Low bone density and high morbidity in patients between 55 and 70 years with displaced femoral neck fractures: a case-control study of 50 patients vs 150 normal controls.

BACKGROUND: A displaced femoral neck fracture (FNF) in patients 55-70 years is a serious injury with a high risk of treatment failure and the optimal surgical treatment remains unclear. We aimed to describe characteristics of fracture patients compared to a sample from the normal population. METHODS: Fifty patients aged 55-70 years with a displaced FNF were gender- and age- matched with a control group of 150 persons without a hip fracture using computergenerated randomization and the Norwegian National Population Register. To reduce the risk of spurious selection bias, the sample size of the control group was trebled compared to the fracture group. Dual-energy x-ray absorptiometry (DXA) was performed. Demographics and hip function (Harris Hip Score, Oxford Hip Score, and Hip Dysfunction and Osteoarthritis Outcome Score) were collected. RESULTS: There were more than 75% women in both groups. The mean age was 64.5 years in the fracture group and 65.1 in the control group. Results for DXA measured for lumbar spine, total hip and the femoral neck showed that patients with displaced FNF were significantly more osteoporotic. Fracture patients had significantly lower body mass index, higher Charlson comorbidity index (CCI), and higher ASA (American Society of Anesthesiologists) score than the control group. No clinically relevant differences in hip function were found. There were 48% smokers in the fracture group compared to 10% in the control group. The odds ratio for obtaining a displaced FNF was high if the patients suffered from osteoporosis, smoked or had several comorbidities. CONCLUSIONS: This study showed that patients aged 55-70 years with a displaced femoral neck fracture had lower bone density and higher comorbidity compared with a gender- and age-matched population without femoral neck fractures. This suggests that this patient group is epidemiologically similar to older patients with femoral neck fractures.

High failure rate after internal fixation and beneficial outcome after arthroplasty in treatment of displaced femoral neck fractures in patients between 55 and 70 years.

Background and purpose - The treatment of patients between 55 and 70 years with displaced intracapsular femoral neck fracture remains controversial. We compared internal fixation (IF), bipolar hemiarthroplasty (HA) and total hip arthroplasty (THA) in terms of mortality, reoperations and patient-reported outcome by using data from the Norwegian Hip Fracture Register. Patients and methods - We included 2,713 patients treated between 2005 and 2012. 1,111 patients were treated with IF, 1,030 with HA and 572 patients with THA. Major reoperations (defined as re-osteosynthesis, secondary arthroplasty, exchange, or removal of prosthesis components and Girdlestone procedure), patient-reported outcome measures (satisfaction, pain, and health-related quality of life (EQ5D) after 4 and 12 months), 1-year mortality, and change in treatment methods over the study period were investigated. Results - Major reoperations occurred in 27% after IF, 3.8% after HA and 2.8% after THA. 549 patients (20% of total study population) answered both questionnaires. Compared with IF, patients treated with THA were more satisfied after 4 and 12 months, reported less pain after 4 months and 12 months, had a higher EQ5D-index score after 4 months and 12 months, and EQ-VAS score after 4 months. Compared with IF, patients treated with HA were more satisfied and reported less pain after 4 months. EQ5D-index and EQ-VAS were similar. Patients treated with HA had higher 1-year mortality and had more comorbidities than both the THA and IF group. All these differences were statistically and clinically significant. Interpretation - This study showed high reoperation rate after IF and better patient-reported outcome after both THA and HA with medium follow-up. Patients selected for HA represented a frailer group than patients treated with THA or IF.

Polyclonal fluctuation of lentiviral vector-transduced and expanded murine hematopoietic stem cells.

Gene therapy has proven its potential to cure diseases of the hematopoietic system. However, severe adverse events observed in clinical trials have demanded improved gene-transfer conditions. Whereas progress has been made to reduce the genotoxicity of integrating gene vectors, the role of pretransplantation cultivation is less well investigated. We observed that the STIF (stem cell factor [SCF], thrombopoietin [TPO], insulin-like growth factor-2 [IGF-2], and fibroblast growth factor-1 [FGF-1]) cytokine cocktail developed to effectively expand murine hematopoietic stem cells (HSCs) also supports the expansion of leukemia-initiating insertional mutants caused by gammaretroviral gene transfer. We compared 4 protocols to examine the impact of prestimulation and posttransduction culture in STIF in the context of lentiviral gene transfer. Observing 56 transplanted mice for up to 9.5 months, we found consistent engraftment and gene-marking rates after prolonged ex vivo expansion. Although a lentiviral vector with a validated insertional-mutagenic potential was used, longitudinal analysis identifying > 7000 integration sites revealed polyclonal fluctuations, especially in "expanded" groups, with de novo detection of clones even at late time points. Posttransduction expansion in STIF did not enrich clones with insertions in proto-oncogenes but rather increased clonal diversity. Our data indicate that lentiviral transduction in optimized media mediates intact polyclonal hematopoiesis without selection for growth-promoting hits by posttransduction expansion.

Adjuvant therapy reduces the benefit of palliative treatment in disseminated breast cancer - own findings and review of the literature.

BACKGROUND: Adjuvant treatment concepts have improved the 10-year cure rate of breast and colon cancer, but new treatments for metastatic disease have yielded only incremental benefit. If treatments for disseminated cancer were actually prolonging life rather than only increasing remission rates, this effect should have been documented over the last 30+ years. However, published data concerning advances in treatment for disseminated cancer have been contradictory. PATIENTS AND METHODS: To add data-based information, we analyzed 2 sources: a regional population-based cancer registry (Hamburgisches Krebsregister, HKR), and a research cancer registry (Projektgruppe Internistische Onkologie, PIO). We compared the survival of several thousand patients with metastatic disease who received treatment only after dissemination with that of patients who received initial adjuvant therapy. RESULTS: After adjuvant treatment, survival in patients with disseminated breast cancer is up to a third shorter than that of patients without adjuvant therapy. CONCLUSIONS: In accordance with published evidence, we conclude that ineffective adjuvant treatment shortens survival after documentation of metastatic disease. This is probably due to the elimination of chemo-sensitive tumor cells or to the induction of resistance in remaining micrometatases. This negative effect on survival after dissemination has been shown clearly for breast cancer and is also probable for cancer of the colon and other sites.

Mapping the Oncological Basis Dataset to the Standardized Vocabularies of a Common Data Model: A Feasibility Study.

In their joint effort against cancer, all involved parties within the German healthcare system are obligated to report diagnostics, treatments, progression, and follow-up information for tumor patients to the respective cancer registries. Given the federal structure of Germany, the oncological basis dataset (oBDS) operates as the legally required national standard for oncological reporting. Unfortunately, the usage of various documentation software solutions leads to semantic and technical heterogeneity of the data, complicating the establishment of research networks and collective data analysis. Within this feasibility study, we evaluated the transferability of all oBDS characteristics to the standardized vocabularies, a metadata repository of the observational medical outcomes partnership (OMOP) common data model (CDM). A total of 17,844 oBDS expressions were mapped automatically or manually to standardized concepts of the OMOP CDM. In a second step, we converted real patient data retrieved from the Hamburg Cancer Registry to the new terminologies. Given our pipeline, we transformed 1773.373 cancer-related data elements to the OMOP CDM. The mapping of the oBDS to the standardized vocabularies of the OMOP CDM promotes the semantic interoperability of oncological data in Germany. Moreover, it allows the participation in network studies of the observational health data sciences and informatics under the usage of federated analysis beyond the level of individual countries.

Total Hip Arthroplasty Leads to Better Results After Low-Energy Displaced Femoral Neck Fracture in Patients Aged 55 to 70 Years: A Randomized Controlled Multicenter Trial Comparing Internal Fixation and Total Hip Arthroplasty.

BACKGROUND: The optimal treatment of displaced femoral neck fractures in patients 55 to 70 years old remains controversial. The aim of the present study was to assess the effect of closed reduction and internal fixation with cannulated screws (IF) compared with total hip arthroplasty (THA) on hip pain and function, with use of data for outcome measures, complications, and reoperations. METHODS: This multicenter randomized controlled trial included all patients 55 to 70 years old who presented with a low-energy displaced femoral neck fracture between December 2013 and December 2018. Patients were randomly allocated to undergo either IF or THA. The primary outcome was the Harris Hip Score (HHS) at 12 months postoperatively. Secondary outcomes were the HHS at 4 and 24 months postoperatively, Oxford Hip Score (OHS), Hip Disability and Osteoarthritis Outcome Score (HOOS), health-related quality of life (EQ-5D-3L [EuroQol 5 Dimensions 3 Levels] index score and EQ-VAS [visual analogue scale]), VAS for pain, and VAS for patient satisfaction at 4, 12, and 24 months postoperatively. Complications and reoperations were continuously monitored. The primary analyses were performed according to the intention-to-treat principle. RESULTS: A total of 102 patients with a mean (± standard deviation) age of 63.7 ± 4.2 years were allocated to IF (n = 51) or THA (n = 51). The mean difference in the primary outcome, the HHS at 12 months postoperatively (5.3; 95% confidence interval, 0.9 to 9.7; p = 0.017), was below the predefined minimal clinically important difference of 10 points. However, patients who underwent THA had a significantly higher HHS at 4 and 12 months, better OHS at 4 and 12 months, and better HOOS at 4, 12, and 24 months postoperatively. Patients who underwent THA also reported better health-related quality of life at 4 months postoperatively and reported greater satisfaction and less pain at 4 and 12 months postoperatively. A total of 26 patients in the IF group (51%; 95% confidence interval, 37% to 65%) and 2 patients in the THA group (4%; 95% confidence interval, 0.5% to 13%) underwent a major reoperation. CONCLUSIONS: In this randomized controlled trial, we showed that patients between 55 and 70 years old who underwent THA for a low-energy displaced femoral neck fracture experienced better outcomes than those who underwent closed reduction and internal fixation. LEVEL OF EVIDENCE: Therapeutic Level I . See Instructions for Authors for a complete description of levels of evidence.

Rational surgical neck management in total laryngectomy for advanced stage laryngeal squamous cell carcinomas.

PURPOSE: Controversies exist in regard to surgical neck management in total laryngectomies (TL). International guidelines do not sufficiently discriminate neck sides and sublevels, or minimal neck-dissection nodal yield (NY). METHODS: Thirty-seven consecutive primary TL cases from 2009 to 2019 were retrospectively analyzed in terms of local tumor growth using a previously established imaging scheme, metastatic neck involvement, and NY impact on survival. RESULTS: There was no case of level IIB involvement on any side. For type A and B tumor midline involvement, no positive contralateral lymph nodes were found. Craniocaudal tumor extension correlated with contralateral neck involvement (OR: 1.098, p = 0.0493) and showed increased involvement when extending 33 mm (p = 0.0134). Using a bilateral NY of ≥ 24 for 5-year overall survival (OS) and ≥ 26 for 5-year disease-free survival (DFS) gave significantly increased rate advantages of 64 and 56%, respectively (both p < 0.0001). CONCLUSIONS: This work sheds light on regional metastatic distribution pattern and its influence on TL cases. An NY of n ≥ 26 can be considered a desirable benchmark for bilateral selective neck dissections as it leads to improved OS and DFS. Therefore, an omission of distinct neck levels cannot be promoted at this time.

Cell-intrinsic and vector-related properties cooperate to determine the incidence and consequences of insertional mutagenesis.

In gene therapeutic approaches targeting hematopoietic cells, insertional mutagenesis may provoke clonal dominance with potential progress to overt leukemia. To investigate the contribution of cell-intrinsic features and determine the frequency of insertional proto-oncogene activation, we sorted hematopoietic subpopulations before transduction with replication-deficient gamma-retroviral vectors and studied the clonal repertoire in transplanted C57BL/6J mice. Progressive clonal dominance only developed in the progeny of populations with intrinsic stem cell potential, where expanding clones with insertional upregulation of proto-oncogenes such as Evi1 were retrieved with a frequency of approximately 10(-4). Longitudinal studies by high-throughput sequencing and locus-specific quantitative PCR showed clones with >50-fold expansion between weeks 5 and 31 after transplantation. In contrast, insertional events in proto-oncogenes did not endow the progeny of multipotent or myeloid-restricted progenitors with the potential for clonal dominance (risk <10(-6)). Transducing sorted hematopoietic stem cells (HSCs) with self-inactivating (SIN) lentiviral vectors in short-term cultures improved chimerism, and although clonal dominance developed, there was no evidence for insertional events in the vicinity of proto-oncogenes as the underlying cause. We conclude that cell-intrinsic properties cooperate with vector-related features to determine the incidence and consequences of insertional mutagenesis. Furthermore, our study offers perspectives for refinement of animal experiments in the assessment of vector-related genotoxicity.

Screw Fixation Versus Hemiarthroplasty for Nondisplaced Femoral Neck Fractures in Elderly Patients: A Multicenter Randomized Controlled Trial.

BACKGROUND: Elderly patients with a displaced femoral neck fracture treated with hip arthroplasty may have better function than those treated with internal fixation. We hypothesized that hemiarthroplasty would be superior to screw fixation with regard to hip function, mobility, pain, quality of life, and the risk of a reoperation in elderly patients with a nondisplaced femoral neck fracture. METHODS: In a multicenter randomized controlled trial (RCT), Norwegian patients ≥70 years of age with a nondisplaced (valgus impacted or truly nondisplaced) femoral neck fracture were allocated to screw fixation or hemiarthroplasty. Assessors blinded to the type of treatment evaluated hip function with the Harris hip score (HHS) as the primary outcome as well as on the basis of mobility assessed with the timed "Up & Go" (TUG) test, pain as assessed on a numerical rating scale, and quality of life as assessed with the EuroQol-5 Dimension-3 Level (EQ-5D) at 3, 12, and 24 months postsurgery. Results, including reoperations, were assessed with intention-to-treat analysis. RESULTS: Between February 6, 2012, and February 6, 2015, 111 patients were allocated to screw fixation and 108, to hemiarthroplasty. At the time of follow-up, there was no significant difference in hip function between the screw fixation and hemiarthroplasty groups, with a 24-month HHS (and standard deviation) of 74 ± 19 and 76 ± 17, respectively, and an adjusted mean difference of -2 (95% confidence interval [CI] = -6 to 3; p = 0.499). Patients allocated to hemiarthroplasty were more mobile than those allocated to screw fixation (24-month TUG = 16.6 ± 9.5 versus 20.4 ± 12.8 seconds; adjusted mean difference = 6.2 seconds [95% CI = 1.9 to 10.5 seconds]; p = 0.004). Furthermore, screw fixation was a risk factor for a major reoperation, which was performed in 20% (22) of 110 patients who underwent screw fixation versus 5% (5) of 108 who underwent hemiarthroplasty (relative risk reduction [RRR] = 3.3 [95% CI = 0.7 to 10.0]; number needed to harm [NNH] = 6.5; p = 0.002). The 24-month mortality rate was 36% (40 of 111) for patients allocated to internal fixation and 26% (28 of 108) for those allocated to hemiarthroplasty (RRR = 0.4 [95% CI = -0.1 to 1.1]; p = 0.11). Two patients were lost to follow-up. CONCLUSIONS: In this multicenter RCT, hemiarthroplasty was not found to be superior to screw fixation in reestablishing hip function as measured by the HHS (the primary outcome). However, hemiarthroplasty led to improved mobility and fewer major reoperations. The findings suggest that certain elderly patients with a nondisplaced femoral neck fracture may benefit from being treated with a latest-generation hemiarthroplasty rather than screw fixation. LEVEL OF EVIDENCE: Therapeutic Level I. See Instructions for Authors for a complete description of levels of evidence.