Cas3-Derived Target DNA Degradation Fragments Fuel Primed CRISPR Adaptation.

Prokaryotes use a mechanism called priming to update their CRISPR immunological memory to rapidly counter revisiting, mutated viruses, and plasmids. Here we have determined how new spacers are produced and selected for integration into the CRISPR array during priming. We show that Cas3 couples CRISPR interference to adaptation by producing DNA breakdown products that fuel the spacer integration process in a two-step, PAM-associated manner. The helicase-nuclease Cas3 pre-processes target DNA into fragments of about 30-100 nt enriched for thymine-stretches in their 3' ends. The Cas1-2 complex further processes these fragments and integrates them sequence-specifically into CRISPR repeats by coupling of a 3' cytosine of the fragment. Our results highlight that the selection of PAM-compliant spacers during priming is enhanced by the combined sequence specificities of Cas3 and the Cas1-2 complex, leading to an increased propensity of integrating functional CTT-containing spacers.

Impact of geriatric co-management on outcomes in hospitalised cardiology patients aged 85 and over.

OBJECTIVE: Cardiovascular disease and frailty are common among the population aged 85+. We hypothesised these patients might benefit from geriatric co-management, as has been shown in other frail patient populations. However, there is limited evidence supporting geriatric co-management in older, hospitalised cardiology patients. METHODS: A retrospective cohort study was performed in a large teaching hospital in the Netherlands. We compared patients aged 85 and over admitted to the cardiology ward before (control group) and after the implementation of standard geriatric co-management (intervention group). Data on readmission, mortality, length of stay, number of consultations, delirium, and falls were analysed. RESULTS: The data of 1163 patients were analysed (n = 542 control, n = 621 intervention). In the intervention group, 251 patients did not receive the intervention because of logistic reasons or the treating physician's decision. Baseline characteristics were comparable in the intervention and control groups. Patients in the intervention group had a shorter length of stay (-1 day, p = 0.01) and were more often discharged to a geriatric rehabilitation facility (odds ratio [OR] 1.97, 95% confidence interval [CI] 1.10-3.54, p = 0.02) compared with the control patients. Other outcomes were not significantly different between the groups. CONCLUSIONS: After implementation of standard geriatric co-management for hospitalised cardiology patients aged 85 and over, the length of hospital stay shortened and the number of patients discharged to a geriatric rehabilitation facility increased. The adherence to geriatric team recommendations was high. Geriatric co-management would appear to optimise care for older hospitalised patients with cardiac disease.

Meningococcal carriage in children and young adults: a cross-sectional and longitudinal study, Iceland, 2019 to 2021.

BackgroundNeisseria meningitidis is a commensal bacterium which can cause invasive disease. Colonisation studies are important to guide vaccination strategies.AimThe study's aim was to determine the prevalence of meningococcal colonisation, duration of carriage and distribution of genogroups in Iceland.MethodsWe collected samples from 1 to 6-year-old children, 15-16-year-old adolescents and 18-20-year-old young adults. Carriers were sampled at regular intervals until the first negative swab. Conventional culture methods and qPCR were applied to detect meningococci and determine the genogroup. Whole genome sequencing was done on groupable meningococci.ResultsNo meningococci were detected among 460 children, while one of 197 (0.5%) adolescents and 34 of 525 young adults (6.5 %) carried meningococci. Non-groupable meningococci were most common (62/77 isolates from 26/35 carriers), followed by genogroup B (MenB) (12/77 isolates from 6/35 carriers). Genogroup Y was detected in two individuals and genogroup W in one. None carried genogroup C (MenC). The longest duration of carriage was at least 21 months. Serial samples from persistent carriers were closely related in WGS.ConclusionsCarriage of pathogenic meningococci is rare in young Icelanders. Non-groupable meningococci were the most common colonising meningococci in Iceland, followed by MenB. No MenC were found. Whole genome sequencing suggests prolonged carriage of the same strains in persistent carriers.

Women's migration to cities.

This study investigates the consequences of female rural-urban migration with respect to their education, career, and relationship and family formation in the Netherlands. The study is based on four birth cohorts of Dutch women born in 1970-1973 in rural areas, comparing those who had migrated to urban areas before the age of 25 with those who had remained behind. Outcomes were measured at age 42. The data were derived from administrative registers available at Statistics Netherlands. The results show that female migration to cities served to increase women's resources: they were more often university educated and had better paid jobs, in line with the idea of cities as socioeconomic escalators. The city also functioned as a relationship market with a relative abundance of men with resources. Both lower and university educated city women were more likely to be in a relationship with a highly educated man compared to their rural peers. However, lower educated women had an increased probability of being single at age 42 when they lived in cities at age 25. This was not the case for university educated women. In conclusion, for lower educated women urban migration may entail risks as well as benefits, especially with respect to family formation. University educated women on the other hand benefited both in terms of their own socioeconomic outcomes and in terms of their partners' resources.

High Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Household Transmission Rates Detected by Dense Saliva Sampling.

BACKGROUND: Understanding the dynamics of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) household transmission is important for adequate infection control measures in this ongoing pandemic. METHODS: Households were enrolled upon a polymerase chain reaction-confirmed index case between October and December 2020, prior to the coronavirus disease 2019 vaccination program. Saliva samples were obtained by self-sampling at days 1, 3, 5, 7, 10, 14, 21, 28, 35, and 42 from study inclusion. Nasopharyngeal swabs (NPS) and oropharyngeal swabs (OPS) were collected by the research team at day 7 and capillary blood samples at day 42. Household secondary attack rate (SAR) and per-person SAR were calculated based on at least 1 positive saliva, NPS, OPS, or serum sample. Whole genome sequencing was performed to investigate the possibility of multiple independent SARS-CoV-2 introductions within a household. RESULTS: Eighty-five households were included consisting of 326 (unvaccinated) individuals. Comparable numbers of secondary cases were identified by saliva (133/241 [55.2%]) and serum (127/213 [59.6%]). The household SAR was 88.2%. The per-person SAR was 64.3%. The majority of the secondary cases tested positive in saliva at day 1 (103/150 [68.7%]). Transmission from index case to household member was not affected by age or the nature of their relationship. Phylogenetic analyses suggested a single introduction for the investigated households. CONCLUSIONS: Households have a pivotal role in SARS-CoV-2 transmission. By repeated saliva self-sampling combined with NPS, OPS, and serology, we found the highest SARS-CoV-2 household transmission rates reported to date. Salivary (self-) sampling of adults and children is suitable and attractive for near real-time monitoring of SARS-CoV-2 transmission in this setting.

Influenza-like Illness Exacerbates Pneumococcal Carriage in Older Adults.

BACKGROUND: In older adults, pneumococcal disease is strongly associated with respiratory viral infections, but the impact of viruses on Streptococcus pneumoniae carriage prevalence and load remains poorly understood. Here, we investigated the effects of influenza-like illness (ILI) on pneumococcal carriage in community-dwelling older adults. METHODS: We investigated the presence of pneumococcal DNA in saliva samples collected in the 2014/2015 influenza season from 232 individuals aged ≥60 years at ILI onset, followed by sampling 2-3 weeks and 7-9 weeks after the first sample. We also sampled 194 age-matched controls twice 2-3 weeks apart. Pneumococcal DNA was detected with quantitative polymerase chain reaction assays targeting the piaB and lytA genes in raw and in culture-enriched saliva. Bacterial and pneumococcal abundances were determined in raw saliva with 16S and piaB quantification. RESULTS: The prevalence of pneumococcus-positive samples was highest at onset of ILI (42/232 [18%]) and lowest among controls (26/194 [13%] and 22/194 [11%] at the first and second samplings, respectively), though these differences were not significant. Pneumococcal carriage was associated with exposure to young children (odds ratio [OR], 2.71 [95% confidence interval {CI}, 1.51-5.02]; P < .001), and among asymptomatic controls with presence of rhinovirus infection (OR, 4.23 [95% CI, 1.16-14.22]; P < .05). When compared with carriers among controls, pneumococcal absolute abundances were significantly higher at onset of ILI (P < .01), and remained elevated beyond recovery from ILI (P < .05). Finally, pneumococcal abundances were highest in carriage events newly detected after ILI onset (estimated geometric mean, 1.21 × 10-5 [95% CI, 2.48 × 10-7 to 2.41 × 10-5], compared with preexisting carriage). CONCLUSIONS: ILI exacerbates pneumococcal colonization of the airways in older adults, and this effect persists beyond recovery from ILI.

Diagnostic accuracy of Ara h 2 for detecting peanut allergy in children.

BACKGROUND: Specific IgE to Ara h 2 is a diagnostic test for peanut allergy which may reduce the need for double-blind placebo-controlled food challenges (DBPCFC); however, guidance for using Ara h 2 in place of DBPCFCs has not been validated. OBJECTIVE: To prospectively evaluate 1) diagnostic accuracy of previously published Ara h 2 cut-off levels to diagnose peanut allergy in children and 2) costs. METHODS: A consecutive series of 150 children age 3.5 to 18 years was evaluated in secondary and tertiary settings in the Netherlands. sIgE to Ara h 2 was the index test, and oral peanut ingestion was the reference test. Oral peanut ingestion was home or supervised introduction for Ara h 2 ≤ 0.1, DBPCFC for 0.1-5.0 and open food challenge for ≥5.0. Costs were calculated using financial healthcare data. RESULTS: A conclusive reference test was performed in 113 children (75%). Sixty-four children (57%) had peanut allergy, as confirmed by a DBPCFC (27/47) or an open challenge (37/50). Forty-nine children (43%) were considered peanut-tolerant after peanut introduction (19/19), a DBPCFC (20/47) or an open challenge (10/50). Area under the curve for Ara h 2 was 0.94 (95% CI 0.90-0.98). The diagnostic flow chart correctly classified 26/26 (100%; 84-100) of children with Ara h 2 ≤ 0.1 as peanut-tolerant and 34/35 (97%; 83-100) of children with Ara h 2 ≥ 5.0 as peanut-allergic. At a cut-off of ≤0.1 and ≥5.0, a sensitivity of respectively 100% (93-100) and 53% (38-67) was observed and a specificity of 53% (38-67) and 98% (87-100). Mean annual costs of the flow chart were estimated as €320-€636 per patient lower than following national allergy guidelines. CONCLUSIONS: In this diagnostic accuracy study, which did not take into account pretest probability, we have validated previously published Ara h 2 cut-off levels which are associated with peanut tolerance and allergy.

Assessment of Isometric Knee Flexor Strength Using Hand-Held Dynamometry in High-Level Rugby Players Is Intertester Reliable.

OBJECTIVE: To assess intertester reliability of isometric knee flexor strength testing in high-level rugby players with testers of different physical capacity and different methods of dynamometer fixation. DESIGN: Reliability study. PATIENTS: Thirty noninjured high-level (Tegner Activity Score ≥9) rugby players, free from hamstring injury in the previous 2 months. ASSESSMENT: Isometric knee flexor strength (in N) in prone 0/15 degrees (hip/knee flexion) and supine 90/90 degrees position. Tests were performed by 1 female and 2 male testers whose upper-body strength was measured with a 6-repetition maximum bench press test. The prone 0/15 degrees measurement was performed with manual and external belt fixation of the dynamometer. MAIN OUTCOME MEASURES: Absolute and relative intertester reliability were calculated using intraclass correlation coefficient (ICC) and minimal detectable change. Paired t-tests were used to identify systematic measurement error between testers and to test for a difference in recorded knee flexor strength between methods of dynamometer fixation. METHODS: Isometric knee flexor strength was measured in prone 0/15 degrees (hip/knee flexion) and supine 90/90 degrees position. RESULTS: Good intertester reliability was found for all pairwise comparisons (ICC 0.80-0.87). MDCs (as percentage of mean strength) ranged from 15.2% to 25.4%. For tester couples where systematic error was identified, Bland-Altman plots and Pearson correlation coefficients demonstrated no statistically significant correlation between mean knee flexor strength and between-tester difference. There was no significant difference in isometric knee flexor strength between manual and belt fixation of the dynamometer. CONCLUSIONS: In strong high-level rugby players, hand-held dynamometry for isometric knee flexor strength assessment in prone 0/15 degrees and supine 90/90 degrees position is intertester reliable.

Reliability of MRI in Acute Full-thickness Proximal Hamstring Tendon Avulsion in Clinical Practice.

In clinically suspected acute full-thickness proximal hamstring tendon avulsions, MRI is the gold standard for evaluating the extent of the injury. MRI variables such as full-thickness free tendon discontinuity, extent of tendon retraction (>20 mm), and continuity of the sacrotuberous ligament with the conjoint tendon (STL-CT) are used in treatment decision-making. The objective was to assess the intra- and inter-rater reliability of these relevant MRI variables after acute full-thickness proximal hamstring tendon avulsion. Three musculoskeletal radiologists assessed MRIs of 40 patients with an acute full-thickness proximal hamstring tendon avulsion. MRI variables included assessment of free tendon discontinuity and continuity of the STL-CT and extent of tendon retraction. Absolute and relative intra- and inter-rater reliability were calculated. Intra- and inter-rater reliability for the assessment of tendon discontinuity was substantial (Kappa [ĸ]=0.78;0.77). For the retraction measurement of the conjoint and semimembranosus tendons, intra-rater reliability was moderate and poor (Intraclass correlation coefficient (ICC)=0.74;0.45), inter-rater reliability was moderate (ICC=0.73;0.57). Intra- and inter-rater reliability of the STL-CT continuity assessment was substantial and fair (ĸ=0.74;0.31). In conclusion, MRI assessment for full-thickness free tendon discontinuity is reliable. However, assessment of extent of tendon retraction and STL-CT continuity is not reliable enough to guide the treatment decision-making process.

What is the value of 3D virtual reality in understanding acetabular fractures?

BACKGROUND: Acetabular fractures are difficult to classify owing to the complex three-dimensional (3D) anatomy of the pelvis. 3D printing helps to understand and reliably classify acetabular fracture types. 3D-virtual reality (VR) may have comparable benefits. Our hypothesis is that 3D-VR is equivalent to 3D printing in understanding acetabular fracture patterns. METHODS: A total of 27 observers of various experience levels from several hospitals were requested to classify twenty 3D printed and VR models according to the Judet-Letournel classification. Additionally, surgeons were asked to state their preferred surgical approach and patient positioning. Time to classify each fracture type was recorded. The cases were randomized to rule out a learning curve. Inter-observer agreement was analyzed using Fleiss' kappa statistics (κ). RESULTS: Inter-observer agreements varied by observer group and type of model used to classify the fracture: medical students: 3D print (κ = 0.61), VR (κ = 0.41); junior surgical residents: 3D print (0.51) VR (0.54); senior surgical residents: 3D print (0.66) VR (0.52); junior surgeons: 3D print (0.56), VR (0.43); senior surgeons: 3D print (κ = 0.59), VR (κ = 0.42). Using 3D printed models, there was more agreement on the surgical approach (junior surgeons κ = 0.23, senior surgeons κ = 0.31) when compared with VR (junior surgeons κ = 0.17, senior surgeons 0.25). No difference was found in time used to classify these fractures between 3D printing and VR for all groups (P = 1.000). CONCLUSIONS: The Judet-Letournel acetabular classification stays difficult to interpret; only moderate kappa agreements were found. We found 3D-VR inferior to 3D printing in classifying acetabular fractures. Furthermore, the current 3D-VR technology is still not practical for intra-operative use.

Deep-intronic ABCA4 variants explain missing heritability in Stargardt disease and allow correction of splice defects by antisense oligonucleotides.

PURPOSE: Using exome sequencing, the underlying variants in many persons with autosomal recessive diseases remain undetected. We explored autosomal recessive Stargardt disease (STGD1) as a model to identify the missing heritability. METHODS: Sequencing of ABCA4 was performed in 8 STGD1 cases with one variant and p.Asn1868Ile in trans, 25 cases with one variant, and 3 cases with no ABCA4 variant. The effect of intronic variants was analyzed using in vitro splice assays in HEK293T cells and patient-derived fibroblasts. Antisense oligonucleotides were used to correct splice defects. RESULTS: In 24 of the probands (67%), one known and five novel deep-intronic variants were found. The five novel variants resulted in messenger RNA pseudoexon inclusions, due to strengthening of cryptic splice sites or by disrupting a splicing silencer motif. Variant c.769-784C>T showed partial insertion of a pseudoexon and was found in cis with c.5603A>T (p.Asn1868Ile), so its causal role could not be fully established. Variant c.4253+43G>A resulted in partial skipping of exon 28. Remarkably, antisense oligonucleotides targeting the aberrant splice processes resulted in (partial) correction of all splicing defects. CONCLUSION: Our data demonstrate the importance of assessing noncoding variants in genetic diseases, and show the great potential of splice modulation therapy for deep-intronic variants.

Magnetic Bistability in Crystalline Organic Radicals: The Interplay of H-bonding, Pancake Bonding, and Electrostatics in 4-(2'-Benzimidazolyl)-1,2,3,5-dithiadiazolyl.

The neutral radical 4-(2'-benzimidazolyl)-1,2,3,5-dithiadiazolyl (HbimDTDA) exhibits a first order phase transition around 270 K without symmetry breaking, preserving its orthorhombic Pbca space group between 340 and 100 K. Associated with this reversible single-crystal-to-single-crystal phase transition, thermal hysteresis of the magnetic susceptibility is observed. The low temperature (LT) phase is diamagnetic owing to pancake bonding between the π-radicals. In the paramagnetic high temperature (HT) phase, the pancake bonds are broken, and new electrostatic contacts are apparent. As a result of the dense 3D network of supramolecular contacts, which includes H-bonds, the HbimDTDA system provides the first example of magnetic bistability for a DTDA radical.

The fecal incontinence quality of life scale (FIQL) and fecal incontinence severity index (FISI): Validation of the Dutch versions.

AIMS: Fecal incontinence (FI) is known to have a major impact on quality of life. The Fecal Incontinence Quality of Life scale (FIQL) and Fecal Incontinence Severity Index (FISI) have been developed to assess this impact. The aim of this study was to validate the FIQL and FISI in the Dutch language. METHODS: The study population consisted of women and men experiencing FI and a reference group. The FIQL (four domains) and FISI questionnaires were validated by testing standardized measurement properties: discriminative ability, internal consistency, reproducibility, construct validity, and responsiveness. RESULTS: A total of 55 patients and 277 reference participants were included. Patients had significant lower and higher scores at the FIQL and FISI, respectively, than references (FIQL: 2.58 ± 0.70 and 3.92 ± 0.36, FISI: 38.57 ± 10.73 and 23.17 ± 15.01; P < 0.001), indicating worse functioning in patients and with this the discriminative abilities of the measures. The FIQL demonstrated adequate internal consistency on all domains (0.72-0.96), except for the embarrassment domain (0.55). The reproducibility was good for both measures. A negative correlation was found between the FIQL and FISI. Furthermore, the FIQL showed a positive (0.77) and the FISI a negative correlation (-0.31) with the Mental Component Summary scale of the SF-12. Responsiveness analysis showed a minimal important change of 0.40 points for the FIQL. CONCLUSIONS: Validity and reliability were good in the Dutch FIQL, but inconclusive in the FISI. The Dutch FIQL can support physicians in determining the impact of FI on patient's quality of life. Neurourol. Urodynam. 36:710-715, 2017. © 2016 Wiley Periodicals, Inc.

International Consensus Statement on the Clinical and Therapeutic Management of Leber Hereditary Optic Neuropathy.

Leber hereditary optic neuropathy (LHON) is currently estimated as the most frequent mitochondrial disease (1 in 27,000-45,000). Its molecular pathogenesis and natural history is now fairly well understood. LHON also is the first mitochondrial disease for which a treatment has been approved (idebenone-Raxone, Santhera Pharmaceuticals) by the European Medicine Agency, under exceptional circumstances because of the rarity and severity of the disease. However, what remains unclear includes the optimal target population, timing, dose, and frequency of administration of idebenone in LHON due to lack of accepted definitions, criteria, and general guidelines for the clinical management of LHON. To address these issues, a consensus conference with a panel of experts from Europe and North America was held in Milan, Italy, in 2016. The intent was to provide expert consensus statements for the clinical and therapeutic management of LHON based on the currently available evidence. We report the conclusions of this conference, providing the guidelines for clinical and therapeutic management of LHON.

When the spell is broken: gentrification, urban tourism and privileged discontent in the Amsterdam canal district.

Expansion of urban tourism in historic districts in European cities is putting increasing pressure on these areas as places to live. In Amsterdam, an ever-growing number of tourists visit the famous canal district, which also forms the home of a group of long-term, upper-middle-class residents. While such residents are generally depicted as instigators of urban transformation, in this case, they are on the receiving end. Bringing together the literature on the socio-spatial impact of tourism, belonging and the lived experience of place, this article explores the changing relationship between these established residents and their neighbourhood and provides insight into their growing sense of discontent and even powerlessness in the face of neighbourhood change.

Small bites versus large bites for closure of abdominal midline incisions (STITCH): a double-blind, multicentre, randomised controlled trial.

BACKGROUND: Incisional hernia is a frequent complication of midline laparotomy and is associated with high morbidity, decreased quality of life, and high costs. We aimed to compare the large bites suture technique with the small bites technique for fascial closure of midline laparotomy incisions. METHODS: We did this prospective, multicentre, double-blind, randomised controlled trial at surgical and gynaecological departments in ten hospitals in the Netherlands. Patients aged 18 years or older who were scheduled to undergo elective abdominal surgery with midline laparotomy were randomly assigned (1:1), via a computer-generated randomisation sequence, to receive small tissue bites of 5 mm every 5 mm or large bites of 1 cm every 1 cm. Randomisation was stratified by centre and between surgeons and residents with a minimisation procedure to ensure balanced allocation. Patients and study investigators were masked to group allocation. The primary outcome was the occurrence of incisional hernia; we postulated a reduced incidence in the small bites group. We analysed patients by intention to treat. This trial is registered at Clinicaltrials.gov, number NCT01132209 and with the Nederlands Trial Register, number NTR2052. FINDINGS: Between Oct 20, 2009, and March 12, 2012, we randomly assigned 560 patients to the large bites group (n=284) or the small bites group (n=276). Follow-up ended on Aug 30, 2013; 545 (97%) patients completed follow-up and were included in the primary outcome analysis. Patients in the small bites group had fascial closures sutured with more stitches than those in the large bites group (mean number of stitches 45 [SD 12] vs 25 [10]; p<0·0001), a higher ratio of suture length to wound length (5·0 [1·5] vs 4·3 [1·4]; p<0·0001) and a longer closure time (14 [6] vs 10 [4] min; p<0·0001). At 1 year follow-up, 57 (21%) of 277 patients in the large bites group and 35 (13%) of 268 patients in the small bites group had incisional hernia (p=0·0220, covariate adjusted odds ratio 0·52, 95% CI 0·31-0·87; p=0·0131). Rates of adverse events did not differ significantly between groups. INTERPRETATION: Our findings show that the small bites suture technique is more effective than the traditional large bites technique for prevention of incisional hernia in midline incisions and is not associated with a higher rate of adverse events. The small bites technique should become the standard closure technique for midline incisions. FUNDING: Erasmus University Medical Center and Ethicon.

Sexual Dysfunctions in Men and Women with Inflammatory Bowel Disease: The Influence of IBD-Related Clinical Factors and Depression on Sexual Function.

INTRODUCTION: Inflammatory bowel disease (IBD) is likely to have an impact on sexual function because of its symptoms, like diarrhea, fatigue, and abdominal pain. Depression is commonly reported in IBD and is also related to impaired sexual function. This study aimed to evaluate sexual function and its association with depression among patients with IBD compared with controls. METHODS: IBD patients registered at two hospitals participated. The control group consisted of a general practitioner practice population. The web-based questionnaire included the Female Sexual Function Index (FSFI) for women and the International Index of Erectile Function (IIEF) for men. Other variables evaluated were depression, disease activity, IBD-related quality of life, body image, and fatigue. RESULTS: In total, 168 female and 119 male patients were available for analysis (response rate 24%). Overall, patients with IBD did not significantly differ in prevalence of sexual dysfunctions from controls: female patients 52%, female controls 44%, male patients and male controls both 25%. However, men and women with an active disease scored significantly lower than patients in remission and controls, indicating impaired sexual functioning during disease activity. Significant associations were found between active disease, fatigue, depressive mood, quality of life, and sexual function for both male and female patients. The association between disease activity and sexual function was totally mediated by depression. CONCLUSION: Male and female IBD patients with an active disease show impaired sexual function relative to patients in remission and controls. Depression is the most important determinant for impaired sexual function in IBD.

Predictors of outcome after transanal advancement flap repair for high transsphincteric fistulas.

BACKGROUND: Transanal advancement flap repair fails in 1 of every 3 patients with a high transsphincteric fistula. It has been reported that smoking, obesity, and previous attempts at repair adversely affect the outcome of transanal advancement flap repair. Because these findings could not be confirmed by other studies, it is still unclear whether these and other factors have an impact on the outcome. OBJECTIVE: The aim of this study was to identify predictors of outcome in a large cohort of patients who underwent transanal advancement flap repair for a high transsphincteric fistula. DESIGN: This study was performed as a retrospective review. SETTINGS: The study was conducted at the Division of Colon and Rectal Surgery, Erasmus MC, between 2000 and 2012. PATIENTS: A consecutive series of 252 patients with a high transsphincteric fistula of cryptoglandular origin were included. Patients with a rectovaginal or Crohn fistula were excluded. INTERVENTIONS: All patients underwent transanal advancement flap repair. Preoperatively, patients underwent endoanal MRI. MAIN OUTCOME MEASURES: Healing was defined as complete wound healing with absence of symptoms. Patients were followed up to assess failure. Seventeen patient- and fistula-related variables were assessed. RESULTS: Median duration of follow-up was 21 months (range, 6-136 months). The failure rate at 3 years was 41% (95% CI, 34-48). None of the studied variables predicted the outcome of flap repair except horseshoe extension. In univariate and multivariate analyses, significantly less failures were observed in patients with a horseshoe extension (p < 0.05). LIMITATIONS: Retrospective design, a single surgeon series, and potential selection bias caused by the tertiary referral center status are the limitations of this study. CONCLUSIONS: Of all studied variables, horseshoe extension was found to be the only positive predictor of outcome after flap repair for high transsphincteric fistulas.

Polyethylene thickness does not influence aseptic revision rate with highly cross-linked liners in THA with 36-mm femoral heads.

BACKGROUND: To reduce the risk of dislocation, larger head size can be used in total hip arthroplasty (THA). However, larger head size leads to thinner acetabular liners. With conventional polyethylene, thickness of >8 mm has been advocated to reduce stress and wear rate of the polyethylene. Modern polyethylene has become more wear-resistant. In this study, we investigated if the thickness of sequentially cross-linked polyethylene (XLPE) liners is associated with failure of THA in the medium term. PATIENTS AND METHODS: 3654 THAs were included (2009-2016), in which THA was performed with a XLPE liner in combination with a 36-mm femoral head. Patient and surgical characteristics were collected. We compared implant survival of THA with thin liners (<7.9 mm) and thick liners (⩾7.9 mm) with a Kaplan Meier survival analysis at 5 years, median follow-up and 10 years of follow-up with and point aseptic loosening and performed a multivariate analysis to estimate hazard ratios (HR). RESULTS: Median follow-up was 7.7 years (IQR 5.6-9.8). In total, 179 revision procedures were performed, where 82 revisions (46%) were performed for aseptic loosening. The survival rate at 5 years, median and 10 years of follow-up showed no statistically significant difference in implant survival. The survival rate at 10 years follow-up was for thin liners 97.1% (95% CI, 96.3-97.9) and for thick liners 98.2% (95% CI, 97.4-99.0) in the aseptic loosening group (chi-square 2.55; p = 0.11).The adjusted HR for thick liners (⩾7.9 mm) was 0.65 (95% CI, 0.38-1.08) compared with the thin liners (<7.9 mm), which was not significantly different. CONCLUSIONS: From this single-centre retrospective study it appears that thinner polyethylene liners are well tolerated when using second-generation highly cross-linked polyethylene. Thickness of the XLPE liners did not influence the risk of aseptic loosening of the implants in the medium term.

[Labor migrants are not safe on Dutch workplaces]. / Arbeidsmigranten niet veilig op Nederlandse werkvloer.

OBJECTIVE: In recent years, several international studies have been published, that describe a relationship between country of origin and the occurrence of work-related injury. Since we regularly treat migrant workers in our hospital after work-related injury, we wanted to gain more insight into the characteristics of this group. DESIGN: Descriptive retrospective cohort study. METHOD: Patients were identified from the Dutch Nationwide Trauma Registration (LTR). Patients that were included in the study were admitted and treated in our hospital after a work-related injury from 2017 to 2021. Additional information regarding patient characteristics and outcomes were retrieved from our electronic hospital information system. RESULTS: 14,9% of the 397 patients were found to have an injury with an Injury Severity Score (ISS) of 16 or higher. The most common mechanism of injury was a fall from height (ISS≤15: 26.0%, ISS≥16: 57.6%). In the study population, 15,4% had a non-Dutch origin. The majority consisted of employees with an Eastern European nationality (70,5%), mainly from Poland. Within this group relatively more often patients were encountered that had no valid insurance (14% of patients with an Eastern European origin) or were intoxicated (19% of patients with Eastern European origin). CONCLUSION: A relatively large part of our patient population consisted of migrant workers. We did not observe large differences in mechanism of injury, severity of injury and outcome between native patients and migrant workers. We did observe a relatively high frequency of insurance problems and intoxications among migrant workers.