Manometric findings in relation to functional outcomes in different types of anorectal malformations

Aims: To compare anorectal manometry (AM) in patients with different types of anorectal malformations (ARMs) in relation to functional outcomes. Methods: A single-institution, cross-sectional study. After ethical approval, all patients >= 7 years old treated for anterior anus (AA), perineal fistula (PF), vestibular fistula (VF), or rectourethral fistula (RUF) from 1983 onwards were invited to answer the Rintala bowel function score (BFS) questionnaire and to attend anorectal manometry (AM). Patients with mild ARMs (AA females and PF males) had been treated with minimally invasive perineal procedures. Females with VF/PF and males with RUF had undergone internal-sphincter saving sagittal repairs. Results: 55 of 132 respondents (42%; median age 12 (7-29) years; 42% male) underwent AM. Patients with mild ARMs displayed good anorectal function after minimally invasive treatments. The median anal resting and squeeze pressures among patients with mild ARMs(60 cm H2O and 116 cm H2O respectively) were significantly higher than among patients with more severe ARMs (50 cm H2O, and 80 cm H2O respectively; p Conclusions: Our findings support the appropriateness of our minimally invasive approaches to the management of mild ARMs, and IAS-saving anatomical repairs for patients with more severe malformations. (C) 2017 Elsevier Inc. All rights reserved.Peer reviewe

Anorektaalianomalioiden hoidon pitkäaikaistulokset

Aims – To perform a detailed evaluation of the bowel functional outcomes of anorectal malformations (ARMs) after standardized treatment and systematic follow-up in relation to matched controls. To study the bowel habits of a large cohort of individuals from the general population to obtain a baseline for comparison to patients. Methods – A single-institution, cross-sectional study of all patients treated between 1983-2006 for anterior anus (AA, conservative or anal dilatations), perineal fistula (PF) males (anoplasty and/or dilatations) vestibular fistula (VF) or PF females (anterior sagittal anorectoplasty - ASARP) rectourethral fistula (RUF; posterior sagittal anorectoplasty – PSARP). Patients with significant cognitive impairment, total sacral agenesis/caudal regression syndrome, Currarino syndrome, or meningomyelocele were excluded. Participants answered a detailed questionnaire on bowel function by post. Parents of children <16 years assisted in responses. Case details were obtained from records. Patients were matched by age and gender to 3 individuals from the general population who had answered identical questionnaires. Ethical approval was obtained. Results – Our study of 594 individuals from the general population identified that minor aberrations in bowel function, especially soiling prevail in healthy individuals in an age-dependent manner. A total of 159 patients (72%; median age 12.5 (4-29) years) participated in the study on outcomes for ARMs (79 females: 45 AA and 34 VF/PF and 80 males: 46 PF/low ARM and 34 RUF males (35% bulbar, 53% prostatic, 12% bladder neck fistula). Fecal control in AA females and low ARM males was not significantly different from controls in the long-term (p=NS). In VF/PF in females, 68% of patients attained a functional outcome comparable to controls and 85% were socially continent (vs 100% of controls; p<0.001) Among RUF males, 76% of patients were social continent (vs 95% of controls; p<0.002). Despite some improvement in symptoms with increasing age, both soiling and fecal accidents among patients with VF/PF (65% and 24% respectively) and RUF (59% and 37% respectively) remained significantly higher than in controls in the long-term (18-26% for soiling and 4-6% for fecal accidents; p≤0.006 vs patients).The median BFS, the proportion with voluntary bowel movements and total continence decreased with increasing level of fistula in RUF. Constipation was an important sequel in all types of ARMs, affecting 31-44% of patients vs 2-13% of controls (p≤0.003 vs patients). Social restrictions affected a 15-36% of patients with severe ARMs (vs ≤5% of controls; p≤0.01). Conclusions - Our results support the appropriateness of sagittal repair methods for the treatment of VF/PF in females and RUF, and minor perineal procedures for mild ARMs. Patients with mild ARMs can generally be expected to develop bowel functional outcomes comparable to matched peers. In females with VF/PF and males with RUF, problems with fecal control persist at higher levels than controls into adulthood. However, the majority can be expected to achieve social continence with appropriate aftercare and effective management of constipation.Anorektumin synnynnäisten kehityshäiriöiden esiintyvyys on 1:2500 ja nämä muodostavat jatkumon erittäin monimutkaisista peräsuolen, virtsatiet ja genitaalit käsittävistä kehityshäiriöistä pelkkään lievästi ahtaaseen peräaukkoon. Tämän tutkimuksen tavoitteena oli kartoittaa laaja-alaisesti nykyaikaisin leikkausmenetelmin hoidettujen anorektaalianomaliapotilaiden suolen toiminnallisia tuloksia ikä- ja sukupuolivakioituihin verrokkeihin nähden. Poikkileikkauskyselytutkimukseen osallistui 159 vuosina 1983-2006 hoidettua anorektaalianomalia potilasta (72%; mediaani ikä 12,5 (4-29) vuotta). Verrokkiaineisto koostui 594:stä satunnaisesti väestöstä poimitun henkilön vastauksista. Verrokkien keskuudessa lievät toiminnalliset häiriöt kuten ajoittainen tuhriminen oli yleistä varsinkin lapsuudessa. Matalissa/lievissä anorektaalianomalioissa, joissa perä-aukko päättyy sulkijalihaskompleksin keskelle ja joiden hoitona oli käytetty yksinkertaista anoplastiaa ja/tai perä-aukon laajennuksia, normaali suolen toiminta ja ulosteenpidätyskyky saavutettiin lähes kaikilla potilailla aikuisikään mennessä. Nykyaikaisilla menetelmillä posteriorisella tai anteriorisella sagittaalisella anorektoplastialla (PSARP/ASARP) korjatuissa korkeissa tai monimutkaisissa anorektaalianomalioissa, joissa peräsuoli päättyy sulkijalihaskompleksin etupuolelle tai virtsaputkeen, normaali suolen toiminta saavutettiin 39%-68% potilaista anorektaalianomalian vaikeusasteesta riippuen. Sekä tuhriminen (59-65%) että tahaton ulosteenkarkailu (24-37%) pysyivät merkitsevästi yleisempinä kuin verrokeilla vielä aikuisiässä (p≤0.006) vaikka oirekuva lieventyi ajan myötä. Neljäsosalla uretrafisteli potilaista oli käytössään ACE-suolihuuhteluavanne suolen toiminnan hallitsemiseksi ja sosiaalisen ulosteenpidätyskyvyn ylläpitämiseksi. Ummetus oli tavallista lapsuudessa kaikissa anorektaalianomaliatyypeissä (31-44%) mutta hyvä hoitovaste oli yleensä saavutettavissa laksatiivohoidoilla. Hyvien toiminnallisten hoitotulosten saavuttaminen edellytti säännöllistä kliinistä seurantaa sekä tehokasta ummetuksen hoitoa. Lievää tai matalaa anorektaalianomaliaa sairastavat potilaat eivät kokeneet merkittäviä sosiaalisia ongelmia sairaudestaan johtuen verrokkeihin nähden mutta 15-36% korkeaa tai monimutkaista anorektaalianomaliaa sairastavista potilasta koki sairauden rajoittavan heidän elämäänsä ja harrastuksiaan. Tulokset sagittaalisen anorektoplastian jälkeen olivat kuitenkin paremmat kuin näitä edeltävillä leikkausmenetelmillä korjattujen anorektaalianomalioiden pitkäaikaistulokset, ja nykyinen tutkimus tukee näiden anatomiseen rekonstruktioon pyrkivien menetelmien käyttöä vaikealaatuisten anorektaalianomalioiden korjaamisessa sekä yksinkertaista anoplastiaa tai perä-aukon laajennuksia lievien anorektaalianomalioiden hoidossa

Neuromodulaatiomenetelmät masennuksen hoidossa

Masennus on kansanterveydellisesti merkittävä ongelma, sillä suomalaisista n. 5 % sairastuu vuoden aikana. Sairaus vaikuttaa selvästi elämänlaatuun heikentämällä toiminta- ja työkykyä. Erilaisia neuromodulaatiomenetelmiä on käytetty jo pitkään masennuksen hoidossa, erityisesti hoitoresistentissä taudissa. Vanhin niistä on sähköhoito, jota on käytetty jo 1930-luvulta lähtien. Viime aikoina on myös kehitetty uusia, ei-invasiivisia hoitoja. Uusin niistä on tDCS, eli transkraniaalinen tasavirtastimulaatio. Tähän työhön liittyy lyhyt katsaus masennuksesta ja erilaisista neuromodulaatiomenetelmistä. Tämän lisäksi tehtiin HYKS psykiatrian kautta pilottitutkimus tasavirtastimulaatiohoidosta. Tutkimuksen tarkoituksena oli selvittää hoitomenetelmän hyötyä vaikeahoitoisten masennuspotilailla. Potilaita rekrytoitiin HUS alueelta Keravalta ja Järvenpäästä. Yhteensä tutkimukseen osallistui 15 potilasta. Tutkimuksessa annettiin 2 mA tasavirtastimulaatiohoitoa 30 minuutin ajan 5 päivänä viikossa 3 viikon ajan. Tuloksia mitattiin ensijaisesti PHQ9-oirekyselyllä, lisäksi potilaat täyttivät BDI-, Oasis-, Sheehan toimintakykyasteikko-, Core5- ja 15D-kaavakkeet. Kaavakkeita kerättiin potilailta hoidon alussa ja jokaisen hoitoviikon jälkeen. Tutkimuksella ei osoitettu tilastollisesti merkittävää hyötyä tDCS-hoidosta. Potilaiden PHQ9 pisteet vähenivät keskimäärin n. 20 %. Kolme potilasta, eli 20 % osallistuneista, saavuttivat remission, joka määriteltiin 50 % laskuksi PHQ9 pisteissä. Pisteet vähenivät keskiarvoltaan 18,80 (SD ±6,3) pisteestä 15,00 (SD±7,3) pisteeseen. P-arvo oli 0,06. Tutkimuksen tulokset viittaavat aiempiin tutkimuksiin vertaillen heikompaan tehoon, mikä osittain voi selittyä vaikeahoitoisemmalla potilasmateriaalilla ja tutkimuksen pienellä otoksella.Depression är ett allvarligt problem för folkhälsan i och med att ca. 5 % av finländarna insjuknar i det varje år . Sjukdomen påverkar märkbart livskvaliteten genom att sänka på funktions- och arbetsförmågan. Olika neuromodulationsmetoder har redan länge använts inom depressionsvården, speciellt för vårdresistent depression. Elektrisk chockbehandling är den äldsta av dem och har använts ända sedan 1930-talet. På senare tiden har det också utvecklats nya, icke-invasiva behandlingar. Den nyaste av dem är tDCS, dvs. transkraniell likströmsstimulering. Till det här arbetet hör en kort översikt över depression och olika neuromodulationsmetoder. Utöver det gjordes det via HUCS psykiatri en pilotundersökning om likströmsstimulering. Syftet med undersökningen var att testa nyttan av vårdmetoden hos svårskötta depressionspatienter. Till undersökningen rekryterades patienter inom HNS området från Kervo och Träskända. Allt som allt deltog 15 patienter i undersökningen. I undersökningen gavs det 2 mA likström i 30 minuter 5 dagar i veckan i 3 veckors tid. Resultaten mättes i första hand med PHQ9-symptomförfrågan och dessutom fyllde patienterna BDI-, Oasis-, Sheehans mätare av funktionsförmåga-, Core5- och 15 D-blanketterna. Blanketterna samlades in i början av vården och i slutet av varje vårdvecka. Vi kunde inte påvisa en statiskt betydelsefull effekt av tDCS-behandling. Patienternas PHQ9 poäng sjönk i medeltal med ca. 20 %. 3 patienter, dvs. 20 % av deltagarna, nådde remission, vilket definierades som en 50 % minskning av PHQ9 poängen. Poäng sjönk i medeltal från 18,80 (SD ±6,3) till 15,00 (SD±7,3). P-värdet var 0,06. Jämfört med tidigare undersökningar uppnådde vi sämre resultat, vilket delvis kan förklaras med mera svårskött patientmaterial och undersökningens låga deltagarantal

Sexual Function, Fertility and Quality of Life after Modern Treatment of Anorectal Malformations

Purpose: Sexual dysfunction and impaired quality of life due to fecal incontinence are common after classic operations for anorectal malformations. We hypothesized that modern repairs may result in improved outcomes. Materials and Methods: Following ethical approval for this single institution cross-sectional study, all patients 16 years or older treated for rectourethral, vestibular or perineal fistula from 1983 onward were sent detailed postal questionnaires on sexual function and quality of life. Each respondent was age and gender matched to 3 controls randomly selected from the general population. Penoscrotal/gynecologic abnormalities were obtained from the records. Results: A total of 41 patients (62%) with a median age of 22 years participated in the study. Of the patients 20 were males with rectourethral fistula (prostatic in 60%), 10 were females with vestibular/perineal fistula and 11 were males with low malformations. Although experience of sexual relationships and orgasmic function were reported in comparable proportions to controls, age at coital debut was significantly delayed in all groups of patients (p Conclusions: While erectile and orgasmic function appear preserved after sagittal repair, further evaluation of fertility issues in males with rectourethral fistula is indicated. Larger multicenter studies are needed to confirm our findings.Peer reviewe

Lower urinary tract symptoms and sexual functions after endorectal pull-through for Hirschsprung disease : controlled long-term outcomes

Background/purpose: To define the prevalence of lower urinary tract symptoms (LUTS) and outcomes for sexual function after endorectal pull-through (EPT) for Hirschsprung disease (HD) compared to controls. To date, similar controlled studies are lacking. Methods: Patients aged = 4 years (n= 123) operated on forHDat our center between 1987 and 2011were invited to answer questionnaires on LUTS and sexual function (aged = 16 years). Patients with an intellectual disability and patients with a definitive endostomy were excluded. Patients were matched to three controls and also invited to a clinical follow-up for urological investigations including urine flow measurement, renal tract ultrasound, and urinalysis. Results: Altogether, 59 responses concerning LUTS and 24 responses concerning sexual functions were analyzed. No significant differences were demonstrated in the overall prevalence of LUTS between patients (67%) and controls (80%), nor in the prevalence of frequent LUTS (14% vs. 16%; P = NS for both). One patient (2%) had a urethral stricture after laparotomy-assisted EPT. Male patients reported sexual satisfaction and erectile function similar to controls (P N 0.10). Female patients were currently less in stable relationships compared to controls (25% vs. 83%, P= 0.005). Conclusions: Our results support the safety of EPT in patientswith HDwith regard to preservation of the integrity and functioning of the genitourinary tract. (C) 2017 Elsevier Inc. All rights reserved.Peer reviewe

A comparative cohort study of Duhamel and Endorectal Pullthrough for Hirschsprung's Disease

Background: There are limited data available to compare outcomes between surgical approaches for Hirschsprung’s disease. Duhamel and endorectal pull-through (ERPT) are two of the most common procedures performed worldwide. // Methods: Objective outcomes were compared between contemporary cohorts (aged 4–32 years) after Duhamel or ERPT using case–control methodology. Data were collected using prospectively administered standardized questionnaires on bowel and bladder function and quality of life (Pediatric Quality of Life Inventory, Short form 36 and Gastrointestinal Quality of Life Index). Patients were compared in two age groups (18 years and younger and older than 18 years) and reference made to normative control data. Multivariable analysis explored factors associated with poor outcomes. // Results: Cohorts were well matched by demographics, disease characteristics and incidence of postoperative complications (120 patients who underwent Duhamel versus 57 patients who had ERPT). Bowel function scores were similar between groups. Patients who underwent Duhamel demonstrated worse constipation and inferior faecal awareness scores (P < 0.01 for both age groups). Recurrent postoperative enterocolitis was significantly more common after ERPT (34 versus 6 per cent; odds ratio 15.56 (95 per cent c.i. 6.19 to 39.24; P < 0.0001)). On multivariable analysis, poor bowel outcome was the only factor significantly associated with poor urinary outcome (adjusted odds ratio 6.66 (95 per cent c.i. 1.74 to 25.50; P = 0.006)) and was significantly associated with markedly reduced quality of life (QoL) in all instruments used (P < 0.001 for all). There were no associations between QoL measures and pull-through technique. // Conclusion: Outcomes from Duhamel and ERPT are good in the majority of cases, with comparable bowel function scores. Constipation and impaired faecal awareness were more prevalent after Duhamel, with differences sustained in adulthood. Recurrent enterocolitis was significantly more prevalent after ERPT. Clustering of poor QoL and poor functional outcomes were observed in both cohorts, with seemingly little effect by choice of surgical procedure in terms of QoL

Humoral immune response to heat shock protein 60 of Aggregatibacter actinomycetemcomitans and cross-reactivity with malondialdehyde acetaldehyde-modified LDL

Publisher Copyright: Copyright: © 2020 Kyrklund et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Atherosclerosis is a chronic inflammatory disease and major cause of mortality worldwide. One of the crucial steps for atherosclerotic plaque development is oxidation of low-density lipoprotein (LDL). Through the oxidation, highly immunogenic epitopes are created and the immune system is activated. Association between atherosclerosis and periodontal diseases is well documented, and one of the main oral pathogens common in periodontitis is Aggregatibacter actinomycetemcomitans (Aa). Heat shock protein 60 (HSP60) is an important virulence factor for Aa bacteria and a strong activator of the immune system. Cross-reactivity of HSP60 and oxidized LDL (OxLDL) antibodies could be a potential mechanism in the progression of atherosclerosis and one possible link between atherosclerosis and periodontitis. Human plasma samples from neonates and mothers were analyzed to determine if antibody titer to Aa-HSP60 protein is already present in newborns. Further objectives were to characterize antibody response in Aa-HSP60 immunized mice and to determine possible antibody cross-reaction with oxidized LDL. We demonstrated that newborns already have IgM antibody levels to Aa-HSP60. We also showed that in mice, Aa-HSP60 immunization provoked IgG and IgM antibody response not only to Aa-HSP60 but also to malondialdehyde acetaldehyde-modified LDL (MAA-LDL). Competition assay revealed that the antibodies were specific to Aa-HSP60 and cross-reacted with MAA-LDL. Our results suggest a possibility of molecular mimicry between Aa-HSP60 and MAA-LDL, making it intriguing to speculate on the role of HSP60 protein in atherosclerosis that manifests at young age.Peer reviewe

C-type related order in the defective fluorites La2Ce2O7 and Nd2Ce2O7 studied by neutron scattering and ab initio MD simulations

This work presents a structural investigation of La2-xNdxCe2O7 (x = 0.0, 0.5, 1.0, 1.5, 2.0) using X-ray powder diffraction and total scattering neutron powder diffraction, analysed using Rietveld and the reverse Monte Carlo method (RMC). Ab initio molecular dynamics (MD) modelling is also performed for further investigations of the local order. The main intensities in the neutron diffraction data for the La2-xNdxCe2O7 series correspond to the fluorite structure. However, additional C-type superlattice peaks are visible for x > 0 and increase in intensity with increasing x. The Nd-containing compositions (x > 0) are best fitted with Rietveld analysis by using a combination of oxygen deficient fluorite and oxygen excess C-type structures. No indications of cation order are found in the RMC or Rietveld analysis, and the absence of cation order is supported by the MD modelling. We argue that the superlattice peaks originate from oxygen vacancy ordering and associated shift in the cation position away from the ideal fluorite site similar to that in the C-type structure, which is seen from the Rietveld refinements and the observed ordering in the MD modelling. The vacancies favour alignments in the , and especially the direction. Moreover, we find that such ordering might also be found to a small extent in La2Ce2O7, explaining the discernible modulated background between the fluorite peaks. The observed overlap of the main Bragg peaks between the fluorite and C-type phase supports the co-existence of vacancy ordered and more disordered domains. This is further supported by the observed similarity of the radial distribution functions as modelled with MD. The increase in long range oxygen vacancy order with increasing Nd-content in La2-xNdxCe2O7 corresponds well with the lower oxide ion conductivity in Nd2Ce2O7 compared to La2Ce2O7 reported earlier

Comparative cohort study of Duhamel and endorectal pull-through for Hirschsprung's disease

Background: There are limited data available to compare outcomes between surgical approaches for Hirschsprung's disease. Duhamel and endorectal pull-through (ERPT) are two of the most common procedures performed worldwide. Methods: Objective outcomes were compared between contemporary cohorts (aged 4-32 years) after Duhamel or ERPT using case-control methodology. Data were collected using prospectively administered standardized questionnaires on bowel and bladder function and quality of life (Pediatric Quality of Life Inventory, Short form 36 and Gastrointestinal Quality of Life Index). Patients were compared in two age groups (18 years and younger and older than 18 years) and reference made to normative control data. Multivariable analysis explored factors associated with poor outcomes. Results: Cohorts were well matched by demographics, disease characteristics and incidence of postoperative complications (120 patients who underwent Duhamel versus 57 patients who had ERPT). Bowel function scores were similar between groups. Patients who underwent Duhamel demonstrated worse constipation and inferior faecal awareness scores (P < 0.01 for both age groups). Recurrent postoperative enterocolitis was significantly more common after ERPT (34 versus 6 per cent; odds ratio 15.56 (95 per cent c.i. 6.19 to 39.24; P < 0.0001)). On multivariable analysis, poor bowel outcome was the only factor significantly associated with poor urinary outcome (adjusted odds ratio 6.66 (95 per cent c.i. 1.74 to 25.50; P = 0.006)) and was significantly associated with markedly reduced quality of life (QoL) in all instruments used (P < 0.001 for all). There were no associations between QoL measures and pull-through technique. Conclusion: Outcomes from Duhamel and ERPT are good in the majority of cases, with comparable bowel function scores. Constipation and impaired faecal awareness were more prevalent after Duhamel, with differences sustained in adulthood. Recurrent enterocolitis was significantly more prevalent after ERPT. Clustering of poor QoL and poor functional outcomes were observed in both cohorts, with seemingly little effect by choice of surgical procedure in terms of QoL.Peer reviewe