The Diagnostic Utility of Lip Biopsy in Paediatric Crohn's Disease: A 10-year Single-centre Retrospective Study.

BACKGROUND: Oral manifestations of paediatric Crohn's disease (CD) are reported in up to 60% of cases. Lip biopsy can be used to histologically diagnose oral CD. We evaluated the utility of lip biopsy in children under initial investigation for potential CD. METHODS: A 10-year retrospective review of electronic patient records at a single tertiary paediatric surgery centre was performed. All patients aged ≤16 years who underwent lip biopsy were included. Clinical features, histology, and diagnostic details were extracted. RESULTS: Forty-two children underwent lip biopsy. Median age at biopsy was 13.3 years (11.0-14.9). Final diagnosis was CD in 21/42 (50%) children, indeterminant colitis in 3/42 (7%), orofacial granulomatosis (OFG) in 3/42 (7%), coeliac disease in 1/42 (2%), and eosinophilic oesophagitis in 1/42 (2%). Thirteen children (31%) received no formal diagnosis. The most common symptoms reported were oral ulceration (33/42, 79%), lip swelling (21/42, 50%), and abdominal pain (19/42, 45%). Lip biopsy histology was normal in 11/42 (26%). In 24/42 (57%), non-granulomatous inflammation was seen. In 7/42 (17%) lip biopsy identified granulomatous inflammation: three (7%) had endoscopic biopsies concordant for CD, three (7%) had negative endoscopic biopsies but were diagnosed with CD, and one was diagnosed with OFG (2%). Sensitivity was 29% and specificity was 95%. CONCLUSION: Lip biopsy has low sensitivity but high specificity for diagnosing CD. Lip biopsy diagnosed CD in 7% when endoscopic biopsies were negative, enabling treatment. LB is a useful diagnostic test for CD in children presenting with oral symptoms. LEVEL OF EVIDENCE: III.

A Minimally Interventional Approach to Oesophageal Atresia Repair With Early Enteral Feeding is Safe, Optimises Neonatal Outcomes, and Reduces Resource use.

PURPOSE: Recent series of newborn Oesophageal Atresia (OA) repair continue to report widespread use of chest drains, gastrostomy, routine contrast studies and parenteral nutrition (PN) despite evidence suggesting these are superfluous. We report outcomes using a minimally interventional approach to post-operative recovery. METHODS: Ethically approved (15/WA/0153), single-centre, retrospective case-note review of consecutive infants with OA 2000-2022. Infants with OA and distal trache-oesophageal fistula undergoing primary oesophageal anastomosis at initial surgery were included (including those with comorbidities such as duodenal atresia, anorectal malformation and cardiac lesions). Our practice includes routine use of a trans-anastomotic tube (TAT), no routine chest drain nor gastrostomy, early enteral and oral feeding, no routine PN and no routine contrast study. Data are median (IQR). RESULTS: Of total 186 cases of OA treated during the time period, 157 met the inclusion criteria of which 2 were excluded as casenotes unavailable. TAT was used in 150 infants. A chest drain was required in 13 (8%) and two infants had a neonatal gastrostomy. Enteral feeds were started on postoperative day 2 (2-3), full enteral feeds established by day 4 (4-6) and oral feeds started on day 5 (4-8). PN was required in 15%. Median postoperative length of stay was 10 days (8-17). Progress was quicker in term infants than preterm. One infant died of cardiac disease prior to neonatal discharge. Two planned post-operative contrast studies were performed (surgeon preference) and a further 7 due to clinical suspicion of anastomotic leak. Contrast study was therefore avoided in 94%. There were 2 anastomotic leaks; both presented clinically at day 4 and day 8 after oral feeds had been started. CONCLUSION: Our minimally interventional approach is safe. It facilitates prompt recovery with lower resource use, reduced demand on nursing staff, reduced radiation burden, and early discharge home compared to published series without adversely affecting outcomes. LEVEL OF EVIDENCE: Level 4.

The Association of Coloproctology of Great Britain and Ireland guideline on the management of anal fissure.

AIM: The management of anal fissure: ACPGBI position statement was written 15 years ago. [KLR Cross et al., Colorectal Dis, 2008]. Our aim was to update the guideline and provide recommendations on the most effective treatment for patients with anal fissures utilising a multidisciplinary, rigorous guideline methodology. METHODS: The development process consisted of six phases. In phase 1 we defined the scope of the guideline. The patient population included patients with acute and chronic anal fissure. The target group was all practitioners (primary and secondary care) treating patients with fissures and, in addition, healthcare workers and patients who desired information regarding fissure management. In phase 2 we formed a guideline development group (GDG) including a methodologist. In phase 3 review questions were formulated, using a reversed PICO process, starting with possible recommendations based on the GDG's knowledge. In phase 4 a comprehensive literature search focused on existing systematic reviews addressing each review question, supplemented by more recent studies if appropriate. In phase 5 data were extracted from the included papers and checked by the GDG. If indicated, meta-analysis of systematic review data was updated by the GDG. During phase 6 the GDG members decided what recommendations could be made based on the evidence in the literature and strength of the recommendation was assessed using 'grade'. RESULTS: This guideline is divided into two sections: Primary care which includes (i) diagnosis; (ii) basic treatment; (iii) topical treatment; and secondary care which includes (iv) botulinum toxin therapy; (v) surgical intervention and (vi) special situations (including pregnancy and breast-feeding patients, children, receptive anal intercourse and low-pressure fissures). A total of 23 recommendations were formulated. A new term clinically healed was described by the GDG. CONCLUSION: This guideline provides an up-to-date evidence-based summary of the current knowledge of the management of anal fissure and may serve as a useful guide for clinicians as well as a potential reference for patients.

The American Psychosomatic Society Antiracism Task Force: Implementation, Activities, and Lessons Learned.

ABSTRACT: The American Psychosomatic Society (APS) is an international professional society that aims to advance the scientific study of biological, behavioral, and social factors in health among educators, clinicians, and researchers. In pledging to be an antiracist organization in 2020, APS formed the Antiracism Task Force to identify different manifestations of systemic racism within the society and to make recommendations for building a more inclusive and equitable professional organization. The goal of this paper was to be maximally transparent to membership about our activities and lessons learned, as well as offer a case study to other organizations striving toward antiracism. We describe the inaugural year of activities of the APS Antiracism Task Force, which included proposing amendments to the society's bylaws, collecting data on member attitudes toward diversity, and consulting on other member efforts to implement antiracism activities (e.g., increasing access to early career awards). In addition to reflecting on task force and society-specific factors that were facilitative in our first year, we describe future plans and potential challenges we may face as we support sustained commitment to APS's antiracism efforts.

A systematic review of the potential consequences of abnormal serum levels of vitamin B6 in people living with Parkinson's disease.

The prevalences of polyneuropathy and epilepsy are higher in people living with Parkinson's disease (PwPD) when compared to older adults. Vitamin B6 is widely available and affordable. PwPD are at higher risk of having abnormal serum levels of vitamin B6, which are associated with polyneuropathy and epilepsy that are potentially preventable and treatable. Potential contributors to abnormal B6 levels in PwPD include age, dietary habits, vitamin supplement misuse, gastrointestinal dysfunction and complex interactions with levodopa. The literature on the potential consequences of abnormal B6 levels in PwPD is limited by a small number of observational studies focused on polyneuropathy and epilepsy. Abnormal B6 levels have been reported in 60 of 145 PwPD (41.4% relative frequency). Low B6 levels were reported in 52 PwPD and high B6 levels were reported in 8 PwPD. There were 14 PwPD, polyneuropathy and low B6. There were 4 PwPD, polyneuropathy and high B6. There were 4 PwPD, epilepsy and low B6. Vitamin B6 level was low in 44.6% of PwPD receiving levodopa-carbidopa intestinal gel and in 30.1% of PwPD receiving oral levodopa-carbidopa. In almost all studies reporting low B6 in PwPD receiving oral levodopa-carbidopa, the dose of levodopa was ≥1000 mg/day. Rigorous epidemiological studies will clarify the prevalence, natural history and clinical relevance of abnormal serum levels of vitamin B6 in PwPD. These studies should account for diet, vitamin supplement use, gastrointestinal dysfunction, concurrent levels of vitamin B12, folate, homocysteine and methylmalonic acid, formulations and dosages of levodopa and other medications commonly used in PwPD.

Patient-centred outcomes following non-operative treatment or appendicectomy for uncomplicated acute appendicitis in children.

While non-operative treatment has emerged as an alternative to surgery for the treatment of uncomplicated acute appendicitis in children, comparative patient-centred outcomes are not well documented. We investigated these in a feasibility randomised trial. Of 57 randomised participants, data were available for 26. Compared with appendicectomy, children allocated to non-operative treatment reported higher short-term quality of life scores, shorter duration of requiring analgesia, more rapid return to normal activities and shorter parental absence from work. These preliminary data suggest differences exist in recovery profile and quality of life between these treatments that are important to measure in a larger RCT. Trial registration number is ISRCTN15830435.

Copper-Catalyzed Decarboxylative Elimination of Carboxylic Acids to Styrenes.

A copper-catalyzed decarboxylative elimination reaction of (hetero)aromatic propionic acids to vinyl (hetero)arenes has been developed. This method furnishes alkenes from carboxylic acids without the need for stochiometric Pb or Ag additives or expensive or specialized photocatalysts. A series of mechanistic experiments indicate that the reaction proceeds via benzylic deprotonation and subsequent radical decarboxylation; a pathway that is distinct from the single-electron-transfer mechanisms implicated in related decarboxylative elimination reactions.

Prevalence of Substance Use Disorders in Sickle Cell Disease Compared to Other Chronic Conditions: a Population-Based Study of Black American Adults.

BACKGROUND: Sickle cell disease (SCD) is a heritable chronic health condition characterized by pain symptoms throughout the life course that are routinely treated with opioids. OBJECTIVE: This study examined differences in substance use disorders in Black American adults with SCD compared to those with other chronic conditions or with no chronic conditions. DESIGN: Data from a population-representative sample of Black Americans with SCD, other chronic conditions, and no chronic conditions were obtained from the National Survey of American Life (NSAL) database. Diagnosis of substance use disorder was determined by structured clinical interview. Hierarchical models controlling for covariates (demographics, socioeconomic status, self-rated health, and mood disorders) compared odds of diagnosis between the three groups. PARTICIPANTS: The sample included 4238 African-American and Black Caribbean participants from the NSAL study who were 18 years of age or older. MAIN MEASURES: Measures included age, sex, income, education, marital status, employment, possession of health insurance, health conditions, and substance use disorders diagnosed by structured clinical interview. KEY RESULTS: Controlling for age, sex, and socioeconomic status, there were no differences in odds of a drug use disorder when comparing individuals with SCD to Black adults with other chronic conditions (OR = 1.12; p = 0.804) or no chronic condition (OR = 2.09; p = 0.102). SCD was, however, associated with greater odds of alcohol use disorders when compared to the groups with other chronic conditions (OR = 2.15; p = 0.01) and no chronic conditions (OR = 5.11; p < 0.001). This effect was not better accounted for by socioeconomic status, marital status, self-rated physical health, or the presence of a mood disorder. CONCLUSIONS: SCD was not a risk factor for drug use disorders. Further data will be needed to understand the factors contributing to increased risk of alcohol use disorders in SCD and the role uncontrolled pain symptoms may have in driving substance use.

Relationship among interpersonal stressors in adolescence, social support buffers, and obesity in adulthood 14 years later.

OBJECTIVE: Early life stress may be linked to adult obesity. Alternatively, social support can buffer the effects of stress. The study's objective was to examine in a nationally representative sample, whether adolescent interpersonal and financial stress predict later obesity in adulthood and whether social support and social cohesion might buffer this effect. METHOD: The sample includes 6,504 participants across four waves in the Add Health dataset. Researchers created a structural equation model whereby latent measures of interpersonal stress and financial stress during adolescence were used to predict obesity (Body Mass Index, BMI ≥ 30) at Wave 4, 14 years later. Latent measures of social support and social cohesion were added to observe whether they buffered the effect of stress on adult BMI. Covariates included race/ethnicity, gender, self-rated health, smoking status, and age. RESULTS: In an initial model of interpersonal and financial stressors and covariates predicting BMI, interpersonal stress (p < .001) but not financial stress (p > .05) predicted adult BMI. In the full model including stressors, buffers and covariates, social support (p < .001) and social cohesion (p = .038) negatively predicted adult BMI, and they covaried with interpersonal stress in opposing directions, buffering the effects of interpersonal stress on adult BMI. CONCLUSIONS: Stressful interpersonal life events in adolescence such as having family members in jail or being the victim of a crime are linked to adult obesity 14 years later. However, these stress effects are buffered by the effects of social support and social cohesion, which are linked to lower adult BMI. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

The Management of Asymptomatic Congenital Pulmonary Airway Malformation: Results of a European Delphi Survey.

Consensus on the optimal management of asymptomatic congenital pulmonary airway malformation (CPAM) is lacking, and comparison between studies remains difficult due to a large variety in outcome measures. We aimed to define a core outcome set (COS) for pediatric patients with an asymptomatic CPAM. An online, three-round Delphi survey was conducted in two stakeholder groups of specialized caregivers (surgeons and non-surgeons) in various European centers. Proposed outcome parameters were scored according to level of importance, and the final COS was established through consensus. A total of 55 participants (33 surgeons, 22 non-surgeons) from 28 centers in 13 European countries completed the three rounds and rated 43 outcome parameters. The final COS comprises seven outcome parameters: respiratory insufficiency, surgical complications, mass effect/mediastinal shift (at three time-points) and multifocal disease (at two time-points). The seven outcome parameters included in the final COS reflect the diversity in priorities among this large group of European participants. However, we recommend the incorporation of these outcome parameters in the design of future studies, as they describe measurable and validated outcomes as well as the accepted age at measurement.

The Influence of the Introduction of Biologic Agents on Surgical Intervention in Paediatric Inflammatory Bowel Disease.

OBJECTIVES: To determine how the use of biological therapy is associated with surgical intervention for paediatric inflammatory bowel disease (PIBD) at a population level. METHODS: Hospital Episode Statistics data were obtained for all admissions within England (1997-2015), in children aged 0-18 years, with an ICD-10 code for diagnosis of Crohn disease (CD), ulcerative colitis (UC), or inflammatory bowel disease-unclassified (IBD-U). Office of Population Censuses and Surveys Classification of Surgical Operations and Procedures codes for major surgical resection associated with PIBD and for biological therapy were also obtained. Data are presented as median values (interquartile range). RESULTS: In total, 22,645 children had a diagnosis of PIBD of which 13,722 (61%) had CD, 7604 (34%) had UC, and 1319 (5.8%) cases had IBD-U. Biological therapy was used in 4054 (17.9%) cases. Surgical resection was undertaken in 3212 (14%) cases, more commonly for CD than UC (17.5 vs 10.3%, P < 0.0001). Time from diagnosis to major surgical resection was 8.3 (1.2-28.2) months in CD and 8.2 (0.8-21.3) months in UC. As the time-frame of the dataset progressed, there was a decreased rate of surgical intervention ( P = 0.04) and an increased use of biological therapy ( P < 0.0001). Additionally, the number of new diagnoses of PIBD increased. CONCLUSIONS: The introduction of biologic agents has been associated with a reduction in cases undergoing surgery in children with a known diagnosis of PIBD. As time progresses we will be able to determine whether biological therapies prevent the need for surgery altogether or just delay this until adulthood.

COVID-19 stressors and health behaviors: A multilevel longitudinal study across 86 countries.

Anxiety associated with the COVID-19 pandemic and home confinement has been associated with adverse health behaviors, such as unhealthy eating, smoking, and drinking. However, most studies have been limited by regional sampling, which precludes the examination of behavioral consequences associated with the pandemic at a global level. Further, few studies operationalized pandemic-related stressors to enable the investigation of the impact of different types of stressors on health outcomes. This study examined the association between perceived risk of COVID-19 infection and economic burden of COVID-19 with health-promoting and health-damaging behaviors using data from the PsyCorona Study: an international, longitudinal online study of psychological and behavioral correlates of COVID-19. Analyses utilized data from 7,402 participants from 86 countries across three waves of assessment between May 16 and June 13, 2020. Participants completed self-report measures of COVID-19 infection risk, COVID-19-related economic burden, physical exercise, diet quality, cigarette smoking, sleep quality, and binge drinking. Multilevel structural equation modeling analyses showed that across three time points, perceived economic burden was associated with reduced diet quality and sleep quality, as well as increased smoking. Diet quality and sleep quality were lowest among respondents who perceived high COVID-19 infection risk combined with high economic burden. Neither binge drinking nor exercise were associated with perceived COVID-19 infection risk, economic burden, or their interaction. Findings point to the value of developing interventions to address COVID-related stressors, which have an impact on health behaviors that, in turn, may influence vulnerability to COVID-19 and other health outcomes.

Stressful Life Events and Obesity in the United States: The Role of Nativity and Length of Residence.

PURPOSE: Obesity is a public health issue in the United States (US), that disproportionately affects marginalized group members. Stressful life events (SLE) have been implicated as an obesogenic risk factor. However, there is scant research examining of the role of nativity status and length of residence in the relationship between SLE and obesity. DESIGN: Cross-sectional survey. SETTING: Wave 2 of the National Epidemiologic Survey on Alcohol and Related Conditions. SAMPLE: A total of 34,653 participants were included in these analyses, of whom 10,169 (29.39%) had obesity. MEASURES: Obesity (measured using body mass index), stressful life events, race/ethnicity, gender, educational attainment, family income, marital status, current smoking status, and alcohol abuse. ANALYSIS: Weighted logistic regression analysis. RESULTS: A total of 10,169 (29.39%) had obesity. There was a significant interaction between SLE and nativity status/length of residence [F (3, 34,642) = 60.50, p < 0.01]. Based on stratified analyses, SLE were associated with greater odds of obesity for US-born individuals (OR = 1.07; 95% CI [1.05, 1.08]) and foreign-born individuals living in the US for ≥ 20 years (OR = 1.17; 95% CI [1.10, 1.25]). There was no evidence that SLE were associated with greater odds of obesity for foreign-born individuals living in the US <10 years (OR = 1.06; 95% CI [0.94, 1.21]) and 11-19 years (OR = 1.00; 95% CI [0.91, 1.09]). CONCLUSIONS: Number of SLE may be a risk factor for obesity, particularly for US-born adults and foreign-born adults living the US >20 years. Further research is needed to understand the pathways that may link SLE to obesity among these groups.

Anti-Black racism and behavioral medicine: confronting the past to envision the future.

Behavioral medicine research and practice have not traditionally acknowledged the detrimental effects of anti-Black racism (and other forms of systemic oppression) on health, interventions, or research. This commentary describes four ways that behavioral medicine researchers and clinicians can address the past to envision the future of behavioral medicine to promote equitable health for all: 1) name anti-Black racism, 2) ensure interventions address structural inequities, 3) advocate for systemic change, and 4) change expectations for publications.

Excellent Tolerability of Ifosfamide and Mesna Via Continuous Infusion in a Pediatric Patient Population.

Ifosfamide is an antitumor agent with activity against various malignancies in pediatric patients. As a prodrug, ifosfamide requires metabolic activation, which occurs via a saturable, multistep equilibrium-based process. Due to these metabolic characteristics, the method of administration can affect its therapeutic and toxic effects. This single-center, retrospective review describes the tolerability of continuous infusion and bolus administration of ifosfamide in 10 pediatric patients with Ewing sarcoma. The primary objective was to report the hematologic toxicities of patients with differing administration methods. Secondary objectives included collecting information on nonhematologic toxicities and incidence of treatment delays and dose reductions. Ultimately, 48 cycles of ifosfamide were administered as bolus administration and 24 as continuous infusion. Patients receiving bolus administration had lower hemoglobin and platelet nadirs resulting in more transfusions and treatment delays when compared proportionally to continuous infusion. With the results of this case series, continuous infusion ifosfamide appears to be safe and feasible for outpatient administration and may offer an advantage from a hematologic adverse event profile but would need to be confirmed in a larger cohort.

Temporal trends in ileoanal pouch surgery for paediatric onset ulcerative colitis in England from 1997 to 2015 using hospital episode statistics.

INTRODUCTION: Ileal pouch-anal anastomosis (IPAA) following colectomy for ulcerative colitis (UC) achieves restoration of intestinal continuity with potential return of continence. It is undertaken relatively infrequently in children. We aimed to investigate the national frequency of IPAA in paediatric UC and report outcomes useful for surgeon/centre benchmarking. METHODS: Hospital Episode Statistics data were obtained for all admissions in England (1997-2015) in children (< 18 years) who underwent IPAA for UC using OPCS-4 procedural codes. Surgeon specialty, readmission, and reoperation rates were identified. Data are median (interquartile range). RESULTS: UC was diagnosed in 7604 children in whom 346 (4.6%) underwent IPAA at age 15 [13-17] years. Laparoscopy was used in 55 (15.9%) cases and in the most recent 10 years more commonly by specialist paediatric surgeons (SPS) than general surgeons (GS) (34.3%vs14.7%, p = 0.001). National frequency of IPAA ranged from 12 to 34 annually. Where specialty was available, 95/342 (57%) cases were undertaken by GS and 147/342 (43%) cases by SPS. The proportion of cases undertaken by SPS increased significantly compared to GS over the study period, p = 0.0003. Post-operative length of stay was 8 [6-11] days. During the index admission, unplanned return to theatre was required in 25/346 (7.2%). Following discharge 58 (16.8%) were readmitted within 30 days. Overall return to theatre rate within 30 days of pouch surgery was 11.0% (38/346). CONCLUSION: IPAA for UC within childhood is undertaken infrequently in England, with a shift towards SPS undertaking surgery. These data can be used by surgeons to benchmark outcomes. LEVEL OF EVIDENCE: IV.

Recovery of foot drop in chronic inflammatory demyelinating polyneuropathy (CIDP).

INTRODUCTION/AIMS: Foot drop is common in chronic inflammatory demyelinating polyneuropathy (CIDP), but its prognosis is uncertain. METHODS: CIDP patients with less than anti-gravity strength (<3/5 power) of ankle dorsiflexion (ADF) on Medical Research Council manual muscle testing on presentation at our center were identified by retrospective review. After initiation of standard treatment, ADF power was serially tabulated, and predictors of recovery were determined. RESULTS: Of the 27 identified patients, ADF power at presentation was <3/5 in 48/54 legs. At 1 y after treatment, ADF power improved to >/= 3/5 in 17/27 patients in one (N = 6) or both (N = 11) legs. On multi-variate analysis, predictors of recovery of ADF power were tibialis anterior compound muscle action potential amplitude at presentation, shorter disease duration, and female gender. DISCUSSION: Foot drop improves to anti-gravity power in most treated CIDP patients depending in part on the severity of fibular motor axon loss at onset of treatment.

Expression profile of the matricellular protein periostin in paediatric inflammatory bowel disease.

The precise role of periostin, an extra-cellular matrix protein, in inflammatory bowel disease (IBD) is unclear. Here, we investigated periostin in paediatric IBD including its relationship with disease activity, clinical outcomes, genomic variation and expression in the colonic tissue. Plasma periostin was analysed using ELISA in 144 paediatric patients and 38 controls. Plasma levels were assessed against validated disease activity indices in IBD and clinical outcomes. An immuno-fluorescence for periostin and detailed isoform-expression analysis in the colonic tissue was performed in 23 individuals. We integrated a whole-gene based burden metric 'GenePy' to assess the impact of variation in POSTN and 23 other genes functionally connected to periostin. We found that plasma periostin levels were significantly increased during remission compared to active Crohn's disease. The immuno-fluorescence analysis demonstrated enhanced peri-cryptal ring patterns in patients compared to controls, present throughout inflamed, as well as macroscopically non-inflamed colonic tissue. Interestingly, the pattern of isoforms remained unchanged during bowel inflammation compared to healthy controls. In addition to its role during the inflammatory processes in IBD, periostin may have an additional prominent role in mucosal repair. Additional studies will be necessary to understand its role in the pathogenesis, repair and fibrosis in IBD.