Prevalence and detection rate of major congenital heart disease in twin pregnancies in Denmark.

OBJECTIVE: To investigate the national prevalence and prenatal detection rate (DR) of major congenital heart disease (mCHD) in twin pregnancies without twin-to-twin transfusion syndrome (TTTS)-associated CHD in a Danish population following a standardized prenatal screening program. METHODS: This was a national registry-based study of data collected prospectively over a 10-year period. In Denmark, all women with a twin pregnancy are offered standardized screening and surveillance programs in addition to first- and second-trimester screening for aneuploidies and malformation, respectively: monochorionic (MC) twins every 2 weeks from gestational week 15 and dichorionic (DC) twins every 4 weeks from week 18. The data were retrieved from the Danish Fetal Medicine Database and included all twin pregnancies from 2009-2018, in which at least one fetus had a pre- and/or postnatal mCHD diagnosis. mCHD was defined as CHD requiring surgery within the first year of life, excluding ventricular septal defects. All pregnancy data were pre- and postnatally validated in the local patient files at the four tertiary centers covering the entire country. RESULTS: A total of 60 cases from 59 twin pregnancies were included. The prevalence of mCHD was 4.6 (95% CI, 3.5-6.0) per 1000 twin pregnancies (1.9 (95% CI, 1.3-2.5) per 1000 live births). The prevalences for DC and MC were 3.6 (95% CI, 2.6-5.0) and 9.2 (95% CI, 5.8-13.7) per 1000 twin pregnancies, respectively. The national prenatal DR of mCHD in twin pregnancies for the entire period was 68.3%. The highest DRs were in cases with univentricular hearts (100%) and the lowest with aortopulmonary window, total anomalous pulmonary venous return, Ebstein's anomaly, aortic valve stenosis and coarctation of the aorta (0-25%). Mothers of children with prenatally undetected mCHD had a significantly higher body mass index (BMI) compared to mothers of children with a prenatally detected mCHD (median, 27 kg/m2 and 23 kg/m2 , respectively; P = 0.02). CONCLUSIONS: The prevalence of mCHD in twins was 4.6 per 1000 pregnancies and was higher in MC than DC pregnancies. The prenatal DR of mCHD in twin pregnancies was 68.3%. Maternal BMI was higher in cases of prenatally undetected mCHD. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Scandcleft randomized trials of primary surgery for unilateral cleft lip and palate: Speech proficiency at 10 years of age.

BACKGROUND & AIM: To assess consonant proficiency and velopharyngeal function in 10-year-old children born with unilateral cleft lip and palate (UCLP) within the Scandcleft project. METHODS & PROCEDURES: Three parallel group, randomized, clinical trials were undertaken as an international multicentre study by nine cleft teams in five countries. Three different surgical protocols for primary palate repair (Arm B-Lip and soft palate closure at 3-4 months, hard palate closure at 36 months, Arm C-Lip closure at 3-4 months, hard and soft palate closure at 12 months, and Arm D-Lip closure at 3-4 months combined with a single-layer closure of the hard palate using a vomer flap, soft palate closure at 12 months) were tested against a common procedure (Arm A-Lip and soft palate closure at 3-4 months followed by hard palate closure at 12 months) in the total cohort of 431 children born with a non-syndromic UCLP. Speech audio and video recordings of 399 children were available and perceptually analysed. Percentage of consonants correct (PCC) from a naming test, an overall rating of velopharyngeal competence (VPC) (VPC-Rate), and a composite measure (VPC-Sum) were reported. OUTCOMES & RESULTS: The mean levels of consonant proficiency (PCC score) in the trial arms were 86-92% and between 58% and 83% of the children had VPC (VPC-Sum). Only 50-73% of the participants had a consonant proficiency level with their peers. Girls performed better throughout. Long delay of the hard palate repair (Arm B) indicated lower PCC and simultaneous hard and soft palate closure higher (Arm C). However, the proportion of participants with primary VPC (not including velopharyngeal surgeries) was highest in Arm B (68%) and lowest in Arm C (47%). CONCLUSIONS & IMPLICATIONS: The speech outcome in terms of PCC and VPC was low across the trials. The different protocols had their pros and cons and there is no obvious evidence to recommend any of the protocols as superior. Aspects other than primary surgical method, such as time after velopharyngeal surgery, surgical experience, hearing level, language difficulties and speech therapy, need to be thoroughly reviewed for a better understanding of what has affected speech outcome at 10 years. WHAT THIS PAPER ADDS: What is already known on the subject Speech outcomes at 10 years of age in children treated for UCLP are sparse and contradictory. Previous studies have examined speech outcomes and the relationship with surgical intervention in 5-year-olds. What this study adds to the existing knowledge Speech outcomes based on standardized assessment in a large group of 10-year-old children born with UCLP and surgically treated according to different protocols are presented. While speech therapy had been provided, a large proportion of the children across treatment protocols still needed further speech therapy. What are the potential or actual clinical implications of this work? Aspects other than surgery and speech function might add to the understanding of what affects speech outcome. Effective speech therapy should be available for children in addition to primary surgical repair of the cleft and secondary surgeries if needed.

Open versus laparoscopic umbilical and epigastric hernia repair: nationwide data on short- and long-term outcomes.

BACKGROUND: It is unclear whether an open or laparoscopic approach results in the best outcomes for repair of umbilical and epigastric hernias. The aim of the study was to evaluate the rates of 90-day readmission and reoperation for complication, together with rate of operation for recurrence after either open or laparoscopic mesh repair for primary umbilical or epigastric hernias with defect widths above 1 cm. METHODS: A merge of data between the Danish Hernia Database and the National Patient Registry provided data from 2007 to 2018 on perioperative information, 90-day readmission, 90-day reoperation for complication, and long-term operation for hernia recurrence. RESULTS: A total of 6855 patients were included, of whom 4106 (59.9%) and 2749 (40.1%) patients had an open or laparoscopic repair, respectively. There were significantly more patients readmitted with a superficial surgical site infection 2.5% (102/4106) after open repair compared with laparoscopic repair (0.5% (15/2749), P < 0.001. The 90-day reoperation rate for complications was significantly higher for open repairs 5.0% (205/4106) compared with laparoscopic repairs 2.7% (75/2749), P < 0.001. The incidence of a reoperation for a severe condition was significantly increased after laparoscopic repair 1.5% (41/2749) compared with open repair 0.8% (34/4106), P = 0.010. The 4-year cumulative incidence of operation for hernia recurrence was 3.5% after open and 4.2% after laparoscopic repairs, P = 0.302. CONCLUSIONS: Recurrence rates were comparable between open and laparoscopic repair of umbilical and epigastric hernias. Open repair was associated with a significantly higher rate of readmission and reoperation due to surgical site infection, whereas the rate of reoperation due to a severe complication was significantly higher after laparoscopic repair.

Differential recurrence after laparoscopic incisional hernia repair: importance of a nationwide registry-based mesh surveillance.

BACKGROUND: Identification of suboptimal mesh products is essential to improve the outcome after hernia surgery. This study investigated whether a national clinical database combined with administrative registries may serve as a tool for postmarketing evaluation of mesh products for hernia surgery. METHODS: This was a propensity score-matched case-control cohort study comparing outcomes in patients undergoing laparoscopic incisional hernia repair with either one particular mesh or any other synthetic mesh. Data on patients registered in the Danish Ventral Hernia Database between 2010 and 2016 were combined with administrative data from the Danish National Patient Registry. The primary outcome was operation for recurrence. Secondary outcomes were 30-day readmission, 30-day reoperation for complications (excluding hernia recurrence), and mortality after 30 and 90 days. RESULTS: In total, 740 patients who underwent repair with one particular mesh were matched with 1479 patients who received any other synthetic mesh. The rate of repair for hernia recurrence was significantly higher in the particular mesh group than in the reference group: 12·8 versus 6·3 per cent respectively (hazard ratio 2·09, 95 per cent c.i. 1·57 to 2·79; P < 0·001). Use of the particular mesh increased the risk of readmission (odds ratio (OR) 1·53, 1·16 to 2·01; P = 0·002) and reoperation for a complication (OR 1·60, 1·03 to 2·47, P = 0·030). No difference in mortality was found. CONCLUSION: Clinical registries with prospectively collected data can provide long-term surveillance of commercial mesh. Laparoscopic incisional hernia repair with one particular mesh was associated with an increased rate of short-term complications and double the risk of repair for recurrence.

ANTECEDENTES: Es esencial identificar los productos subóptimos referidos a las mallas para mejorar los resultados en la cirugía de la hernia. Este estudio analizó si un registro clínico nacional combinado con registros de bases de datos administrativos puede servir como herramienta para la evaluación post-comercialización de productos de mallas para cirugía de la hernia. MÉTODOS: Se efectuó un estudio de emparejamiento por puntaje de propensión de una cohorte de casos y controles en el que se comparaban los resultados de la malla Physiomesh® frente a cualquier otra malla sintética en pacientes sometidos a una reparación laparoscópica de una eventración. Se combinaron los datos de los pacientes del registro danés de hernia entre 2010 y 2016 con los datos administrativos del registro nacional de pacientes de Dinamarca. La variable principal fue la reintervención por recidiva. Las variables secundarias fueron el reingreso a 30 días, la reoperación a 30 días por complicaciones (excluyendo la recidiva de la hernia) y la mortalidad a 30 y 90 días. RESULTADOS: Para la reparación herniaria se utilizó la malla Physiomesh® en 740 pacientes, que se emparejaron mediante el análisis por puntaje de propensión con 1.479 pacientes en los que se colocó otra malla sintética. La reintervención por recidiva herniaria fue significativamente mayor en el grupo Physiomesh® (12,8%) que en el grupo de referencia (6,3%); cociente de riesgos instantáneos (hazard ratio, HR): 2,09 (i.c. del 95%: 1,57-2,79), P < 0,001. El riesgo de reingreso (razón de oportunidades, odds ratio, OR: 1,53, 1,16-2,01, P = 0,002)) y de reoperación por una complicación (OR: 1,60, 1,03-2,47, P = 0,030) fueron superiores en el grupo Physiomesh®. No hubo diferencia en la mortalidad. CONCLUSIÓN: Los grandes registros clínicos con datos recogidos de forma prospectiva pueden ser útiles para efectuar el seguimiento a largo plazo de una malla comercializada para garantizar la seguridad del producto y su calidad quirúrgica. La reparación laparoscópica de una eventración con la malla Physiomesh® se asociaba con un riesgo doble de recidiva y un aumento de la tasa de complicaciones a corto plazo.

Diagnosis and prevalence of diabetic polyneuropathy: a cross-sectional study of Danish patients with type 2 diabetes.

BACKGROUND AND PURPOSE: Diabetic polyneuropathy (DPN) is a common complication of diabetes. Using the Toronto criteria for diabetic polyneuropathy and the grading system for neuropathic pain, the performance of neuropathy scales and questionnaires were assessed by comparing them to a clinical gold standard diagnosis of DPN and painful DPN in a cohort of patients with recently diagnosed type 2 diabetes. METHODS: A questionnaire on neuropathy and pain was sent to a cohort of 5514 Danish type 2 diabetes patients. A sample of 389 patients underwent a detailed clinical examination and completed neuropathy questionnaires and scales. RESULTS: Of the 389 patients with a median diabetes duration of 5.9 years, 126 had definite DPN (including 53 with painful DPN), 88 had probable DPN and 53 had possible DPN. There were 49 patients with other causes of polyneuropathy, neuropathy symptoms or pain, 10 with subclinical DPN and 63 without DPN. The sensitivity of the Michigan Neuropathy Screening Instrument questionnaire to detect DPN was 25.7% and the specificity 84.6%. The sensitivity of the Toronto Clinical Neuropathy Scoring System, including questionnaire and clinical examination, was 62.9% and the specificity was 74.6%. CONCLUSIONS: Diabetic polyneuropathy affects approximately one in five Danish patients with recently diagnosed type 2 diabetes but neuropathic pain is not as common as previously reported. Neuropathy scales with clinical examination perform better compared with questionnaires alone, but better scales are needed for future epidemiological studies.

Incidence and predictors of recurrent and other new diabetic foot ulcers: a retrospective cohort study.

AIMS: To estimate progression rates, evaluate risk factors for progression, and study rate ratios for progression among people with a healed diabetic foot ulcer according to whether the healed ulcer was neuropathic, neuro-ischaemic or critically ischaemic. METHODS: We conducted a retrospective cohort study in all individuals with a healed diabetic foot ulcer treated at the Steno Diabetes Centre Copenhagen foot clinic in the period 2010 to 2016. The outcome of interest was recurrent/other new diabetic foot ulcers. RESULTS: A total of 780 people had a healed diabetic foot ulcer in the study period (2010-2016). The participants were followed for 1249 person-years [median (Q1-Q3) 1.04 (0.38-2.46) person-years] in total. One-third (33.1%) developed a recurrent/other new diabetic foot ulcer per year. Male gender, people with Type 2 diabetes and smokers had a statistically significantly higher risk of progression to a recurrent/other new diabetic foot ulcer compared to participants without these risk factors. Participants with neuro-ischaemic or critically ischaemic diabetic foot ulcers had statistically significantly higher progression rates than participants with neuropathic diabetic foot ulcers. CONCLUSIONS: Focus should be on preventing future recurrent/other new diabetic foot ulcers especially in people with ischaemia.

Asymptomatic hypoglycaemia in Type 1 diabetes: incidence and risk factors.

AIM: The epidemiology of asymptomatic (silent) hypoglycaemia is not well-described. We investigated incidence and risk factors for asymptomatic hypoglycaemia in Type 1 diabetes. METHODS: A cohort of 153 people with Type 1 diabetes participated in 6 days of blinded continuous glucose monitoring (CGM) and recording of hypoglycaemia symptoms. At entry, hypoglycaemia awareness was classified (by three different methods) and HbA1c and C-peptide were measured. Hypoglycaemic episodes were defined as interstitial glucose ≤ 3.9 mmol/l (IG3.9 ) or ≤ 3.0 mmol/l (IG3.0 ) for ≥ 15 min, and were considered asymptomatic if no hypoglycaemic symptoms were reported. RESULTS: At thresholds IG3.9 and IG3.0 , the incidence rates of hypoglycaemic episodes were 5.0 (7.9) [median (IQR)] and 1.3 (3.4) episodes/person-week, respectively. Three-quarters of episodes were asymptomatic. In total, 77% and 52% of participants experienced one or more episode of asymptomatic hypoglycaemia at IG3.9 and IG3.0 [3.0 (6.2) and 1.0 (2.3) asymptomatic episodes/person-week]. At multivariate analysis, reduced awareness was positively associated with asymptomatic hypoglycaemia, particularly nocturnal events, and negatively with symptomatic hypoglycaemia. High insulin dose was associated with increased risk of both asymptomatic and symptomatic hypoglycaemia, whereas low HbA1c and long diabetes duration were risk factors only for symptomatic hypoglycaemia. CONCLUSIONS: Asymptomatic hypoglycaemia constitutes the majority of hypoglycaemic events in Type 1 diabetes. Reduced hypoglycaemia awareness and high insulin dose are risk factors for asymptomatic hypoglycaemia but other conventional risk factors for severe hypoglycaemia do not correlate with risk of asymptomatic episodes.

A Upf3b-mutant mouse model with behavioral and neurogenesis defects.

Nonsense-mediated RNA decay (NMD) is a highly conserved and selective RNA degradation pathway that acts on RNAs terminating their reading frames in specific contexts. NMD is regulated in a tissue-specific and developmentally controlled manner, raising the possibility that it influences developmental events. Indeed, loss or depletion of NMD factors have been shown to disrupt developmental events in organisms spanning the phylogenetic scale. In humans, mutations in the NMD factor gene, UPF3B, cause intellectual disability (ID) and are strongly associated with autism spectrum disorder (ASD), attention deficit hyperactivity disorder (ADHD) and schizophrenia (SCZ). Here, we report the generation and characterization of mice harboring a null Upf3b allele. These Upf3b-null mice exhibit deficits in fear-conditioned learning, but not spatial learning. Upf3b-null mice also have a profound defect in prepulse inhibition (PPI), a measure of sensorimotor gating commonly deficient in individuals with SCZ and other brain disorders. Consistent with both their PPI and learning defects, cortical pyramidal neurons from Upf3b-null mice display deficient dendritic spine maturation in vivo. In addition, neural stem cells from Upf3b-null mice have impaired ability to undergo differentiation and require prolonged culture to give rise to functional neurons with electrical activity. RNA sequencing (RNAseq) analysis of the frontal cortex identified UPF3B-regulated RNAs, including direct NMD target transcripts encoding proteins with known functions in neural differentiation, maturation and disease. We suggest Upf3b-null mice serve as a novel model system to decipher cellular and molecular defects underlying ID and neurodevelopmental disorders.

Antipruritic effects of transient heat stimulation on histaminergic and nonhistaminergic itch.

BACKGROUND: Chronic itch is notoriously difficult to treat. Counterstimuli are able to inhibit itch, but this principle is difficult to apply in clinical practice, and the mechanisms behind counterstimulation-induced itch suppression in humans are unclear. OBJECTIVES: Firstly, to analyse the stimulus-response effects of transient heat stimuli on histaminergic and nonhistaminergic itch, and secondly, to investigate whether the antipruritic effect depends on homotopic (peripheral mediation) or heterotopic (central mediation) counterstimulation relative to the itch provocation site. METHODS: Eighteen healthy volunteers participated (eight female, mean age 25·7 ± 0·8 years). Itch was evoked on premarked areas of the volar forearms, by either histamine (1% solution) or cowhage (35-40 spicules). In addition to the itch provocations (experiment 1), 5-s homotopic heat stimuli at 32, 40, 45 or 50 °C were applied. In experiment 2, heat stimuli were applied either homotopically, intrasegmentally (next to the provocation site) or extrasegmentally (dorsal forearm). Itch intensity was evaluated throughout the procedures using a digital visual analogue scale. RESULTS: Homotopic counterstimuli inhibited histaminergic itch by 41·3% at 45 °C (P < 0·01) and by 76·7% at 50 °C (P < 0·001). Cowhage-induced itch was less prone to counterstimulation and was significantly diminished only at 50 °C, by 43·6% (P = 0·009). Counterstimulations applied heterotopically were not able to inhibit itch significantly. CONCLUSIONS: Itch pathway-specific effects of counterstimuli were observed between homo- and heterotopic stimulation. Histaminergic itch was robustly inhibited by short-term homotopic noxious heat stimuli for up to 10 min. Nonhistaminergic itch was only weakly inhibited. The inhibitory effects exerted by the short-term heat stimuli only occurred following homotopic counterstimulation.

Randomized trial of facilitated subcutaneous immunoglobulin in multifocal motor neuropathy.

BACKGROUND AND PURPOSE: To optimize subcutaneous therapy with immunoglobulins, large volume infusion of immunoglobulin G facilitated by pretreatment with hyaluronidase (fSCIG) was compared to conventional infusion of multiple small dosages (cSCIG) in 20 patients with multifocal motor neuropathy. METHODS: A randomized, non-inferiority and observer-blinded cross-over design was applied with a treatment period of 24 weeks for each therapy. RESULTS: In 18 patients fSCIG was feasible, two patients leaving the study due to side-effects. The primary study variable, isometric strength, was unchanged, being 100.8% [95% confidence interval (CI) 94.8%-107.1%) in fSCIG and 105.9% (95% CI 99.8%-112.0%) in cSCIG. Secondary end-points of disability, functions, impairments and quality of life showed no differences between the two treatments. Mild and short-lasting generalized side-effects were similar in the two groups, whereas the relative frequency of localized side-effects at the injection site was increased after fSCIG [0.63 (95% CI 0.23-1.00) vs. 0.09 (95% CI 0.00-0.22), P = 0.005]. The preference of the patients favoured fSCIG for two out of five visual analogue scale scores as well as the total mean score of all preferences (P = 0.03). CONCLUSIONS: Facilitated SCIG seems effective, feasible and safe. In addition, it is preferred by patients but is accompanied by a higher frequency of short-lasting localized side-effects.

Screening for late-onset Pompe disease in western Denmark.

OBJECTIVE: Late-onset Pompe disease (LOPD) is a rare autosomal recessively inherited metabolic myopathy caused by reduced activity of the lysosomal enzyme alpha-glucosidase. In a previous screening study at two large neuromuscular university clinics in Denmark, three patients with LOPD were identified out of 103 patients screened. No systematic screening has been performed at the other neurological departments in the western part of Denmark. Thus, patients with a diagnosis of unspecified myopathy were screened for LOPD. MATERIALS AND METHODS: At seven neurological departments in the western part of Denmark, medical records were evaluated for all patients registered with myopathy diagnosis codes (ICD 10 codes: G 71.0-71.9 and G 72.0-72.9) during the period January 1, 2002, to December 31, 2012. If no specific diagnosis has been reached, patients were invited for screening. Dried blood spot (DBS) test was used to analyze the activity of the enzyme alpha-glucosidase. RESULT: A total of 654 patients were identified. From the medical records, information was obtained concerning symptoms, family history, electromyography, muscle biopsy results and creatine kinase levels. Eighty-seven patients (13.3%) (males 61%) at a mean age of 53.3 years (SD 16.5) fulfilled the criteria for screening. A DBS test was performed in 47 (54%) patients. In all patients, the enzyme activity was within reference values. CONCLUSION: None of the screened patients had a reduced activity of the enzyme alpha-glucosidase. Although the cohort studied was small, our findings do not suggest that LOPD is underdiagnosed in patients with unspecified myopathy in western Denmark.

Partitioning of PCBs from air to clothing materials in a Danish apartment.

Polychlorinated biphenyl (PCB) contamination of buildings continues to pose an exposure threat, even decades after their application in the form of calks and other building materials. In this research, we investigate the ability of clothing to sorb PCBs from contaminated air and thereby influence exposure. The equilibrium concentration of PCB-28 and PCB-52 was quantified for nine used clothing fabrics exposed for 56 days to air in a Danish apartment contaminated with PCBs. Fabric materials included pure materials such as cotton and polyester, or blends of polyester, cotton, viscose/rayon, and/or elastane. Air concentrations were fairly stable over the experimental period, with PCB-28 ranging from 350 to 430 ng/m3 and PCB-52 ranging from 460 to 550 ng/m3 . Mass accumulated in fabric ranged from below detection limits to 4.5 mg/g of fabric. Cotton or materials containing elastane sorbed more than polyester materials on a mass basis. Mass-normalized partition coefficients above detection limits ranged from 105.7 to 107.0  L/kg. Clothing acts as a reservoir for PCBs that extends dermal exposure, even when outside or in uncontaminated buildings.

Role of BDNF and neurotrophic receptors in human inner ear development.

The expression patterns of the neurotrophin, brain-derived neurotrophic factor, BDNF, and the neurotrophic receptors-p75NTR and Trk receptors-in the developing human fetal inner ear between the gestational weeks (GW) 9 to 12 are examined via in situ hybridization and immunohistochemistry. BDNF mRNA expression was highest in the cochlea at GW 9 but declined in the course of development. In contrast to embryonic murine specimens, a decline in BDNF expression from the apical to the basal turn of the cochlea could not be observed. p75NTR immunostaining was most prominent in the nerve fibers that penetrate into the sensory epithelia of the cochlea, the urticule and the saccule as gestational age progresses. TrkB and TrkC expression intensified towards GW 12, at which point the BDNF mRNA localization was at its lowest. TrkA expression was limited to fiber subpopulations of the facial nerve at GW 10. In the adult human inner ear, we observed BDNF mRNA expression in the apical poles of the cochlear hair cells and supporting cells, while in the adult human utricle, the expression was localized in the vestibular hair cells. We demonstrate the highly specific staining patterns of BDNF mRNA and its putative receptors over a developmental period in which multiple hearing disorders are manifested. Our findings suggest that BDNF and neurotrophin receptors are important players during early human inner ear development. In particular, they seem to be important for the survival of the afferent sensory neurons.

Antipruritic effect of pretreatment with topical capsaicin 8% on histamine- and cowhage-evoked itch in healthy volunteers: a randomized, vehicle-controlled, proof-of-concept trial.

BACKGROUND: Chronic itch is difficult to treat. Low-concentration topical capsaicin (0·006-0·05%) has previously been applied in itch therapy but evidence on its efficacy is contradictory. OBJECTIVES: This vehicle-controlled, double-blinded study investigated the effect of topical capsaicin 8% after 1- and 24-h application on evoked itch, neurogenic inflammation and itch-associated dysaesthesia. METHODS: Sixteen healthy volunteers (aged 22 ± 0·5 years, nine female) were treated with capsaicin for 1 h and 24 h, and vehicle for 24 h on each volar forearm. Subsequently, histamine (1%, administered prick test lancets) and cowhage (40-45 spicules) were applied to the pretreated areas. Evoked itch and pain intensities were recorded for 10 min using a visual analogue scale (0-10 cm), while sensitivity to touch-evoked itch was evaluated using von Frey filaments before and after itch provocations. Neurogenic inflammation was assessed using perfusion imaging. RESULTS: In the vehicle areas peak itch responses to histamine and cowhage were 4·67 ± 0·58 and 5·15 ± 0·71, respectively. Capsaicin pretreatment reduced peak itch responses to histamine and cowhage after 24-h pretreatment to 1·41 ± 0·58 (P = 0·003) and 0·81 ± 0·18, (P < 0·001), respectively. Capsaicin pretreatment for 1 h reduced only cowhage-induced itch (P = 0·023). Furthermore, 24-h capsaicin pretreatment abolished punctuate hyperknesis and lowered histamine-induced neurogenic inflammation but did not affect weal reactions. CONCLUSIONS: Topical capsaicin 8% pretreatment for 24 h reduced histaminergic and nonhistaminergic itch by about 75%, while a significant reduction (≈60%) was achieved for only nonhistaminergic itch in a standard 1-h treatment. Further investigations are needed to elucidate the clinical potential of high-concentration capsaicin as an antipruritic.

Subcutaneous immunoglobulin as first-line therapy in treatment-naive patients with chronic inflammatory demyelinating polyneuropathy: randomized controlled trial study.

BACKGROUND AND PURPOSE: Subcutaneous immunoglobulin (SCIG) is effective as maintenance treatment in chronic inflammatory demyelinating polyneuropathy (CIDP). We investigated whether multiple subcutaneous infusions are as effective as conventional therapy with intravenous loading doses in treatment-naive patients with CIDP. METHODS: Twenty patients fulfilling the clinical and electrophysiological criteria for CIDP were included and treated with either SCIG (0.4 g/kg/week) for 5 weeks or intravenous immunoglobulin (IVIG) (0.4 g/kg/day) for 5 days. After 10 weeks, patients were switched to the opposite treatment arm and followed for a further 10 weeks. All participants were evaluated at weeks 0, 2, 5 and 10 during both therapies. Primary outcome was combined isokinetic muscle strength (cIKS). Secondary outcomes were disability, clinical evaluation of muscle strength and the performance of various function tests. RESULTS: All participants received both therapies, 14 completing the protocol. Overall, cIKS increased by 7.4 ± 14.5% (P = 0.0003) during SCIG and by 6.9 ± 16.8% (P = 0.002) during IVIG, the effect being similar (P = 0.80). Improvement of cIKS peaked 2 weeks after IVIG and 5 weeks after SCIG. Disability improved during SCIG treatment only. Muscle strength determined by manual muscle testing improved after 5 and 10 weeks during SCIG but only after 5 weeks during IVIG. The remaining parameters improved equally during both treatments. Plasma immunoglobulin G levels at baseline and improvement of cIKS were related. CONCLUSION: In treatment-naive patients with CIDP, short-lasting SCIG and IVIG therapy improve motor performance to a similar degree, but with earlier maximal improvement following IVIG than SCIG treatment.

Autoimmune encephalitis associated with voltage-gated potassium channels-complex and leucine-rich glioma-inactivated 1 antibodies - a national cohort study.

BACKGROUND AND PURPOSE: The aim of this study was to describe clinical and paraclinical characteristics of all Danish patients who tested positive for anti-voltage-gated potassium channels (VGKC)-complex, anti-leucine-rich glioma-inactivated 1 (LGI1) and anti-contactin-associated protein-2 antibodies in the serum/cerebrospinal fluid between 2009 and 2013 with follow-up interviews in 2015 and 2016. METHODS: We evaluated antibody status, symptoms leading to testing, course of disease, suspected diagnosis and time of admission as well as diagnosis and treatment. All magnetic resonance imaging, electroencephalography and 18 F-fluorodeoxyglucose positron emission tomography scans were re-evaluated by experts in the field. RESULTS: A total of 28/192 patients tested positive for VGKC-complex antibodies by radioimmunoassay and indirect immunofluorescence; 17 had antibodies to LGI1 and 6/7 of the available cerebrospinal fluids from these patients were seropositive. These 17 patients all had a clinical phenotype appropriate to LGI1 antibodies. The remaining 11 were LGI1 negative (n = 4) or not tested (n = 7). Of these, two had a phenotype consistent with limbic encephalitis. The remaining phenotypes were Guillain-Barré syndrome, Creutzfeldt-Jakob disease, neuromyotonia and anti-N-methyl-D-aspartate receptor encephalitis. Magnetic resonance imaging abnormalities were demonstrated in 69% of the LGI1-positive patients. Two patients with normal magnetic resonance imaging demonstrated temporal lobe hypermetabolism using 18 F-fluorodeoxyglucose positron emission tomography. Abnormal electroencephalography recordings were found in 86% of the patients. Upon follow-up (median 3.2 years), the median modified Rankin Scale score of anti-LGI1-positive patients was 2 and only two patients reported seizures in the past year. CONCLUSIONS: Patients diagnosed with anti-LGI1 autoimmune encephalitis increased significantly from 2009 to 2014, probably due to increased awareness. In contrast to seropositive anti-VGKC-complex patients, all anti-LGI1-positive patients presented with a classical limbic encephalitis. The majority of patients recovered well.

Polypropelene-mesh properties and type of anchoring do not influence strength of parietal ingrowth.

PURPOSE: In laparoscopic ventral hernia repair, parietal ingrowth of the mesh is of crucial importance. Until significant ingrowth occurs integrity of the repair depends solely on mesh overlap and anchoring device. Relatively few studies have addressed the effect of mesh properties and anchoring device on long-term parietal ingrowth. METHODS: In 20 sheep, using laparoscopy, we inserted two different polypropylene-based meshes, Physiomesh™ and Ventralight™ ST, anchored with Protack™, SecureStrap™, or Glubran™. After 6 and 12 months, 10 sheep at each time point were euthanized, and we harvested the meshes with corresponding fascia. Mesh with fascia was attached on an Alwetron™ materials testing machine and pulled apart obtaining the peel-off energy (kilojoule (kJ)). RESULTS: The strength of parietal ingrowth at 6 months was 5.99 ± 0.54 kJ (mean ± SEM), 4.94 ± 0.54 kJ and 7.35 ± 0.55 kJ when anchored with Protack™, Glubran™, or SecureStrap™, respectively. At 6 months, the strength of parietal ingrowth of SecureStrap™ was significantly higher than Glubran™ (p = 0.04). No significant difference was seen between any other combinations. Parietal ingrowth at 12 months was 7.05 ± 0.56 kJ, 7.55 ± 0.54 kJ, and 5.73 ± 0.54 kJ when anchored with Protack™, Glubran™, and SecureStrap™, respectively. No significant difference in strength of parietal ingrowth was seen between the three types of anchoring, (p = 1.00, p = 1.00, and p = 0.29). CONCLUSIONS: At 12 months, the strength of parietal ingrowth was the same for all comparisons. The two polypropylene meshes showed equal strength of parietal ingrowth independent of mesh properties and anchoring devices used.

Accelerated anaerobic hydrolysis rates under a combination of intermittent aeration and anaerobic conditions.

Anaerobic hydrolysis in activated return sludge was investigated in laboratory scale experiments to find if intermittent aeration would accelerate anaerobic hydrolysis rates compared to anaerobic hydrolysis rates under strict anaerobic conditions. The intermittent reactors were set up in a 240 h experiment with intermittent aeration (3 h:3 h) in a period of 24 h followed by a subsequent anaerobic period of 24 h in a cycle of 48 h which was repeated five times during the experiment. The anaerobic reactors were kept under strict anaerobic conditions in the same period (240 h). Two methods for calculating hydrolysis rates based on soluble chemical oxygen demand were compared. Two-way analysis of variance with the Bonferroni post-test was performed in order to register any significant difference between reactors with intermittent aeration and strictly anaerobic conditions respectively. The experiment demonstrated a statistically significant difference in favor of the reactors with intermittent aeration showing a tendency towards accelerated anaerobic hydrolysis rates due to application of intermittent aeration. The conclusion of the work is thus that intermittent aeration applied in the activated return sludge process can improve the treatment capacity further in full scale applications.

Conditioning pain stimulation does not affect itch induced by intra-epidermal histamine pricks but aggravates neurogenic inflammation in healthy volunteers.

This study investigated whether itch induced by intra-epidermal histamine is subjected to modulation by a standardized conditioned pain modulation (CPM) paradigm in 24 healthy volunteers. CPM was induced by computer-controlled cuff pressure algometry and histamine was introduced to the volar forearm by skin prick test punctures. Moreover, neurogenic inflammation and wheal reactions induced by histamine and autonomic nervous system responses (heart rate variability and skin conductance) were monitored. CPM did not modulate the intensity of histamine-induced itch suggesting that pruriceptive signaling is not inhibited by pain-recruited endogenous modulation, however, CPM was found to aggravate histamine-induced neurogenic inflammation, likely facilitated by efferent sympathetic fibers.