Novel blended SNRPE-related spliceosomopathy phenotype characterized by microcephaly and congenital atrichia.

Variants in genes encoding core components of the spliceosomes are associated with craniofacial syndromes, collectively called craniofacial spliceosomopathies. SNRPE encodes a core component of pre-mRNA processing U-rich small nuclear ribonuclear proteins (UsnRNPs). Heterozygous variants in SNRPE have been reported in six families with isolated hypotrichosis simplex in addition to one case of isolated non syndromic congenital microcephaly. Here, we report a patient with a novel blended phenotype of microcephaly and congenital atrichia with multiple congenital anomalies due to a de novo intronic SNRPE deletion, c.82-28_82-16del, which results in exon skipping. As discussed within, this phenotype, which we propose be named SNRPE-related syndromic microcephaly and hypotrichosis, overlaps other craniofacial splicesosomopathies.

An effective sub-quadratic scaling atomic-orbital reformulation of the scaled opposite-spin RI-CC2 ground-state model using Cholesky-decomposed densities and an attenuated Coulomb metric.

An atomic-orbital reformulation of the Laplace-transformed scaled opposite-spin (SOS) coupled cluster singles and doubles (CC2) model within the resolution of the identity (RI) approximation (SOS-RI-CC2) is presented that extends its applicability to molecules with several hundreds of atoms and triple-zeta basis sets. We exploit sparse linear algebra and an attenuated Coulomb metric to decrease the disk space demands and the computational efforts. In this way, an effective sub-quadratic computational scaling is achieved with our ω-SOS-CDD-RI-CC2 model. Moreover, Cholesky decomposition of the ground-state one-electron density matrix reduces the prefactor, allowing for an early crossover with the molecular orbital formulation. The accuracy and performance of the presented method are investigated for various molecular systems.

Efficient Integral-Direct Methods for Self-Consistent Reduced Density Matrix Functional Theory Calculations on Central and Graphics Processing Units.

Reduced density matrix functional theory (RDMFT), a promising direction in the problem of describing strongly correlated systems, is currently limited by its explicit dependence on natural orbitals and, by extension, the costly need to construct two-electron integrals in the molecular orbital basis. While a resolution-of-the-identity approach can reduce the asymptotic scaling behavior from O(N5) to O(N4), this is still prohibitively expensive for large systems, especially considering the usually slow convergence and the resulting high number of orbital optimization steps. In this work, efficient integral-direct methods are derived and benchmarked for various approximate functionals. Furthermore, we show how these integral-direct methods can be integrated into existing self-consistent energy minimization frameworks in an efficient manner, including improved methods for calculating diagonal elements of the two-electron integral tensor as required in self-interaction-corrected functionals and second derivatives of the energy with respect to the occupation numbers. In combination, these methods provide speedups of up to several orders of magnitude while greatly diminishing memory requirements, enabling the application of RDMFT to large molecular systems of general chemical interest, such as the challenging triplet-quintet gap of the iron(II) porphyrin complex.

Management of primary and renal hyperparathyroidism: guidelines from the German Association of Endocrine Surgeons (CAEK).

BACKGROUND AND AIMS: The purpose of this review is to provide updated recommendations for the surgical management of primary (pHPT) and renal (rHPT) hyperparathyroidism, formulating a new guideline of the German Association of Endocrine Surgeons (CAEK). METHODS: Evidence-based recommendations for the diagnosis and therapy of pHPT and rHPT were assessed by a multidisciplinary panel using PubMed for a comprehensive literature search together with a structured consensus dialogue (S2k guideline of the Association of the German Scientific Medical Societies, AWMF). RESULTS: During the last 20 years, a variety of new preoperative localization procedures, such as sestamibi-SPECT, 4D-CT, and various PET/CT procedures, were established for pHPT. High-resolution imaging, together with intraoperative parathyroid hormone (IOPTH) measurement, enabled focused or minimally invasive surgery to become the most favored surgical technique. Patients with pHPT and nonlocalizing imaging have a higher risk of multiglandular disease. Surgical therapy provides very high cure rates, with a clear relation to the surgeon's experience in parathyroid procedures. Reoperative parathyroidectomy, children with pHPT or familial forms, and parathyroid carcinoma are addressed and require special surgical expertise. A multidisciplinary team of experienced nephrologists, transplant, and endocrine surgeons should assess the diagnosis and treatment of renal HPT. CONCLUSION: Surgery is the only curative treatment for pHPT and should be considered for all patients with pHPT. For rHPT, a more selective approach is required, and parathyroidectomy is indicated only when conservative treatment options fail. In parathyroid carcinoma, the adequacy of local resection influences local disease control.

[Update of the S2k guidelines : Surgical treatment of benign thyroid diseases]. / Aktualisierung der S2k-Leitlinie : Operative Therapie benigner Schilddrüsenerkrankungen.

Thyroid resections represent one of the most common operations with 76,140 interventions in the year 2016 in Germany (source Destatis). These are predominantly benign thyroid gland diseases. Recommendations for the operative treatment of benign thyroid diseases were last published by the CAEK in 2010 as S2k guidelines (Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften e.V. [AWMF] 003/002) against the background of increasingly more radical resection procedures. Hemithyroidectomy and thyroidectomy are routinely performed for benign thyroid disease in practice. The operation-specific risks show a clear increase with the extent of the resection. Therefore, weighing-up of the risk-indications ratio between unilateral lobectomy or thyroidectomy necessitates an independent evaluation of the indications for both sides. This principle in particular has been used to update the guidelines. In addition, the previously published recommendations of the CAEK for correct execution and consequences of intraoperative neuromonitoring were included into the guidelines, which in particular serve the aim to avoid bilateral recurrent laryngeal nerve paralysis. Moreover, the recommendations for the treatment of postoperative complications, such as hypoparathyroidism and postoperative infections were revised. The updated guidelines therefore represent the current state of the science as well as the resulting surgical practice.

Communication: A reduced scaling J-engine based reformulation of SOS-MP2 using graphics processing units.

We present a low-prefactor, cubically scaling scaled-opposite-spin second-order Møller-Plesset perturbation theory (SOS-MP2) method which is highly suitable for massively parallel architectures like graphics processing units (GPU). The scaling is reduced from O(N5) to O(N³) by a reformulation of the MP2-expression in the atomic orbital basis via Laplace transformation and the resolution-of-the-identity (RI) approximation of the integrals in combination with efficient sparse algebra for the 3-center integral transformation. In contrast to previous works that employ GPUs for post Hartree-Fock calculations, we do not simply employ GPU-based linear algebra libraries to accelerate the conventional algorithm. Instead, our reformulation allows to replace the rate-determining contraction step with a modified J-engine algorithm, that has been proven to be highly efficient on GPUs. Thus, our SOS-MP2 scheme enables us to treat large molecular systems in an accurate and efficient manner on a single GPU-server.

Symptom reporting in cancer patients II: relations to social desirability, negative affect, and self-reported health behaviors.

BACKGROUND: Patients' appraisal of somatic symptoms is correlated with their negative affect. The authors have investigated whether social desirability is associated with patients' symptom and health behavior reporting. METHODS: One hundred fourteen surgical cancer patients who participated in either an outpatient or an inpatient follow-up care program filled out the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-C30, the New Social Desirability Scale, and a health behavior checklist. RESULTS: Patients' reports of somatic symptoms were correlated inversely with social desirability (r = -0.50) and positively with negative affect (r = 0.72). When objective health and demographic variables (e.g., prognosis, adjuvant therapy prior to follow-up, and gender) were entered first in hierarchical multiple regression analyses, social desirability and negative affect accounted for an additional 16% and 36% of the symptom variance, respectively. Similar results were found when global quality of life was the dependent variable. Self-reported health behaviors were explained only through the set of health and demographic variables (14%), and social desirability and negative affect did not account for additional variance. On the average, patients reported that they had a median of 4.7 (out of a list of 21) self-initiated health behaviors, and 11% of the patients admitted to having used unproven therapies. CONCLUSIONS: Symptom reports do not give a pure picture of patients' health status, but they are strongly correlated with social desirability and negative affect. Detection of such psychologic variables is essential to understanding the dynamics of quality of life. In applied settings, quality-of-life measures should be used together with conventional criteria. As practical experience and scientific understanding grow, the relative positioning of these patient-oriented versus clinic-oriented endpoints will become clear.

[Malignant non-epithelial tumors of the pancreas]. / Maligne nichtepitheliale Tumoren des Pankreas.

Nonepithelial malignant tumors of the pancreas are extremely rare neoplasms with a frequency of approximately 0.6%. They are always explored because of a suspected diagnosis of pancreatic carcinoma. Amongst the more than 600 primary pancreatic neoplasms in our pancreatic tumor archive only 5 neoplasms were of nonepithelial origin (one was a malignant peripheral nerve sheath tumor [MPNST], one a leiomyosarcoma, one a malignant mesothelioma, and two were peripheral neuroectodermal tumors [PNET]. The differential diagnosis includes secondary infiltration of the pancreas by mesenchymal tumors of the retroperitoneum, undifferentiated pancreatic carcinoma and, especially in the case of PNET, malignant lymphoma. Preoperative chemotherapy and down-staging can improve the operability and prognosis, especially in PNET.

[Not Available]. / Die Bedeutung der präoperativen Gerinnungsanalytik für die Einschätzung des Blutungsrisikos in der Allgemeinchirurgie.

Coagulation studies, i. e. platelet count, prothrombin time (PT) and activated partial thrombin time (aPTT) are commonly employed preoperatively to identify patients at risk. In a retrospective study we evaluated the usefulness of these screening tests to predict postoperative bleeding in 1447 patients with abdominal and thoracic surgery. Forty-six patients (3.2 %) experienced postsurgical bleeding. 12.2 % of our patients had abnormal coagulation studies. The sensitivity of abnormal coagulation studies with respect to postoperative bleeding was 23.9 %. The sensitivity of the parameter "patient at risk", i. e. patients with suspected coagulopathies due to drugs or disease of the liver or kidney, was 56.5 %. Thirty-four out of 1008 patients without risk factors had abnormal coagulation tests but an uneventful postoperative course. Preoperative screening of PT and aPTT should be reserved for patients with known or suspected inherited or acquired coagulopathies.

[Radiological thorax monitoring in ventilated intensive-care patients]. / Radiologisches Thoraxmonitoring bei beatmeten Intensivpatienten.

PURPOSE: At many institutions chest x-rays (CXR) are routinely performed on mechanically ventilated patients on a daily basis. Among the aims of this study was the assessment of a) frequency of clinically relevant findings from routine CXR in surgical patients under mechanical ventilation, b) comparison of expectations of clinically important CXR findings with estimation of clinical relevance of findings once films were obtained, c) indications and clinical consequences of findings from CXR requested in addition to routine films. METHODS: Prospective study, 40 patients with 741 CXR. Standardised film reporting. Daily recording of clinical data by means of an evaluation score. Interview of intensive-care physicians for assessment of: what information was expected from any routine CXR? did CXR offer helpful information for further treatment planning? RESULTS: 26% of routine CXR had a considerable therapeutical impact. 43% of all routine CXR were expected to have an influence on patient management, 57% were not. 16% of those CXR that had been expected not to offer essential information, disclosed relevant findings. Of the additionally obtained CXR, 53% were performed to check position of endotracheal tube and catheters and 47% related to other indications. CONCLUSION: Critically ill surgical patients under mechanical ventilation should have daily CXR follow-up, as one-fourth of these films has an impact on the patient's management.

[Anticoagulation after vascular surgery interventions]. / Antikoagulation nach gefässchirurgischen Interventionen.

Questionnaires regarding postoperative antiplatelet and anticoagulant therapy were answered by personal interviews with 35 German vascular surgeons. A 3/4 majority follow the recommendations of literature by anticoagulation after embolectomy in patients with persistent atrial fibrillation. Antiplatelet therapy is common in patients after thrombendarteriectomy and justified by improving the natural history of atherosclerotic disease. Considerable differences exist in postoperative therapy following peripheral bypass surgery. Controlled clinical trials are rare and present contradicting results. Prospective randomized multicenter studies are necessary.

[Blood-saving surgery]. / Blutsparendes Operieren.

Trauma, blood loss and autologous blood transfusions induce a variety of changes in the reactivity of patients' immune systems. In clinical studies the differentiation of these effects is difficult. Association between autologous blood transfusion and postoperative infection is highly likely. In surgical oncology blood transfusions are associated with poor prognosis, but probably this is more because of the circumstances that necessitate them.

[Measuring quality of life in after-care of tumor surgery. Methods, problems and applications]. / Die Messung von Lebensqualität in der chirurgischen Tumornachsorge. Methoden, Probleme und Einsatzmöglichkeiten.

The present paper deals with the feasibility and applications of quality of life measurement in the routine of a tumor follow-up clinic. 61 patients filled out the EORTC-30 questionnaire plus additional scales. Filling out the questionnaire constituted no burden for patients. Patients' responses were computed in a way as to allow for graphically presenting individual QL-profiles, as well as to compare different groups of patients. Considerations concerning the role of QL-measurement in clinical practice, in medical decision making, and in future research endeavours were brought forward.

[Daily "routine chest x-ray" in ventilated surgical intensive care patients]. / Der tägliche "Routine-Röntgenthorax" beim beatmeten chirurgischen Intensivpatienten.

We investigated the relevance of daily routine chest x-ray in intensive care for therapeutical decision. A special emphasis was put on clinical laboratory parameters according to the APACHE-II-score. Within a prospective study we investigated 40 intubated patients of our surgical intensive care unit with a total of 609 x-ray films. 26% of all pictures gained influence on therapeutical procedure. Analysis of different patient subgroups showed only between those under 50 and those above 70 years of age an important discrepancy quote of relevant films (19 vs. 31%).

[Manifestations of ruptured liver hematoma as a severe complication of HELLP syndrome]. / Symptomatik eines rupturierten Leberhämatoms als schwere Komplikation des HELLP-Syndroms.

A case of a ruptured haematoma of the liver with intra-abdominal bleeding is reported. The 26-year old primigravida was admitted in the 31st week of gestation because of a HELLP syndrome. She presented additional symptoms, that are considered typical for a HELLP syndrome, complicated by a ruptured haematoma of the liver: severe right upper-quadrant pain, decrease of haemoglobin content, enlarged liver with structural irregularities and free fluid in the abdominal cavity as examined by sonography. During Caesarean section, a subcapsular haematoma of the liver, combined with a 5 cm laceration of the organ surface, was found. The defect was closed with collagen gauze and clotted with fibrin. Additionally the liver was compressed by abdominal compression towels, which were removed 2 days later. The postoperative development was, in the main, complication free.