Experiences of youth growing up with anorectal malformation or Hirschsprung's disease: a multicenter qualitative in-depth interview study.

PURPOSE: Patients with anorectal malformation (ARM) and Hirschsprung's disease (HD) live with long-term impact of these diseases even into adulthood. We aimed to explore the physical, social and emotional impact of these diseases in adolescents and young adults to develop best practices for transition care. METHODS: We conducted one-on-one in-depth interviews with ARM and HD patients aged ≥ 11 years who had undergone surgery at four tertiary referral centers. All interviews were audio-recorded and transcribed verbatim. We analyzed transcripts for recurring themes, and data were collected until data saturation was reached. Three researchers independently coded the transcripts for major themes using thematic analysis approach. RESULTS: We interviewed 16 participants (11 males) between October 2022 and April 2023. Ages ranged from 11 to 26 years. Five major themes emerged: (1) personal impact (subthemes: physical, emotional and mental health, social, school), (2) impact on family, (3) perceptions of their future (subthemes: relationships, career, state of health), (4) sources of support (subthemes: family, peers, partner), and (5) transition care (subthemes: concerns, expectations). Only females expressed concerns regarding future fertility. CONCLUSION: This study highlights the evolving problems faced by adolescents and young adults with ARM and HD, especially gender-specific concerns. Our findings can inform efforts to provide individualized care.

Photoreceptor laminin drives differentiation of human pluripotent stem cells to photoreceptor progenitors that partially restore retina function.

Blindness caused by advanced stages of inherited retinal diseases and age-related macular degeneration are characterized by photoreceptor loss. Cell therapy involving replacement with functional photoreceptor-like cells generated from human pluripotent stem cells holds great promise. Here, we generated a human recombinant retina-specific laminin isoform, LN523, and demonstrated the role in promoting the differentiation of human embryonic stem cells into photoreceptor progenitors. This chemically defined and xenogen-free method enables reproducible production of photoreceptor progenitors within 32 days. We observed that the transplantation into rd10 mice were able to protect the host photoreceptor outer nuclear layer (ONL) up to 2 weeks post transplantation as measured by full-field electroretinogram. At 4 weeks post transplantation, the engrafted cells were found to survive, mature, and associate with the host's rod bipolar cells. Visual behavioral assessment using the water maze swimming test demonstrated visual improvement in the cell-transplanted rodents. At 20 weeks post transplantation, the maturing engrafted cells were able to replace the loss of host ONL by extensive association with host bipolar cells and synapses. Post-transplanted rabbit model also provided congruent evidence for synaptic connectivity with the degenerated host retina. The results may pave the way for the development of stem cell-based therapeutics for retina degeneration.

Anal canal and sphincter function in children with Hirschsprung disease after definitive surgery.

INTRODUCTION: Anorectal manometry may be useful to objectively evaluate anorectal function following definitive pullthrough for Hirschsprung Disease (HD) but there is little published data. Our study aims to investigate anorectal manometry findings and their association with bowel function. METHODOLOGY: This was a prospective observational study. Convenience sampling method was used to recruit all HD patients who had definitive pullthrough from January 2019 to December2020 in our institution. High-resolution anorectal manometry (HRAM) was used to record anal resting pressure (ARP), length of high-pressure zone (HPZ), and presence/absence of recto-anal inhibitory reflex (RAIR). The Paediatric Incontinence/Constipation Scoring System (PICSS) was scored for all participants. PICSS is a validated questionnaire with scores mapped to an age-specific normogram to denote constipation, incontinence, and their combinations. Non-parametric and chi-square tests at significance p<0.05 were conducted to examine the relationship between PICSS categories and manometry findings. Ethical approval was obtained. RESULTS: There were 32 participants (30 boys). Median age at participation was 26.5 months (range: 13.8-156). Twenty-four (75%) had transanal pullthrough, 8(25%) underwent Duhamel procedure. PICSS scored 10(31.3%) as normal, 8(25%) as constipation, 10(31.3%) as incontinent, and 4(12.5%) as mixed. RAIR was present in 12 patients (37.5%). HPZ, maximum ARP, mean ARP were comparable across all PICSS groups without statistically significant differences. Presence of RAIR was not significantly associated with any PICSS groups (p = 0.13). CONCLUSION: Bowel function does not appear to be significantly associated with HRAM findings after definitive pullthrough for HD, but our study is limited by small sample size. RAIR was present in 37.5% patients after pullthrough. LEVEL OF EVIDENCE: Level II.

Utility of postoperative anorectal manometry in children with anorectal malformation: a systematic review.

Children with anorectal malformation (ARM) often continue to have disturbances in bowel function long after reconstructive surgery. Anorectal manometry may be utilized to evaluate bowel function in these children. We aimed to describe the reported protocols and manometric findings in children with ARM post-reconstructive surgery and to investigate the correlation between manometric evaluation and bowel functional outcome. PubMed, EMBASE, and Google Scholar databases were searched from 1980 to 2021. Data were reviewed and extracted independently by two authors, in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses. Included studies were English articles reporting postoperative assessment of children (≤ 18 years) with ARM using anorectal manometry. From 128 articles obtained in the initial search, five retrospective cohort studies and one prospective study fulfilled inclusion criteria. The rectoanal inhibitory reflex and mean anal resting pressure were parameters most often reported to correlate with postoperative bowel function. The least reported parameters among the studies were high-pressure zone, rectal volume, and rectal sensation. Anorectal manometry could be an objective method providing important information for personalized management of postoperative ARM patients with bowel function issues, but lack of standardized protocols limits a comprehensive analysis of their utility.

Validation of non-invasive transcutaneous measurement for glomerular filtration rate in lean and obese C57BL/6J mice.

AIM: The measurement of glomerular filtration rate (GFR) in experimental rodents is pivotal to understanding the progression of kidney disease and benefits of treatment strategies. A non-invasive clearance device has been developed, which measures transcutaneous decay of injected FITC-sinistrin in conscious rodents. The technique was validated against the well-established plasma clearance method in the same mice, but on consecutive days, using only models of uninephrectomy and polycystic kidney disease. We aimed to validate this widely used technique in the same lean or obese mice, at the same time. METHODS: Five-week-old male C57BL/6J mice were randomised to a high fat diet (n = 12) or normal diet (n = 11) for 10 weeks. Transcutaneous and plasma clearance of FITC-sinistrin were measured simultaneously in each mouse. RESULTS: In lean mice, there was a positive correlation between transcutaneous and plasma derived GFR (P < .01, R2 = .704), although there was an approximate 40% underestimation by the transcutaneous method (P < .0001). In obese mice, no correlation was observed between transcutaneous and plasma derived GFR, nor elimination half-life which removes any effect of the conversion factor and injected dose. The limits of agreement in a Bland-Altman plot were narrower when we used new conversion factors derived from mice in the current study and, in lean mice, a generic conversion factor which assumes 20% extracellular volume. CONCLUSION: The non-invasive clearance device may be useful for serial GFR measurements in lean and healthy mice, provided validation studies have been carried out, but its utility in obesity requires further study.

Modeling heart failure risk in diabetes and kidney disease: limitations and potential applications of transverse aortic constriction in high-fat-fed mice.

There is an increased incidence of heart failure in individuals with diabetes mellitus (DM). The coexistence of kidney disease in DM exacerbates the cardiovascular prognosis. Researchers have attempted to combine the critical features of heart failure, using transverse aortic constriction, with DM in mice, but variable findings have been reported. Furthermore, kidney outcomes have not been assessed in this setting; thus its utility as a model of heart failure in DM and kidney disease is unknown. We generated a mouse model of obesity, hyperglycemia, and mild kidney pathology by feeding male C57BL/6J mice a high-fat diet (HFD). Cardiac pressure overload was surgically induced using transverse aortic constriction (TAC). Normal diet (ND) and sham controls were included. Heart failure risk factors were evident at 8-wk post-TAC, including increased left ventricular mass (+49% in ND and +35% in HFD), cardiomyocyte hypertrophy (+40% in ND and +28% in HFD), and interstitial and perivascular fibrosis (Masson's trichrome and picrosirius red positivity). High-fat feeding did not exacerbate the TAC-induced cardiac outcomes. At 11 wk post-TAC in a separate mouse cohort, echocardiography revealed reduced left ventricular size and increased left ventricular wall thickness, the latter being evident in ND mice only. Systolic function was preserved in the TAC mice and was similar between ND and HFD. Thus combined high-fat feeding and TAC in mice did not model the increased incidence of heart failure in DM patients. This model, however, may mimic the better cardiovascular prognosis seen in overweight and obese heart failure patients.

Partner Notification Outcomes for Men Who Have Sex With Men Diagnosed With Syphilis Referred to Partner Notification Officers, Melbourne, Australia.

BACKGROUND: We examined the extent of partner notification for men who have sex with men (MSM) who were diagnosed with syphilis, and offered referral to a partner notification officer (PNO), to assist them with informing recent sexual partners. METHODS: Between October 2013 and March 2015, MSM diagnosed with syphilis at the Melbourne Sexual Health Centre were routinely offered a referral to a PNO. The outcomes of this intervention were evaluated including the proportion of men who accepted PNO services and the number of sexual partners informed by the PNO. RESULTS: There were 380 MSM diagnosed with syphilis. Those with primary or secondary syphilis reported a total of 813 partners over 3 months and those with early latent syphilis reported a total of 1400 partners over 12 months. Sixty nine percent of index men (n = 262) had documented discussion of partner notification, 34% (n = 128) accepted PNO referral, and 28% (n = 105) were contacted by the PNO, 58 of whom reported they had already notified partners themselves. Only 14 index men (4%) provided the PNO with contact details for 28 partners, 25 of whom were notified by the PNO. Among those interviewed, the most common barrier to partner notification was the presence of anonymous partners and absence of contact details for partners. CONCLUSIONS: Despite offering an effective PNO service in our centre, ultimately only 4% of MSM with syphilis had at least 1 partner notified by the PNO with patients declining the PNO service and anonymous partners posing the major barriers. Alternative patient initiated methods for improving partner notification for syphilis among MSM using newer communication technologies are required.

Sensitivity of HIV rapid tests compared with fourth-generation enzyme immunoassays or HIV RNA tests.

OBJECTIVE: Determine the sensitivity of HIV rapid tests compared with fourth-generation enzyme immunoassays (EIA) or nucleic acid amplification tests (NAAT) in clinical settings. DESIGN: Systematic review and meta-analysis. METHODS: Medline, PubMed, Embase, Cochrane Controlled Trials Register, Cochrane reviews and Cumulative Index to Nursing and Allied Health Literature were searched until 14 July 2015 for studies of adults comparing point-of-care HIV rapid tests to fourth-generation HIV EIA antibody/p24 antigen or HIV NAAT. RESULTS: From 953 titles, 18 studies were included, involving 110 122 HIV rapid test results. Compared with EIA, the estimated sensitivity (random effects) of HIV rapid tests was 94.5% [95% confidence interval (CI): 87.4-97.7]. Compared with NAAT, the sensitivity of HIV rapid tests was 93.7% (95% CI: 88.7-96.5). The sensitivity of HIV rapid tests in high-income countries was 85.7% (95% CI: 81.9-88.9) and in low-income countries was 97.7% (95% CI: 95.2-98.9) compared with either EIA or NAAT (P < 0.01 for difference between settings). Proportions of antibody negative acute infections were 13.6 (95% CI: 10.1-18.0) and 4.7% (95% CI: 2.8-7.7) in studies from high-income and low-income countries, respectively (P < 0.01). CONCLUSION: In clinical settings, HIV rapid tests were less sensitive in high-income countries compared with low-income countries, missing about one in seven infections, possibly because of the larger proportion of acute infections in targeted populations. This suggests that in high-income countries, HIV rapid tests should be used in combination with fourth-generation EIA or NAAT tests, except in special circumstances. Prospective Registration of Systematic Reviews registration number CRD42015020154.Supplementary video link: http://links.lww.com/QAD/A924.

Trends in gonorrhoea positivity by nucleic acid amplification test versus culture among Australian heterosexual men with a low prevalence of gonorrhoea, 2007-2014.

BACKGROUND: Testing for gonorrhoea with nucleic acid amplification tests (NAATs) is not recommended in low-prevalence populations as it results in high numbers of false positive results. The aim of this study was to examine temporal trends of gonorrhoea positivity by NAAT and culture in heterosexual men in Victoria, Australia following recent increases in gonorrhoea notifications. METHODS: Three data sources between 2007 and 2014 were used in this study: notification data from the Victorian Department of Health, Medicare testing numbers of single chlamydia and dual NAATs performed, and electronic records on heterosexual men attending Melbourne Sexual Health Centre (MSHC). RESULTS: Notifications of gonorrhoea by NAAT (with/without culture) in heterosexual men in Victoria rose threefold from 74 in 2007 to 238 in 2014, while the number of dual NAATs ordered over the same period underwent a fivefold increase from 14 061 to 71 860. The overall proportion of NAATs that were positive for gonorrhoea in Victoria was low and fell from 0.53% in 2007 to 0.33% in 2014 (Ptrend=0.002). Of the 28014 new heterosexual men attending MSHC, the gonorrhoea positivity by culture was 0.9%, and chlamydia positivity by NAAT was 8.5%. The positivity of both infections did not change over time. CONCLUSIONS: These data suggest that gonorrhoea prevalence in heterosexual men is low and stable, despite annual increases in notifications. Guidelines in most countries recommend restricting testing to groups or populations with prevalence over 1%, symptomatic individuals or those at increased epidemiological risk. These data indicate gonorrhoea testing should not automatically accompany chlamydia screening in low-risk heterosexual men.

Extensive prurigo nodularis: characterization and etiology.

BACKGROUND/AIMS: Prurigo nodularis (PN) has multiple reported disease associations, and this study analyzes the demographics, clinical distribution and underlying etiologies in an Asian cohort. METHODS: A 1-year retrospective study was carried out on PN patients with extensive lesions (≥10) who attended a specialized itch clinic. RESULTS: 37 patients (46% male, median age 53 years) were included. In all patients, an underlying etiologic factor associated with pruritus could be identified. 49% (n = 18) of patients had a single attributable etiology, whilst 51% (n = 19) had multiple etiologies. Among all patients, dermatological disease was the most common cause (82%), of which endogenous eczema comprised the majority of cases (54%), followed by systemic disease (38%). CONCLUSIONS: All patients with extensive PN had identifiable factors associated with pruritus in this study, and a dermatological condition was the predominant etiology in both patients with mono- and multifactorial disease. A significant number of patients had underlying systemic causes.