Surgical management of chest injuries in patients with multiple and/or severe trauma- a systematic review and clinical practice guideline update.

PURPOSE: Our aim was to update evidence-based and consensus-based recommendations for the surgical and interventional management of blunt or penetrating injuries to the chest in patients with multiple and/or severe injuries on the basis of current evidence. This guideline topic is part of the 2022 update of the German Guideline on the Treatment of Patients with Multiple and/or Severe Injuries. METHODS: MEDLINE and Embase were systematically searched to May and June 2021 respectively for the update and new questions. Further literature reports were obtained from clinical experts. Randomised controlled trials, prospective cohort studies, cross-sectional studies and comparative registry studies were included if they compared interventions for the surgical management of injuries to the chest in patients with multiple and/or severe injuries. We considered patient-relevant clinical outcomes such as mortality, length of stay, and diagnostic test accuracy. Risk of bias was assessed using NICE 2012 checklists. The evidence was synthesised narratively, and expert consensus was used to develop recommendations and determine their strength. RESULTS: One study was identified. This study compared wedge resection, lobectomy and pneumonectomy in the management of patients with severe chest trauma that required some form of lung resection. Based on the updated evidence and expert consensus, one recommendation was modified and two additional good practice points were developed. All achieved strong consensus. The recommendation on the amount of blood loss that is used as an indication for surgical intervention in patients with chest injuries was modified to reflect new findings in trauma care and patient stabilisation. The new good clinical practice points (GPPs) on the use of video-assisted thoracoscopic surgery (VATS) in patients with initial circulatory stability are also in line with current practice in patient care. CONCLUSION: As has been shown in recent decades, the treatment of chest trauma has become less and less invasive for the patient as diagnostic and technical possibilities have expanded. Examples include interventional stenting of aortic injuries, video-assisted thoracoscopy and parenchyma-sparing treatment of lung injuries. These less invasive treatment concepts reduce morbidity and mortality in the primary surgical phase following a chest trauma.

Advanced diffusion MRI provides evidence for altered axonal microstructure and gradual peritumoral infiltration in GBM in comparison to brain metastases.

PURPOSE: In contrast to peritumoral edema in metastases, GBM is histopathologically characterized by infiltrating tumor cells within the T2 signal alterations. We hypothesized that depending on the distance from the outline of the contrast-enhancing tumor we might reveal imaging evidence of gradual peritumoral infiltration in GBM and predominantly vasogenic edema around metastases. We thus investigated the gradual change of advanced diffusion metrics with the peritumoral zone in metastases and GBM. METHODS: In 30 patients with GBM and 28 with brain metastases, peritumoral T2 hyperintensity was segmented in 33% partitions based on the total volume beginning at the enhancing tumor margin and divided into inner, middle and outer zones. Diffusion Tensor Imaging (DTI)-derived fractional anisotropy and mean diffusivity as well as Diffusion Microstructure Imaging (DMI)-based parameters Dax-intra, Dax-extra, V­CSF and V-intra were employed to assess group-wise differences between inner and outer zones as well as within-group gradients between the inner and outer zones. RESULTS: In metastases, fractional anisotropy and Dax-extra were significantly reduced in the inner zone compared to the outer zone (FA p = 0.01; Dax-extra p = 0.03). In GBM, we noted a reduced Dax-extra and significantly lower intraaxonal volume fraction (Dax-extra p = 0.008, V­intra p = 0.006) accompanied by elevated axial intraaxonal diffusivity in the inner zone (p = 0.035). Between-group comparison of the outer to the inner zones revealed significantly higher gradients in metastases over GBM for FA (p = 0.04) as well as the axial diffusivity in the intra- (p = 0.02) and extraaxonal compartment (p < 0.001). CONCLUSION: Our findings provide evidence of gradual alterations within the peritumoral zone of brain tumors. These are compatible with predominant (vasogenic) edema formation in metastases, whereas our findings in GBM are in line with an axonal destructive component in the immediate peritumoral area and evidence of tumor cell infiltration with accentuation in the tumor's vicinity.

Impact of Time of Surgery on the Outcome after Surgical Stabilization of Rib Fractures in Severely Injured Patients with Severe Chest Trauma-A Matched-Pairs Analysis of the German Trauma Registry.

Purpose: In severely injured patients with multiple rib fractures, the beneficial effect of surgical stabilization is still unknown. The existing literature shows divergent results, and the indication and especially the right timing of an operation are the subject of a broad discussion. The aim of this study was to determine the influence of the time point of surgical stabilization of rib fractures (SSRF) on the outcome in a multicenter database with special regard to the duration of ventilation, intensive care, and overall hospital stay. Methods: Data from the TraumaRegister DGU collected between 2010 and 2019 were used to evaluate patients above 16 years of age with severe rib fractures [Abbreviated Injury Score (AIS) ≥ 3] who received an SSRF in a matched-pairs analysis. In this matched-pairs analysis, we compared the effects of an early SSRF within 48 h after initial trauma vs. late SSRF 3-10 days after trauma. Results: After the selection process, we were able to find 142 matched pairs for further evaluation. Early SSRF was associated with a significantly shorter length of stay in the intensive care unit (16.2 days vs. 12.7 days, p = 0.020), and the overall hospital stay (28.5 days vs. 23.4 days, p = 0.005) was significantly longer in the group with late SSRF. Concerning the days on mechanical ventilation, we were able to demonstrate a trend for an approximately 1.5 day shorter ventilation time for patients after early SSRF, although this difference was not statistically significant (p = 0.226). Conclusions: We were able to determine the significant beneficial effects of early SSRF resulting in a shorter intensive care unit stay and a shorter length of stay in hospital and additionally a trend to a shorter time on mechanical ventilation.

Two-dimensional parametric parenchymal blood flow in transarterial chemoembolisation for hepatocellular carcinoma: perfusion change quantification and tumour response prediction at 3 months post-intervention.

AIM: To evaluate the feasibility and potential value of two-dimensional (2D) parametric parenchymal blood flow (2D-PPBF) for the assessment of perfusion changes during transarterial chemoembolisation with drug-eluting beads (DEB-TACE) and to analyse correlations of 2D-PPBF parameters and tumour response. MATERIALS AND METHODS: Thirty-two patients (six women, 26 men, mean age: 67±8.9 years) with unresectable hepatocellular carcinoma (HCC) who underwent their first DEB-TACE were included in this study. To quantify perfusion changes using 2D-PPBF, the acquired digital subtraction angiography (DSA) series were post-processed. Ratios were calculated between the reference region of interest (ROI) and the wash-in rate (WIR), the arrival to peak (AP) and the area under the curve (AUC) of the generated time-density curves. Comparisons between pre- and post-embolisation data were made using the Wilcoxon signed-rank test. Tumour response was assessed at 3 months using the modified Response Evaluation Criteria in Solid Tumours (mRECIST) and correlated to changes of 2D-PPBF parameters. RESULTS: All 2D-PPBF parameters derived from the ROI-based time-attenuation curves were significantly different pre-versus post-DEB-TACE. Although the AUC, the WIR and target lesion size measured in accordance with mRECIST decreased (p≤0.0001) significantly, AP values showed a significant increase (p = 0.0033). Tumour response after DEB-TACE correlated with changes in the AUC (p = 0.01, r = -0.45). CONCLUSION: 2D-PPBF offers an objective approach to analyse perfusion changes of embolised tumour tissue following DEB-TACE and can therefore be used to predict tumour response.

Percutaneous isolated hepatic perfusion (chemosaturation) with melphalan following right hemihepatectomy in patients with cholangiocarcinoma and metastatic uveal melanoma: peri- and post-interventional adverse events and therapy response compared to a matched group without prior liver surgery.

To evaluate feasibility, frequency and severity of peri-procedural complications and post-procedural adverse events (AEs) in patients with advanced cholangiocarcinoma or liver metastasis of uveal melanoma and prior hemihepatectomy undergoing chemosaturation percutaneous hepatic perfusion (CS-PHP) and to analyze therapy response and overall survival compared to a matched group without prior surgery. CS-PHP performed between 10/2014 and 02/2018 were retrospectively assessed. To determine peri-procedural safety and post-procedural adverse events, hospital records and hematological, hepatic and biliary function were categorized using Common Terminology Criteria for Adverse Events (CTCAE) v5.0 (1-5; mild-death). Significance was tested using Wilcoxon signed-rank and Mann-Whitney U test. Kaplan-Meier estimation and log-rank test assessed survival. Overall 21 CS-PHP in seven patients (4/7 males; 52 ± 10 years) with hemihepatectomy (grouphemihep) and 22 CS-PHP in seven patients (3/7 males; 63 ± 12 years) without prior surgery (groupnoresection) were included. No complications occurred during the CS-PHP procedures. Transient changes (CTCAE grade 1-2) of liver enzymes and blood cells followed all procedures. In comparison, grouphemihep presented slightly more AEs grade 3-4 (e.g. thrombocytopenia in 57% (12/21) vs. 41% (9/22; p = 0.37)) 5-7 days after CS-PHP. These AEs were self-limiting or responsive to treatment (insignificant difference of pre-interventional to 21-45 days post-interventional values (p > 0.05)). One patient in grouphemihep with high tumor burden died eight days following CS-PHP. No deaths occurred in groupnoresection. In comparison, overall survival after first diagnosis was insignificantly shorter in groupnoresection (44.7(32-56.1) months) than in grouphemihep (48.3(34.6-72.8) months; p = 0.48). The severity of adverse events following CS-PHP in patients after hemihepatectomy was comparable to a matched group without prior liver surgery. Thus, the performance of CS-PHP is not substantially compromised by a prior hemihepatectomy.

Transjugular intrahepatic portosystemic shunt placement: portal vein puncture guided by 3D/2D image registration of contrast-enhanced multi-detector computed tomography and fluoroscopy.

BACKGROUND: To assess the technical feasibility, success rate, puncture complications and procedural characteristics of transjugular intrahepatic portosystemic shunt (TIPS) placement using a three-dimensional vascular map (3D-VM) overlay based on image registration of pre-procedural contrast-enhanced (CE) multi-detector computed tomography (MDCT) for portal vein puncture guidance. MATERIALS AND METHODS: Overall, 27 consecutive patients (59 ± 9 years, 18male) with portal hypertension undergoing elective TIPS procedure were included. TIPS was guided by CE-MDCT overlay after image registration based on fluoroscopic images. A 3D-VM of the hepatic veins and the portal vein was created based on the pre-procedural CE-MDCT and superimposed on fluoroscopy in real-time. Procedural characteristics as well as hepatic vein catheterization time (HVCT), puncture time (PT), overall procedural time (OPT), fluoroscopy time (FT) and the dose area product (DAP) were evaluated. Thereafter, HVCT, PT, OPT and FT using 3D-VM (61 ± 9 years, 14male) were compared to a previous using classical fluoroscopic guidance (53 ± 9 years, 21male) for two interventional radiologist with less than 3 years of experience in TIPS placement. RESULTS: All TIPS procedure using of 3D/2D image registered 3D-VM were successful with a significant reduction of the PSG (p < 0.0001). No clinical significant complication occurred. HVCT was 14 ± 11 min, PT was 14 ± 6 min, OPT was 64 ± 29 min, FT was 21 ± 12 min and DAP was 107.48 ± 93.84 Gy cm2. HVCT, OPT and FT of the interventionalist with less TIPS experience using 3D/2D image registered 3D-VM were statistically different to an interventionalist with similar experience using fluoroscopic guidance (pHVCT = 0.0022; pOPT = 0.0097; pFT = 0.0009). PT between these interventionalists was not significantly different (pPT = 0.2905). CONCLUSION: TIPS placement applying registration-based CE-MDCT vessel information for puncture guidance is feasible and safe. It has the potential to improve hepatic vein catherization, portal vein puncture and radiation exposure.

A paternal methyl donor-rich diet altered cognitive and neural functions in offspring mice.

Dietary intake of methyl donors, such as folic acid and methionine, shows considerable intra-individual variation in human populations. While it is recognized that maternal departures from the optimum of dietary methyl donor intake can increase the risk for mental health issues and neurological disorders in offspring, it has not been explored whether paternal dietary methyl donor intake influences behavioral and cognitive functions in the next generation. Here, we report that elevated paternal dietary methyl donor intake in a mouse model, transiently applied prior to mating, resulted in offspring animals (methyl donor-rich diet (MD) F1 mice) with deficits in hippocampus-dependent learning and memory, impaired hippocampal synaptic plasticity and reduced hippocampal theta oscillations. Gene expression analyses revealed altered expression of the methionine adenosyltransferase Mat2a and BK channel subunit Kcnmb2, which was associated with changes in Kcnmb2 promoter methylation in MD F1 mice. Hippocampal overexpression of Kcnmb2 in MD F1 mice ameliorated altered spatial learning and memory, supporting a role of this BK channel subunit in the MD F1 behavioral phenotype. Behavioral and gene expression changes did not extend into the F2 offspring generation. Together, our data indicate that paternal dietary factors influence cognitive and neural functions in the offspring generation.

Factors associated with second-line triplet therapy in routine care in relapsed/refractory multiple myeloma.

WHAT IS KNOWN AND OBJECTIVE: Second-line therapy (SLT) trials in relapsed/refractory multiple myeloma (RRMM) report superior outcomes with triplet combinations. We sought to determine factors associated with triplet SLT in routine practice. METHODS: A retrospective cohort with claims for MM between 01/01/2008 and 03/31/2015 was grouped by 1-2 ("doublet") or 3+ ("triplet") agent therapy. Charlson comorbidity index (CCI) and disability status; CRAB symptoms (hypercalcaemia, renal/bone disease, anaemia); and relapse risk were determined. RESULTS: Among 623 patients, the triplet group (n=146 [23%]) was younger (65.2 vs 69.8 years) and more likely to have high-risk relapse (67% vs 50%), CRAB symptoms (94.5% vs 81.1%), triplet first-line treatment (75% vs 51%) and frontline stem cell transplant (38% vs 20%) (P<0.001 for all). In multivariate analyses, CRAB symptoms (OR: 3.22, 95% CI: 1.47, 7.10), high-risk relapse (OR: 1.71, 95% CI: 1.12, 2.62) and prior triplet therapy (OR: 2.16, 95% CI: 1.38, 3.40), but neither CCI nor disability, were associated with triplet SLT. A trend towards triplets among younger patients (<65 vs >75 years, OR: 1.73, 95% CI: 0.99, 3.04) was observed. WHAT IS NEW AND CONCLUSION: The majority of patients did not receive triplet regimens. Treatment selection with triplet therapy for RRMM should carefully consider comorbidities and patient-specific characteristics.

Tissue Expression of Aquaporin 2 Is Correlated to Urine Output and Allograft Function in Sensitized Kidney Transplant Patients.

BACKGROUND: Salt and water disturbances often occur during acute kidney allograft dysfunction that contribute to graft failure, but this condition has been poorly investigated in the alloreactivity setting. We evaluated the tissue expression of aquaporins (AQP1 and AQP2) and the epithelial sodium channel (ENAC) in kidney biopsy specimens from sensitized kidney transplant recipients. METHODS: Eighty-six biopsy specimens from 33 sensitized patients were divided into 3 groups according to clinical context: time-zero (n = 9), protocol (n = 9), and indication (n = 68). The indication biopsy specimens were further divided into 3 subgroups according to the presence of acute tubular necrosis or rejection. Normal kidney tissue samples (n = 6) served as the control specimens. Immmunohistochemical expression of AQP1, AQP2, and ENAC was determined by using image analyzing software. RESULTS: Significantly lower AQP1 expression was observed in the time-zero and indication biopsy specimens with rejection compared with control specimens (P = .03 and P = .04, respectively). AQP2 expression was significantly lower in patients with an indication biopsy specimen compared with control and protocol biopsy specimens (P = .05 and P = .005). For ENAC, a lower expression was noted in the indication biopsy specimens compared with the control specimens (P = .04). Both AQP1 and AQP2 tissue expressions were significantly correlated to urine output (r = 0.45 and r = 0.32; P = .001 and P = .02), and AQP2 was correlated with the glomerular filtration rate estimated by using the Modification of Diet in Renal Disease Study equation at biopsy (r = 0.23; P = .05). CONCLUSIONS: These findings partially confirm previous experimental data showing downregulation of AQP1 expression after ischemia/reperfusion injury and during rejection. AQP2 downregulation seems to be rejection-independent, occurring during deteriorating or poor kidney graft function.

Pre-transplant soluble CD30 in combination with total DSA but not pre-transplant C1q-DSA predicts antibody-mediated graft loss in presensitized high-risk kidney transplant recipients.

Presensitized kidney transplant recipients are at high-risk for early antibody-mediated rejection. We studied the impact of pre- and post-transplant donor-specific human leukocyte antigen (HLA) antibodies (DSA) and T-cell-activation on the occurrence of antibody-mediated rejection episodes (AMR) and graft loss (AMR-GL) in a unique cohort of 80 desensitized high-risk kidney transplant recipients. Patients with pre-transplant DSA demonstrated more AMR episodes than patients without DSA, but did not show a significantly increased rate of AMR-GL. The rates of AMR and AMR-GL were not significantly increased in patients with complement split product (C1q)-binding pre-transplant DSA. Pre-transplant C1q-DSA became undetectable post-transplant in 11 of 13 (85%) patients; 2 (18%) of these 11 patients showed AMR but no AMR-GL. In contrast, the post-transplant presence of C1q-DSA was associated with significantly higher rates of AMR (86 vs 33 vs 0%; P < 0.001) and AMR-GL (86 vs 0 vs 0%; log-rank P < 0.001) compared with post-transplant DSA without C1q-binding or the absence of DSA. Patients with both pre-transplant DSA and evidence of pre-transplant T-cell-activation as indicated by soluble CD30-positivity showed a significantly increased risk for AMR-GL [HR = 11.1, 95% confidence interval (CI) = 1.68-73.4; log-rank P = 0.013]. In these high-risk patients, AMR-GL was associated with total DSA in combination with T-cell-activation pre-transplant, and de novo or persistent C1q-binding DSA post-transplant.

A Single-center Experience on the Value of Pancreas Graft Biopsies and HLA Antibody Monitoring After Simultaneous Pancreas-Kidney Transplantation.

BACKGROUND: In simultaneous pancreas-kidney transplantation (SPKT), monitoring of the pancreas allograft is more complex than the kidney allograft due to difficulties in obtaining pancreas histology and weak clinical evidence supporting the role of donor-specific antibodies (DSA). METHODS: We performed a single-center retrospective analysis of all 17 SPKT recipients who underwent a total of 22 pancreas allograft indication biopsies from October 2009 to September 2012. Fifteen patients had at least 2 DSA measurements: pretransplantation and at the time of biopsy. RESULTS: All 7 patients (100%) with post-transplantation DSA-positivity (de novo: n = 6; persistent: n = 1) at biopsy had at least 1 rejection episode either of the pancreas (n = 4) or the kidney (n = 3), with 3 antibody-mediated rejections (AMR). In contrast, only 4 of 8 patients (50%) without post-transplantation DSA had evidence of rejection, with 1 AMR. Findings during pancreas allograft biopsy procedures led to a change of immunosuppressive therapy in 11 of 15 (73%) patients. Patient survival, graft survival, and function were not adversely affected by the presence of post-transplantation DSA. One major and 2 minor procedure-related complications occurred during the pancreas biopsies. CONCLUSIONS: In this small retrospective analysis, pancreas allograft histology provided the most therapeutically relevant information, rather than the kidney histology or DSA monitoring.

Evaluation of simultaneous 201Tl/99mTc dual-isotope cardiac SPECT imaging with model-based crosstalk compensation using canine studies.

BACKGROUND: Simultaneous (201)Tl/(99m)Tc-sestamibi dual-isotope myocardial perfusion SPECT imaging can reduce imaging time and produce perfectly registered rest/stress images. However, crosstalk from (99m)Tc into (201)Tl images can significantly reduce (201)Tl image quality. We have developed a model-based compensation (MBC) method to compensate for this crosstalk. The method has previously been validated with phantom and simulation studies. In this study, we evaluated the MBC method using a canine model. METHODS: Left anterior descending or left circumflex coronary artery stenoses were created in 50 adult mongrel dogs weighing 20-30 kg. The dogs were injected with 111 MBq (3 mCi) of (201)Tl at rest, and a SPECT study acquired. Stress was induced by administering adenosine to the dog, followed by injection of 740 MBq (20 mCi) of (99m)Tc-sestamibi at peak stress. A second SPECT study was performed with data acquired in both (201)Tl and (99m)Tc energy windows to provide simultaneous dual-isotope projection data. The images were reconstructed using the ordered-subsets expectation-maximization reconstruction algorithm with compensation for attenuation, scatter, and detector response. For simultaneously acquired (201)Tl data, we also applied the MBC method to compensate for crosstalk contamination from (99m)Tc. RESULTS: Without compensation, (99m)Tc crosstalk increased the estimated (201)Tl activity concentration in the rest images and reduced defect contrast. After MBC, the (201)Tl images were in good agreement with the registered single-isotope images and ex vivo count data. The ischemic (IS) to non-ischemic (NIS) region (201)Tl activity concentration ratios were computed for single-isotope and dual-isotope studies. The correlation with ex vivo IS-NIS ratios was 0.815 after MBC, compared to the 0.495 from data without compensation. In addition, the regression line for the IS-NIS ratios with MBC was almost parallel to the line of identity with a slope of 0.93, compared to a slope of 0.45 without compensation. CONCLUSIONS: These results demonstrate that model-based crosstalk compensation can provide substantial reduction of crosstalk effects in simultaneously acquired myocardial perfusion SPECT images in living biological systems.

Promising results after the treatment of simple and complex distal humerus type C fractures by angular-stable double-plate osteosynthesis.

INTRODUCTION: The aim of this study was to evaluate the functional results and complications following open reduction and internal fixation of distal humerus type C fractures (AO classification) using an anatomically precontoured, angular-stable double-plate system. PATIENTS AND METHODS: The study is a retrospective analysis of 45 patients with 46 type C fractures. There was one C1, eight C2 and 31 C3 fractures. Twelve fractures were open (Gustilo classification). Follow-up was performed on 38 patients with 39 fractures (84%) after 14 months (range, 12-22). The mean age was 50 years (range, 14-87). Functional results were evaluated using the Mayo Elbow Performance Score (MEPS); the Disabilities of the Arm, Shoulder and Hand score (DASH); and range-of motion (ROM) measurements. Complications were classified as minor or major, and the postoperative and follow-up X-rays were analyzed. RESULTS: Thirty-four fractures were considered stable to allow early physical therapy. With a mean MEPS of 85 points, 36 results (36/39 [92%]) were rated as excellent or good. The mean DASH was 22.5 points, and the ROM for extension-flexion was 105° (range, 50-145). Sixteen major complications (eventually coexistent: 6 × implant failure, 3 × non-union, 6 × stiffness, 2 × necrosis capitulum, 4 × failure olecranon osteotomy refixation) and two minor complications were recorded in 17 patients. These adverse events led to 14 revision surgeries (14/39 [36%]). Except for extension deficit, no statistically significant differences were found between the articular simple and articular complex fractures and when comparing the results between patients with and without a major complication. CONCLUSION: The anatomically precontoured and angular-stable double-plate system provides sufficient immediate postoperative stability to allow early physiotherapy, even in C3-type fractures. Excellent or good results could be achieved in the vast majority of patients, independent on having suffered a complication or not. Complication rates were remarkably high, emphasizing the difficulties associated with this rare type of fracture. LEVEL OF EVIDENCE: Level IV Retrospective study.

Comparative effectiveness of pegfilgrastim, filgrastim, and sargramostim prophylaxis for neutropenia-related hospitalization: two US retrospective claims analyses.

OBJECTIVE: Few studies have compared the effectiveness of filgrastim (FIL), pegfilgrastim (PEG), and sargramostim (SAR) to reduce the risk of febrile neutropenia (FN) associated with myelosuppressive chemotherapy (M-CT). Two large commercial database analyses were separately conducted to examine the incidence of neutropenia-related and all-cause hospitalizations associated with FIL, PEG, and SAR prophylaxis for patients receiving M-CT for non-Hodgkin lymphoma (NHL), Hodgkin lymphoma, or solid tumors. METHODS: Separate retrospective US claims database analyses utilized patient data from January 1, 2004 to April 30, 2010 using the HealthCore Integrated Research Database (HIRD(SM)) and January 1, 2001 to August 31, 2009 using OptumInsight's (formerly Ingenix) database. Patients were ≥18 years old and treated with M-CT for NHL, Hodgkin lymphoma, and solid tumors. All identified M-CT cycles with prophylactic (first 5 days of cycle) FIL, PEG, or SAR were included in the analysis. Patterns of administration and incidence rates of all-cause and neutropenia-related hospitalization were examined on a per-cycle basis. RESULTS: In total, 9330 and 8762 patients with cancer, representing 30,264 and 24,215 chemotherapy cycles (28,189 and 22,649 (PEG), 1669 and 1351 (FIL), 406 and 215 (SAR)) from the HIRD(SM) and OptumInsight databases, respectively, were included in the separate database analyses. Both the HIRD(SM) and OptumInsight analysis showed that SAR and FIL prophylaxis had a higher risk of neutropenia-related hospitalization (SAR: OR = 3.48 [95%CI = 2.11, 5.74] and 2.81 [1.62, 4.87]; FIL: 1.78 [1.28, 2.48] and 2.36 [1.82, 3.06], respectively) and all-cause hospitalization (SAR: 2.18 [1.41, 3.36] and 2.41 [1.58, 3.68]; FIL:1.57 [1.25, 1.97] and 1.95 [1.60, 2.38], respectively) vs PEG. LIMITATIONS: Medical claims do not contain information about chemotherapy dose, and hospitalizations were not validated against the patient's chart. CONCLUSION: In this comparative effectiveness study, use of PEG was associated with a lower risk of neutropenia-related and all-cause hospitalizations compared to use of FIL or SAR prophylaxis.

Genome-wide meta-analyses of smoking behaviors in African Americans.

The identification and exploration of genetic loci that influence smoking behaviors have been conducted primarily in populations of the European ancestry. Here we report results of the first genome-wide association study meta-analysis of smoking behavior in African Americans in the Study of Tobacco in Minority Populations Genetics Consortium (n = 32,389). We identified one non-coding single-nucleotide polymorphism (SNP; rs2036527[A]) on chromosome 15q25.1 associated with smoking quantity (cigarettes per day), which exceeded genome-wide significance (ß = 0.040, s.e. = 0.007, P = 1.84 × 10(-8)). This variant is present in the 5'-distal enhancer region of the CHRNA5 gene and defines the primary index signal reported in studies of the European ancestry. No other SNP reached genome-wide significance for smoking initiation (SI, ever vs never smoking), age of SI, or smoking cessation (SC, former vs current smoking). Informative associations that approached genome-wide significance included three modestly correlated variants, at 15q25.1 within PSMA4, CHRNA5 and CHRNA3 for smoking quantity, which are associated with a second signal previously reported in studies in European ancestry populations, and a signal represented by three SNPs in the SPOCK2 gene on chr10q22.1. The association at 15q25.1 confirms this region as an important susceptibility locus for smoking quantity in men and women of African ancestry. Larger studies will be needed to validate the suggestive loci that did not reach genome-wide significance and further elucidate the contribution of genetic variation to disparities in cigarette consumption, SC and smoking-attributable disease between African Americans and European Americans.

One-third tubular-hook-plate osteosynthesis for olecranon osteotomies in distal humerus type-C fractures: a preliminary report of results and complications.

INTRODUCTION: Distal humerus fractures are rare and challenging to treat. Anatomic reduction of the articular surface and stable osteosynthesis are mandatory for satisfactory results. The transolecranon approach allows superior visualisation of the joint. However, controversy exists regarding how best to fix the osteotomy. The purpose of the present study was to investigate the eligibility of a one-third tubular hook plate for osteosynthesis of olecranon osteotomies in distal humerus type-C fractures. PATIENTS AND METHODS: A consecutive series of 34 patients who were treated through an olecranon osteotomy and underwent fixation using a one-third tubular hook plate were identified. Thirty-one patients (17 females, 14 males) with a median age of 50 years (14-87, standard deviation (SD) 18.3) were available for a comprehensive assessment after a mean of 12.3 months (6-20, SD 3.7). Using the Arbeitsgemeinschaft für Osteosynthesefragen (AO) classification, six (19.4%) fractures were categorised as type C2 and 25 (80.6%) were categorised as C3. Physical and radiological examinations were performed. The Mayo Elbow Performance Score (MEPS) and the Disabilities of the Arm, Shoulder and Hand score (DASH) were evaluated. RESULTS: Mean extension-flexion ROM was found to be 102° (50-145°, SD 25). Pronation and supination were only slightly compromised. The mean MEPS was 87.2 points (50-100, SD 12.4). Fourteen patients (45.2%) were rated as excellent, and 15 (48.4%) were rated as good. One patient was rated fair, and one patient was rated as poor, respectively. Mean DASH score was 24.4 points (0-65, SD 20.3). Complications regarding the osteotomy occurred in seven patients (22.5%). Revision surgery was necessary in five cases (16%). At follow-up, all osteotomies went on to union. Mild joint degeneration (Broberg I) was found in 10 patients (32.2%). Implant removal was carried out in 15 patients (48.4%). CONCLUSION: Based on this study, the osteosynthesis of olecranon osteotomies using a one-third tubular hook plate can be regarded as a safe procedure with a low complication rate. The implant needed is widely available and cost-efficient, in contrast to specially designed plates or nails.

[Total elbow arthroplasty as a treatment option in complex injuries of the elbow in elderly patients]. / Die Ellenbogentotalendoprothese in der Versorgung schwerer Ellenbogenverletzungen des älteren Patienten.

AIM: The aim of this study was to evaluate the functional outcome of patients with severe elbow injuries treated by primary and secondary implantation of an elbow prosthesis using two different functional scores. METHOD: To determine whether or not total elbow replacement is an acceptable treatment option in such cases, we analysed the functional outcome of patients after primary or secondary implantation of the semi-constrained Coonrad-Morrey prosthesis. Between March 2005 and September 2009 we implanted 25 Coonrad-Morrey prostheses in 24 patients with acute or chronic elbow injuries. Eight patients had complex type C3 fractures according to the AO classification and were treated with primary implantation. 16 patients received a secondary implantation including 3 chronic luxations, 3 non-unions of the bone, 3 failed osteosyntheses, 7 patients with post-traumatic arthrosis and 1 reimplantation. The mean follow-up after the operation was 12 (± 8) months. The functional outcome was measured by assembling the "Mayo elbow prosthesis score" and the "Mayo elbow performance score". We had 15 female and 9 male patients with a mean age of 67 (± 6) years. RESULTS: All 24 patients achieved very good results based on the used scores with a mean of 97 points each with a maximum performance of 100 points. The mean range of motion concerning extension and flexion was 92 degrees (range 55 to 115 degrees), concerning pronation and supination 144 degrees (range 100 to 160 degrees). The mean flexion deformity was 19 degrees (range 10 to 50 degrees), the mean maximum flexion was 112 degrees (range 90 to 130 degrees). During the follow-up we had two partial ruptures of the triceps tendon, one temporary lesion of the ulnar nerve with complete recovery after surgical revision and one postoperative haematoma which needed surgical treatment. One patient needed revision surgery and resection arthroplasty due to a deep infection, but received a new prosthesis after two months. We recorded no radiographic loosening or other mechanical problems. CONCLUSIONS: Due to the good functional outcome and pain relief of patients treated by total elbow replacement, we suggest that total elbow arthroplasty is a reasonable treatment option for complex acute and chronic injuries of the elbow in elderly patients.

The effects of Cannabis sativa L. seed (hempseed) in the ovariectomized rat model of menopause.

Cannabis sativa L. has been used for the treatment of various gynecological diseases in traditional medicine. The potential of this plant to protect against complications of menopause has been raised but rarely studied. Twenty female rats were divided into five groups: sham-operated (sham), ovariectomized (OVX) and three other ovariectomized groups: HST1%, HST2% and HST10% which received 1%, 2% and 10% hempseed, respectively, in their diet for 3 weeks. The effects of hempseed on plasma lipid and lipoprotein profiles, estradiol and calcium levels were evaluated. Rats were tested for behavioral changes using the forced swimming test. The results showed that ovariectomy, independent of the type of diet, caused elevation of plasma calcium, total cholesterol and HDL-cholesterol levels, while hempseed modified this effect. Plasma estradiol levels were significantly lower in the OVX group compared to other groups. The swimming times for the OVX and sham groups were significantly shorter than that of the HSD10% group. All hempseed-treated groups were less anxious and showed significant declines in fecal boli compared to the sham group. The exploratory diving percent decreased in the HST10% group compared with other groups. These results suggest that hempseed may improve post-ovariectomy complications in rats.

Economic burden and healthcare utilization associated with castration-resistant prostate cancer in a commercial and Medicare Advantage US patient population.

OBJECTIVE: Prostate cancer is a leading cause of cancer death in men in the US. Castration-resistant prostate cancer (CRPC) is an advanced form of the disease and has a poor prognosis and limited treatment options. The objective of this study was to identify patients with CRPC from a medical claims database, and determine the prostate cancer-related economic burden and healthcare utilization of these patients. METHODS: This was a retrospective study using claims and enrollment information from a large US database linkable to laboratory data. Male patients aged 40 or older who were diagnosed with prostate cancer and received surgical or medical castration between July 1, 2001 and December 1, 2007 were considered for study inclusion. Patients with CRPC were initially identified based on at least two increases in prostrate-specific antigen (PSA) values. Due to the small number of patients with available PSA results data, logistic regression modeling using characteristics of patients with known CRPC was used to identify a larger set of patients with likely CRPC. Per-patient per-month healthcare utilization and costs were determined using medical and pharmacy claims data. RESULTS: The final sample of patients with likely CRPC as determined by regression modeling included 349 patients with known CRPC identified from the database on the basis of PSA results and an additional 2391 with likely CRPC. Within this final sample of 2740 CRPC patients, there was a per-patient per-month average of 1.43 prostate cancer-related ambulatory visits, 0.04 prostate cancer-related inpatient stays, and 0.01 prostate cancer-related ER visits. Average per-patient per-month prostate cancer-related costs were $1152 (SD = $2073) for ambulatory visits, $559 (SD = $2383) for inpatient stays, $72 (SD = $229) for pharmacy costs, and $1 (SD = $14) for ER visits. Total per-patient per-month prostate cancer-related costs were on average $1799 (SD = $3505), and these costs comprised about half of the all-cause healthcare costs for these patients. CONCLUSIONS: CRPC is a costly disease, with ambulatory visits and inpatient care accounting for a substantial proportion of the economic burden. Limitations related to the use of retrospective claims data should be considered when interpreting these results.

[Functional results after osteosynthesis of the distal humerus fracture with an anatomically precontoured, angular-stable double plate system]. / Funktionelle Ergebnisse nach winkelstabiler Osteosynthese der distalen Humerusfraktur mit einem anatomisch präformierten Doppelplattensystem.

AIM: The aim of this study was to evaluate the functional results and determine/record the complications after treating distal humerus fractures with an anatomically precontoured and angular-stable double plate system (LCP Distal Humerus Plates, Synthes GmbH, Umkirch). METHOD: 51 patients (30 female, 21 male) with 52 fractures of the distal humerus and a mean age of 51 years (14-94) were prospectively recorded over a period of 42 months and treated by open reduction and internal fixation using the above-mentioned LCP Distal Humerus Plates System. Follow-up was performed in 44 patients with 45 fractures after a mean of 13 months (6-24). According to the classification system introduced by the "Arbeitsgemeinschaft für Osteosynthesefragen" (AO [Association for the study of internal fixation, ASIF]) there were six A fractures (13.3%), five B fractures (11.1%) and 34 C fractures (75.5%). The AO/ASIF rate of type C3 fractures was 53%. Seven fractures were grade I (15.6 %) and three fractures grade II (6.7%) open. In addition to clinical examination and measuring range of motion (ROM), functional results were evaluated using the Mayo elbow performance score (MEPS) and the disabilities of the arm, shoulder and hand score (DASH). RESULTS: Using the MEPS, excellent results were achieved in 19 patients (43.2%), good in 23 (52.3%), fair and poor each in one. Mean MEPS was 87.5 +/- 11.8 points (50-100). The mean DASH score reached 14.2 +/- 19.9 (0-65.8). Having a mean extension deficit of 10 +/- 14.1 degrees (0-40 degrees) and flexion up to 127.5 +/- 17.2 degrees (80-145 degrees), the mean ROM was 110 +/- 23.8 degrees (50-145 degrees). A primary stable osteosynthesis which allows early physiotherapy was gained in 38 fractures, in seven cases additional immobilisation was carried out (10 to 28 days). Postoperative complications were seen in eleven patients (24.4%). Overall revision surgery was necessary in nine cases. CONCLUSION: By using the anatomically precontoured and angular-stable LCP distal humerus plates system a stable osteosynthesis allowing early physiotherapy is achieved in the majority of patients. Due to early initiation of physical therapy the functional results might be improved. Despite using the LCP system complications at the distal humerus fracture side were seen frequently, emphasising the challenging surgical procedure and demonstrating the need for further implant and surgical procedure improvement.