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Aim of the study For out-of-hospital-cardiac-arrest (OHCA) due to ventricular fibrillation (VF) guidelines recommend early defibrillation followed by chest compressions for two minutes before analyzing shock success. If rhythm analysis reveals VF again, it is obscure whether VF persisted or reoccurred within the two-minutes-cycle of chest compressions after successful defibrillation. We investigated the time of VF-recurrence in OHCA. Methods We examined all cases of OHCA presenting with initial VF rhythm at arrival of ALS-ambulance (Marburg-Biedenkopf-County, 246.648 inhabitants) from January 2014 to March 2018. Three independent investigators analyzed corpuls3® ECG-recordings. We included ECG-data from CPR-beginning until four minutes after the third shock. VF termination was defined as the absence of a VF-waveform within 5 s of shock delivery. VF recurrence was defined as the presence of a VF-waveform in the interval 5 s post shock delivery. Results We included 185 shocks in 82 patients. 74.1% (n = 137) of all shocks terminated VF, but VF recurred in 81% (n = 111). The median (IQR) time of VF-recurrences was 27 s (13.5 s/80.5 s) after shock. 51.4% (n = 57) of VF-recurrence occurred 5–30 s after shock, 13.5% (n = 15) VF-recurrence occurred 31−60 s after shock, 21.6% (n = 24) of VF-recurrence occurred 61–120 s after shock, 13.5% (n = 15) of VF-recurrence occurred 121–240 s after shock. Conclusions Although VF was terminated by defibrillation in 74.1%, VF recurred in 81% subsequent to the chest compression interval. Thus, VF reappears frequently and early. It is unclear to which extend chest compressions influence VF-relapse. Further studies need to re-evaluate the algorithm, timing of antiarrhythmic therapy or novel defibrillation strategies to minimize refibrillation during shockable OHCA.

Introdução: Traqueobroncomegalia ou síndrome de Mounier-Kuhn é uma doença rara, observada principalmente em homens de meia idade antes da 5ª década de vida, caracterizada por atrofia ou ausência das fibras elásticas ou da musculatura lisa da parede da traquéia e dos brônquios principais, determinando dilatação dessas estruturas. Acredita-se que a fraqueza do tecido conjuntivo, associada à inalação de poluentes aéreos e fumaça de cigarro, sejam os principais fatores no desenvolvimento desta síndrome. O diagnóstico pode ser ocasional em indivíduos assintomáticos, contudo cursa frequentemente com infeções respiratórias de repetição e bronquiectasias. Descrição: A.H.A.G., 65 anos, masculino, solteiro, branco. Relatava tosse crônica com aumento da frequência há 10 dias associado a um aumento de expectoração, no momento, esverdeado. Queixava-se também de febre irregular diária não termometrada, dispneia aos mínimos esforços, e sudorese noturna. Paciente menciona diagnóstico de bronquiectasia, porém sem adesão ao acompanhamento ambulatorial de pneumologia no HRT desde 2015. Conclusão: A síndrome de Mounier-Kuhn se caracteriza pelo aumento do diâmetro da traqueia e dos brônquios principais associado a redução do clearence mucociliar, o que leva o indivíduo a desenvolver infecções respiratórias com frequência. O diagnóstico é feito por TC de tórax. O tratamento só é realizado nos sintomáticos, objetivando tratar o fator desencadeante da descompensação.

Embora o acometimento do nervo fibular seja uma das neuropatias mais comuns nos membros inferiores, a lesão bilateral ainda é pouco citada na literatura. Apresentamos uma mulher jovem com doença de nervo fibular comum pouco tempo após a descompressão cirúrgica bem sucedida no membro contralateral. O principal achado é o déficit motor, com a típica marcha escarvante. A eletroneuromiografia continua sendo a propedêutica ideal, considerando atualmente novas modalidades em estudo. Mesmo que em diferentes apresentações, até o momento, a descompressão cirúrgica do nervo fibular parece ser a modalidade terapêutica de melhor resultado.

Hutchinson–Gilford progeria syndrome (HGPS) is a rare, premature ageing syndrome in children. HGPS is normally caused by a mutation in the LMNA gene, encoding nuclear lamin A. The classical mutation in HGPS leads to the production of a toxic truncated version of lamin A, progerin, which retains a farnesyl group. Farnesyltransferase inhibitors (FTI), pravastatin and zoledronic acid have been used in clinical trials to target the mevalonate pathway in HGPS patients to inhibit farnesylation of progerin, in order to reduce its toxicity. Some other compounds that have been suggested as treatments include rapamycin, IGF1 and N-acetyl cysteine (NAC). We have analysed the distribution of prelamin A, lamin A, lamin A/C, progerin, lamin B1 and B2 in nuclei of HGPS cells before and after treatments with these drugs, an FTI and a geranylgeranyltransferase inhibitor (GGTI) and FTI with pravastatin and zoledronic acid in combination. Confirming other studies prelamin A, lamin A, progerin and lamin B2 staining was different between control and HGPS fibroblasts. The drugs that reduced progerin staining were FTI, pravastatin, zoledronic acid and rapamycin. However, drugs affecting the mevalonate pathway increased prelamin A, with only FTI reducing internal prelamin A foci. The distribution of lamin A in HGPS cells was improved with treatments of FTI, pravastatin and FTI + GGTI. All treatments reduced the number of cells displaying internal speckles of lamin A/C and lamin B2. Drugs targeting the mevalonate pathway worked best for progerin reduction, with zoledronic acid removing internal progerin speckles. Rapamycin and NAC, which impact on the MTOR pathway, both reduced both pools of progerin without increasing prelamin A in HGPS cell nuclei. Electronic supplementary material The online version of this article (10.1007/s10522-019-09807-4) contains supplementary material, which is available to authorized users.

Background Birth defects are a major cause of poor health outcomes during both childhood and adulthood. A growing body of evidence demonstrated associations between air pollution exposure during pregnancy and birth defects. To date, there is no study looking at birth defects and exposure to wildfire-related air pollution, which is suggested as a type of air pollution source with high toxicity for reproductive health. Objective Our study addresses this gap by examining the association between birth defects and wildfire smoke exposure in Brazil between 2001 and 2018. Based on known differences of impacts of wildfires across different regions of Brazil, we hypothesized differences in risks of birth defects for different regions. Methods We used a logistic regression model to estimate the odds ratios (ORs) for individual birth defects (12 categories) associated with wildfire exposure during each trimester of pregnancy. Results Among the 16,825,497 birth records in our study population, there were a total of 7595 infants born in Brazil between 2001 and 2018 with birth defects in any of the selected categories. After adjusting for several confounders in the primary analysis, we found statistically significant OR for three birth defects, including cleft lip/cleft palate [OR: 1.007 (95% CI: 1.001; 1.013)] during the second trimester of exposure, congenital anomalies of the respiratory system [OR: 1.013 (95% CI: 1.002; 1.023)] in the second trimester of exposure, and congenital anomalies of the nervous system [OR: 1.002 (95% CI: 1.001; 1.003)] during the first trimester of exposure for the regions South, North, and Midwest, respectively. Significance Our results suggest that maternal exposure to wildfire smoke during pregnancy may increase the risk of an infant being born with some congenital anomaly. Considering that birth defects are associated with long-term disability, impacting families and the healthcare system (e.g., healthcare costs), our findings should be of great concern to the public health community. Impact statement Our study focused on the association between maternal exposure to wildfire smoke in Brazil during pregnancy and the risk of an infant being born with congenital anomalies, which presents serious public health and environmental challenges.

Background Metabolic and electrolyte imbalances are some of the reversible causes of cardiac arrest and can be diagnosed even in the pre-hospital setting with a mobile analyser for point-of-care testing (POCT). Methods We conducted a retrospective observational study, which included analysing all pre-hospital resuscitations in the study region between October 2015 and December 2016. A mobile POCT analyser (Alere epoc®) was available at the scene of each resuscitation. We analysed the frequency of use of POCT, the incidence of pathological findings, the specific interventions based on POCT as well as every patient’s eventual outcome. Results N = 263 pre-hospital resuscitations were included and in n = 98 of them, the POCT analyser was used. Of these measurements, 64% were performed using venous blood and 36% using arterial blood. The results of POCT showed that 63% of tested patients had severe metabolic acidosis (pH 6.0 mmol/l/ p = 0.07). Overall, 21% of patients survived to hospital discharge (POCT 30% vs no POCT 16%, p = 0.01, Φ = 0.16). Conclusions Using a POCT analyser in pre-hospital resuscitation allows rapid detection of pathological acid–base imbalances and potassium concentrations and often leads to specific interventions on scene and could improve the probability of survival.

Background The amount of epicardial adipose tissue (EAT) is associated with prevalent and incident myocardial infarction. However, clinical studies, specifically designed to determine, how the assessment of EAT can affect patient management, are lacking. Within Epicardial adipose tissue thickness PredIcts obstructive Coronary artery disease in Acute Coronary Syndrome patients (EPIC-ACS) study we tested the hypothesis that EAT quantification improves the prediction of the presence of culprit lesions in patients presenting with acute chest pain to the emergency department. Methods In this observational cohort study, we prospectively included consecutive patients presenting to the emergency department with acute chest pain suggestive of acute coronary syndrome between December 2018 and August 2020. Patients with ST-elevation myocardial infarction, hemodynamic instability, or known coronary artery disease were excluded. As part of the initial workup, bedside echocardiography for quantification of EAT thickness was performed by a dedicated study physician, blinded to all patients' characteristics. Treating physicians remained unaware of the results of the EAT assessment. The primary endpoint was defined as presence of a culprit lesion, as detected in subsequent invasive coronary angiography within 90 days after initial presentation. Logistic regression analysis was performed in different models adjusted for traditional cardiovascular risk factors, cardiac biomarkers as well as established cardiovascular risk scores. Results Overall, 657 patients (mean age 58.06±18.04 years, 53% male) were included in our study. Patients reaching the primary endpoint had significantly more EAT than patients without culprit lesions (7.90±2.56mm vs. 3.96±1.91mm, p Conclusion EAT strongly and independently predicts the presence of culprit lesions in patients presenting with acute chest pain to the emergency department. Our results suggest that the bedside echocardiographic assessment including the quantification of EAT may improve diagnostic algorithms of patients with acute chest pain. Funding Acknowledgement Type of funding sources: None. Distribution of EAT thickness

Die extrakorporale kardiopulmonale Reanimation („extracorporeal cardiopulmonary resuscitation“, eCPR) kann als Rettungsversuch fur hoch selektierte Patienten mit refraktarem Herz-Kreislauf-Stillstand und potenziell reversibler Atiologie erwogen werden. Aktuell fehlen randomisiert-kontrollierte Studien zur eCPR und es existieren keine validen Pradiktoren fur Nutzen und Risiko, die bei der Indikationsstellung hilfreich sein konnten. Die bisherigen Selektionskriterien und Ablaufe sind klinikspezifisch und ein (nationaler) standardisierter Algorithmus fehlt. Das vorliegende Konsensuspapier bietet basierend auf einer konsentierten Expertenmeinung den Vorschlag fur ein standardisiertes Vorgehen bei eCPR.

To compare survival outcomes of Impella support and medical treatment in patients with post-cardiac arrest cardiogenic shock related to acute myocardial infarction (AMI).Retrospective single center study of patients resuscitated from out of hospital cardiac arrest (OHCA) due to AMI with post-cardiac arrest cardiogenic shock between September 2014 and September 2016. Patients were either assisted with Impella or received medical treatment only. Survival outcomes were compared using propensity score-matched analysis to account for differences in baseline characteristics between both groups.A total of 90 consecutive patients with post-cardiac arrest shock due to AMI were included; 27 patients in the Impella group and 63 patients in the medical treatment group. Patients with Impella support had a longer duration of low-flow time (29.54 ± 10.21 versus 17.57 ± 8.3 min, p 0.001), higher lactate levels on admission (4.75 [IQR 3.8-11] versus 3.6 [IQR 2.6-3.9] mmol/L, p = 0.03) and lower baseline systolic LVEF (25% [IQR 25-35] versus 45% [IQR 35-51.25], p 0.001) as compared to patients without circulatory support. After propensity score matching, patients with Impella support had a significantly higher survival to hospital discharge (65% versus 20%, p = 0.01) and 6-months survival (60% versus 20%, p = 0.02).The results from our study suggest that Impella support is associated with significantly better survival to hospital discharge and at 6 months compared to medical treatment in OHCA patients admitted with post-cardiac arrest cardiogenic shock and AMI.

Introdução: A trombose venosa cerebral é uma entidade de grande importância na clínica neurológica. Consiste de evento de grande morbidade e mortalidade, sendo potencialmente recuperável se diagnosticada precocemente. É uma condição rara, constituindo menos de 1% dos acidentes vasculares. A transformação hemorrágica é uma complicação preditora deprognóstico desfavorável. O manejo desta patologia é de alta complexidade e demanda tratamento agressivo. Objetivo: revisar a literatura sobre esta patologia e relatar um caso clinico para exemplificar o beneficio do junto ao tratamento precoce. Conclusão: A trombose dos seios da dura-mater é entidade patológica de grande importância, e sua etiologia deve ser amplamente pesquisada para o tratamento adequado e prevenção secundária.

Successful Balloon Angioplasty with Low-pressure Balloon on Early Transplant Renal Artery Stenosis at Postoperative Day 7 Doo Youp Kim, M.D., Hyun Do Jung, M.D., Jin Ho Lee, M.D., Han Sae Kim, M.D., Dong Yeol Lee, M.D., Joon Seok Oh, M.D., Seong Min Kim, M.D., Yong Hun Sin, M.D., Joong Kyung Kim, M.D., Kill Huh, M.D., Jong Hyun Park, M.D. and Gyu Sik Jung, M.D. Departments of Nephrology, General Surgery, Bong Seng Memorial Hospital, Department of Radiology, Kosin University Gospel Hospital, Busan, Korea

OBJECTIVE: To compare the interlaminar and transforaminal block techniques with regard to the state of pain and presence or absence of complications.METHOD: This was a randomized double-blind prospective study of descriptive and comparative nature, on 40 patients of both sexes who presented lumbar sciatic pain due to central-lateral or foraminal disk hernias. The patients had failed to respond to 20 physiotherapy sessions, but did not present instability, as diagnosed in dynamic radiographic examinations. The type of block to be used was determined by means of a draw: transforaminal (group 1; 20 patients) or interlaminar (group 2; 20 patients).RESULTS: Forty patients were evaluated (17 males), with a mean age of 49 years. There was a significant improvement in the state of pain in all patients who underwent radicular block using both techniques, although the transforaminal technique presented better results than the interlaminar technique.CONCLUSION: Both techniques were effective for pain relief and presented low complication rates, but the transforaminal technique was more effective than the interlaminar technique. OBJETIVO: comparar a técnica de bloqueio interlaminar com a de bloqueio transforaminal, quanto ao quadro álgico e à presença ou não de complicações.MÉTODO: estudo prospectivo, de caráter descritivo e comparativo, duplo-cego e randomizado, em que são sujeitos 40 pacientes, de ambos os sexos, portadores de lombociatalgia por hérnia de disco, do tipo centro-lateral ou foraminal, sem resposta a 20 sessões de fisioterapia e sem instabilidade, diagnosticada em exame de radiografia dinâmica. O tipo de bloqueio, transforaminal (grupo 1) ou interlaminar (grupo 2), a ser feito foi determinado por meio de sorteio e constituiu 20 pacientes do grupo 1 e 20 do grupo 2.RESULTADOS: foram avaliados 40 pacientes, 17 do sexo masculino, média de 49 anos, nos quais houve melhoria significativa do quadro álgico em todos os submetidos ao bloqueio radicular em ambas as técnicas, embora a técnica transforaminal apresentasse melhores resultados quando comparada com a interlaminar.CONCLUSÃO: ambas as técnicas são eficazes no alívio da dor e apresentam baixa taxa de complicação, mas a transforaminal foi mais eficaz do que a interlaminar.

Hutchinson–Gilford progeria syndrome (HGPS) is a rare and fatal premature ageing disease in children. HGPS is one of several progeroid syndromes caused by mutations in the LMNA gene encoding the nuclear structural proteins lamins A and C. In classic HGPS the mutation G608G leads to the formation of a toxic lamin A protein called progerin. During post-translational processing progerin remains farnesylated owing to the mutation interfering with a step whereby the farnesyl moiety is removed by the enzyme ZMPSTE24. Permanent farnesylation of progerin is thought to be responsible for the proteins toxicity. Farnesyl is generated through the mevalonate pathway and three drugs that interfere with this pathway and hence the farnesylation of proteins have been administered to HGPS children in clinical trials. These are a farnesyltransferase inhibitor (FTI), statin and a bisphosphonate. Further experimental studies have revealed that other drugs such as N-acetyl cysteine, rapamycin and IGF-1 may be of use in treating HGPS through other pathways. We have shown previously that FTIs restore chromosome positioning in interphase HGPS nuclei. Mis-localisation of chromosomes could affect the cells ability to regulate proper genome function. Using nine different drug treatments representing drug regimes in the clinic we have shown that combinatorial treatments containing FTIs are most effective in restoring specific chromosome positioning towards the nuclear periphery and in tethering telomeres to the nucleoskeleton. On the other hand, rapamycin was found to be detrimental to telomere tethering, it was, nonetheless, the most effective at inducing DNA damage repair, as revealed by COMET analyses. Electronic supplementary material The online version of this article (10.1007/s10522-018-9758-4) contains supplementary material, which is available to authorized users.

Rationale: Systemic sclerosis (SSc)-associated pulmonary arterial hypertension (PAH) portends worse outcome than other forms of PAH. Vasoconstrictive and vascular remodeling actions of endothelin (ET) 1 and angiotensin (Ang) II via endothelin receptor type A (ETAR) and Ang receptor type-1 (AT1R) activation are implicated in PAH pathogenesis.Objectives: We hypothesized that stimulating autoantibodies (Abs) targeting and activating AT1R and ETAR may contribute to SSc-PAH pathogenesis, and tested their functional and biomarker relevance.Methods: Anti-AT1R and -ETAR Abs were detected by ELISA in different cohorts of patients and tested in vitro and in an animal model for their pathophysiological effects.Measurements and Main Results: The Abs were significantly higher and more prevalent in patients with SSc-PAH (n = 81) and connective tissue disease–associated PAH (n = 110) compared with other forms of PAH/pulmonary hypertension (n = 106). High anti-AT1R and anti-ETAR Abs predicted development of SSc-PAH and S...

Longevity and lifetime productivity are important factors influencing profitability for the cow-calf producer. Heifers that conceive earlier in the breeding season will calve earlier in the calving season and have a longer interval to rebreeding. Calves born earlier in the calving season will also be older and heavier at weaning. Longevity data were collected on 2,195 heifers from producers in South Dakota Integrated Resource Management groups. Longevity and weaning weight data were collected on 16,549 individual heifers at the U.S. Meat Animal Research Center (USMARC). Data were limited to heifers that conceived during their first breeding season. Heifers were grouped into 21-d calving periods. Heifers were determined to have left the herd when they were diagnosed not pregnant at the end of the breeding season. Heifers that left the herd for reasons other than reproductive failure were censored from the data. Heifers that calved with their first calf during the first 21-d period of the calving season had increased (P < 0.01) longevity compared with heifers that calved in the second 21-d period, or later. Average longevity for South Dakota heifers that calved in the first or later period was 5.1 ± 0.1 and 3.9 ± 0.1 yr, respectively. Average longevity for USMARC heifers that calved in the first, second, or third period was 8.2 ± 0.3, 7.6 ± 0.5, and 7.2 ± 0.1 yr, respectively. Calving period as a heifer influenced (P < 0.01) unadjusted weaning BW of the first 6 calves. Estimated postpartum interval to conception as a 2-yr-old cow was greater for females that calved in the first period as heifers but did not differ between heifer calving periods in subsequent calving seasons. In summary, heifers that calved early in the calving season with their first calf had increased longevity and kilograms weaned, compared with heifers that calved later in the calving season.

Sauerstoff ist das bekannteste Notfallmedikament und ist allgemein akzeptiert. Als Teil nahezu jeder Notfalltherapie wird Sauerstoff regelmasig in hohen Dosen eingesetzt und galt lange als praktisch nebenwirkungsfrei. Daten der letzten 2 Jahrzehnte zeigen mogliche negative Effekte einer Hyperoxie besonders in der Postreanimationsphase und beim Myokardinfarkt auf. Eine kritische Betrachtung dieser Daten sollte die Grundlage eines rationalen Einsatzes von Sauerstoff in der Notfallmedizin sein.

Acute antibody-mediated rejection is the major cause of graft failure in the early stage of kidney transplantation. Preoperative treatment and early diagnosis of acute rejection is very important to prevent graft loss in sensitized patients. High panel reactive antibody (PRA) means a likelihood of acute rejection, and the recipient of high PRA needs adequate pretreatment for kidney transplantation. However, there is not sufficient time and chances for desensitization in deceased kidney transplants. We report a successful renal transplant outcome in a 47-year-old-woman with high PRA levels (Class I 97.5%, Class II 36.7%). The cross match was negative on the CDC (ELISA) and flowcytometric methods. Plasma exchange was performed on the recipient before transplantation (fresh frozen plasma replacement, 1.3 plasma volume) and immediately after plasma exchange she was given 200 mg of rituximab. She received basiliximab and methyl prednisolone induction therapy and was maintained on steroids, mycophenolate mofetil, and tacrolimus. Graft function was normal immediately after transplantation, but decreased urinary output and elevated serum creatinine was noted on POD 5. On POD 6, a graft biopsy revealed acute cellular rejection (Type IIa) and antibody-mediated rejection (Type II). On 9∼13 days after transplantation, additional plasma exchange was performed every other day, and steroid pulse therapy was performed 3 times. After normalization of urinary output and serum creatinine, the patient was discharged and is being followed up on. In conclusion, immunologically careful preparation and pretransplant treatment may be needed on the negative cross match in cadaveric kidney recipients with high levels of PRA.

Hutchinson-Gilford Progeria Syndrome (HGPS) is a severe premature aging syndrome that affects children. These children display characteristics associated with normal aging and die young usually from cardiovascular problems or stroke. Classical HGPS is caused by mutations in the gene encoding the nuclear structural protein lamin A. This mutation leads to a novel version of lamin A that retains a farnesyl group from its processing. This protein is called Progerin and is toxic to cellular function. Pre-lamin A is an immature version of lamin A and also has a farnesylation modification, which is cleaved in the maturation process to create lamin A.

BackgroundIrregular sleep–wake cycles and cognitive impairment are frequently observed in schizophrenia, however, how they interact remains unclear.AimsTo investigate the repercussions of circadian rhythm characteristics on cognitive performance and psychopathology in individuals with schizophrenia.MethodFourteen middle-aged individuals diagnosed with schizophrenia underwent continuous wrist actimetry monitoring in real-life settings for 3 weeks, and collected saliva samples to determine the onset of endogenous melatonin secretion as a circadian phase marker. Moreover, participants underwent multiple neuropsychological testing and clinical assessments throughout the study period.ResultsSleep–wake cycles in individuals with schizophrenia ranged from well entrained to highly disturbed rhythms with fragmented sleep epochs, together with delayed melatonin onsets and higher levels of daytime sleepiness. Participants with a normal rest–activity cycle (objectively determined by high relative amplitude of day/night activity) performed significantly better in frontal lobe function tasks. Stepwise regression analysis revealed that relative amplitude and age represented the best predictors for cognitive performance (Stroop colour–word interference task, Trail Making Test A and B, semantic verbal fluency task), whereas psychopathology (Positive and Negative Syndrome Scale) did not significantly correlate with either cognitive performance levels or the quality of sleep–wake cycles.ConclusionsConsolidated circadian rhythms and sleep may be a prerequisite for adequate cognitive functioning in individuals with schizophrenia.

Daily routine procedures in anesthesia may be associated with critical events including cardiac arrest. Therefore every anesthesiologist must be informed completely about standards and guidelines for resuscitation to provide adequate patient safety. In October 18 (th), 2010, new international guidelines for resuscitation were published. The main changes in these resuscitation guidelines are described.

In regional anaesthesia, there is a risk of direct nerve injury. The purpose of this study was to determine whether the diameter of the applied needle is associated with the magnitude of nerve injury after needle nerve perforation.In five anaesthetized pigs, the brachial plexus were exposed bilaterally. Up to eight nerves underwent needle nerve perforation using a 24 G pencil-point cannula (small diameter) or a 19 G pencil-point needle (large diameter). After 48 h, the nerves were resected during anaesthesia. The specimens were processed for visual examination and the detection of inflammatory cells, myelin damage and intraneural haematoma. The grade of nerve injury was scored ranging from 0 (no injury) to 4 (severe injury).Forty-eight nerves were examined. The applied injury score was significantly lower in the small-diameter group [median (inter-quartile range) 2.0 (2.0-2.0)] compared with the large-diameter group [3.5 (3.0-4.0) P0.01]. Myelin damage and intraneural haematoma occurred predominantly in the large-diameter group. Signs of post-traumatic regional inflammation were comparable among both groups.The severity of nerve injury after needle nerve perforation was related to the diameter of the applied cannula. However, no such difference exists for regional inflammation. Functional consequences of these findings need to be determined. Currently, small-diameter cannulae may be advisable for peripheral nerve blocks to minimize the risk of nerve injury in the case of nerve perforation.

HGPS (Hutchinson–Gilford progeria syndrome) is a rare genetic disease affecting children causing them to age and die prematurely. The disease is typically due to a point mutation in the coding sequence for the nuclear intermediate-type filament protein lamin A and gives rise to a dominant-negative splice variant named progerin. Accumulation of progerin within nuclei causes disruption to nuclear structure, causes and premature replicative senescence and increases apoptosis. Now it appears that accumulation of progerin may have more widespread effects than previously thought since the demonstration that the presence and distribution of some nucleolar proteins are also adversely affected in progeria cells. One of the major breakthroughs both in the lamin field and for this syndrome is that many of the cellular defects observed in HGPS patient cells and model systems can be restored after treatment with a class of compounds known as FTIs (farnesyltransferase inhibitors). Indeed, it is demonstrated that FTI-277 is able to completely restore nucleolar antigen localization in treated progeria cells. This is encouraging news for the HGPS patients who are currently undergoing clinical trials with FTI treatment. Abbreviations: DFC, dense fibrillar component; FC, fibrillar centre; FTI, farnesyltransferase inhibitor; HGPS, Hutchinson–Gilford progeria syndrome; rDNA, ribosomal DNA

The laminopathy Hutchinson–Gilford progeria syndrome (HGPS) is caused by the mutant lamin A protein progerin and leads to premature aging of affected children. Despite numerous cell biological and biochemical insights into the basis for the cellular abnormalities seen in HGPS, the mechanism linking progerin to the organismal phenotype is not fully understood. To begin to address the mechanism behind HGPS using Drosophila melanogaster, we have ectopically expressed progerin and lamin A. We found that ectopic progerin and lamin A phenocopy several effects of laminopathies in developing and adult Drosophila, but that progerin causes a stronger phenotype than wild-type lamin A.

The prehospital management of patients with severe trauma should focus on stabilization of vital signs. Major goal is the early transport in a specialized trauma center. After immobilization of cervical spine maintenance of oxygen delivery is the primary and most important intervention. Unconscious patients and patients with respiratory distress should receive endotracheal intubation and controlled ventilation on scene. Amounts of Infusion should be decided on blood loss, patients with traumatic brain injury need at least a normotensive blood pressure. Patients with uncontrolled severe bleeding should not receive excessive infusion before urgent surgical treatment can be performed. Prehospital induction of anesthesia must be carefully considered because of the enhanced risk.

To evaluate the association of subretinal hyperreflective material (SHRM) with visual acuity (VA), geographic atrophy (GA), and scar in the Comparison of Age-Related Macular Degeneration Treatments Trials (CATT).Prospective cohort study within a randomized clinical trial.The 1185 CATT participants.Masked readers graded scar and GA on fundus photography and fluorescein angiography and graded SHRM on time-domain and spectral-domain (SD) optical coherence tomography (OCT) throughout 104 weeks. Measurements of SHRM height and width in the fovea, within the center 1 mm(2), or outside the center 1mm(2) were obtained on SD OCT images at 56 (n = 76) and 104 (n = 66) weeks.Presence of SHRM, as well as location and size, and associations with VA, scar, and GA.Among CATT participants, the percentage with SHRM at enrollment was 77%, decreasing to 68% at 4 weeks after treatment and to 54% at 104 weeks. At 104 weeks, scar was present more often in eyes with persistent SHRM than in eyes with SHRM that resolved (64% vs. 31%; P0.0001). Among eyes with detailed evaluation of SHRM at weeks 56 (n = 76) and 104 (n = 66), mean VA letter score was 73.5 (standard error [SE], 2.8), 73.1 (SE, 3.4), 65.3 (SE, 3.5), and 63.9 (SE, 3.7) when SHRM was absent, present outside the central 1 mm(2), present within the central 1 mm(2) but not the foveal center, or present at the foveal center (P = 0.02), respectively. When SHRM was present, the median maximum height under the fovea, within the central 1 mm(2) including the fovea and anywhere within the scan, was 86 μm, 120 μm, and 122 μm, respectively. Visual acuity was decreased with greater SHRM height and width (P0.05).In eyes with neovascular age-related macular degeneration (AMD), SHRM is common and often persists after anti-vascular endothelial growth factor treatment. At 2 years, eyes with scar were more likely to have SHRM than other eyes. Greater SHRM dimensions were associated with worse VA. In eyes with neovascular AMD, SHRM is an important morphologic biomarker.

Circulating antinuclear autoantibodies contribute to the diagnosis of systemic sclerosis (SSc) and correlate with disease-specific organ manifestations. Recent findings show the induction of interstitial lung disease and obliterative vasculopathy by transfer of IgG from SSc patients in healthy mice indicating a contribution of antibodies to SSc pathogenesis. Several functional or agonistic autoantibodies have been described in SSc, thus putting autoimmunity into a new spotlight. Autoantibodies against the angiotensin II receptor type-1 and the endothelin1 receptor type-A are associated with severe disease and provide new insights into its pathogenesis. They link the hallmarks of SSc, vasculopathy, immune activation, and fibrosis. At present, the contribution of the specific antibodies to disease manifestations remains to be examined. However; functional autoantibodies could represent a significant piece in the puzzle of SSc pathogenesis and may open new gateways and opportunities for therapeutic intervention. This review focuses on the features of functional autoantibodies in SSc.

The ex-utero intra-partum (EXIT) procedure enables the surgeon to perform invasive procedures in an infant during cesarean section before clamping the umbilical cord. Specific anesthesiological concepts are necessary for ensuring sufficient umbilical perfusion. We report the case of a 33-year-old female undergoing cesarean section in the 36th week of pregnancy because of a large fetal cervical tumor. The EXIT procedure was performed in order to secure the infant's airway during delivery. The anesthesiological management and interdisciplinary tasks are discussed in the literature review.

Introduction: Upon analysis of the risk factors affecting renal graft survival and function, the time-dependent effects of each risk factor should be differentiated from their net effects. To evaluate the chronologically different impacts of risk factors on graft renal function, we reviewed 390 recipients who received a kidney from 1-haplotype-matched living-related donors. Materials and methods: Until 5-yr post-transplantation (TX), yearly serum creatinine (Scr), 24-h urinary excretion of protein, and their yearly changes were compared by the episodes of acute rejection within 1 yr, the kidney weight to recipient body weight (KW/BW) ratio, the donor/recipient (D/R) age ratio, and the D/R gender pairing. The Kaplan–Meier method, Cox proportional hazard model, ANOVA, and repeated measures ANOVA were each applied for different purposes. Results: Only the episodes of acute rejection were a significant risk factor affecting graft survival. The episodes of acute rejection, KW/BW ratio, D/R age ratio, and D/R gender pairing consistently and independently had significant influences on Scr. Recipients having the lowest KW/BW ratio (first quartile) or the highest D/R age ratio (fourth quartile) had rapid increments of Scr after 4-yr post-TX. After 3-yr post-TX, there were significant correlations between the number of non-immunologic risk factors present and the yearly changes in Scr. Conclusions: Non-immunologic factors had a detrimental effect on renal graft function, especially after 3-yr post-TX. If immunologic risks seem to be similar, size matching, age, and gender pairing should be considered for better long-term graft function in renal TX recipients.

Die Versorgung polytraumatisierter Patienten in der Akutphase ist ein Musterbeispiel fach- und berufsgruppenubergreifender Zusammenarbeit unter besonders zeitkritischen Bedingungen. Mit der Leitlinie Polytrauma der Deutschen Gesellschaft fur Unfallchirurgie (DGU) sind umfassende Anforderungen formuliert, deren Ubertragung in die Praxis zusatzliche Prozessbeschreibungen erfordert. Auf der Basis der Leitlinie und anhand validierter Qualitatsindikatoren wurde die optimale Versorgungsqualitat als Soll-Zustand definiert.Unter Berucksichtigung lokaler Ressourcen wurden im Konsens aller an der Versorgung Beteiligten die wichtigsten Interventionen und Entscheidungsebenen in logischer Sequenz dargestellt (klinischer Algorithmus) und personelle Zustandigkeiten mit Zeitbezug festgelegt. Optimierungspotenziale wurden in Bereichen identifiziert, fur die in der Leitlinie keine expliziten Empfehlungen gemacht werden. Diese bilden die zentralen Elemente des Algorithmus. Zur Gewahrleistung der Kontinuitat des Qualitatsmanagements wurden Indikatoren, Zeitfenster und Verantwortlichkeit fur eine Reevaluation des Ist-Zustands und die Uberarbeitung des Behandlungspfads definiert. Die Implementierung von Leitlinien erfordert auf lokaler Ebene eine problem- und prozessorientierte, arbeitsplatzspezifische Ausarbeitung im Konsens aller Beteiligten. Diese Ausarbeitung der Leitlinie zum Behandlungspfad ist die Basis der quantitativen Prozess- und Kostenanalyse.

Background Guidelines recommend mechanical ventilation with Intermitted Positive Pressure Ventilation (IPPV) during resuscitation. The influence of the novel ventilator mode Chest Compression Synchronized Ventilation (CCSV) on gas exchange and arterial blood pressure compared with IPPV was investigated in a pig model. Methods In 12 pigs (general anaesthesia/intubation) ventricular fibrillation was induced and continuous chest compressions were started after 3min. Pigs were mechanically ventilated in a cross-over setting with 5 ventilation periods of 4min each: Ventilation modes were during the first and last period IPPV (100% O2, tidalvolumes = 7ml/kgKG, respiratoryrate = 10/min), during the 2nd, 3rd and 4th period CCSV (100% O2), a pressure-controlled and with each chest compression synchronized breathing pattern with three different presets in randomized order. Presets: CCSVA: Pinsp = 60mbar, inspiratorytime = 205ms; CCSVB: Pinsp = 60mbar, inspiratorytime = 265ms; CCSVC: Pinsp = 45mbar, inspiratorytime = 265ms. Blood gas samples were drawn for each period, mean arterial (MAP) and centralvenous (CVP) blood pressures were continuously recorded. Results as median (25%/75%percentiles). Results Ventilation with each CCSV mode resulted in higher PaO2 than IPPV: PaO2: IPPVfirst: 19.6(13.9/36.2)kPa, IPPVlast: 22.7(5.4/36.9)kPa (p = 0.77 vs IPPVfirst), CCSVA: 48.9(29.0/58.2)kPa (p = 0.028 vs IPPVfirst, p = 0.0001 vs IPPVlast), CCSVB: 54.0 (43.8/64.1) (p = 0.001 vs IPPVfirst, p = 0.0001 vs IPPVlast), CCSVC: 46.0 (20.2/58.4) (p = 0.006 vs IPPVfirst, p = 0.0001 vs IPPVlast). Both the MAP and the difference MAP-CVP did not decrease during twelve minutes CPR with all three presets of CCSV and were higher than the pressures of the last IPPV period. Conclusions All patterns of CCSV lead to a higher PaO2 and avoid an arterial blood pressure drop during resuscitation compared to IPPV in this pig model of cardiac arrest.

Supracervical hysterectomy, a surgical technique that involves removal of the uterus while preserving the cervix, places women at an increased risk for future morbidity.The patient presented 7 years after laparoscopic supracervical hysterectomy for benign disease, with pelvic pain, urinary frequency, abdominal bloating, and tenderness. Surgical exploration revealed myometrial implants, along with a larger mass on the mesentery of the sigmoid composed of endometrium with complex atypical hyperplasia in a patient without a prior history of complex atypical hyperplasia. The patient was symptom-free 6 months postoperatively.Histology found during reoperation after laparoscopic supracervical hysterectomy includes endometriosis, residual endometrium, and leiomyomas. In this case, a woman with no prior history of endometrial atypia later developed complex adenomatous endometrial hyperplasia in a peritoneal implant. This finding adds to the list of possible complications after laparoscopic-assisted supracervical hysterectomy and uterine morcellation.

OBJECTIVE Investigation of blood gas analysis during hospital-to-hospital transport of ventilated ICU-patients to detect critical events, changes of gas exchange and reliability of non-invasive monitoring. METHODS 47 ventilated patients (age 9-76 years, mean 50 years, diagnosis: ARDS = 16, intracranial bleeding = 14, severe trauma = 4, acute hemodynamic failure = 3, others = 10), transported by a special physician staffed intensive care ambulance using invasive hemodynamic monitoring. Blood gas analysis was performed before and during transport every 30 minutes and respirator mode, vital signs and events were documented. RESULTS In 19 (40.4%) patients there were critical events during transport (paO2 55 mmHg, pH 7.55). In 4 patients with PaO2 or = 97% (by pulsoximetry), correlation between SaO2 (invasive) and SpO2 (by pulsoximetry) was r = 0.81 (P < 0.001) with a maximum difference of 8 percent. In several patients critical changes of condition could be recognized in an early stage by blood gas analysis. CONCLUSIONS Blood gas analysis during hospital-to-hospital transport of ICU-patients can be performed easily and allows to optimize artificial ventilation and to recognize earlier and safer severe problems of gas exchange.

The genomes of a wide range of different organisms are non-randomly organized within interphase nuclei. Chromosomes and genes can be moved rapidly, with direction, to new non-random locations within nuclei upon a stimulus such as a signal to initiate differentiation, quiescence or senescence, or also the application of heat or an infection with a pathogen. It is now becoming increasingly obvious that chromosome and gene position can be altered in diseases such as cancer and other syndromes that are affected by changes to nuclear architecture such as the laminopathies. This repositioning seems to affect gene expression in these cells and may play a role in progression of the disease. We have some evidence in breast cancer cells and in the premature aging disease Hutchinson–Gilford Progeria that an aberrant nuclear envelope may lead to genome repositioning and correction of these nuclear envelope defects can restore proper gene positioning and expression in both disease situations.

Pregnancy, due to its adaptive physiological changes, is a risk factor for deep vein thrombosis. Incidence of thromboembolic complications during pregnancy ranges from 0.76 to 1.72 per 1000 births. We present in this case report a pregnant woman with iliofemoral-popliteal deep vein thrombosis diagnosed at the 35(th) week of her pregnancy, who was treated with vena cava blockage and thrombectomy followed by cesarean section. Unfortunately, a rethrombosis developed in the patient after three days. We determined that the a-v fistula was blocked and not working. We found additionally that the deep vein thrombosis was closing the iliac vein completely on the left side and the blockage descending down through the inferior vena cava inlet with MRI. The patient underwent insertion of a retrievable vena cava filter, two stent implantation to the venous narrowings and surgical iliofemoral venous thrombectomy with concomitant re-creation of a temporary femoral arterio-venous fistula. Anticoagulation therapy with enoxaparine was started after the operation. The patient was discharged with warfarin under control of the INR value, and also with additional compression therapy (compression stockings) from the clinic. Without jeopardizing the mother and the baby, planning a combined surgical procedure, with a multidisciplinary approach is the best way to eliminate the risks of serious complications such as pulmonary embolism and mortality.Gebelik, bu dönemdeki fizyolojik değişikliklere bağlı olarak, derin ven trombozu açısından bir risk faktörüdür. Gebelik sırasındaki tromboembolik komplikasyonların insidansı her 1000 doğumda 0.76 ila 1.72 arasında değişir. Biz bu olgu sunumunda, gebeliğin 35. haftasında iliofemoral-popliteal derin ven trombozu tanısı konan ve vena kava blokajı ve trombektomiyi takiben sezaryen seksiyo ile tedavi edilen bir gebeyi sunuyoruz. Ne yazık ki bu hastada üç gün sonra tekrar tromboz gelişti. Arterio-venöz fistülün tıkandığını ve çalışmadığını saptadık. Ayrıca MR görüntüleme ile sol tarafta iliak venin tamamen tıkandığını ve tıkanıklığın aşağıda inferior vena kavanın girişine kadar uzandığını tespit ettik. Hastaya çıkarılabilir vena kava filtresi yerleştirildi, venöz daralma bölgelerine iki stent yerleştirildi, cerrahi olarak iliofemoral venöz trombektomi yapıldı ve eşzamanlı olarak geçici femoral arterio-venöz fistül yeniden oluşturuldu. Operasyondan sonra enoxaparine ile antikoagulan tedavi başlandı. Hasta INR kontrolü altında warfarin ve ek olarak kompresyon tedavisi (kompresyon çorapları) ile klinikten taburcu edildi. Pulmoner emboli ve ölüm gibi ciddi komplikasyon risklerini, anne ve bebeğin hayatını tehlikeye atmadan, elimine etmenin en iyi yolu multidisipliner yaklaşımla kombine cerrahi işlemlerin planlanmasıdır.

Introduction Sudden cardiac arrest is one of the most frequent causes of death in the world. In highly qualified emergency medical service (EMS) systems, including well-trained emergency physicians, spontaneous circulation may be restored in up to 53% of patients at least until admission to hospital. Compared with these highly qualified EMS systems, markedly lower success rates are observed in other systems. These data clearly show that there are considerable differences between EMS systems concerning treatment success following cardiac arrest and resuscitation, although in all systems international guidelines for resuscitation are used. In this study, we investigated the impact of response time reliability (RTR) on cardiopulmonary resuscitation (CPR) incidence and resuscitation success by using the return of spontaneous circulation (ROSC) after cardiac arrest (RACA) scores and data from seven German EMS systems participating in the German Resuscitation Registry. Methods Anonymised patient data after out-of-hospital cardiac arrest gathered from seven EMS systems in Germany from 2006 to 2009 were analysed with regard to socioeconomic factors (population, area and EMS unit-hours), process quality (RTR, CPR incidence, special CPR measures and prehospital cooling), patient factors (age, gender, cause of cardiac arrest and bystander CPR). End points were defined as ROSC, admission to hospital, 24-hour survival and hospital discharge rate. χ2 tests, odds ratios and the Bonferroni correction were used for statistical analyses. Results Our present study comprised 2,330 prehospital CPR patients at seven centres. The incidence of sudden cardiac arrest ranged from 36.0 to 65.1/100,000 inhabitants/year. We identified two EMS systems (RTR < 70%) that reached patients within 8 minutes of the call to the dispatch centre 62.0% and 65.6% of the time, respectively. The other five EMS systems (RTR > 70%) reached patients within 8 minutes of the call to the dispatch centre 70.4% up to 95.5% of the time. EMS systems arriving relatively later at the patients side (RTR < 70%) initiate CPR less frequently and admit fewer patients alive to hospital (calculated per 100,000 inhabitants/year) (CPR incidence (1/100,000 inhabitants/year) RTR > 70% = 57.2 vs RTR < 70% = 36.1, OR = 1.586 (99% CI = 1.383 to 1.819); P < 0.01) (admitted to hospital with ROSC (1/100,000 inhabitants/year) RTR > 70% = 24.4 vs RTR < 70% = 15.6, OR = 1.57 (99% CI = 1.274 to 1.935); P < 0.01). Using ROSC rate and the multivariate RACA score to predict outcomes, we found that the two groups did not differ, but ROSC rates were higher than predicted in both groups (ROSC RTR > 70% = 46.6% vs RTR < 70% = 47.3%, OR = 0.971 (95% CI = 0.787 to 1.196); P = n.s.) (ROSC RACA RTR > 70% = 42.4% vs RTR < 70% = 39.5%, OR = 1.127 (95% CI = 0.911 to 1.395); P = n.s.) Conclusion This study demonstrates that, on the level of EMS systems, faster ones more often initiate CPR and increase the number of patients admitted to hospital alive. Furthermore, we show that, with very different approaches, all centres that adhere to and are intensely trained according to the 2005 European Resuscitation Council guidelines are superior and, on the basis of international comparisons, achieve excellent success rates following CPR. peerReviewed

BACKGROUND: Continuous peripheral nerve blocks typically are performed with a “through-the-needle technique” and require needles with an inner diameter allowing catheter placement. In case of direct needle–nerve contact, the pencil-point needletip is currently considered less traumatic than are other needle configurations. In this study we determined whether nerve puncture with pencil-point needles is associated with fewer nerve injuries in comparison with Tuohy needles. METHODS: In 6 anesthetized pigs the brachial plexus were exposed bilaterally. Up to 8 nerves underwent nerve puncture with a pencil-point or a Tuohy needle. After 48 hours, the nerves were resected during anesthesia. The specimens were processed for visual examination and the detection of inflammatory cells, myelin damage, and intraneural hematoma. The grade of nerve injury was assessed using an objective score ranging from 0 (no injury) to 4 (severe injury). RESULTS: Fifty-eight nerves, including controls, were examined. According to the applied injury score, there was no significant difference between the pencil-point needle group [median (interquartile range) 3 (3–4)] and the Tuohy needle group [3 (3–4) P = 0.97]. The occurrence of posttraumatic regional inflammation, myelin damage, and intraneural hematoma was similarly high in both groups. CONCLUSIONS: Regardless of the needletip configuration applied for nerve puncture, pencil-point and Tuohy needletips may both lead to comparable magnitude of posttraumatic inflammation and considerable structural changes within the nerve. No significant differences were found comparing pencil-point with Tuohy tip–configured needles.

BackgroundSystemic sclerosis (SSc) features autoimmunity, vasculopathy and tissue fibrosis. The renin-angiotensin and endothelin systems have been implicated in vasculopathy and fibrosis. A role for autoantibody-mediated receptor stimulation is hypothesised, linking three major pathophysiological features consistent with SSc.MethodsSerum samples from 478 patients with SSc (298 in the study cohort and 180 from two further independent cohorts), 372 healthy subjects and 311 control-disease subjects were tested for antibodies against angiotensin II type 1 receptor (AT1R) and endothelin-1 type A receptor (ETAR) by solid phase assay. Binding specificities were tested by immunoprecipitation. The biological effects of autoantibodies in microvascular endothelial cells in vitro were also determined, as well as the quantitative differences in autoantibody levels on specific organ involvements and their predictive value for SSc-related mortality.ResultsAnti-AT1R and anti-ETAR autoantibodies were detected in most patients with SSc. Autoantibodies specifically bound to respective receptors on endothelial cells. Higher levels of both autoantibodies were associated with more severe disease manifestations and predicted SSc-related mortality. Both autoantibodies exert biological effects as they induced extracellular signal-regulated kinase 1/2 phosphorylation and increased transforming growth factor β gene expression in endothelial cells which could be blocked with specific receptor antagonists.ConclusionsFunctional autoimmunity directed at AT1R and ETAR is common in patients with SSc. AT1R and ETAR autoantibodies could contribute to disease pathogenesis and may serve as biomarkers for risk assessment of disease progression.