[Findings from 10 years of CIRS-AINS : An analysis of usepatterns and insights into new challenges]. / Erkenntnisse aus 10 Jahren CIRS­AINS : Eine Analyse von Nutzerverhalten und Ausblick auf neue Herausforderungen.

BACKGROUND: Critical incident reporting systems (CIRS) serve to sensitize organizations and individuals to unknown events relevant to patient safety and therefore help in developing safer systems; however, the use and impact of these systems in healthcare has recently been questioned for a variety of reasons, among them unclear and imprecise reporting criteria. Some authors claim that fundamental aspects of successful CIRS have been misunderstood, misapplied or entirely missed during the adaptation to the healthcare context. The aim of this study was the analysis of all reports accumulated over 10 years in the German system CIRSmedical Anesthesiology (CIRS-AINS) as a basis for improved reporting guidelines, user training and generation of further hypotheses. METHODS: In a retrospective analysis all reports from CIRS-AINS entered between April 2010 and June 2019 were analyzed for structure and content. RESULTS: A total of 6013 reports were filed consisting of 3492 incidents (58.1%), 1734 near misses (28.8%) and 787 others (13.1%). Those other reports contained 21 interpersonal conflicts (0.4%), 102 general complaints (1.7%), 89 stress or workload complaints (1.5%) and 575 reports that did not contain any critical incident or safety-related content (9.6%). Since 2015 these other reports have increased 2.8-fold from 7.4% to 20.8%. Of the reports 20.1% contained information about technical problems and 27.7% about certified medical devices. Medication was mentioned in 10.7% of reports, 47.8% of inpatient incidents concerned the perioperative setting, 24.6% were reported from intensive care units (ICU) and postanesthesia care units (PACU). Of the cases 198 (3.3%) explicitly mentioned communication issues, 346 cases (5.8%) concerned incomplete or inadequate documentation involving orders, blood products or laboratory tests. Of the reports 36.1% were analyzed and commented on by the CIRS team of the German Society of Anesthesiologists (BDA). CONCLUSION: The analysis provides insights into reporting practices and can influence both reporting guidelines as well as user training. Report format, content and context are of utmost importance for further analysis: A distinction has to be made between reports that contain locally rational information and cannot be understood without further context and reports that may help inform about patient safety activities on a national level. Especially in light of the limited resources for incident analysis, the content should be critically reflected upon by the user when submitting a report to support a wise allocation of available capacities. In this respect, the increase of non-CIRS reports has to be considered in the future implementation of nationwide IRS. Also, it has to be questioned whether adequate alternative means of communication for these non-CIRS reports exist. The majority of reports were made by physicians, which is in contrast to international experiences with increased engagement of nursing staff and underlines the need for increased interprofessional collaboration with incident reporting and analysis activities in Germany. Reports containing workload complaints, while constituting important signals on a local level, usually fail to address the idea of learning from others inherent to the philosophy of national IRS.

Extension of the clinical and molecular phenotype of DIAPH1-associated autosomal dominant hearing loss (DFNA1).

In about 20% of non-syndromic hearing loss (NSHL) cases, inheritance is autosomal dominant (ADNSHL). DIAPH1 mutations define the ADNSHL locus DFNA1. We identified two new families with heterozygous truncating DIAPH1 mutations (p.Ala1210Serfs*31 and p.Arg1213*). In contrast to the extensively studied original DFNA1 family, hearing loss was not confined to low frequencies, but congenital manifestation and rapid progression were confirmed. In line with a recent unrelated study, we identified an association with thrombocytopenia, reclassifying DFNA1 as a syndrome. Consequently, we suggest to include the blood count into the initial clinical workup of patients with autosomal dominant hearing loss to guide the genetic diagnosis. We provide the first data on DIAPH1 expression in the organ of Corti, where it localizes to the inner pillar cells, at the base of the outer hair cells. Homozygous truncating DIAPH1 mutations located N-terminally to the DFNA1 mutations have recently been identified in autosomal recessive microcephaly. It is therefore noteworthy that we found DIAPH1 expression also in spiral ganglion neurons and in the barrier between the myelinating glia of the peripheral nervous system and oligodendrocytes that form the myelinating glia of the central nervous system (CNS).

["Why mothers die". Learning from the analysis of anaesthesia-related maternal deaths (1985-2013)]. / "Why mothers die". Was wir von der Analyse anästhesiebedingter mütterlicher Sterbefälle (1985-2013) gelernt haben.

Every day, more than 800 women die from causes related to pregnancy or childbirth. Since 1952 the Confidential Enquiry of Maternal Deaths Reports (CEMD) have collected and analysed data on maternal mortality in the United Kingdom and Northern Ireland. This publication analyses the CEMD from 1985-2013 regarding anaesthesia- and analgesia related maternal deaths during pregnancy or peripartum. During this period, there has been a reduction in directly anaesthesia-related maternal deaths to 4.3%. Yet, an increase in anaesthesia-associated maternal deaths has been recorded. The rate of fatal complications during obstetric regional anaesthesia doubled in recent years, while the fatality risk for obstetric general anaesthesia has decreased. Many of the reported maternal deaths could presumably have been avoided. The anaesthesiologist has to be familiar with state-of-the-art, guideline-based concepts for anaesthesia during pregnancy, childbirth or post partum, especially using tools like simulation. Vital sign monitoring after obstetric anaesthesia has to be identical to other postoperative monitoring, and Modified Early Warning Scores should be used for this purpose. In regional anaesthesia, current standards for hygiene have to be adhered to and patients have to be visited after spinal/epidural anaesthesia. Interdisciplinary communication and collaboration still have to be improved; careful interdisciplinary planning of childbirth in high-risk obstetric patients is strongly advised.

[Patient safety in anesthesiology : Multimodal strategies for perioperative care]. / Patientensicherheit in der Anästhesie : Multimodale Strategien für die perioperative Versorgung.

The concept of patient safety is more of a presence in modern day medicine than ever before. All measures and processes aiming at preempting and preventing critical incidents and accidents in patient care are collectively grouped under this concept. With the Declaration of Helsinki in 2010 modern anesthesiology has undertaken a fundamental role in the clinical implementation and perioperative clinicians are confronted with a multitude of theories, models, methods and tools targeted at improving or facilitating optimized patient safety. One of the biggest challenges lies in their synergistic combination to create a functioning concept for perioperative risk management while also incorporating individual strengths and weaknesses. The aim of the present paper is to provide a structured overview of the various components presently available for increasing perioperative patient safety.

[Special emergency situations and hazard control in German hospitals-A survey on the current state]. / Sonderlagen und Gefahrenabwehr in deutschen Krankenhäusern ­ eine Umfrage zum Ist-Zustand.

BACKGROUND AND RESEARCH QUESTION: In case of events such as a cyber attack or a mass casualty incident, ad hoc measures have to be taken in hospitals. As part of the critical infrastructure, hospitals are required by law to prepare, update and exercise alarm and emergency plans for various special situations. The processes and instruments involved for emergency response are defined in the hospital alert and emergency planning. The present study aims to explain with which resources and for which special situations hospitals are prepared. METHODS: A prospective, exploratory, anonymous survey of hospitals in Germany was conducted. Hospitals with both internal medicine and surgery departments were included. Out of 2497 hospitals listed in the German Hospital Directory ( www.deutsches-krankenhaus-verzeichnis.de ), 1049 met the inclusion criteria. After correcting for hospital groups with shared administrations, 850 employees were identified and contacted by e­mail. Quality and risk management managers were asked about resources, risks, and content of their own hospital alert and emergency planning using a standardized questionnaire. The survey was conducted using the online platform EFS Survey (Tivian XI GmbH, Cologne) via www.unipark.de . Access to the survey was via a nonpersonalized hyperlink. Apart from the size and type of hospital surveyed, no data were collected that would allow identification of an individual person. RESULTS: Of the participating hospitals 45% (n = 43) were primary care hospitals, 24% (n = 23) were specialty care hospitals, 10% (n = 9) were nonuniversity maximum care hospitals, and 21% (n = 20) were university maximum care hospitals. In total 95 hospitals participated in the survey, of which 98% (n = 93) reported having a hospital alert and emergency plan. Preparation for individual scenarios varied widely. Of the participating hospitals 45% (n = 43) reported having been the target of cyber attacks with an emphasis on maximum care hospitals (55%, n = 11 of 20). Technical redundancy for computer systems is available in 67% (n = 63) of participating hospitals, while independent means of communication exist in 50% (n = 47) of hospitals. A physician-staffed crisis and disaster management unit existed in 60% (n = 56) of the surveyed hospitals. At least a part time position for planning issues was installed in 12 hospitals. CONCLUSION: Most participating hospitals are aware of the need for a hospital alert and emergency plan and have various scenario-specific plans in place. Especially mass casualty events, fire and hospital evacuation scenarios are uniformly covered among participating hospitals; however, gaps appear to exist not only for chemical, biological or radionuclear situations but also especially in the area of extreme weather events and infrastructure failures. Only about two thirds of all participating hospitals have contingency plans for water supply and/or heating failures. An important limitation of the study is the comparatively low response rate of 12.9% (n = 95 of 850). While primary care hospitals were underrepresented in the study, 32% of Germany's larger hospitals (> 800 beds) participated. In the future, there is a particular need to engage enough medical staff in the area of hospital alert and emergency planning and refunding of these measures by hospitals.

Revealing four decades of snow cover dynamics in the Hindu Kush Himalaya.

Knowledge about the distribution and dynamics of seasonal snow cover (SSC) is of high importance for climate studies, hydrology or hazards assessment. SSC varies considerably across the Hindu Kush Himalaya both in space and time. Previous studies focused on regional investigations or the influence of snow melt on the local hydrological system. Here, we present a systematic assessment of metrics to evaluate SSC dynamics for the entire HKH at regional and basin scale based on AVHRR GAC data at a 0.05° spatial and daily temporal resolution. Our findings are based on a unique four-decade satellite-based time series of snow cover information. We reveal strong variability of SSC at all time scales. We find significantly decreasing SSC trends in individual summer and winter months and a declining tendency from mid-spring to mid-fall, indicating a shift in seasonality. Thanks to this uniquely spatio-temporally resolved long-term data basis, we can particularly highlight the unique temporally variable character of seasonal snow cover and its cross-disciplinary importance for mountain ecosystems and downstream regions.

[Multimodal diagnostic of CSNB1 with NYX gene mutation]. / Stufendiagnostik einer CSNB1 mit NYX-Genmutation.

This article presents the case of a young male patient with complete congenital stationary night blindness (CSNB1). The informative value of the general medical history and clinical findings for the diagnosis was impaired due to language barriers and low compliance. Full-field electroretinography and optical coherence tomography help to define particular hereditary retinal dystrophies. Molecular genetic analysis by next generation sequencing as a part of multimodal diagnostics finally uncovered a rare, causal missense mutation in the nyctalopin (NYX) gene.

Allelic losses at chromosomes 1p, 2p, 6p, 10p, 13q, 17p, and 21q significantly correlate with the chromophobe subtype of renal cell carcinoma.

We analyzed 50 sporadic renal cell carcinomas (RCCs) for loss of heterozygosity (LOH) at the chromosomal regions 1p, 2p, 6p, 7q, 10p, 11p, 13q, 14q, 17p, 21q, and 22q. Histologically, the tumors were distinguished into clear cell, chromophilic, and chromophobe carcinomas. Whereas LOH at 14q was identified in 42-64% of all three tumor types, only the chromophobe tumors showed high frequencies of LOH (73-91%) at 1p, 2p, 6p, 10p, 13q, 17p, and 21q. These findings provide substantial evidence that the chromophobe subtype of RCC represents a distinct genetic entity. Thus, specific LOH patterns may define the histogenesis and oncogenesis of chromophobe RCC and may be useful in tumor diagnosis and clinical prognosis.

VHL alterations in human clear cell renal cell carcinoma: association with advanced tumor stage and a novel hot spot mutation.

To elucidate the role of somatic alterations for renal cancer etiology and prognosis, we analyzed 227 sporadic renal epithelial tumors for mutations and hypermethylations in the von Hippel-Lindau tumor suppressor gene VHL. Tumors were classified according to the recommendations of the Union Internationale Contre le Cancer (UICC) and the American Joint Committee on Cancer (AJCC). Somatic VHL mutations were identified by PCR, single-strand conformation polymorphism analysis, and sequencing, and hypermethylations were identified by restriction enzyme digestion and Southern blotting. Frequencies of VHL alterations were established, and an association with tumor type or tumor type and tumor stage was evaluated. VHL mutations and hypermethylations were identified in 45% of clear cell renal cell carcinomas (CCRCCs) and occasionally (3 of 28) in papillary (chromophilic) renal cell carcinomas (RCCs). Lack of VHL mutations and hypermethylations in chromophobe RCCs and oncocytomas was statistically significant (P = 0.0001 and P = 0.0004, respectively). RCCs carrying VHL alterations showed, in nine cases (12%), mutations at a hot spot involving a thymine repeat (ATT.TTT) in exon 2. Tumor staging was critical to the VHL mutation/hypermethylation detection rate in CCRCCs shown by separate evaluation of patients from medical centers in Munich, Heidelberg, and Mainz. The spectrum of pT1, pT2, and pT3 CCRCCs and the VHL mutation/hypermethylation detection rate varied among these three groups. Altogether, VHL alterations were significantly associated with pT3 CCRCCs (P = 0.009). This is the first evidence of frequent somatic VHL mutations at a particular site within exon 2 and an association of VHL mutations/hypermethylations with a standard prognostic factor.

Solubilization of nuclear steroid 5 alpha-reductase from rat ventral prostate.

delta 4-Steroid-5 alpha-reductase (3-oxo-5 alpha-steroid:NADP+ delta 4-oxidoreductase, EC 1.3.1.22), is a membrane-bound enzyme. In the ventral prostate of the rat, its activity is found within the nuclear envelope. Solubilization of this enzyme can only be achieved in the presence of detergents. We studied the inhibitory effect of various detergents on 5 alpha-reductase activity as a function of detergent concentration, of pH, of incubation time, of salt concentration and of additives to the buffer system. Four detergents (Lubrol WX, CHAPS, L-alpha-lysophosphatidylcholine and octyl D-glucopyranoside) were selected for subsequent solubilization studies. The overall recovery of solubilized enzyme activity was about 30% when compared to 100% of 5 alpha-reductase activity found in freshly prepared nuclei. Up to 20-30% of the nuclear proteins were extracted during the solubilization procedure. Among the various treatments tested, a concentration of 3 mg/ml L-alpha-lysophosphatidylcholine per 10 mg/ml of nuclear protein in the presence of 5 mM MgCl2, 0.1 M KCl, 0.1 M sodium citrate and 5 mM NADPH yielded the maximal enzymic activity of 56%, 15% of the nuclear proteins being solubilized in an active and stable form. The activity in these extracts could be kept stable for 2 days at 4 degrees C with a recovery of 75% of enzymic activity. A 3-fold increase of specific 5 alpha-reductase activity was obtained during solubilization under optimal conditions.

Increased frequency of a null-allele for NAD(P)H: quinone oxidoreductase in patients with urological malignancies.

The NQO1 locus on chromosome 16q2.2 encodes NAD(P)H:quinone oxidoreductase, an enzyme implicated in detoxication and protection against redox cycling. Two alleles have been identified in the human population, the rarer one, termed the null-allele, coding for a nonfunctional enzyme. Since lack of NQOR activity has been suggested to increase susceptibility to certain cancers, the distribution of the two alleles was determined by polymerase chain reaction-restriction fragment length polymorphism analysis in patients with renal cell carcinoma (n = 131) and urothelial carcinoma (n = 99) compared with a normal population (n = 260). Allele distribution in the normal population followed a Hardy-Weinberg distribution with frequencies of 0.867 for the major allele and 0.133 for the null-allele. Increased frequencies of the null-allele were found in the tumour patient groups (0.191 and 0.182, respectively) due to an increased number of both homo- and heterozygotes. The odds ratios for homozygous null-allele vs. wild-type genotypes were 1.7 and 3.6 for renal cell carcinoma and urothelial carcinoma, respectively. These data are compatible with the assumption that diminished activity of NQOR in some individuals increases susceptibility to certain cancers.

Gastroenteropancreatic endocrine tumors: effect of Sandostatin on tumor growth. The German Sandostatin Study Group.

One hundred fifteen gastroenteropancreatic (GEP) patients with malignant endocrine tumors entered a prospective multicenter trial (12 patients with gastrinoma, 53 with carcinoid syndrome, 45 with nonfunctioning tumors, and five with other endocrine GEP tumors) to determine the efficacy of 200 micrograms Sandostatin three times a day in the control of tumor growth. This interim report describes the results in 85 patients. Thirty-four patients died, 14 before and 20 after the first follow-up investigation, indicating a "negative" selection of patients included in the trial and suggesting that Sandostatin cannot prevent disease progress when it is far advanced. In the evaluation of 68 patients monitored for at least 3 months, partial regression was observed in 4.4%, stable disease in 50%, and tumor progression in 45%. However, an initially favorable response frequently occurred with a decrease in response later: 54.4% at 3 months to 38% at 12 months for the whole group of patients. Proven inhibition of tumor growth was mirrored by suppression of serum and urine hormone parameters. It is concluded that Sandostatin exerts a beneficial effect on tumor growth in patients with metastatic endocrine GEP tumors. This beneficial effect decreases with time and is as yet unpredictable in the individual patient.

Involvement of the chromosomal region 11q13 in renal oncocytoma: case report and literature review.

Renal oncocytomas comprise a cytogenetically heterogeneous group of tumors consisting potentially of cytogenetic distinguishable subgroups. Review of the literature revealed loss of chromosome 1 and Y as a possible anomaly for at least one subset oncocytomas. The frequent finding of rearrangements involving chromosome 11 band q13 characterizes another subset of oncocytomas. We report the cytogenetic and pathological features of a renal oncocytoma diagnosed in a 72-year-old woman and found a t(9;11)(p23;q13) as a consistent abnormality. This supports the idea that translocations involving 11q13 define a further subset of oncocytoma.

[Receptor scintigraphy using 111In-pentetreotide in endocrine gastroenteropancreatic tumors]. / Rezeptorszintigraphie mit 111In-Pentetreotid bei endokrinen gastroenteropankreatischen Tumoren.

Receptor scintigraphy with 111In-pentetreotide is a complementary imaging technique with a sensitivity of 88% for the localization of the primary tumor and its metastases in patients presenting with the clinical and biochemical symptoms of an endocrine tumor of the gastrointestinal tract or the pancreas. As a whole-body scintigraphic technique it covers all body regions and is also able to reveal small tumors which can only be detected with difficulty or not at all by the usual imaging methods. In 104 patients with GEP tumors or after operative removal of such tumors, receptor scintigraphy proved to be superior to ultrasound and computed tomography in 34%, equal in 52% and inferior in 14% of the cases.

[Genetics of congenital aniridia]. / Genetik der kongenitalen Aniridie.

BACKGROUND: Mutations in the PAX6 gene mostly cause non-syndromic aniridia with autosomal dominant inheritance and familial occurrence. The underlying point mutations and deletions in the PAX6 locus cause loss-of-function of one gene copy (haploinsufficiency). Mutations with residual PAX6 function often result in milder disease expression but may also cause distinct and more severe ocular phenotypes. Combined deletion of PAX6 and the adjacent WT1 tumor suppressor gene causes Wilms tumor, aniridia, genitourinary anomalies and mental retardation (WAGR) syndrome with a high risk for Wilms tumors in infancy. PURPOSE: Genetic diagnostics are important for confirming the clinical diagnosis, for the assessment of the risk of recurrence and early recognition of children with associated tumor risk. RESULTS AND DISCUSSION: Sequencing of the PAX6 gene and quantitative analysis of the PAX6 locus allow for efficient molecular genetic evaluation of the clinical diagnosis of both isolated and syndromic aniridia. In cases of clinical overlap with other entities, high-throughput sequencing of multiple additional genes can simultaneously cover genes for differential diagnoses (e.g. microphthalmia syndromes). Optimal care of aniridia patients requires close cooperation of ophthalmologists and medical geneticists.