Coeliac disease is a strong risk factor for Gastro-oesophageal reflux disease while a gluten free diet is protective: a systematic review and meta-analysis.

Background: Gastro-oesophageal reflux disease (GORD) mechanisms are well described, but the aetiology is uncertain. Coeliac disease (CD), a gluten enteropathy with increased duodenal eosinophils overlaps with GORD. Functional dyspepsia is a condition where duodenal eosinophilia is featured, and a 6-fold increased risk of incident GORD has been observed. Perturbations of the duodenum can alter proximal gastric and oesophageal motor function. We performed a systematic review and meta-analysis assessing the association between CD and GORD. Methods: A systematic search of studies reporting the association of GORD and CD was conducted. CD was defined by combined serological and histological parameters. GORD was defined based on classical symptoms, oesophagitis (endoscopic or histologic) or abnormal 24-h pH monitoring; studies reporting oesophageal motility abnormalities linked with GORD were also included. Pooled odds ratios (OR) and 95% confidence intervals (CI) were calculated using a random-effects model. Findings: 31 papers were included. Individuals with CD on a gluten containing diet were 3 times more likely to have GORD than controls (OR: 3.37, 95% CI: 2.09-5.44), and over 10 times more likely when compared to those on a gluten free diet (GFD) (OR: 10.20, 95% CI: 6.49-16.04). Endoscopic oesophagitis was significantly associated with CD (OR: 4.96; 95% CI: 2.22-11.06). One year of a GFD in CD and GORD was more efficacious in preventing GORD symptom relapse than treatment with 8 weeks of PPI in non-CD GORD patients (OR: 0.18, 95% CI: 0.08-0.36). Paediatric CD patients were more likely to develop GORD (OR: 3.29, 95% CI: 1.46-7.43), compared to adult CD patients (OR: 2.55, 95% CI: 1.65-3.93). Interpretation: CD is strongly associated with GORD but there was high heterogeneity. More convincingly, a GFD substantially improves GORD symptoms, suggesting a role for duodenal inflammation and dietary antigens in the aetiology of a subset with GORD. Ruling out CD in patients with GORD may be beneficial. Funding: The study was supported by an Investigator Grant from the NHMRC to Dr. Talley.

Global prevalence of MAFLD-related hepatocellular carcinoma: A systematic review and meta-analysis.

BACKGROUND & AIMS: The global proportion of hepatocellular carcinoma (HCC) attributable to metabolic dysfunction-associated fatty liver disease (MAFLD) is unclear. The MAFLD diagnostic criteria allows objective diagnosis in the presence of steatosis plus defined markers of metabolic dysfunction, irrespective of concurrent liver disease. We aimed to determine the total global prevalence of MAFLD in HCC cohorts (total-MAFLD), including the proportion with MAFLD as their sole liver disease (single-MAFLD), and the proportion of those with concurrent liver disease where MAFLD was a contributary factor (mixed-MAFLD). METHODS: This systematic review and meta-analysis included studies systematically ascertaining MAFLD in HCC cohorts, defined using international expert panel criteria including ethnicity specific BMI cut-offs. A comparison of clinical and tumour characteristics was performed between single-MAFLD, mixed-MAFLD and non-MAFLD HCC. RESULTS: 22 studies (56,565 individuals with HCC) were included. Total and single-MAFLD HCC prevalence was 48.7% (95% CI; 34.5% - 63.0%) and 12.4% (95% CI; 8.3% - 17.3%), respectively. In HCC due to chronic hepatitis B, C and alcohol-related liver disease, mixed-MAFLD prevalence was 40.0% (95% CI; 30.2% - 50.3%), 54.1% (95% CI; 40.4% - 67.6%) and 64.3% (95% CI; 52.7% - 75.0%), respectively. Mixed-MAFLD HCC had significantly higher likelihood of cirrhosis and lower likelihood of metastatic spread compared to single-MAFLD HCC, and a higher platelet count and lower likelihood of macrovascular invasion compared to non-MAFLD HCC. CONCLUSION: MAFLD is common as a sole aetiology, but more so and as a co-factor in mixed-aetiology HCC, supporting the use of a positive diagnostic criteria.

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.

Bidirectional association between breast cancer and meningioma: a systematic review and meta-analysis.

BACKGROUND: An association between breast cancer and meningioma has been suggested in cohort studies. We aimed to perform a systematic review and meta-analysis to determine whether there is an association between initial breast cancer and subsequent meningioma diagnosis and vice versa. METHODS: A systematic literature search was performed on Medline, Embase, Scopus and Google scholar from inception up to April 2023. A meta-analysis of selected studies was performed using Review Manager 5.4. RESULTS: There were eight studies included in the systematic review. Seven had reported Standardized Incidence Ratio (SIR) for female patients and were suitable for the meta-analysis. Only one study reported SIR for male patients. For the association between initial breast cancer and subsequent meningioma, in 795 000 female patients with follow-up ranging from 7 to 13 years, the SIR was 1.27 (95% CI: 1.20-1.34, P-value <0.00001). For the association between initial meningioma and subsequent breast cancer, in 28 000 female patients with follow-up ranging from 6 to 15 years, the SIR was 1.32 (95% CI: 1.21-1.45, P-value <0.00001). There were low heterogeneity and no significant publication bias. CONCLUSION: There was a small but significant association between initial breast cancer and subsequent meningioma as well as initial meningioma and subsequent breast cancer in female patients. The potential underlying mechanisms and risk factors were unclear from current literature and would be a potential area for future research.

Demystifying the global outbreak of severe acute hepatitis of unknown aetiology in children: A systematic review and meta-analysis.

BACKGROUND: The sudden outbreak of severe acute hepatitis of unknown aetiology (SAHUA) in the first half of 2022 affected more than 1010 children in 35 countries worldwide. Dire clinical outcomes, such as acute liver failure necessitating transplantation, neurological symptoms, long-term sequelae, and death, highlight the need to determine the pathogenesis of this condition. Hypotheses on the aetiology include adenovirus and SARS-CoV-2 infections and an aberrant immune response to multiple pathogen exposure following lifting of lockdown measures but further investigation is required to reach an informed consensus. METHODS: A literature search was performed on MEDLINE and EMBASE in accordance with PRISMA guidelines for systematic reviews. Primary studies reporting data on severe acute hepatitis of unknown aetiology in children from the COVID-19 era were selected for inclusion in our review. Data on patient demographics, clinical presentation and outcomes, and diagnostic testing for coinfection were extracted. Meta-analysis used a random-effects model. RESULTS: The 33 included studies (30 case series and 3 case-control studies) described a total of 3636 cases of SAHUA (reported 1 January, 2019-31 December, 2022), with a median age of 3.5 years. Of these, 214 children (5.9%) received a liver transplant and 66 (1.8%) died. Whilst data on diagnostic testing was incomplete, the most frequently detected coinfections were with adenovirus and/or adeno-associated virus 2 (AAV2). Other common childhood respiratory and enteric pathogens, such as enterovirus, rhinovirus, and herpesviruses (EBV and HHV-6), were also identified. CONCLUSION: Coinfection with AAV2 and other common childhood pathogens may predispose children to develop this novel severe hepatitis. Altered susceptibility and response to such pathogens may be a consequence of immunological naivety following pandemic restrictions. Further investigations are needed to generate high-quality evidence on aetiology for different patient demographics and geographical areas.

The Impact of Dietary Interventions on the Microbiota in Inflammatory Bowel Disease: A Systematic Review.

BACKGROUND AND AIMS: Diet plays an integral role in the modulation of the intestinal environment, with the potential to be modified for management of individuals with inflammatory bowel disease (IBD). It has been hypothesised that poor "Western-style" dietary patterns select for a microbiota that drives IBD inflammation and that through dietary intervention, a healthy microbiota may be restored. This study aimed to systematically review the literature and assess current available evidence regarding the influence of diet on the intestinal microbiota composition in IBD patients and how this may affect disease activity. METHODS: MEDLINE, EMBASE, Scopus, Web of Science and Cochrane Library were searched from January 2013 to June 2023, to identify studies investigating diet and microbiota in IBD. RESULTS: Thirteen primary studies met the inclusion criteria and were selected for narrative synthesis. Reported associations between diet and microbiota in IBD were conflicting due to the considerable degree of heterogeneity between studies. Nine intervention studies trialled specific diets and did not demonstrate significant shifts in the diversity and abundance of intestinal microbial communities or improvement in disease outcomes, whilst the remaining four cross-sectional studies did not find a specific microbial signature associated with habitual dietary patterns in IBD patients. CONCLUSIONS: Diet modulates the gut microbiota, and this may have implications for IBD; however, the body of evidence does not currently support clear dietary patterns or food constituents that are associated with a specific microbiota profile or disease marker in IBD patients. Further research is required with a focus on robust and consistent methodology to achieve improved identification of associations.

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.

Erratum to Commun Dis Intell (2018) 2023;47. (https://doi.org/10.33321/cdi.2023.47.46).

The text within this report, as originally published, incorrectly stated that the two included cases of dengue had not recently travelled to a dengue-endemic country. A reexamination of the case data has shown that both cases had recently travelled to a country where dengue is endemic. The paragraph below provides the corrected text for the dengue case descriptions, and replaces the paragraph at the foot of the right-hand column of text on page 10 of the published report. In 2022, two cases of dengue were notified to the APSU, one confirmed and one probable (Table 1), and the incidence estimate for the surveillance period (1 February - 31 December 2022) is shown in Table 2. Neither child had a prior history of dengue; however, both had recently travelled to an endemic country. One had DENV2 serotype and the serotype was not recorded for the second child. Both children were hospitalised and symptoms included fever, rash, cough, severe abdominal pain, diarrhoea, fatigue, retro-orbital pain and myalgia/arthralagia joint pains. One child had respiratory co-infection with human metapneumovirus. Both children received supportive therapies (intravenous fluids, pain relief) and one child received ceftriaxone. On discharge, one child had ongoing problems including arthralgia, fatigue, thrombocytopaenia and hepatitis.

Australian Paediatric Surveillance Unit (APSU) Annual Surveillance Report 2022.

For 30 years the Australian Paediatric Surveillance Unit (APSU) has conducted national surveillance of rare communicable diseases and rare complications of communicable diseases. In this report, we describe the results of thirteen such studies surveyed by the APSU in 2022, including reported case numbers and incidence estimates, demographics, clinical features, management and short-term outcomes. Conditions described are: acute flaccid paralysis (AFP); congenital cytomegalovirus (cCMV); neonatal and infant herpes simplex virus (HSV) infection; perinatal exposure to human immunodeficiency virus (HIV) and paediatric HIV infection; severe complications of influenza; juvenile-onset recurrent respiratory papillomatosis (JoRRP); congenital rubella infection/syndrome; congenital varicella syndrome (CVS) and neonatal varicella infection (NVI); and the new conditions dengue; Q fever; and severe acute hepatitis. In 2022, cases of severe complications of influenza were reported to the APSU for the first time since 2019. This likely reflects the easing of government-mandated restrictions imposed in 2020-2021 to curb the transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the re-emergence of a range of infectious diseases. As previously, AFP surveillance by the APSU contributed to Australia achieving a minimum target incidence of one AFP case per 105 children aged less than 15 years. Cases of JoRRP and NVI were reported in 2022. This indicates potential gaps in human papillomavirus (HPV) and varicella vaccination coverage respectively, especially in high-risk groups such as young migrant and refugee women of childbearing age from countries without universal vaccination programs. Paediatric HIV case numbers resulting from mother-to-child-transmission (MTCT) of HIV remain low in Australia due to use of effective intervention strategies. However, there has been an increase in the number of imported cases of HIV in children (mainly perinatally-acquired) from countries with a high HIV prevalence. Without effective vaccines, there has been no decline in the incidence of congenital CMV and neonatal HSV, indicating the importance of early identification and management to reduce morbidity and mortality. The first cases of dengue, Q fever and severe acute hepatitis were received by APSU in 2022, including two cases of acute hepatitis in which aetiology has not been confirmed to date. The APSU has an important ongoing role in monitoring rare childhood infections.

Problematic online behaviors and psychopathology in Australia.

This study aimed to ascertain frequency rates and predictors of six problematic online behaviors (POBs) in an Australian sample. Participants (N = 1626) completed instruments measuring problematic online gaming, cyberchondria, problematic cybersex, problematic online shopping, problematic use of social networking sites, problematic online gambling, anxiety, depression and attention deficit/hyperactivity disorder (ADHD). Each POB was presumed to be present based on the cut-off score on the corresponding instrument and at least one indicator of interference with functioning. Generalized linear model analyses were used to determine socio-demographic and psychopathological predictors of each POB. The most common POB was problematic online shopping (12.2%), followed by problematic online gambling (11.4%), problematic use of social networking sites (6.0%), problematic cybersex (5.3%), problematic online gaming (5.2%) and cyberchondria (4.6%). Age group 27-36 had the highest rates of POBs. The intensity of ADHD symptoms predicted all POBs, whereas younger age predicted all POBs except for problematic cybersex and online gambling. Female gender predicted lower scores on the measures of problematic online gaming and cybersex. These findings have implications for age- and gender-adapted education, prevention and treatment efforts and suggest that specific POBs should be investigated separately instead of lumping them together under the umbrella terms such as "Internet addiction".

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.

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.

Clinical and Pathologic Factors Associated With Colonic Spirochete (Brachyspira pilosicoli and Brachyspira aalborgi) Infection: A Comprehensive Systematic Review and Pooled Analysis.

OBJECTIVES: This study aims to determine what pathologic and clinical factors differentiate Brachyspira species that may be useful to clinicians and pathologists. METHODS: We identified 21 studies of Brachyspira infection with individual patient information (n = 113) and conducted a pooled analysis comparing each species. RESULTS: There were differences in the pathologic and clinical profiles of each Brachyspira species. Patients infected with Brachyspira pilosicoli infection were more likely to have diarrhea, fever, HIV, and immunocompromised conditions. Those patients infected with Brachyspira aalborgi were more likely to have lamina propria inflammation. CONCLUSIONS: Our novel data provide potential insights into the pathogenic mechanism(s) and the specific risk factor profile of Brachyspira species. This may be clinically useful when assessing and managing patients.

Does Immediate Breast Reconstruction Lead to a Delay in Adjuvant Chemotherapy for Breast Cancer? A Meta-Analysis and Systematic Review.

Timely delivery of adjuvant chemotherapy is crucial. With an increasing frequency of immediate breast reconstructions (IBR) following mastectomy (MAS), concerns have arisen regarding its complication rates and effects on time to chemotherapy. The aim was to conduct a systematic review and meta-analysis to determine if there is a prolonged time to chemotherapy (TTC) after IBR and MAS. Electronic databases, reference lists and relevant articles were searched systematically. Eligibility criteria included women receiving adjuvant chemotherapy who underwent either MAS only or MAS and IBR. Random-effects models were used in the analysis. A total of 29 studies were included in qualitative analysis, comprising of 156,000 patients (IBR: 57,159; MAS: 98,841). But 23 studies had sufficient data to be included in the meta-analysis. Sixteen papers concluded there was no difference in TTC compared to MAS. There was a difference of 3.50 days between TTC in IBR versus MAS (95% CI [0.42, 6.57], P value = .0256; IBR = 43.56 days, MAS = 40.38 days). The rate of patients being delayed past 90 days was not significantly higher in IBR (OR = 1.34, 95% CI [0.76, 2.38], P = .310). IBR patients were more likely to have complications compared to the MAS group (OR = 2.04, 95% CI [1.04-4.01], P < .01). We concluded that there is a statistically significant longer time to chemotherapy following IBR of 3.50 days, yet there is no difference in delays past 90 days. Therefore, the longer TTC in IBR is unlikely to be of any clinical significance.

Active prospective national surveillance for congenital and neonatal varicella in Australia shows potential prevention opportunities.

To compare the incidence and outcomes of congenital and neonatal varicella in Australia in the pre-vaccination (1995-1997) and post-vaccination era (after 2005 to November 2020), active prospective national surveillance for congenital varicella syndrome (CVS) and neonatal varicella infection (NVI) was conducted through the Australian Paediatric Surveillance Unit (APSU). Compared with 1995-1997, there was a 91.5% reduction in the incidence of CVS and a 91.3% reduction in the incidence of NVI in 2009-2020. However, almost half of the mothers in 2009-2020 were born overseas and came from countries without a vaccination program. Although there has been a substantial and sustained decrease in the reported incidence of CVS and NVI in Australia since 2006, congenital and neonatal varicella infections persist. Thus, there is an opportunity for targeted screening of varicella in young migrant, asylum seeker and refugee women at risk of varicella infection and prioritisation for vaccination to prevent CVS and NVI.

Association Between Maternal Postnatal Depression and Offspring Anxiety and Depression in Adolescence and Young Adulthood: A Meta-Analysis.

OBJECTIVE: Postnatal depression (PND) is common, with an incidence of 10% to 20% in new mothers. Studies have identified an association between maternal PND and adverse childhood effects. Fewer studies have explored the risk of psychiatric disorders in adolescence and adulthood. METHODS: MEDLINE, PubMed, PsycINFO, Embase, and EmCare were searched. Studies evaluating the association between maternal PND and offspring anxiety or depression in adolescence or adulthood were included. Five prospective cohort studies met the inclusion criteria. The odds ratios were pooled using a random effects model, and heterogeneity and publication bias were assessed. RESULTS: Anxiety: The 4 relevant studies were composed of 273 mothers with PND and 916 controls, followed up for 12 to 23 years. The pooled odds ratio (OR) was 2.19 (1.33-3.61), p = 0.002, with no heterogeneity (I2 = 0.00, p = 0.49). Depression: The 5 studies were composed of 937 mothers with PND and 3099 controls, followed up from 12 to 23 years. The pooled OR was 1.92 (1.08-3.42), p = 0.026, with heterogeneity (I2 = 62.89, p = 0.03). CONCLUSION: Offspring of mothers with PND are twice as likely to suffer from anxiety and almost twice as likely to suffer from depression than those without exposure. This evidence heightens the importance of detection and treatment of postnatal depression. Furthermore, early assessment and support could be provided to the high-risk group of offspring.