Effects of neurodevelopmental risk factors on brainstem maturation in premature infants.

BACKGROUND: Interpeak latencies (IPL), as measured by the auditory brainstem-evoked responses (ABR) test, represent the conduction time, and therefore the maturation of the brainstem auditory pathway. We aimed to study the effect of various risk factors for the neurodevelopmental delay on the conduction time in the auditory pathway among normal hearing premature infants, at term postmenstrual age (PMA). METHODS: Retrospective analysis of 239 premature infants (gestational age 32.5 ± 2.1 weeks, birth weight 1827 ± 483 g). Interpeak latencies, demographic data, and risk factors were recorded. RESULTS: Sex, PMA at ABR test, being small for gestational age (SGA), intraventricular hemorrhage (IVH) or periventricular leukomalacia (PVL), and days of invasive ventilation were found to significantly affect the IPL's in the auditory pathway in a univariate analysis. Multivariable regression analysis revealed that male sex and less advanced PMA at the examination were independent factors associated with prolonged IPL's, while bronchopulmonary dysplasia, IVH or PVL and being SGA shortened the IPL's. Non-invasive mechanical ventilation, did not affect the caudal part of the auditory pathway, despite its high noise level. CONCLUSIONS: Among various risk factors for the neurodevelopmental delay, male sex was associated with delayed, while IVH or PVL, BPD and SGA could be associated with accelerated auditory brainstem maturation. IMPACT: Auditory brainstem-evoked response (ABR) test, among normal hearing infants, can serve as a clinical tool to assess brainstem auditory maturation. Different neurodevelopmental risk factors could have different effects on the maturity of the auditory pathway. Male sex is significantly associated with prolonged interpeak latencies (IPL) among preterm and term infants, while intraventricular hemorrhage or periventricular leukomalacia, bronchopulmonary dysplasia, and being small for gestation age may be associated with shortened IPL The corrected age at ABR testing is of significance, among preterm and term infants.

Three-dimensional histology vs. serial section histology in the treatment of primary basal cell carcinoma: a randomized, prospective, blinded study of 569 tumours.

BACKGROUND: For basal cell carcinoma (BCC), only few controlled data have been published so far, which directly compare micrographically controlled surgery with conventional serial section histology. In addition to Mohs surgery, which uses cryostat sections, also three-dimensional histology (3D-histology), based on paraffin sections, is available to ensure complete control of the margins and basic sections. OBJECTIVES: To investigate the rate of local recurrence (LR) as well as the number of required re-excisions for basal cell carcinomas with serial section histology vs. 3D-histology. METHODS: We compared serial sections histology with 3D-histology in a prospective, randomized, controlled blinded trial and analysed 569 BCC of all subtypes up to 30 mm diameter, 287 BCC in the 3D group and 282 BCC in the serial section group. Excisions were performed with adapted primary resection margin according to location and size of the tumour. Surgeons were blinded at the time of surgery as they did not know which histological method will be used. Both methods used paraffin sections. RESULTS: Both groups did not differ regarding patients age, tumour location, tumour diameter, tumour subtypes or primary resection margins. In the serial section group, re-excisions were required in 21%; 24 tumours (8.4%) recurred after a median of 2.2 years. In the 3D-histology group, re-excisions were required in 39%; 10 tumours recurred (3.5%) after a median of 2.8 years. The recurrence rates differed significantly between both groups. Mean follow-up was 4.5 years. CONCLUSIONS: 3D-histology is a useful technique to detect tumour outgrowths at the excision margins, but required a high rate of re-excisions. 3D-histology was associated with a significantly lower LR rate than serial section histology.

[Infiltration of the skull by dedifferentiated cutaneous leiomyosarcoma]. / Infiltration der Schädelkalotte durch ein dedifferenziertes kutanes Leiomyosarkom.

We present a brief report of an 81-year-old man with a pretreated leiomyosarcoma of the skull. Histologically the diagnosis of a dedifferentiated cutaneous leiomyosarcoma with an infiltration of the skull was confirmed. In an interdisciplinary approach together with the University Clinic for Neurosurgery, complete removal of the tumour was performed. Cutaneous leiomyosarcoma are rare tumors of the skin and typically present as slowly growing erythematosus nodes. Because of the risk of metastatic spread, complete micrographically confirmed resection is necessary.

[Bernhard von Gudden's psychiatric assessment and the deposition of King Ludwig II of Bavaria in 1886 : Comments on the article by R. Steinberg in Der Nervenarzt 01/2019]. / Das psychiatrische Gutachten Bernhard von Guddens und die Entmachtung König Ludwigs II. von Bayern 1886 : Ein Kommentar zum Beitrag von R. Steinberg in Der Nervenarzt 01/2019.

King Ludwig II of Bavaria drowned himself in Lake Starnberg on 13 June 1886 after subduing and drowning Bernhard von Gudden, a Munich-based psychiatrist who had tried to hold him back. Commissioned by Prince Luitpold, Ludwig's successor to the throne, von Gudden had provided a psychiatric assessment on the king. Finding him to be suffering from a progressive mental illness and paranoia (madness), he declared Ludwig incapable of ruling. On the basis of this report Ludwig was unlawfully declared incapacitated, deposed, arrested and locked up in the Berg Castle under von Gudden's medical supervision. We conducted a 5-year psychiatric historical study of King Ludwig II, the most thorough of its kind ever undertaken. The main results were: the private, official and political letters the king wrote until his very last day were reasonable, well-argued and impeccable in style. Until his final days Ludwig had invariably fulfilled his administrative tasks in a prompt and proper way. His handling of political affairs was also wise and reasonable. Due to social phobia afflicting him since his youth he neglected his representative duties as a monarch. Von Gudden's report is marred by severe flaws. In his article published in Der Nervenarzt (01/2019) R. Steinberg adopts von Gudden's psychiatric diagnosis and misjudgement. Steinberg writes that the king's illness developed "in a clear crescendo". In fact, it was the behavioral anomalies associated with the king's homosexual relationships that grew increasingly prevalent at the court, whereas Ludwig's mental efficiency improved over time. Given the historical misjudgment and numerous other errors that Steinberg adopts from von Gudden, I considered it necessary to compare and contrast his conclusions with results from our own research.

Surgical treatment of hidradenitis suppurativa: an analysis of postoperative outcome, cosmetic results and quality of life in 255 patients.

BACKGROUND: Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease with increasing incidence. Severe disease stages are seen as a therapeutic challenge and pose the threat of significant restrictions on patients' life quality. OBJECTIVES: We evaluated postoperative outcome after wide local excision for HS as well as postoperative course, cosmetic results, disease recurrence and quality of life. METHODS: All patients receiving radical surgical treatment for HS (Hurley III) between 2006 and 2015 were identified and received a letter-based survey. They were asked about postoperative course, cosmetic results, recurrence and life quality. RESULTS: Two hundred and fifty-five patients (103 men, 152 women) answered the questionnaire. Ninety-five percentage of patients reported disease-specific restrictions on everyday life. Seventy-five percentage of patients did not experience any postoperative adverse events; however, postoperative pain with need for analgesics was reported in 38%. The majority of patients (80%) were very satisfied or satisfied after surgery, and 85% of patients would recommend surgery to other affected persons. LIMITATIONS: The retrospective design of the study was a limitation. CONCLUSIONS: The well-known negative psychological and social effects are a relevant part of HS and emphasize the importance of immediate therapy. As long-lasting local disease-control can be achieved, surgery should be considered as first-line therapy.

Tumescent local anaesthesia for early dermatosurgery in infants.

BACKGROUND: Early paediatric dermatosurgery reveals excellent cosmetic results due to high skin elasticity and pronounced capacity to recover from trauma. Furthermore, the size of skin lesions increases during life proportionally to skin growth and therefore early removal is of major importance. Selected local anaesthetics like prilocaine can cause methaemoglobinemia. However, in contrast to general anaesthesia, many other local anaesthetics do not bare any major risks for infants. OBJECTIVE: In this retrospective study, we analysed infants aged less than 7 months receiving tumescent local anaesthesia (TLA) followed by dermatosurgery at our department between 2005 and 2015. The analysis is mainly based on our records. Additional information for a subset of patients was gained by a postoperative survey. METHODS: Ninety-two infants (39 male, 53 female) with a median age of 4.2 months (range: 1.5 months; 6.7 months) were included in this study. Additional postoperative information was available for 33 of the 92 studied patients (35%). RESULTS: Infants were mainly operated for removal of a melanocytic naevus (n = 54), followed by haemangioma (n = 23), naevus sebaceous (n = 6) and other lesions (n = 9). The lesions were located on the scalp or neck (n = 31), on the extremities (n = 31), on the trunk (n = 21), in the face (n = 6) or on the buttocks (n = 3). The median size of excision was 509 mm2 (range: 16 mm2 ; 3600 mm2 ). Primary defect closure was performed by intracutaneous (n = 68) or extracutaneous (n = 24) suture techniques. No side-effects of local anaesthesia were observed in any patient. Postoperative complications include pain (1/33; 3%), wound-healing disorder (1/33; 3%) and visible severe scarring (2/33; 6%). CONCLUSIONS: The combination of TLA and dermatosurgery in infants is a suitable outpatient treatment option for small lesions without any major risks or side-effects and the benefit of prolonged postoperative analgesia.

[Concept and results of the German Research Network on Schizophrenia]. / Konzept und Ergebnisse des Kompetenznetzes Schizophrenie.

BACKGROUND: The German Research Network on Schizophrenia (GRNS) was funded by the Federal Ministry of Education and Research (BMBF) from 1999 to 2011. The aim was to obtain a better horizontal and vertical networking of German research and care facilities on schizophrenia, in order to investigate open research questions, to transfer the results into clinical practice and improve care and quality of life in patients with schizophrenia. OBJECTIVES/METHODS: This paper describes the concept and operations of the GRNS as well as its results on the basis of selected research projects. RESULTS: The GRNS comprised about 25 clinical trials of high practical relevance, which were closely interrelated regarding content, methodology and organization. The trials primarily served the development and evaluation of new and established diagnostic and therapeutic approaches, the assessment of the status quo of clinical care, as well as its improvements, together with the investigation of basic scientific questions. Many substantial results to highly relevant issues were obtained, which led or will lead to an improvement in mental health care. CONCLUSIONS: Quantitative and qualitative evaluation parameters, such as scientific publications and obtaining additional grants, as well as promotion of young scientists, public relations activities, congress activities and the foundation of a European Schizophrenia Association, document the successful work of the network. Successful funding requests will allow us to continue cooperative schizophrenia research in Germany as initiated by the GRNS, without necessarily always binding these activities formally to the GRNS.

Reduction of central venous line-associated bloodstream infection rates by using a chlorhexidine-containing dressing.

PURPOSE: The reduction of central venous line (CVL)-associated bloodstream infections (CLABSIs) is generally advocated. However, despite implementing infection prevention recommendations, CLABSI rates remain high at some institutions. Therefore, a chlorhexidine-containing dressing should be assessed for its potential for infection reduction, adverse events (AEs) and practicability. METHODS: The number of CVLs, CVL days, CLABSIs and CLABSI rates with regard to the kind of dressing (standard vs. chlorhexidine-containing) were documented from November 2010 to may 2012 (1,298 patients with 12,220 CVL days) at two intensive care units (ICUs) and compared to historical controls. The practicability and safety of the chlorhexidine-containing dressing and reasons for not using this dressing were assessed. RESULTS: Forty CLABSIs occurred in 34 patients, resulting in a significantly lower overall CLABSI rate in patients with the chlorhexidine-containing dressing [1.51/1,000 CVL days; confidence interval (CI): 0.75-2.70] compared to patients with the standard dressing (5.87/1,000 CVL days; CI: 3.93-8.43; p < 0.0001). The CLABSI rate in historical controls receiving the standard dressing was 6.2/1,000 CVL days. The main reason for not using chlorhexidine-containing dressing was bleeding at the insertion site. AEs occurred in five patients and represented self-healing skin macerations (3 cases) and superficial skin necrosis (2 cases). CONCLUSIONS: In case of high CLABSI rates despite the implementation of standard recommendations, our findings suggest that a chlorhexidine-containing dressing safely decreases CLABSI rates.

Quality of life in men with involuntary childlessness: long-term follow-up.

We conducted a longitudinal cohort study on the quality of life of infertile male patients measured at baseline and after 5 years with a specific quality of life instrument for male patients who are involuntarily childless. It was distributed to patients who were seen at the andrology and gynaecology clinics for infertility diagnoses and treatment. At baseline (T1), 275 patients took part in the study. A subset of these patients (N = 133) had released two semen samples, and the results of the semen analysis had been communicated to them before they received the questionnaire. Semen quality of this subset was assessed according to WHO recommendations. After 5 years (T2), the questionnaires were mailed again and were sent back by N = 101 patients. No significant quality of life difference was found between the semen quality groups. After 5 years, an improvement was found for the dimensions 'desire for a child' [mean score 1.92 (T1) versus 1.72 (T2)] and 'gender identity' [mean score 1.56 (T1) versus 1.42 (T2)] while no change was found for 'partnership' and 'psychological well-being'. We did not find significant differences between patients who had fathered a child in the meantime and patients who did not become fathers.

[Genetic basis of seborrheic keratosis and epidermal nevi]. / Genetische Grundlagen seborrhoischer Keratosen und epidermaler Nävi.

Seborrheic keratosis (SK) and epidermal nevi (EN) represent benign skin tumors and congenital lesions, respectively. Oncogenic mutations are fundamentally involved in their pathogenesis and SK is characterized by a broad spectrum of somatic mutations in the FGFR3, PIK3CA, RAS, AKT1 and EGFR genes. In contrast to malignant tumors, SK is genetically stable without alterations of tumor suppressor genes. The ENs are caused by postzygotic activating hot spot mutations in FGFR3, PIK3CA and particularly HRAS, resulting in a genetic mosaicism. The size of the lesions and the differentiation potential of the mutated cell into various tissue types depends on the time point of the mutation during embryogenesis. The genetic mosaic may predispose to a later growth of benign and malignant (adnexal) tumors.

[12 years of competence network schizophrenia: results and perspectives]. / 12 Jahre Kompetenznetz Schizophrenie: Ergebnisse und Perspektiven.

The German Research Network on Schizophrenia (GRNS) was funded by the Federal Ministry of Education and Research (BMBF) from 1999 to 2011. The objectives and the structure of the network with its horizontal and vertical networking of German research and care facilities served for the scientific investigation of open research questions for schizophrenia, and the transfer of the results into clinical practice. In this paper, the functioning and results of the GRNS are described on the basis of selected research projects. Quantitative and qualitative evaluation parameters such as scientific publications and additional external funds, as well as promotion of young scientists, public relations activities, congress activities and foundation of an European Schizophrenia Association demonstrate the successful work of the network. As a final point, the funding programme of the BMBF is critically evaluated using the example of the GRNS and future funding prospects are outlined.

Long-term sustainability of hand hygiene improvements in the hemodialysis setting.

PURPOSE: In a previous observational intervention study, we achieved a more than 100 % increase in overall hand hygiene (HH) compliance in the hemodialysis setting by increasing the number of hand rubs (HR) performed and concomitantly optimizing HH standard operating procedures (SOPs). SOPs were mainly aimed at reducing the number of avoidable opportunities due to a less than perfect workflow. However, the long-term sustainability of this successful intervention was not evaluated. The present study was carried out to evaluate the long-term effects of our previous successful intervention. METHODS: We conducted a follow-up observational study 1 year after the first intervention study in the same hemodialysis unit to assess the sustainability. No HH-related interventions were performed in the 1 year between studies. The main outcome was HH compliance, and the secondary outcome was opportunities per hemodialysis procedure. RESULTS: A total of 1,574 opportunities for HH and 871 hand rubs (HR) were observed during the follow-up observational study. Overall, compliance was 55 %, which was significantly than that at the end of the first study (62 %; p < 0.0001), but significantly higher than that at the start and mid-term phases of the first study (37 and 49 %, p < 0.0001). Both the decrease in HH opportunities and the increase in HR were sustained over the course of this observational study. The number of avoidable opportunities in the present study was similar to that at the end of the previous study. Thus, in 320 opportunities (20 %), gloves were worn instead of HR performed, representing 46 % of all missed HR. CONCLUSIONS: Despite a decrease in HH compliance compared to the last postintervention period, a multifaceted intervention focusing on standardization and workflow optimization resulted in a sustained improvement in HH. We therefore propose that standardization of the hemodialysis workflow aimed at improving HH is a promising avenue for improving the quality of patient care and outcome.

ABC Schizophrenia study: an overview of results since 1996.

PURPOSE: The ABC Schizophrenia study, led by a single research team, investigated a schizophrenia sample systematically over quarter of a century. This paper summarises results from 1996 onwards. The initial goals were to explain the considerably higher age at first admission in women, and to obtain precise information on the onset and early course of schizophrenia as a prerequisite for early intervention. METHOD: The study was hypothesis-driven. People with schizophrenia were compared in the prodrome and at first admission to those with unipolar depression and to healthy controls. We analysed the medium-term (5-year) and the long-term (12-year) course of schizophrenia, its symptom dimensions, social parameters and predictors. SAMPLES: (1) 276 population-based first admissions (232 first episodes) of schizophrenia (age range 12-59 years); (2) a subsample of 130 first admissions for schizophrenia; (3) 130 first admissions for unipolar depression; (4) 130 healthy population controls and (5) 1,109 consecutive first admissions for schizophrenia spectrum disorder without an age limit. RESULTS: The prodromal stages of schizophrenia and depression were very similar until positive symptoms appeared. The most frequent symptom in schizophrenia was depressed mood. The course of psychosis from prodrome to 12 years following first admission was very variable. From 5 to 12 years after first admission the course was characterised by irregular exacerbations of the main symptom dimensions, with no overall deterioration or improvement. CONCLUSIONS: Schizophrenic psychosis and severe affective disorder, rather than representing discrete illnesses, probably mark different stages in the manifestation of psychopathology produced by various degrees of brain dysfunction.

[Surgical treatment of epithelial skin tumors and their precursors]. / Chirurgische Therapie der epithelialen Hauttumore und ihrer Vorstufen.

Squamous cell carcinomas of the skin and their precursors, actinic keratosis as well as basal cell carcinomas are classified as non-melanocytic skin cancer and belong to the group of epithelial skin tumors. This tumor entity is one of the most common forms of malignant cancer in western countries with an incidence of approximately 100-170 per 100,000 inhabitants per year in Europe. In German-speaking countries no exact numbers are available on the early forms of squamous cell carcinoma, actinic keratosis (carcinoma in situ); however, results from Great Britain show that at ages over 70 years old the prevalence of actinic keratosis is 34 % in men and 18 % in women. Because invasive epithelial cancer is very common and most commonly occurs in the head region, a safe but skin-sparing approach to surgical treatment is desirable. The safest procedure with respect to local recurrence is surgical excision with subsequent complete 3-dimensional histological preparation (micrographic surgery). With this method it is possible to excise tissue affected by tumor tissue in small steps. This facilitates defect coverage and leads to very good results as well as good esthetic results. The local recurrence rates are extremely low compared to alternative treatment methods, such as photodynamic therapy, topical application of imiquimod or cryosurgery and for the treatment of basal cell carcinoma, for example is 0.7 %. Dermatological operations are therefore interventions with a very high guarantee of tumor-free survival and functional and esthetic results.

[Karl Jaspers. 100 years of "Allgemeine Psychopathologie" (General Psychopathology)]. / 　Karl Jaspers.100 Jahre "Allgemeine Psychopathologie".

With his "Allgemeine Psychopathologie" (general psychopathology) published in 1913, Karl Jaspers laid a comprehensive methodological and systematic foundation in psychiatry. Following Edmund Husserl, the founder of philosophical phenomenology, Jaspers introduced "static understanding" into psychopathology, i.e. the unprejudiced reproduction of conscious phenomena. From the philosopher Wilhelm Dilthey he further adopted the distinction between causal understanding as a means of accessing nature and pathological processes and hermeneutic understanding, also called genetic understanding, as a way of accessing mental phenomena. The intrusion of an event that is incomprehensible in terms of an understandable development is seen as indicating an extraconscious phenomenon or transition to a somatic process. Jaspers opted for philosophy early in his life. After quitting law studies he graduated in medicine, arrived in psychopathology without any psychiatric training, to psychology without ever studying psychology and to a chair in philosophy without a degree in philosophy. Despite believing himself to be chronically ill and to die early, Jaspers produced a life's work almost immeasurable in scope. He died in 1969 aged 86 years.

[Schizophrenia - a disorder in its own right?: results from 25 years of the ABC study]. / Schizophrenie - eine einheitliche Krankheit?: Ergebnisse aus 25 Jahren ABC-Studie.

BACKGROUND: The ABC schizophrenia study conducted by the same team over 25 years initially aimed at illuminating the onset, prodromal stage and sex differences in age at first hospitalization in schizophrenia. New hypotheses were systematically generated from the results achieved. METHODS: A population-based sample of 276 first admission cases (232 first episodes, age 12-59 years), including a subsample of 130 first admissions (115 first episodes), were assessed to study prodromal stage, first illness episode, medium and long-term course and symptom dimensions in schizophrenia. The samples were compared with age and sex-matched healthy controls and with patients first admitted for unipolar depression. A total of 1,109 consecutive first admissions for schizophrenia spectrum disorders independent from the other study samples were assessed to study changes in symptomatology across the age range. RESULTS: Before the onset of psychotic symptoms the prodromal stages of schizophrenia and severe and moderately severe depression are difficult to distinguish. The most frequent symptom in the course of schizophrenia, depressed mood, also represents the most frequent initial symptom in both disorders. Prodromal depression is a predictor of more depressive and positive symptoms in the first episode but not in the further course of the illness. Psychosis incidence for men, diagnosed according to ICD 9 (295, 297, 298.3/4), shows a pronounced peak at age 15-24 years, for women a lower peak at age 15-29 years and a second, still lower peak at the menopausal age of 45-49 years. The explanation, confirmed in animal experiments, lies in a protective effect of estrogen due to reduced D2 receptor sensitivity. The effect is antagonized by an elevated genetic risk. Functional and social impairment emerge even at the prodromal stage and the severity depends on sex and social status. Young men with schizophrenia show a less favorable social course because of the earlier age of onset and socially adverse illness behavior. Late onset is associated with a milder, primarily paranoid symptomatology and less severe social impairment. Schizophrenia is a disorder of all ages showing roughly equal life time incidence rates for men and women but considerable difference in certain periods of age. The symptom dimensions show a plateau-like course 2-5 years after the first episode. Hidden behind this picture are irregular symptom exacerbations which vary in duration. Schizophrenia conveys the picture of recurrent vulnerability to crisis and not of a stable residual state of disordered brain development or of a progressive neurodegenerative process.

Preventing progression to first-episode psychosis in early initial prodromal states.

BACKGROUND: Young people with self-experienced cognitive thought and perception deficits (basic symptoms) may present with an early initial prodromal state (EIPS) of psychosis in which most of the disability and neurobiological deficits of schizophrenia have not yet occurred. AIMS: To investigate the effects of an integrated psychological intervention (IPI), combining individual cognitive-behavioural therapy, group skills training, cognitive remediation and multifamily psychoeducation, on the prevention of psychosis in the EIPS. METHOD: A randomised controlled, multicentre, parallel group trial of 12 months of IPI v. supportive counselling (trial registration number: NCT00204087). Primary outcome was progression to psychosis at 12- and 24-month follow-up. RESULTS: A total of 128 help-seeking out-patients in an EIPS were randomised. Integrated psychological intervention was superior to supportive counselling in preventing progression to psychosis at 12-month follow-up (3.2% v. 16.9%; P = 0.008) and at 24-month follow-up (6.3% v. 20.0%; P = 0.019). CONCLUSIONS: Integrated psychological intervention appears effective in delaying the onset of psychosis over a 24-month time period in people in an EIPS.