Verhandlungen Ärztlicher Gesellschaften

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Prior intake of new oral anticoagulants adversely affects outcome following surgery for acute type A aortic dissection

Open in a separate window OBJECTIVESOral anticoagulation prior to emergency surgery is associated with an increased risk of perioperative bleeding, especially when this therapy cannot be discontinued or reversed in time. The goal of this study was to analyse the impact of different oral anticoagulants on the outcome of patients who underwent emergency surgery for acute type A aortic dissection (ATAAD).METHODSThis was a single-centre retrospective study of patients treated with oral anticoagulation at the time of surgery for ATAAD. Outcomes of patients on new oral anticoagulant (NOAC) therapy were compared to respective outcomes of patients on Coumadin. Additionally, a survival analysis was performed comparing these 2 groups with patients who were operated on with no prior anticoagulation.RESULTSBetween January 2013 and April 2020, a total of 437 patients (63.8 ± 11.8 years, 68.4% male) received emergency surgery for ATAAD; 35 (8%) were taking oral anticoagulation at the time of hospital admission: 20 received phenprocoumon; 14, rivaroxaban; and 1, dabigatran. Compared to Coumadin, NOAC was associated with a greater need for blood-product transfusions and haemodynamic compromise. Operative mortality was 53% in the NOAC group and 30% in the Coumadin group. A 5-year survival analysis showed no significant difference between the NOAC and the Coumadin group (P = 0.059). Compared to 402 patients treated during the study period without anticoagulation, patients taking NOAC had significantly worse survival (P = 0.001), whereas that effect was not observed in patients undergoing surgery who were taking Coumadin (P = 0.99).CONCLUSIONSEmergency surgery for ATAAD in patients taking NOAC is associated with high morbidity and mortality. NOAC are a major risk factor for uncontrollable bleeding and haemodynamic compromise. New treatment strategies must be defined to improve surgical outcomes in these high-risk patients.     

Studies of women eating diets with different fatty acid composition. III. Fatty acids and prostaglandin synthesis by platelets and cultured human endothelial cells.

The aim of this study was to determine how plasma fatty acids (FA) of subjects eating either a diet designed to match the US diet consumed in 1974 in fat content and composition in accord with the HANES I survey (US74) or a diet modified to meet the US Dietary Goal Recommendations (MOD) are altered, and how the changes affect platelet thromboxane (TXB2) synthesis, and prostacyclin (PGI2) and prostaglandin E2 (PGE2) synthesis by cultured human endothelial cells. Following a period of recorded self-selected diets, 10 women ate the US74 diet for 4 weeks, changing to the MOD diet for the next 4 weeks (sequence 1), and 10 ate the MOD diet followed by the US74 diet (sequence 2). Plasma triglycerides, free FA, platelet FA composition, and red blood cell phospholipids responded to the change from self-selected to controlled diets, but differences in responses were not seen between US74 and MOD diets. Red blood cell total FA did not respond to dietary changes. Under collagen but not thrombin stimulation, platelet TXB2 synthesis was correlated with platelet arachidonate concentration but not serum cholesterol. Endothelial cells were isolated from umbilical cord veins and incubated for 72 hours with a 20% medium of the women's plasma. In sequence 1 (high saturated FA to high polyunsaturated fatty acids), but not in 2 (reverse order), plasma from subjects eating the MOD diet decreased (p less than 0.05) basal and thrombin-stimulated PGI2 and PGE2 synthesis by the cells. These cells had a higher content of linoleic acid than cells from subjects eating the US74 diet. Thus, our study suggests that an increase in the intake of linoleic acid from 4.8 to 7.6 en% decreases PGI2 and PGE2 synthesis by human endothelial cells, and supplementation of the diet with linoleic acid has a longer period of effectiveness than its decrease in the diet.     

The Diurnal Variation of the Serum Iron Concentration

Observations made in an investigation of the diurnal variation of the serum iron concentration suggested that the diurnal variations of serum iron can be explained as a phenomenon secondary to the diurnal variation of the hemoglobin metabolism. This hypothesis is supported by parallel changes in the bilirubin and serum iron values.     

Increased incidence in post-transplant diabetes mellitus in children: a case-control analysis

There is limited information regarding the incidence and features of post-transplant diabetes mellitus (PTDM) in pediatric renal transplant recipients. We noted a recent increased frequency of PTDM and reviewed charts of children who underwent renal transplantation from 1 September 1986 to 31 August 1999 to characterize the risk factors and natural history of PTDM. Sixteen children were identified with PTDM, and were each matched with two transplanted controls who did not develop PTDM. Clinical presentation varied from asymptomatic hyperglycemia to hyperosmolar dehydration or diabetic ketoacidosis. The mean time from transplantation to PTDM presentation was 1.2 years (range 1 day to 6.2 years). Significant risk factors for PTDM included: first degree family history of type 2 DM [odds ratio (OR) 23.9]; second degree family history of type 2 DM (OR 5.8); tacrolimus use (OR 9.1 versus cyclosporin); and hyperglycemia in the 2 weeks immediately after transplantation (OR 4.7). Seven of eight children with persistent PTDM continue to receive insulin. Patients with persistent PTDM had later onset disease (mean 1.9 years) compared to those with transient PTDM (0.3 years), suggesting different pathophysiologic processes. We suggest that all children undergoing renal transplantation be screened routinely for PTDM after transplantation, and that such patients may benefit from the avoidance of tacrolimus, as it may cause permanent beta-cell injury. Received: 23 March 2001 / Revised: 23 August 2001 / Accepted: 24 August 2001     

Jagged1 ablation results in cerebellar granule cell migration defects and depletion of Bergmann glia

Jagged1 is a ligand for members of the Notch family of receptors. Mutations in the human JAG1 gene are the major cause of Alagille syndrome, an autosomal dominant disorder affecting the liver, heart, eye, skeleton, kidneys, and craniofacial structures. Although expressed throughout mammalian embryonic development and in the adult, the function of Jagged1 in the central nervous system is not clear. Jagged1 is broadly expressed in the cerebellum suggesting an important role in Notch signaling. In order to address the function of Jagged1 in the mouse central nervous system, we have inactivated the Jag1 gene in the cerebellar primordium at mid-embryogenesis. Loss of Jagged1 results in aberrant granule cell migration and ectopic differentiation in the external germinal layer and molecular layer of the early postnatal cerebellum. We show that Bergmann glia in the cerebellum lose contact to the pial surface and have stunted processes. In vitro analysis revealed a depletion of Bergmann glia in the Jagged1 mutant mice. Our findings suggest that Jagged1 plays a role in cell fate specification and survival in the cerebellum.     

Survival and prognostic factors in chondrosarcoma: results in 115 patients with long-term follow-up

Background and purpose

There have been few long-term studies on the outcome of chondrosarcoma and the findings regarding prognostic factors are controversial. We examined a homogeneous group of patients with primary central chondrosarcoma of bone who were treated according to a uniform surgical protocol at our institution, in order to determine the factors that influence survival and identify potential improvements to our therapeutic algorithm.

Patients and methods

We performed a retrospective analysis of 115 patients with primary central chondrosarcoma of bone who presented with localized disease and who had a minimum follow-up of 5 years after diagnosis. 68 tumors were localized in the extremities and 47 in the axial skeleton or pelvis. 59 patients had a high-grade (II and III) and 56 a low-grade (I) tumor. 94 patients underwent surgical resection with adequate (wide or radical) margins, while 21 patients had inadequate (marginal or intralesional) margins.

Results

Tumor grade and localization were found to be statistically significant independent predictors of disease-related deaths in multivariate analysis. The quality of surgical margins did not influence survival. The AJCC staging system was able to predict prognosis in patients with chondrosarcoma of the extremities, but not in those with tumors of the axial skeleton and pelvis. Long-term survival after secondary metastatic disease was only observed when metastases were resected with wide margins. Patients with metastases who received further treatment with conventional chemotherapy, radiotherapy, and/or further surgery had significantly better survival compared to those who received best supportive care.

Interpretation

The outcome in patients with primary central chondrosarcoma of bone who present with localized disease is mostly affected by tumor-related parameters.Chondrosarcoma is the second most common primary malignant solid tumor of bone, and accounts for approximately 25% of all bone sarcomas (Bertoni et al. 2002). It is largely considered to be resistant to conventional chemotherapy and radiotherapy (Healey and Lane 1986, Campanacci 1999, Gelderbloom et al. 2008). As such, surgical resection has been the cornerstone of treatment for over 50 years (Dahlin and Henderson 1956, Healey and Lane 1986, Gelderbloom et al. 2008). However, in recent years several novel therapeutic approaches have been evaluated in experimental studies (Morioka et al. 2003, Gouin et al. 2006, Klenke et al. 2007, Delaney et al. 2009, Schrage et al. 2009, 2010).There is no consensus on prognostic factors to determine which patients have a higher risk of treatment failure and disease-related deaths, although several papers have addressed this issue (Evans et al. 1977, Pritchard et al. 1980, Gitelis et al. 1981, Björnsson et al. 1998, Lee et al. 1999, Rizzo et al. 2001, Fiorenza et al. 2002). One reason may be that most studies have included patients treated over several decades, with no account for the different surgical criteria, indications, and methods applied over the years. Furthermore, most studies have included patients with short follow-up, despite the fact that a high rate of late recurrence and metastasis has been reported for chondrosarcoma patients compared to those with other primary bone sarcomas (Evans et al. 1977, Pritchard et al. 1980), as well as patients with rare histopathological subtypes that have a distinct biologic behavior (Lee et al. 1999, Bertoni et al. 2002, Gelderbloom et al. 2008) such as dedifferentiated chondrosarcoma, mesenchymal chondrosarcoma, and clear cell chondrosarcoma, thus reducing the validity of the results.The purpose of this long-term retrospective study was to examine a group of patients with primary central chondrosarcoma of bone who presented with localized disease and were treated with a uniform surgical protocol at our institution, in order to determine the factors that influence overall and event-free survival. We further aimed at identifying potential improvements to our therapeutic algorithm.     

Intrafascial nerve-sparing endoscopic extraperitoneal radical prostatectomy

OBJECTIVES: Based on our recently published anatomic studies, we present the most recent refinement of the endoscopic extraperitoneal radical prostatectomy (EERPE), the intrafascial nerve-sparing EERPE (nsEERPE). METHODS: As part of the intrafascial technique, the dissection plane is directly on the prostatic capsule, freeing the prostate laterally from its thin surrounding fascia that contains small vessels and nerves. The technique enables puboprostatic ligament preservation, leaving intact endopelvic fascia, periprostatic fascia, and neurovascular bundles. The operation was performed in 150 patients with indications for nerve-sparing procedure. RESULTS: The mean operative time was 131 min (range: 50-210 min) and the mean catheterization time was 5.9 d (range: 4-20 d). Twelve months postoperatively, 94.3% of the patients were continent (no need for pads), 4.6% had minimal stress incontinence, and one patient required >2 pads/d. At the 12-mo follow-up, the potency rates (erections sufficient for intercourse with or without the use of phosphodiesterase 5 [PDE5] inhibitors) of the patients who underwent bilateral intrafascial nsEERPE were 89.7% (age: 44-55 yr), 81.1% (age: 56-65 yr), and 61.9% (age: >65 yr). Positive surgical margins in pT2 and pT3 tumors were 4.5% and 29.4%, respectively. CONCLUSIONS: The intrafascial nsEERPE enables the dissection of the prostate with limited trauma to the surrounding fascias and the enclosed neurovascular bundles. We propose that the preserved neurovascular bundles with intrafascial nsEERPE are more viable. The results advocate this proposition.     

Role of stone analysis in metabolic evaluation and medical treatment of nephrolithiasis

BACKGROUND AND PURPOSE: Comprehensive metabolic evaluation has become an important aspect of the management of recurrent nephrolithiasis, yet the role of stone analysis is often neglected or perhaps underestimated. The purpose of this study was to determine the role of stone analysis in medical decision making in patients with recurrent nephrolithiasis. MATERIALS AND METHODS: We evaluated 100 consecutive stone-forming patients who had undergone compositional stone analysis as well as comprehensive metabolic evaluation at our institution. An analysis of stone composition in relation to metabolic disturbances was performed. Patients were stratified into two groups: calcium and non-calcium stone formers. RESULTS: Patients having non-calcium stones were found to have a metabolic analysis reflecting specific metabolic disorders. Alternatively, patients with calcium stones were heterogeneous with regard to metabolic disorders, but there was a significant likelihood of renal tubular acidosis in those patients with calcium phosphate calculi. On the basis of these results, a simplified metabolic evaluation and nonselective medical therapy based on stone composition was formulated to facilitate assessment, management, and monitoring of stone disease. CONCLUSIONS: Compositional stone analysis should be an integral part of the metabolic evaluation of patients with nephrolithiasis. Moreover, stone analysis alone may provide guidance for therapeutic treatment and obviate a formal metabolic evaluation.     

Characteristics of incidental prostatic adenocarcinoma in contemporary radical cystoprostatectomy specimens

OBJECTIVES: To investigate the relationship between prostate-specific antigen (PSA) level and tumour volume for incidental adenocarcinoma of the prostate found in cystoprostatectomy (CP) specimens, and to analyse the incidence of clinically significant prostate cancers in CP specimens and the biochemical recurrence of incidental prostate cancers on short-term follow up. PATIENTS AND METHODS: Complete data from 97 of 105 prostates from CP specimens were available. Prostates were thoroughly analysed and sectioned at 2 mm intervals. PSA levels and the findings at digital rectal examination before surgery were obtained prospectively. None of the patients had any evidence of prostate cancer before CP. RESULTS: Incidental prostate cancer was detected in 58 of 97 (60%) of the CP specimens; of these, 31 (53%) were significant according to the definition of Stamey et al. There was a weak correlation between tumour volume and PSA level, weighted solely by the four larger-volume cancers. The median PSA level for patients with and without prostate cancer was not significantly different (3.1 vs 1.1 ng/mL, P = 0.06). The follow-up of the 35 patients alive with prostate cancer showed four PSA recurrences (PSA >0.02 ng/mL) with one distant metastasis after a median follow-up of 3 years. None of the patients with insignificant tumours developed biochemical recurrence. CONCLUSIONS: The weak correlation between PSA level and tumour volume in these patients supports the argument that PSA is largely produced by benign prostatic hyperplasia and is therefore a poor screening tool for asymptomatic healthy men. Most incidental prostate cancers in CP specimens are significant, contrary to previous analyses, but have little practical importance in terms of oncological outcome.