AIH patients who had at least one pregnancy with a previously known or index presentation diagnosis of AIH. We used a random-effects model using odds ratios (OR) with 95% confidence intervals (CI). RESULTS: Fourteen studies with 1452 AIH patients and with a total of 1556 gestations were included. Analysis revealed statistically significant increased likelihood of diabetes mellitus in the AIH group (OR: 5.73, 95% CI: 2.73-12.02; p < .001, n = 2) compared to controls. Fetal outcomes that indicated a statistically significant association with AIH included premature birth (OR: 2.20, 95% CI:1.66-2.91; p < .001, n = 3), small for gestational age (SGA) births (OR: 2.48, 95% CI:1.37-4.51; p = .003, n = 2) and low birth weight (LBW) (OR: 3.04, 95% CI:1.85-5.01; p < .001, n = 1). AIH pregnancies were significantly less likely to have a full-term birth (OR: 0.32, 95% CI:0.21-0.49; p < .001, n = 2). CONCLUSIONS: This meta-analysis provides the first pooled evidence that autoimmune hepatitis is associated with a substantial increase in maternal Pre-pregnancy and gestational diabetes mellitus, and that AIH females are more likely to have premature births, small for gestational age (SGA) births, and low birth weight (LBW) babies and a substantial decrease in full term birth compared to normal controls. This data is important for clinicians managing these patients before, during and after pregnancy.

GRB7 is an oncogenic driver and potential therapeutic target in oesophageal adenocarcinoma.

Efficacious therapeutic approaches are urgently needed to improve outcomes in patients with oesophageal adenocarcinoma (OAC). However, oncogenic drivers amenable to targeted therapy are limited and their functional characterisation is essential. Among few targeted therapies available, anti-human epidermal growth factor receptor 2 (HER2) therapy showed only modest benefit for patients with OAC. Herein, we investigated the potential oncogenic role of growth factor receptor bound protein 7 (GRB7), which is reported to be co-amplified with HER2 (ERBB2) in OAC. GRB7 was highly expressed in 15% of OAC tumours, not all of which could be explained by co-amplification with HER2, and was associated with a trend for poorer overall survival. Knockdown of GRB7 decreased proliferation and clonogenic survival, and induced apoptosis. Reverse phase protein array (RPPA) analyses revealed a role for PI3K, mammalian target of rapamycin (mTOR), MAPK, and receptor tyrosine kinase signalling in the oncogenic action of GRB7. Furthermore, the GRB7 and HER2 high-expressing OAC cell line Eso26 showed reduced cell proliferation upon GRB7 knockdown but was insensitive to HER2 inhibition by trastuzumab. Consistent with this, GRB7 knockdown in vivo with an inducible shRNA significantly inhibited tumour growth in cell line xenografts. HER2 expression did not predict sensitivity to trastuzumab, with Eso26 xenografts remaining refractory to trastuzumab treatment. Taken together, our study provides strong evidence for an oncogenic role for GRB7 in OAC and suggests that targeting GRB7 may be a potential therapeutic strategy for this cancer. © 2020 The Authors. The Journal of Pathology published by John Wiley & Sons, Ltd. on behalf of The Pathological Society of Great Britain and Ireland.

Clinical pathways and outcomes of patients with Barrett's esophagus in tertiary care settings: a prospective longitudinal cohort study in Australia, 2008-2016.

BACKGROUND: Clinical services for Barrett's esophagus have been rising worldwide including Australia, but little is known of the long-term outcomes of such patients. Retrospective studies using data at baseline are prone to both selection and misclassification bias. We investigated the clinical characteristics and outcomes of Barrett's esophagus patients in a prospective cohort. METHODS: We recruited patients diagnosed with Barrett's esophagus in tertiary settings across Australia between 2008 and 2016. We compared baseline and follow-up epidemiological and clinical data between Barrett's patients with and without dysplasia. We calculated age-adjusted incidence rates and estimated minimally and fully adjusted hazard ratios (HR) to identify those clinical factors related to disease progression. RESULTS: The cohort comprised 268 patients with Barrett's esophagus (median follow-up 5 years). At recruitment, 224 (84%) had no dysplasia, 44 (16%) had low-grade or indefinite dysplasia (LGD/IND). The age-adjusted incidence of esophageal adenocarcinoma (EAC) was 0.5% per year in LGD/IND compared with 0.1% per year in those with no dysplasia. Risk of progression to high-grade dysplasia/EAC was associated with prior LGD/IND (fully adjusted HR 6.55, 95% confidence interval [CI] 1.96-21.8) but not long-segment disease (HR 1.03, 95%CI 0.29-3.58). CONCLUSIONS: These prospective data suggest presence of dysplasia is a stronger predictor of progression to cancer than segment length in patients with Barrett's esophagus.