Atopic dermatitis: disease characteristics and comorbidities in smoking and non-smoking patients from the TREATgermany registry.

BACKGROUND: Atopic dermatitis (AD) is a chronic inflammatory skin disease with a multifactorial genesis including genetic predispositions and environmental risk and trigger factors. One of the latter possibly is smoking, indicated by an increased prevalence of AD in adults and children that are actively or passively exposed to cigarette smoke. OBJECTIVES: In this study, AD characteristics and its atopic comorbidities are compared in smoking and non-smoking AD patients. METHODS: TREATgermany is a non-interventional clinical registry which includes patients with moderate to severe AD in Germany. Baseline data of patients included in TREATgermany from inception in June 2016 to April 2020 in 39 sites across Germany was analysed comparing AD disease characteristics and comorbidities in smokers vs. non-smokers. RESULTS: Of 921 patients, 908 (male: 58.7%) with a mean age of 41.9 ± 14.4 reported their smoking status. The objective Scoring of Atopic Dermatitis (oSCORAD) did not differ between smokers (n = 352; 38.8%) and non-smokers, however, lesions' intensity of oozing/crusts and excoriations as well as patient global assessment scores (PGA) of AD severity were higher in smoking as opposed to non-smoking patients. Smokers reported a lower number of weeks with well-controlled AD and more severe pruritus than non-smokers. Total IgE levels were more elevated in smokers and they displayed a younger age at the initial diagnosis of bronchial asthma. After adjustment for potential confounders, the increased intensity of oozing/crusts, the reduced number of weeks with well-controlled AD and the greater pruritus remained different in smokers compared to non-smokers. In addition, smoking patients with adult-onset AD showed a 2.5 times higher chance of involvement of the feet. CONCLUSIONS: German registry data indicate that AD patients who smoke have a higher disease burden with a different distribution pattern of lesions in adult-onset AD.

Baseline characteristics, disease severity and treatment history of patients with atopic dermatitis included in the German AD Registry TREATgermany.

BACKGROUND: The Atopic Dermatitis (AD) TREATgermany registry was initiated by the German Society for Dermatology (DDG) in 2011 to evaluate the 'real-life' situation of health care for patients with AD. OBJECTIVES: Interim data analysis on baseline characteristics as well as current and prescribed systemic treatments of the TREATgermany registry patients. METHODS: Patients (≥18 years) with moderate-to-severe AD [objective (o)SCORAD > 20], or with current or previous anti-inflammatory systemic treatment for AD within 24 months, were included and are followed up over at least 24 months. To assess clinical signs, the eczema area severity index (EASI, 0-72), the oSCORAD (0-83) and the Investigator Global Assessment (IGA; 6-point scale) were used. The disease severity was globally scored by the patients [Patient Global Assessment (PGA); six-step Likert scale]. Disease symptoms were assessed by the patient-oriented eczema measure (POEM, 0-28) and numeric rating scales (NRS, 0-10). Health-related quality of life was measured using the dermatological life quality index (DLQI, 0-30). RESULTS: A total of 612 patients were recruited across 32 sites between 06/2016 and 01/2019 (mean age: 42.6 ± 14.2 years; mean oSCORAD: 40.8 ± 16.3). The mean POEM score was 16.3 ± 7.5. Pruritus was rated highest among subjective symptoms (NRS: 5.4 ± 2.7). The mean DLQI value was 11.3 ± 7.5. The frequency of arterial hypertension was lower (20.8%) compared with the general population, whilst this was higher for depression (10%). More than 60% of the patients had received systemic glucocorticosteroids, and 36.8% had received cyclosporine A prior to inclusion. Dupilumab was the leading substance documented as either 'current' (12.1%) or 'prescribed' (31.4%) at baseline. CONCLUSIONS: These 'real-life' data clearly demonstrate the substantial disease burden. Most of TREATgermany patients were already treated with or prescribed dupilumab at baseline. Moreover, current findings indicate the urgent need for further alternative agents in order to achieve a perceptible improvement of quality of life of patients with moderate-to-severe AD.

Subcortical gray matter atrophy is associated with cognitive deficit in multiple sclerosis but not in systemic lupus erythematosus patients.

Cognitive impairment is a significant clinical problem both in multiple sclerosis (MS) and systemic lupus erythematosus (SLE) patients. In MS cognitive dysfunction has been associated with brain atrophy and total demyelinating lesion volume. In SLE cognitive impairment is much less understood, and its link to structural brain damage remains to be established. The aim of this study was to identify the relationship between subcortical gray matter volume and cognitive impairment in MS and SLE. We recruited 37 MS and 38 SLE patients matched by age, disease duration and educational level. Patients underwent magnetic resonance imaging (MRI) and a battery of psychometric tests. Severity of cognitive impairment was similar in both cohorts despite larger white matter lesion load in MS patients. Psychometric scores were associated with global and subcortical gray matter atrophy measures and lesion load in MS, but not in SLE. In SLE, the lack of a relationship between cognitive impairment and structural damage, defined either as atrophy or white matter lesions, indicates a different causal mechanism of cognitive deficit.

Distinct regional brain atrophy pattern in multiple sclerosis and neuropsychiatric systemic lupus erythematosus patients.

Differentiation of systemic lupus erythematosus (SLE) from multiple sclerosis (MS) can be challenging, especially when neuropsychiatric (NP) symptoms are accompanied by white matter lesions in the brain. Given the lack of discriminative power of currently applied tools for their differentiation, there is an unmet need for other measures that can aid in distinguishing between the two autoimmune disorders. In this study we aimed at exploring whether brain atrophy measures could serve as markers differentiating MS and SLE. Thirty-seven relapsing-remitting MS and 38 SLE patients with nervous system manifestations, matched according to age and disease duration, underwent 1.5 Tesla magnetic resonance imaging (MRI), including volumetric sequences, and clinical assessment. Voxelwise analysis was performed using ANTS-SyN elastic registration protocol, FSL Randomise and Gamma methods. Cortical and subcortical segmentation was performed with Freesurfer 5.3 pipeline using T1-weighted MPRAGE sequence data. Using MRI volumetric markers of general and subcortical gray matter atrophy and clinical variables, we built a stepwise multivariable logistic diagnostic model to identify MRI parameters that best differentiate MS and SLE patients. We found that the best volumetric predictors to distinguish them were: fourth ventricle volume (sensitivity 0.86, specificity 0.57, area under the curve, AUC 0.77), posterior corpus callosum (sensitivity 0.81, specificity 0.57, AUC 0.68), and third ventricle to thalamus ratio (sensitivity 0.42, specificity 0.84, AUC 0.65). The same classifiers were identified in a subgroup analysis that included patients with a short disease duration. In MS brain atrophy and lesion load correlated with clinical disability, while in SLE age was the main determinant of brain volume. This study proposes new imaging parameters for differential diagnosis of MS and SLE with central nervous system involvement. We show there is a different pattern of atrophy in MS and SLE, and the key structural volumes that are differentially affected include fourth ventricle and posterior section of corpus callosum, followed by third ventricle to thalamus ratio. Different correlation patterns between volumetric and clinical data may suggest that while in MS atrophy is driven mainly by disease activity, in SLE it is mostly associated with age. However, these results need further replication in a larger cohort.

H1-antihistamine-refractory chronic spontaneous urticaria: it's worse than we thought - first results of the multicenter real-life AWARE study.

BACKGROUND: Most data on chronic spontaneous urticaria (CSU) originate from highly selected patient populations treated at specialized centres. Little is known about CSU patient characteristics and the burden of CSU in routine clinical practice. AWARE (A World-wide Antihistamine-Refractory chronic urticaria patient Evaluation) is an ongoing global study designed to assess chronic urticaria in the real-life setting. OBJECTIVE: To describe the baseline characteristics of the first 1539 German AWARE patients with H1-antihistamine-refractory CSU. METHODS: This prospective non-interventional study included patients (18-75 years) with a diagnosis of H1-antihistamine-refractory CSU for > 2 months. Baseline demographic and disease characteristics, comorbidities, and pharmacological treatments were recorded. Quality of life (QoL) was assessed using the dermatology life quality index (DLQI), chronic urticaria QoL questionnaire (CU-Q2 oL), and angioedema QoL questionnaire (AE-QoL, in cases of angioedema). Previous healthcare resource utilization and sick leave data were collected retrospectively. RESULTS: Between March and December 2014, 1539 patients were assessed in 256 sites across Germany. The percentage of females, mean age, and mean body mass index were 70%, 46.3 years, and 27 kg/m2 , respectively. The mean urticaria control test score was 7.9, one in two patients had angioedema, and the most frequent comorbidities were chronic inducible urticaria (CIndU; 24%), allergic rhinitis (18.2%), hypertension (18.1%), asthma (12%), and depression (9.5%). Overall, 57.6% of patients were receiving at least one pharmacological treatment including second-generation H1-antihistamines (46.3%), first-generation H1-antihistamines (9.1%), and corticosteroids (15.8%). The mean DLQI, total CU-Q2 oL, and total AE-QoL scores were 8.3, 36.2, and 46.8, respectively. CSU patients reported frequent use of healthcare resources, including emergency services (29.7%), general practitioners (71.9%), and additional allergists or dermatologists (50.7%). CONCLUSIONS AND CLINICAL RELEVANCE: This study reveals that German H1-antihistamine-refractory CSU patients have high rates of uncontrolled disease, angioedema, and comorbid CIndU, are undertreated, have impaired QoL, and rely heavily on healthcare resources.

The improvement of hirsutism and the decrease of testosterone concentration in the peripheral blood serum after removing an endometrioid ovarian cyst.

The study describes the case of a patient, in which as a result of removing an endometrioid ovarian cyst, there was an improvement as regards hirsutism and the decrease of testosterone concentration in the serum of peripheral blood.

Depressive symptoms' pattern in postmenopausal women.

The study was conducted to elucidate the problem of depressive symptoms' pattern in climacteric women. The study included 128 postmenopausal women aged 47-65 years admitted to the Department of Gynecological Endocrinology, Poznan University of Medical Science because of climacteric symptoms. The authors assessed the intensity of climacteric symptoms with the Kupperman index and the severit of depressive symptoms with the Hamilton depression scale. They measured BMI of all studied women. The average score of the Hami ton scale in the studied group was 11 points (SD ± 7 points). No depressive symptoms were found in 40 (31.2%) of the study participants. A slight increase in the severity of the depression symptoms was found in 64 (50%) and 23 (29.9%) displayed depressive symptoms at moderate severity, while one (1.3%) study participant was diagnosed with very severe depressive symptoms. Depressive symptoms observe most often were: somatic symptoms of anxiety and fear experienced in 90 (70.2%), light and interrupted sleep reported in 88 (68.6%), an general symptoms in 88 (68.6%) of the study participants.

The genetic background of climacteric symptoms in women during menopause.

The subject of the study is the evaluation of the correlation between the polymorphism of candidate genes in the etiology of depression and the occurrence of the symptoms of the climacteric syndrome in women during menopause. The group subjected to the study comprised of 203 women aged between 42-65 years: 71 of them still menstruated (premenopausal group) and 132 at least one year after the last period (postmenopausal group), admitted to the Department of Gynecological Endocrinology at the University of Medical Sciences in Poznan with symptoms of the climacteric syndrome All the examined women were evaluated according to the degree of severity of the climacteric syndrome symptoms using the Kupperman index and the concentration of FSH, LH hormones, 17ß-estradiol, PRL, total testosterone, and DHEAS in peripheral blood serum. Among the candidate genes in the aetiology of depression the following were selected for the research: the serotonergic system receptor genes: 5HTR2A, 5HTR1B, 5HTR2C, TPH 1, TPH2, and MAO-A; the genes of noradrenergic and dopaminergic systems (COMT, NET), the genes of the GABAergic (GABRBl) system, a gene of the estrogen receptor (ESR1), and the genes of the enzymes crucial in the methyl cycle (MTHRF, MTR, and MTHFD1). With regards to the correlation between the examined polymorphisms and the occurrence of the symptoms of the climacteric syndrome, the associations analysis indicated a connection between GABRBl.TaqI polymorphism and the occurrence of vertigo in premenopausal women (0.0198; after correction: 0.0497 CC to CA). The correlation was also found regarding the examined polymorphisms and the concentration of the examined hormones in blood serum: TPH1.MaeI polymorphism and the LH concentration in the postmenopausal group (0.004; after correction: 0.014 CC to CA), NET.Eco1471 polymorphism, and the 17ß-estradiol concentration in the postmenopausal group (0.0208; after correction: 0.048 GG to GA) and HTR2AMspI polymorphism and PRL concentration in all examined women (0.03; after correction: 0.038 TT to CT).

Pregnancy after ovarian wedge resection in a polycystic ovarian patient after laparoscopic ovarian cauterization.

The authors present a case of a pregnancy after ovarian wedge resection by laparotomy after unsuccessful ovarian drilling. A 28-year- old patient was admitted to the present outpatient clinic because of infertility, secondary amenorrhea, and hirsutism. Three years prior she had undergone laparoscopic ovarian drilling with no effect on menstrual pattern and fertility. After clinical and ultrasonographic ex- aminations, polycystic ovarian syndrome (PCOS) was diagnosed and consequently laparotomy with ovarian wedge resection was de- cided upon. Six weeks later patient was diagnosed with an early pregnancy.

Functional genomics in mice by tagged sequence mutagenesis.

Most mammalian genes will soon be characterized as cDNA sequences with little information about their function. To utilize this sequence information for large-scale functional studies, a gene trap retrovirus shuttle vector has been developed to disrupt genes expressed in murine embryonic stem (ES) cells. A library of mutant clones was isolated, and regions of genomic DNA adjacent to 400 independent provirus inserts were cloned and sequenced. The flanking sequences, designated 'promoter-proximal sequence tags', or PSTs, identified 63 specific genes and anonymous cDNAs disrupted as a result of virus integration. The efficiency of tagged sequence mutagenesis suggests that many of the 10,000-20,000 genes expressed in ES cells can be targeted, providing defined mutations for the analysis of gene functions in vivo. In addition, PSTs provide the first expressed sequence tags derived from genomic DNA, and define gene features such as exon boundaries and promoters that are missing from cDNA sequences.

A narrative review on the non-surgical treatment of chronic postoperative inguinal pain: a challenge for both surgeon and anaesthesiologist.

INTRODUCTION: Chronic pain is one of the most frequent clinical problems after inguinal hernia surgery. Despite more than two decades of research and numerous publications, no evidence exists to allow for chronic postoperative inguinal pain (CPIP) specific treatment algorithms. METHODS: This narrative review presents the current knowledge of the non-surgical management of CPIP and makes suggestions for daily practice. RESULTS: There is a paucity for high-level evidence of non-surgical options for CPIP. Different treatment options and algorithms have been published for chronic pain patients in the last decades. DISCUSSION AND CONCLUSION: It is suggested that non-surgical treatment is introduced in the management of all CPIP patients. The overall approach to interventions should be pragmatic, tiered and multi-interventional, starting with least invasive and only moving to more invasive procedures upon lack of effect. Evaluation should be multidisciplinary and should take place in specialized centres. We strongly suggest to follow general guidelines for treatment of persistent pain and to build a database allowing for establishing CPIP specific evidence for optimal analgesic treatments.

Are endocannabinoid type 1 receptor gene (CNR1) polymorphisms associated with obesity and metabolic syndrome in postmenopausal Polish women?

OBJECTIVE: The aim of this study was to determine whether genetic variation at the cannabinoid receptor-1 (CNR1) locus could have an effect on adiposity, fat distribution and obesity-related metabolic disorders in Polish postmenopausal women. DESIGN AND SUBJECTS: The A3813G (rs12720071), G1422A (rs1049353), A4895G (rs806368) and rs806381, rs10485170, rs6454674 and rs2023239 single-nucleotide polymorphisms of CNR1 were genotyped in 348 randomly selected postmenopausal women aged 50-60 years recruited from the Wroclaw city population. MEASUREMENTS: CNR1 genotypes, anthropometric measures (body mass index (BMI), waist circumference (WC) and body fat distribution by dual energy X-ray absorptiometry) and metabolic parameters (glucose, lipid profile and Fasting Insulin Resistance Index for insulin resistance) were determined. RESULTS: The 3813G allele was not significantly associated with higher body mass, BMI, WC, total fat or fat percentage, but was associated with higher android fat deposit (2971.78±1655.08 vs 2472.64±1300.53, P=0.007) and percentage of android fat (37.59±8.45 vs 35.66±7.63, P=0.062). No associations for the G1422A, A4895G, rs806381, rs10485170, rs6454674 and rs2023239 variants were observed. CONCLUSIONS: There is an association of the variants of CNR1 with obesity-related phenotypes in Polish postmenopausal women. As cannabinoid receptor type 1 is a drug target for obesity, pharmacogenetic receptor gene analysis of obesity treatment by endocannabinoid blockade may be of interest to identify the best responders.

Algorithm for management of an incarcerated inguinal hernia in the emergency settings with manual reduction. Taxis, the technique and its safety.

BACKGROUND: An acute inguinal hernia remains a common emergency surgical condition worldwide. While emergency surgery has a major role to play in treatment of acute hernias, not all patients are fit for emergency surgery, nor are facilities for such surgery always available. Taxis is the manual reduction of incarcerated tissues from the hernia sack to its natural compartment, and can help delay the need for surgery from days to months. The aim of this study was to prepare a safe algorithm for performing manual reduction of incarcerated inguinal hernias in adults. METHODS: Medline, Scopus, Ovid and Embase were searched for papers related to emergency inguinal hernias and manual reduction. In addition, the British National Formulary and Safe Sedation Practice for Healthcare Procedures: Standards and Guidance were reviewed. RESULTS: A safe technique of manual reduction of an acute inguinal hernia, called GPS (Gentle, Prepared and Safe) Taxis, is described. It should be performed within 24 h from the onset of a painful irreducible lump in groin, and when concomitant symptoms and signs of bowel strangulation are absent. Conscious sedation guidelines should be followed. The most popular drug combination is of intravenous morphine and short-acting benzodiazepine, both titrated carefully for optimal and safe effect. The dose of drugs must be individualised, and the smallest effective dosage should be used to avoid oversedation. Following successful taxis, the patient should undergo a short period of observation. Urgent surgery can be undertaken during the same admission or up to several weeks later. CONCLUSIONS: Taxis is a benign/non-invasive method for patients with an acute, non-strangulated inguinal hernias. It likely reduces the risk and complications of anaesthesia and surgery in the emergency settings. GPS Taxis should be considered as first line treatment in the majority of patients presenting with an acute inguinal hernia when existing bowel infarction is unlikely.

The darn technique for small (< 2 cm diameter) midline hernias.

PURPOSE: Primary midline hernias arising in the linea alba are common. While mesh repair has been shown to reduce recurrence rates even in small hernias, many surgeons still use a suture repair for defects of less than 2 cm. The recent European and Americas Hernia Societies Guidelines recommended suture repair only for hernias smaller than 1 cm. A suture repair implies edge-to-edge or overlapping fascial margins, which necessarily involves tension on the repair. A darn is a tension-free repair where, in effect, a "mesh" is hand-woven across the defect in situ. METHODS: The darn repair is a modification of the darn techniques for inguinal hernia repair. Eligible patients undergoing this repair at the Royal Infirmary of Edinburgh between 1 January 2008 and 31 December 2017 were identified from a prospective computer-based medical record system and their case notes reviewed. Inclusion criteria were adult patients with a primary midline abdominal wall defect smaller than 2 cm in the widest diameter of the hernia defect measured intra-operatively. Patients were followed up by telephone in 2019. Those who reported possible recurrence or other symptoms in the region of their hernia repair were reviewed in the outpatient clinic. RESULTS: 47 suture-darn repairs were undertaken over the 10-year period. Fifteen of the darn repair operations (32%) were performed under local anaesthesia. Forty-one patients were followed up with a mean of 80 ± 35 and median of 87 months after surgery. Six patients (13%) were lost to follow-up. Recurrence was found in two cases (5%) and one patient has since been diagnosed with a new epigastric hernia some 5 cm cranial to the previous repair. CONCLUSIONS: The darn repair for small primary midline hernias is quick and inexpensive with promising long-term results. It can be performed under local anaesthesia. It can serve as an alternative to mesh repair for defects less than 2 cm in maximum dimension.

Current trends in hernia surgery in NHS England.

BACKGROUND: Mesh is recommended for the repair of most hernias when prevention of recurrence is the primary endpoint. However, mesh may be associated with increased complications for the patient. The aim of this study was to quantify the use of mesh for abdominal wall hernia surgery in NHS England in recent years. MATERIALS AND METHODS: The NHS Digital Secondary Uses Service database for 2016/17 and 2017/18 was interrogated for numbers of patient undergoing elective primary hernia surgery. Using the specific hernia code inguinal (T201-9), umbilical (T241-9), incisional (T251-9) and other abdominal wall hernia (T271-9), the use of mesh or suture repair was determined. Recurrent and emergency hernia surgery were excluded. All data were provided by NHS RightCare. RESULTS: There are almost 100,000 hernia repairs performed annually in NHS England. For every four hernias, three are repaired with mesh. The percentage repaired by mesh varies by hernia type. Mesh repairs in inguinal, umbilical and incisional hernias accounted for 95%, 50% and 82%, respectively. CONCLUSIONS: Mesh repair for all hernia types is more common than suture repair. However, for umbilical and other abdominal wall hernias, a significant proportion are repaired without the use of mesh.

A manual reduction of hernia under analgesia/sedation (Taxis) in the acute inguinal hernia: a useful technique in COVID-19 times to reduce the need for emergency surgery-a literature review.

BACKGROUND: Acute IH is a common surgical presentation. Despite new guidelines being published recently, a number of important questions remained unanswered including the role of taxis, as initial non-operative management. This is particularly relevant now due to the possibility of a lack of immediate surgical care as a result of COVID-19. The aim of this review is to assess the role of taxis in the management of emergency inguinal hernias. METHODS: A review of the literature was undertaken. Available literature published until March 2019 was obtained and reviewed. 32,021 papers were identified, only 9 were of sufficient value to be used. RESULTS: There was a large discrepancy in the terminology of incarcerated/strangulated used. Taxis can be safely attempted early after the onset of symptoms and is effective in about 70% of patients. The possibility of reduction en-mass should be kept in mind. Definitive surgery to repair the hernia can be delayed by weeks until such time as surgery can be safely arranged. CONCLUSIONS: The use of taxis in emergency inguinal hernia is a useful first line of treatment in areas or situations where surgical care is not immediately available, including the COVID-19 pandemic. Emergency surgery remains the mainstay of management in the strangulated hernia setting.

Correction to: European Hernia Society (EHS) guidance for the management of adult patients with a hernia during the COVID­19 pandemic.

The originally published article: The surname and given name of authors, M. Pawlak and A.C. de Beaux has been incorrectly published.

Is sharing speaker's slides from conference presentations on social media a breach of intellectual property or a delegate's right? Depends who you ask.

BACKGROUND: The contemporary practice of the sharing of speaker's slides from medical conference presentations is common but raises a number of complex ethical and legal questions. We investigated the views of a large group of international hernia surgeons to evaluate the comtemporary view on this topic. METHODS: A questionnaire was widely promoted on Twitter and distributed by email to target the membership of the British and European Hernia Societies. Demographics and responses were recorded. RESULTS: There were 185 respondents; 68 BHS email (37%), 76  EHS email (41%) and 41 respondents via Twitter (22%). 49 (34%) society members used social media for professional communication. 23 (56%) of Twitter respondents had posted speakers slides versus 5 (12%) from society members email respondents. A majority of respondents held the view that either the specific congress (37%) or individual speakers (24%) should set the rules on the distribution of speakers slides explicitly. 10 (24%) of Twitter respondents felt that sharing content violated intellectual property compared to 88 (61%) of email respondents. CONCLUSION: Contemporary opinion regarding this subject differs depending on the modality of questionnaire and population interrogated. Respondents who use social media in their professional practice are more comfortable with the practice of sharing speaker's slides. Whilst, the sharing of speaker's slides is legal in Europe, but it may be good practice to seek consent and acknowledge the author in any communication.