Interstitial expression of alpha-SMA: an early marker of chronic renal allograft dysfunction.

BACKGROUND: Renal myofibroblast infiltration has been shown to be strongly associated with renal function decline in several chronic renal diseases. The purpose of the present study was to investigate whether early detection of myofibroblast infiltration using alpha-smooth-muscle actin (alpha-SMA) expression in time-zero biopsies predicts renal allograft dysfunction. METHODS: We studied renal tissue from 38 renal transplant patients from whom biopsies had been taken after vascular anastomosis during transplantation to ascertain whether myofibroblasts infiltration predicts renal graft survival. Immunohistochemistry was performed on time-zero biopsies to determine alpha-SMA expression, and this was compared to annual glomerular filtration rate (GFR) variation and other parameters including cold ischaemic time (CIT), donor and recipient age, number of acute rejections, and delayed graft function (DGF). GFR was measured by inulin clearance during of 3 years of follow-up after the transplantation. Progressors were defined as patients with an annual GFR decline >5 ml/min/year. RESULTS: We found a significant correlation between interstitial alpha-SMA expression in time-zero biopsies and GFR evolution during the post-transplantation course (r=0.60, P<0.001). Although progressors had greater interstitial alpha-SMA expression than non progressors (7.9+/-0.7 vs 4.3+/-0.4%), they showed only a tendency towards higher glomerular alpha-SMA expression. In addition, progressors had more interstitial fibrosis in time-zero biopsies than non-progressors. There was no relationship between alpha-SMA expression and CIT, donor and recipient ages, number of acute rejections, and occurrence of DGF. CONCLUSION: This study suggests that alpha-SMA evaluation in time-zero biopsies, especially the combination of alpha-SMA expression and interstitial fibrosis, can strongly predict chronic renal allograft dysfunctions.     

Splenectomy improves survival by increasing arterial blood supply in a rat model of reduced‐size liver

Prevention of acute portal hyperperfusion in small‐for‐size livers by inflow modulation results in beneficial postoperative outcome. The objective of this study was to unravel the underlying mechanism, emphasizing the intimate relationship between portal venous (PV) and hepatic arterial (HA) blood flow (BF). Rats underwent partial hepatectomy (pHx), splenectomy before pHx or splenectomy and ligation of the A. hepatica before pHx. Portal venous blood flow (PVBF), hepatic arterial blood flow (HABF), and tissue pO₂ were assessed during stepwise resection from 30% to 90%. Hepatic regeneration and hypoxia‐responsive gene expression were analyzed in each group after nonlethal 85% pHx. 90% pHx caused a fourfold rise in PVBF, a slight decrease in HABF with a 50% reduction in pO₂, and high mortality. Splenectomy before pHx reduced the PVBF and caused a rise in HABF with doubling in tissue pO₂. An attenuation of hypoxia‐responsive gene expression turned into enhanced hepatocellular regeneration and improved survival. A. hepatica ligation abolished the beneficial effect of splenectomy on tissue oxygenation, proliferation, and outcome. In conclusion, the beneficial effect of splenectomy in small‐for‐size livers can be attributed to a rise in HABF with sufficient oxygen supply rather than to a reduced portal venous hyperperfusion to the remnant liver.     

Quality of Life After TKA for Patients With Juvenile Rheumatoid Arthritis

Total knee arthroplasty frequently is required during early adulthood in patients with advanced juvenile rheumatoid arthritis. We queried patients on issues of importance to them, asked whether they were satisfied with surgical outcomes, and ascertained their postoperative status. We retrospectively reviewed 14 adult patients (22 knees) with severe juvenile rheumatoid arthritis who were treated with primary total knee arthroplasty between 1989 and 2001. All patients were evaluated by pain and stiffness visual analog scales, range of motion, the Patient-Specific Index, Hospital for Special Surgery knee score, WOMAC Osteoarthritis Index, EuroQuol in five dimensions, and SF-36 Health Survey. Preoperative scores were assessed by recall. Patients had a minimum followup of 2 years (mean, 8 years; range, 2-13 years). Quality of life improved after TKA as measured by the Patient-Specific Index. Eighteen of 22 patients rated themselves satisfied with the functional outcome of their surgery; all patients were satisfied with pain relief. Final SF-36, EuroQuol in five dimensions, and WOMAC scores were low compared with age-matched population norms. A mean postoperative flexion arc of 77 degrees (range, 30 degrees -130 degrees ) was observed. Total knee arthroplasty had a major positive impact on quality of life as reported by patients. LEVEL OF EVIDENCE: Level IV, therapeutic study.     

Left ventricular architecture after valve replacement due to critical aortic stenosis: an approach to dis-/qualify the myth of valve prosthesis–patient mismatch?

Objectives: Left ventricular hypertrophy in patients with critical aortic stenosis (AS) is an adaptive process that compensates for high intracavitary pressure and reduces systolic wall stress followed by an increase in myocardial masses. In the present prospective clinical trial, we investigated long-term compensatory changes in left ventricular geometry and function after aortic valve replacement using mechanical bileaflet prostheses with the main emphasis on the small-sized aortic annulus and valve prosthesis–patient mismatch. Methods: A total of 58 patients with critical AS were assigned to the following groups according to the predictive value of prosthetic valve area index (VAI): group EXMIS: 29 patients (VAI≤0.99), expected mismatch; group NOMIS: 29 patients (VAI≤0.99), no mismatch. At controls T₀ (before operation/operation (OP), T₁ and T₂ (4 and 20 months after OP) the left ventricular geometry was recorded by means of Imatron^® electron beam tomography and the transprosthetic velocities were measured by echocardiography. Results: Statistical analysis showed a consistent reduction in the absolute (P=0.04) and indexed (P=0.04) left ventricular myocardial mass for both cohorts; furthermore, there was a significant difference between EXMIS and NOMIS patients concerning the factors, time and mass reduction (P=0.005), because of distinct baselines. A logistic regression report revealed preoperative cardiac output, absolute left ventricular myocardial mass, perfusion, body surface area and the native valve orifice area as predicting coefficients and factors for a minimum mass reduction of 25%. We explain a mathematical formula that turned out to be the most sensitive for correctly classified factors. Conclusions: The left ventricular geometry and transprosthetic velocities resulted in the same postoperative recovery for both EXMIS and NOMIS patients. The presented data showed that valve prosthesis–patient mismatch had no influence in several stepwise logistic regression models. We conclude that modern mechanical bileaflet prostheses allow both acceptable hemodynamics and recovery of left ventricular hypertrophy, even in small aortic annuli.     

Grading of internal carotid artery stenosis: validation of Doppler/duplex ultrasound criteria and angiography against endarterectomy specimen.

OBJECTIVES: duplex ultrasound has replaced angiography prior to carotid endarterectomy (CEA) in many institutions. However, the indications for CEA are based on angiographically controlled studies and widely accepted ultrasound criteria do not exist. Consequently, the reliability of Doppler and/or duplex ultrasound to predict a high-grade ICA stenosis has to be proven. DESIGN: prospective validation study. MATERIALS: one hundred and fifty carotid bifurcations assessed by ultrasound and selective angiography and 68 acrylat outcasts of carotid specimen after eversion CEA. METHODS: ICA stenosis was measured angiographically according to the ECST criteria. Combined Doppler acoustic standard criteria (CDASC), peak systolic frequency (PSF), peak systolic velocity (PSV) and end-diastolic velocity (EDV) served as criteria for the ultrasound assessment. These criteria and the results of angiography were compared to the degree of ICA stenosis determined by specimen measurements. RESULTS: the median degree of ICA stenosis as assessed by angiography (82%, range 56-97%) and CDASC (83%, range 50-99%) corresponded well to the specimen measurements (80%, range 50-95%). The sensitivity of angiography and CDASC to predict a 70-90% ICA stenosis (ECST criteria) compared to the specimen measurements was 88% and 95%, respectively. The positive predictive value (PPV) reached 92% and 96%, respectively. CDASC were equivalent to angiography and were superior to the best single frequency or velocity parameters. If CDASC do not indicate a >/=70% ICA stenosis in spite of a PSV >/=180 cm/s and/or an EDV >/=50 cm/s, angiography may detect patients with a >70% ICA stenosis. CONCLUSIONS: CDASC are valid in the quantification of high-grade ICA stenosis. They are more reliable than single velocity and/or frequency measurements. However, if velocity criteria and CDASC do not agree, angiography should be performed.     

Total transvaginal mesh (TVM) technique for treatment of pelvic organ prolapse: a 3-year prospective follow-up study

Introduction and hypothesis

To evaluate clinical outcomes at 3 years following total transvaginal mesh (TVM) technique to treat vaginal prolapse.

Methods

Prospective, observational study in patients with prolapse ≥stage II. Success was defined as POP-Q-stage 0-I and absence of surgical re-intervention for prolapse. Secondary outcome measures were: quality of life (QOL), prolapse-specific inventory (PSI), impact on sexual activity and complications.

Results

Ninety women underwent TVM repair, 72 a hysterectomy. Anatomical failure rate was 20.0% at 3 years. Three patients required re-intervention for prolapse. Improvements in QOL- and PSI-scores were observed at 1 and 3 years. Vaginal mesh extrusion occurred in 14.4% patients. After 3 years, 4.7% asymptomatic extrusions remained present. Of 61 sexually active women at baseline, a significant number of patients (41%) ceased sexual activity by 3 years; de novo dyspareunia was reported by 8.8%. One vesico-vaginal fistula resolved after surgery.

Conclusion

Medium-term results demonstrate that the TVM technique provides a durable prolapse repair.     

Prognosis of lupus membranous nephropathy in children

The occurrence of membranous nephropathy in pediatric series of systemic lupus erythematosus has been reported only rarely, probably due to a very low frequency. One hundred fifty-four children who were seen in 100 French pediatric centers between January 2002 and April 2005 were included. Fifteen (12 girls and three boys) out of the 81 (18.5 %) children with renal involvement presented histological features of membranous nephropathy. Their ages ranged from six to 15 years old (mean=11.3) at the age of SLE diagnosis and 8/15 children were of African origin. Isolated membranous nephropathy was observed in nine patients, of whom five patients displayed a complete recovery following immunosuppressive treatment. Associated proliferative lesions were observed on the first kidney specimen in two patients and in a further renal biopsy in four other patients, leading to a less favorable course of lupus nephropathy.     

A Cross-Cultural Comparison of ICD-11 Complex Posttraumatic Stress Disorder Symptom Networks in Austria,the United Kingdom,and Lithuania

The 11th revision of the World Health Organization's International Classification of Diseases (ICD-11) includes a new disorder, complex posttraumatic stress disorder (CPTSD). The network approach to psychopathology enables investigation of the structure of disorders at the symptom level, which allows for analysis of direct symptom interactions. The network structure of ICD-11 CPTSD has not yet been studied, and it remains unclear whether similar networks replicate across different samples. We investigated the network models of four different trauma samples that included a total of 879 participants (M age = 47.17 years, SD = 11.92; 59.04% women) drawn from Austria, Lithuania, and Scotland and Wales in the United Kingdom. The International Trauma Questionnaire was used to assess symptoms of ICD-11 CPTSD in all samples. The prevalence of PTSD and CPTSD ranged from 23.7% to 37.3% and from 9.3% to 53.1%, respectively. Regularized partial correlation networks were estimated and the resulting networks compared. Despite several differences in the symptom presentation and cultural background, the networks across the four samples were considerably similar, with high correlations between symptom profiles (ρs = .48–.87), network structures (ρs = .69–.75), and centrality estimates (ρs = .59–.82). These results support the replicability of CPTSD network models across different samples and provide further evidence about the robust structure of CPTSD. The most central symptom in all four sample-specific networks and the overall network was “feelings of worthlessness.” Implications of the network approach in research and practice are discussed.     

Risikostratifizierung und Therapie kardialer Amyloidosen

Cardiac amyloidoses are a heterogeneous group of cardiomyopathies that are resistant to treatment and are associated with a poor outcome. Standard heart failure treatment is usually not well tolerated and the underlying disease remains unaffected. The clinical picture is uncharacteristic. Cardiac amyloidosis is often associated with dysfunction of additional organs. Early cardiac amyloid involvement usually reveals left ventricular hypertrophy, impairment of longitudinal shortening and diastolic ventricular function. Without adequate therapy (bi-)ventricular hypertrophy will progress to severe systolic ventricular function decrease. The combination of low voltage pattern, left ventricular hypertrophy and granular sparkling is characteristic for advanced cardiac amyloid involvement. Cardiac magnetic resonance imaging and scintigraphy yield further information on the pattern and severity of cardiac involvement. In unclear cases (left ventricular) endomyocardial biopsy is necessary. Detection of early cardiac involvement and proper identification of patients at high risk for sudden cardiac death due to rapid progressive amyloidosis is still incompletely defined. Referral to specialized centers is strongly recommended.