Short bowel mucosal morphology,proliferation and inflammation at first and repeat STEP procedures

Background

Although serial transverse enteroplasty (STEP) improves function of dilated short bowel, a significant proportion of patients require repeat surgery. To address underlying reasons for unsuccessful STEP, we compared small intestinal mucosal characteristics between initial and repeat STEP procedures in children with short bowel syndrome (SBS).

The effect of maintenance immunosuppression medication on the change in kidney allograft function

BACKGROUND: The optimum maintenance immunosuppression regimen for kidney transplant recipients is uncertain. In this study we determined the effect of maintenance immunosuppression medications on the rate of kidney allograft function loss defined by the annualized change in glomerular filtration rate (GFR). METHODS: We studied 40,963 first kidney only transplant recipients between 1987 and 1996 with allograft survival of at least two years in the United States Renal Data System. Linear regression methods were applied to serial GFR estimates after transplantation to determine the annualized change in GFR. Patients were classified according to the type of maintenance calcineurin and purine metabolism inhibitor received after transplantation. Multiple linear regression was used to determine the independent effect of maintenance immunosuppression medications on the annualized change in GFR (mL/min/1.73m2/year). RESULTS: Compared to patients who received cyclosporine microemulsion (Neoral), a slower decline in GFR was observed in tacrolimus-treated patients (1.60 mL/min/1.73m2/year, 95% CI 1.22-1.97, P < 0.001) and patients who did not receive calcineurin inhibitors (0.82 mL/min/1.73m2/year, 95% CI 0.08-1.56, P= 0.03). In contrast, compared to compared to patients who received Neoral, a faster decline in GFR was observed in patients who received the original oil-based formulation of cyclosporine (Sandimmune) (-0.16 mL/min/1.73m2/year, 95% CI -0.003 to -0.32, P= 0.04) and patients with unknown calcinuerin inhibitor exposure (-2.11 mL/min/1.73m2/year, 95% CI -2.27 to -1.95, P < 0.001). Compared to patients who received azathioprine, patients who received mycophenolate mofetil (MMF) had a slower decline in GFR (0.61 mL/min/1.73m2/year, 95% CI 0.14-1.08, P= 0.01) and patients with unknown purine metabolism inhibitor exposure had a faster decline in GFR (-0.61 mL/min/1.73m2/year, 95% CI -0.75 to -0.47, P < 0.001.) In a subgroup analysis of patients who received a transplant after 1993, the decline in GFR was slower for tacrolimus compared to neoral treated patients (1.64 mL/min/1.73m2/year, 95% CI 1.15-2.14, P < 0.001) but was not different for MMF compared to azathioprine-treated patients (0.24 mL/min/1.73m2/year, 95% CI -0.38-0.85, P= 0.45). CONCLUSION: Tacrolimus and MMF were the calcineurin inhibitor and purine metabolism inhibitor associated with the most favorable effects on rates of change in allograft function. Because most transplant recipients establish a low baseline level of allograft function, the effect of immunosuppression medication on GFR decline should be considered when selecting a maintenance immunosuppression regimen.     

Comparison of Gadolinium-BOPTA and Ferucarbotran-enhanced three-dimensional T1-weighted dynamic liver magnetic resonance imaging in the same patient

OBJECTIVES: We sought to compare signal changes using Ferucarbotran and gadobenate dimeglumine (Gd-BOPTA) in dynamic 3D T1-weighted (T1w) GRE imaging of the liver. MATERIAL AND METHODS: Thirty patients were prospectively included in the study. All patients underwent 2 high-field magnetic resonance (MR) examinations: first with Gd-BOPTA (Gd) and then after a mean interval of 4 days with ferucarbotran (Feru). Dynamic MRI was obtained with a 3D T1w GRE sequence (TR 6.33, TE 2.31, flip angle 20 degrees ). Contrast enhanced scans were assessed before intravenous injection of the contrast agent (precontrast), and postcontrast during the arterial phase (30 seconds), portal venous phase (60 seconds), and equilibrium phase (120 seconds). The signal intensities (SIs) of liver, spleen, aorta, and portal vein were defined by region of interest measurements. Signal intensity changes (SICs) and percentage signal intensity change (PSIC) were calculated using the formulas SIC=(SI pre - SI post)/SI pre and PSIC=SIC x 100%. RESULTS: Positive signal enhancement was observed after intravenous injection of Feru during all dynamic measurements, whereas the mean SI values were lower compared with Gd. During the portal venous phase the mean SI of Gd was up to a factor of 2.1 higher (portal vein). The widest difference of SIC was observed during the equilibrium phase for liver parenchyma (Gd, 1.03; Feru, 0.24). The dynamic signal courses were similar for liver, portal vein and aorta. Different signal courses were obtained for the spleen. CONCLUSIONS: Feru-enhanced T1w dynamic images demonstrated significant signal increases for liver, vessels, and spleen but overall lower signal intensities than Gd-BOPTA. The dynamic signal courses of ferucarbotran were similar to that of Gd-BOPTA during ll perfusion phases except in the spleen. Thus, it may be possible to detect typical enhancement pattern of focal liver lesions with Feru-enhanced dynamic T1w MRI.     

Increased thrombin generation in splanchnic vein thrombosis is related to the presence of liver cirrhosis and not to the thrombotic event

Introduction

In recent years there have been increasing evidence associating liver disease with hypercoagulability, rather than bleeding. The aim of the study was to evaluate the haemostatic potential in patients with liver disease.

Patients and methods

We measured thrombin generation in the presence and absence of thrombomodulin in patients with portal vein thrombosis (PVT, n = 47), Budd-Chiari syndrome (BCS, n = 15) and cirrhosis (n = 24) and compared the results to those obtained from healthy controls (n = 21). Fifteen patients with PVT and 10 patients with BCS were treated with warfarin and were compared to an equal number of patients with atrial fibrillation matched for prothrombin time-international normalized ratio. We assessed resistance to thrombomodulin by using ratios [marker measured in the presence/absence of thrombomodulin].

Results

There were no differences in thrombin generation between patients on warfarin treatment and their controls. Cirrhotic patients generated more thrombin in the presence of thrombomodulin and exhibited thrombomodulin resistance compared to controls [p = 0.006 for endogenous thrombin potential (ETP) and p < 0.001 for peak thrombin and both ratios ETP and peak] and patients with non-cirrhotic PVT (p = 0.001, p = 0.006, p < 0.001, p < 0.001 for ETP, peak, ratio ETP, ratio peak, respectively). The patients with cirrhotic PVT exhibited higher ETP (p = 0.044) and peak (p = 0.02) in the presence of thrombomodulin than controls, as well as thrombomodulin resistance (ETP and peak ratios: p = 0.001).

Conclusions

Hypercoagulability and thrombomodulin resistance in patients with cirrhosis were independent of the presence of splanchnic vein thrombosis. The hypercoagulability in patients with cirrhotic PVT could have implications for considering longer or more intensive treatment with anticoagulants in this group.     

Psychometric properties of the apathy evaluation scale in patients with Parkinson's disease

Parkinson's disease (PD) frequently entails non‐motor symptoms, worsening the course of the disease. Apathy is one of the core neuropsychiatric symptoms that has been investigated in recent years; research is however hampered by the limited availability of well‐evaluated apathy scales for these patients. We evaluated the psychometric properties of the Apathy Evaluation Scale (AES) in a sample of PD patients. Psychometric properties, convergent and discriminant validity and sensitivity/specificity were evaluated in patients with (n = 582) or without dementia/depression (n = 339). Internal consistency was high in the entire sample as well as in patients without dementia/depression. Correlations were moderate for convergent validity (UPDRS I item 4: motivation). While apathy could be differentiated from cognitive decline, it was related to depression (Geriatric Depression Scale, GDS‐15). The overall classification accuracy based on the UPDRS I item 4 was comparable for AES and GDS scores. The AES exhibits good psychometric properties in PD patients with and without dementia and/or depression. Commonly used screenings on the presence of apathy had low detection rates compared to the AES and reflected both apathetic and depressive symptoms. Psychometric evaluation of available instruments will support further research on the clinical relevance of apathy for disease progression and treatment approaches in PD patients.     

Conditional Disease-Free and Overall Survival of 1,858 Young Women with Non-Metastatic Breast Cancer and with Participation in a Post-Therapeutic Rehab Programme according to Clinical Subtypes

BackgroundBreast cancer in young women is associated with unfavourable tumour biology and is the main cause of death in this group. Conditional survival analysis estimates survival rates under the pre-condition of already having survived a certain time.ObjectivesTo describe conditional disease-free and overall survival of female breast cancer patients according to clinical subtypes and age.MethodsThis study analyses information from 1,858 breast cancer patients aged between 21 and 54 years, who were taking part in a post-therapeutic rehab programme (time between diagnosis and rehab start: maximum 24, median 11 months). Mean follow-up time was 3.6 years. We describe biological, clinical and pathological features in regard to different age groups (<40 and ≥40 years) and report conditional 5-year survival rates for overall and disease-free survival, and Cox proportional hazard models.ResultsVery young and young patients differed in regard to hormone receptor negativity, tumour grade, lymphovascular invasion, and molecular subtypes. Young women bore triple-negative and HER2-like disease more frequently. Conditional 5-year overall survival did not differ substantially between women <40 and 40–54 years of age (95 vs. 96%). It was highest for women with cancer of the luminal A subtype (98%) and lowest for the triple-negative subtype (91%). Lymphangiosis was a significant predictor of death. Results for disease-free survival were comparable.ConclusionsConditional 5-year overall survival after non-metastatic breast cancer was as high as 95.5%, and disease-free survival was 85.2%. When controlling for time between diagnosis and rehab start, molecular subtypes influenced overall and disease-free survival prospects. When additionally controlling for clinical characteristics, this effect only remained stable for disease-free survival.     

Blick in und Wünsche für die Zukunft der Unfallchirurgie

Die Unfallchirurgie -     

Lernen und üben wir das Richtige?

Notfall + Rettungsmedizin - Der Massenanfall von Verletzten (MANV) ist eine Ausnahmesituation für Rettungsdienst und andere Einsatzkräfte. Trotz niedriger Inzidenz müssen sich die...     

Propranolol Promotes Bone Formation and Limits Resorption Through Novel Mechanisms During Anabolic Parathyroid Hormone Treatment in Female C57BL/6J Mice

Although the nonselective β-blocker, propranolol, improves bone density with parathyroid hormone (PTH) treatment in mice, the mechanism of this effect is unclear. To address this, we used a combination of in vitro and in vivo approaches to address how propranolol influences bone remodeling in the context of PTH treatment. In female C57BL/6J mice, intermittent PTH and propranolol administration had complementary effects in the trabecular bone of the distal femur and fifth lumbar vertebra (L₅), with combination treatment achieving microarchitectural parameters beyond that of PTH alone. Combined treatment improved the serum bone formation marker, procollagen type 1 N propeptide (P1NP), but did not impact other histomorphometric parameters relating to osteoblast function at the L₅. In vitro, propranolol amplified the acute, PTH-induced, intracellular calcium signal in osteoblast-like cells. The most striking finding, however, was suppression of PTH-induced bone resorption. Despite this, PTH-induced receptor activator of nuclear factor κ-B ligand (RANKL) mRNA and protein levels were unaltered by propranolol, which led us to hypothesize that propranolol could act directly on osteoclasts. Using in situ methods, we found Adrb2 expression in osteoclasts in vivo, suggesting β-blockers may directly impact osteoclasts. Consistent with this, we found propranolol directly suppresses osteoclast differentiation in vitro. Taken together, this work suggests a strong anti-osteoclastic effect of nonselective β-blockers in vivo, indicating that combining propranolol with PTH could be beneficial to patients with extremely low bone density. © 2022 American Society for Bone and Mineral Research (ASBMR).