Bucket-Handle Meniscal Tears Might Not Be an Urgency: The Time to Meniscus Repair Does Not Seem to Affect the Mid-Term Outcome-A Retrospective Study of Sixty Tears with a Mean Follow-Up of 6 Years.

Background: Bucket-handle meniscal tears are mostly treated arthroscopically. However, there is no clear evidence as to whether the time to surgery impacts the outcome and whether or not lesions should be treated urgently. Methods: Sixty patients were interviewed about the current status of their knee with a mean follow-up of 6.1 years (SD = 3.5). Forty-one patients underwent meniscus repair, and fifteen patients received partial resections. The primary outcome was the rate of reoperation after meniscus repair. Secondary outcomes were pain at rest and during exercise, return to sports, and Tegner and Lysholm scores. Results: The average time to surgery was 14.4 days, with no significant impact of surgical timing on the rate of reoperation. Furthermore, no significant differences were found in pain levels, return to sports, or Tegner and Lysholm scores based on the timing of surgery. Conclusions: In our cohort, the time to surgery was not a prognostic factor for the reoperation rate or postoperative outcome in repairing bucket-handle meniscal tears. Therefore, arthroscopic repair should not be performed in an emergency setting but conducted after careful planning by experienced arthroscopy surgeons. Regarding the return to sports, postoperative factors such as rehabilitation protocols or surgical techniques could be more important than the time to surgery.

[Disproportionately increased incidence of proximal femoral fractures in a level one trauma center : Epidemiological analysis from 2016 to 2022]. / Überproportional angestiegene Inzidenz proximaler Femurfrakturen in einem Level-One-Traumazentrum : Epidemiologische Analyse von 2016 bis 2022.

BACKGROUND: Proximal femoral fractures represent the most frequent fracture entity in Germany accounting for more than 20% of all fractures. According to a decision of the Federal Joint Committee from 2019, proximal femoral fractures also have to be surgically treated within 24 h. In order to quantify a subjectively perceived increase in workload in trauma surgery at a supraregional trauma center, a retrospective analysis of the number of surgically treated proximal femoral fractures was performed. Proximal femoral fractures were chosen due to their high incidence and homogeneous treatment. METHODS: Using ICD-10 codes, all surgically treated proximal femoral fractures from 2016 to 2022, including the patient's zip code, were retrieved from the database of the trauma center. RESULTS: The number of surgically treated proximal femoral fractures doubled from 2016 to 2022. The highest increase (60%) was recorded from 2020 to 2022. Heat maps show an increase in the catchment area radius as well. CONCLUSION: When compared (inter)nationally, a disproportionate increase in the amount of surgically treated proximal femoral fractures was recorded at the trauma center studied. The increase of the catchment area radius and the number of patients treated in the urban area show that less and less hospitals participate in emergency treatment. Possible explanations are a lack of resources aggravated by the recent COVID-19 pandemic and a lack of qualified personnel, interface problems between the federal states or the strict requirements of the Federal Joint Committee in the treatment of proximal femoral fractures. It must be assumed that there is a clearly increased workload for all professions involved in the trauma center investigated, although the infrastructure has remained unchanged.

Optimism and pessimism are antithetically associated with post-operative knee function in patients' undergoing total knee arthroplasty.

PURPOSE: Personality traits, such as dispositional optimism and pessimism, have impact on a variety of health-related problems. Influence on outcome in total knee arthroplasty (TKA) could only be shown for other personality trait concepts, but not for dispositional optimism/pessimism. This study aims to examine the association of dispositional optimism/pessimism with pre-operative joint function and post-operative outcome in TKA. METHODS: Data were acquired in a multicentre, cross-sectoral, prospective study (the PROMISE Trial). Patients were followed for 12 months post-operatively. Dispositional optimism/pessimism was measured pre-operatively via the revised Life Orientation Test (LOT-R), pre- and post-operative function was measured via the 12 Item Knee-osteoarthritis outcome Scores (KOOS-12). Log-linear regression models considering known confounders and t-test were carried out to show the association of LOT-R scores with pre- and post-operative KOOS-12 scores. RESULTS: 740 patients were analyzed. Optimistic LOT-R was significantly positively associated to the mean scores of KOOS-12 pre- and post-operative, while pessimistic LOT-R was significantly associated negatively (pre-operative: optimistic p = 0.001, pessimistic p = 0.001; post-operative optimistic: 3M p = 0.001, 6M p = 0.001, 12M p = 0.001; post-operative pessimistic: 3M p = 0.01, 6M p = 0.004, 12M p = 0.001). CONCLUSION: Optimism was positively associated with pre-operative joint function and, more importantly, post-operative functional outcome in TKA, while pessimism was associated with the opposite. Assessing patients' general personality traits prior to surgery to identify pessimistic patients, hence being at risk for poor outcome in TKA, should be considered to react to the patients' special needs and possible pessimistic expectations, i.e., through a cognitive-behavioral intervention, to potentially increase optimism and hereby post-operative outcome in TKA. LEVEL OF EVIDENCE: Prognostic Level III.

Simultaneous bilateral TKA in the context of fast track surgery - Do patients meet discharge criteria as anticipated?

BACKGROUND: The efficacy and safety of enhanced recovery after surgery (ERAS) protocols for patients undergoing total knee arthroplasty (TKA) have been generally proven. Previous studies investigating patients undergoing simultaneous bilateral TKA (SBTKA) focused on complications, mortality, and pain and did not examine patients' functional limitations. Therefore, the aim of this study was to investigate to what extent patients undergoing SBTKA are able to meet functional discharge criteria originally designed for their counterparts undergoing unilateral TKA (UTKA) in an ERAS setting. MATERIALS AND METHODS: All patients who received primary SBTKA between June 2015 and December 2018 were included in this retrospective analysis. For comparison, UTKA patients were matched 1:1 to SBTKA patients using Propensity Score Matching based on age, gender, and BMI. The times to achieving the rehabilitation checkpoints of walking 150 m, walking a flight of stairs, and 90° knee flexion were evaluated. RESULTS: 63 (SBTKA group) and 64 (UTKA group) patients were included. Due to the Propensity-Score-Matching there were no differences regarding age, gender, and BMI. The mean length of stay (LOS) was 9.1 days in the SBTKA and 7.6 days in the UTKA group (p = 0.003). On average, it took SBTKA patients 5.4 days to achieve an uninterrupted walking distance of at least 150 m, while it took UTKA patients 4.1 days (p < 0.001). Mean time to walking a flight of stairs was 6.3 days for SBTKA patients and 4.7 days for UTKA patients (p < 0.001). 90° flexion was achieved after 4.1 days by SBTKA patients and 3.5 days by UTKA patients (p = 0.241). CONCLUSION: The vast majority of SBTKA patients were able to achieve functional discharge criteria within their inpatient stay when allowed about 30% extra time. Therefore, functional discharge criteria in ERAS protocols designed for UTKA can be considered appropriate for SBTKA patients. LEVEL OF EVIDENCE: Therapeutic Level III.

The INDICATE Knee expectations survey detects general patient treatment goals for total knee arthroplasty and the influence of demographic factors on patients expectations.

PURPOSE: Post-operative outcome after total knee arthroplasty (TKA) in the treatment of end-stage osteoarthritis correlates strongly with pre-operative impairment-driven patient treatment goals. However, a clinical tool for measuring patient treatment goals in correlation to impairments is still missing, which impedes patient-oriented indication in TKA. METHODS: Patients scheduled for TKA were recruited in four German hospitals. All patients were handed the INDICATE Knee Score pre-operatively. The score contains 31 treatment goals with respective impairments, subdivided into seven categories. They were asked to rank all treatment goals and impairments on a 3-point scale. Treatment goals and impairments were then checked for frequency of occurrence. Correlation of goal and impairment was tested. Analysis for associations of treatment goals and different cohort characteristics (age, sex, BMI) was conducted. RESULTS: 1.298 patients were included in the study. Seven treatment goals were categorised as "main goal" from more than 90% of all patients ("knee pain", "range of motion", "walking distance", "overall physical function", "climbing stairs", "quality of life", "implant survival"). Comparing age groups, there were significant associations towards higher expectations regarding working, physical and sports related treatment goals in younger patients (< 65y) ("ability to work" (P ≤ .001), "sports activities" (P ≤ .001), "sex life" (P ≤ .001), "dependence on help of others" (P = .015), "preventing secondary impairment" (P = .03), "dependence on walking aids" (P = .005)). Higher BMI resulted in increasing relevance of "weight reduction" (P ≤ .001), "climbing stairs" (P = .039) "global health status" (P = .015) and "long standing" (P = .007) as a "main goal". Analysis for differences in treatment goals regarding sex showed women choosing more treatment goals as "main goals" than men. CONCLUSION: Seven treatment goals which were expected by > 90% in our collective can be classified as general treatment goals for TKA. Demographic factors (age, sex, BMI) were significantly associated with patients' expectations for TKA. We conclude physicians should clearly assess their patients' demands prior to TKA to maximise post-operative outcome. LEVEL OF EVIDENCE: Prognostic Level III.

Replication stress drives chromosomal instability in fibroblasts of childhood cancer survivors with second primary neoplasms.

New development and optimization of oncologic strategies are steadily increasing the number of long-term cancer survivors being at risk of developing second primary neoplasms (SPNs) as a late consequence of genotoxic cancer therapies with the highest risk among former childhood cancer patients. Since risk factors and predictive biomarkers for therapy-associated SPN remain unknown, we examined the sensitivity to mild replication stress as a driver of genomic instability and carcinogenesis in fibroblasts from 23 long-term survivors of a pediatric first primary neoplasm (FPN), 22 patients with the same FPN and a subsequent SPN, and 22 controls with no neoplasm (NN) using the cytokinesis-block micronucleus (CBMN) assay. Mild replication stress was induced with the DNA-polymerase inhibitor aphidicolin (APH). Fibroblasts from patients with the DNA repair deficiency syndromes Bloom, Seckel, and Fanconi anemia served as positive controls and for validation of the CBMN assay supplemented by analysis of chromosomal aberrations, DNA repair foci (γH2AX/53BP1), and cell cycle regulation. APH treatment resulted in G2/M arrest and underestimation of cytogenetic damage beyond G2, which could be overcome by inhibition of Chk1. Basal micronuclei were significantly increased in DNA repair deficiency syndromes but comparable between NN, FPN, and SPN donors. After APH-induced replication stress, the average yield of micronuclei was significantly elevated in SPN donors compared to FPN (p = 0.013) as well as NN (p = 0.03) donors but substantially lower than for DNA repair deficiency syndromes. Our findings suggest that mild impairment of the response to replication stress induced by genotoxic impacts of DNA-damaging cancer therapies promotes genomic instability in a subset of long-term cancer survivors and may drive the development of an SPN. Our study provides a basis for detailed mechanistic studies as well as predictive bioassays for clinical surveillance, to identify cancer patients at high risk for SPNs at first diagnosis.

[Discharge readiness versus discharge-Results of the PROMISE study]. / Entlassbarkeit versus Entlassung ­ Ergebnisse der PROMISE-Studie.

BACKGROUND: In the context of optimized treatment processes for knee and hip replacements, lengths of stay are given for Germany that clearly exceed the internationally published ones. In this context, the present analysis of data from the PROMISE study deals with the relationship between discharge readiness and discharge. METHODS: In the PROMISE study, a jointly developed, optimized standard of care was established in three hospitals of different levels of care and realized for a typical, largely unselected cohort of patients. Among others, data were collected on achievement of discharge criteria (DC) and actual discharge. Univariate comparisons were performed by chi-square tests or the Mann-Whitney­U tests. RESULTS: A total of 1782 patients were included, of whom a mean of 85.3% achieved all previously defined DCs at a mean of 2.4 (median 2) days postoperatively. Discharge for this group occurred after a mean of 5.4 (median 5) days. 14.7% of the participants did not achieve at least one DC. This group was discharged after a mean of 6.5 (median 6) days. Significant differences in outcomes were observed for different subgroups. CONCLUSION: The so-called DCs are used as relative criteria. Achievement generally does not result in timely discharge. If this were to happen, internationally established lengths of stay would also be a reality in Germany. What actually determines discharge from inpatient treatment remains open. A variety of medical, organizational, structural and financial factors could be of importance.

Comparison of Postoperative Coronal Leg Alignment in Customized Individually Made and Conventional Total Knee Arthroplasty.

Neutral coronal leg alignment is known to be important for postoperative outcome in total knee arthroplasty (TKA). Customized individually made implants (CIM) instrumented with patient-specific cutting guides are an innovation aiming to increase the precision and reliability of implant positioning and reconstruction of leg alignment. We aimed to compare reconstruction of the hip-knee-ankle angle (HKA) of the novel CIM system iTotal™ CR G2 (ConforMIS Inc.) to a matched cohort of the off-the-shelf (OTS) knee replacement system Vanguard™ CR (Zimmer Biomet). Retrospective analysis of postoperative coronal full-leg weight-bearing radiographs of 562 TKA (283 CIM TKA, 279 OTS TKA) was conducted. Via a medical planning software, HKA and rotation of the leg were measured in postoperative radiographs. HKA was then adjusted for rotational error, and 180° ± 3° varus/valgus was defined as the target zone HKA. Corrected postoperative HKA in the CIM group was 179.0° ± 2.8° and 179.2° ± 3.1° in the OTS group (p = 0.34). The rate of outliers, outside of the ±3° target zone, was equal in both groups (32.9%). Our analysis showed that TKA using patient-specific cutting guides and implants and OTS TKA implanted with conventional instrumentation resulted in equally satisfying restoration of the coronal leg alignment with less scattering in the CIM group.

The Use of Computer Navigation in Total Hip Arthroplasty Is Associated with a Reduced Rate of Revision for Dislocation: A Study of 6,912 Navigated THA Procedures from the Australian Orthopaedic Association National Joint Replacement Registry.

BACKGROUND: The use of computer navigation has been shown to produce more accurate cup positioning when compared with non-navigated total hip arthroplasty (THA), but so far there is only limited evidence to show its effect on clinical outcomes. The present study analyzed data from the Australian Orthopaedic Association National Joint Replacement Registry to assess the impact of computer navigation on the rates of all-cause revision and revision for dislocation following THA. METHODS: Data for all non-navigated and navigated primary THAs performed for osteoarthritis in Australia from January 1, 2009, to December 31, 2019, were examined to assess the rate of revision. We analyzed the effects of navigation on rate, reason, and type of revision. Hazard ratios (HRs) from Cox proportional hazard models, adjusted for age, sex, and head size, were utilized. Because of known prosthesis-specific differences in outcomes, we performed a further analysis of the 5 acetabular and femoral component combinations most commonly used with navigation. RESULTS: Computer navigation was utilized in 6,912 primary THAs for osteoarthritis, with the use of navigation increasing from 1.9% in 2009 to 4.4% of all primary THAs performed in 2019. There was no difference in the rate of all-cause revision between navigated and non-navigated THAs looking at the entire group. There was a lower rate of revision for dislocation in the navigation THA cohort. The cumulative percent revision for dislocation at 10 years was 0.4% (95% confidence interval [CI], 0.2% to 0.6%) for navigated compared with 0.8% (95% CI, 0.8% to 0.9%) for non-navigated THAs (HR adjusted for age, sex, and head size, 0.46; 95% CI, 0.29 to 0.74; p = 0.002). In the 5 component combinations most commonly used with navigation, the rate of all-cause revision was significantly lower when these components were navigated compared with non-navigated. The cumulative percent revision at 10 years for these 5 prostheses combined was 2.4% (95% CI, 1.6% to 3.4%) for navigated compared with 4.2% (95% CI, 4.0% to 4.5%) for non-navigated THAs (HR, 0.64; 95% CI, 0.48 to 0.86; p = 0.003). CONCLUSIONS: This study showed that the use of computer navigation was associated with a reduced rate of revision for dislocation following THA. Furthermore, in the component combinations most commonly used with navigation there was also a reduction in the rate of all-cause revision. LEVEL OF EVIDENCE: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

Minimal important change and minimum clinically important difference values of the KOOS-12 after total knee arthroplasty.

PURPOSE: The minimal important change (minimal amount of change vs. baseline that a patient recognizes as a clinical change) and minimum clinically important difference (smallest difference between two measurements that are deemed important by patients) are important values to evaluate the clinical relevance of changes over time and differences between groups. This study aims to establish these values for the KOOS-12 at 1 year postoperatively. METHODS: KOOS-12 scores were calculated from the full-length KOOS completed by patients undergoing primary TKA preoperatively and at 1 year follow up. Minimal important change (MIC) values were estimated using the anchor-based predictive modeling approach and adjustment for the large proportion of improved patients in the study cohort was performed. The MCID was defined as the difference in the mean change in the KOOS-12 between the 'no improvement' and 'little improvement' groups. RESULTS: A total of 352 patients (161 male:191 female) with an overall mean age of 67.9 years (standard deviation (SD) 8.2) and a mean body mass index of 31.4 kg/m2 (SD 6.3) were included: 97.1% of patients reported an important improvement, 1.1% reported being about the same and 1.7% reported being importantly worse. The MIC improvement values were 11.5 for Pain, 13.7 for Function, 5.5 for Quality of Life (QoL) and 14.9 for the total KOOS-12 score. MCID values were 13.5 for Pain, 15.2 for Function, 8.0 for QoL and 11.1 for the total KOOS-12 score. CONCLUSION: MIC of 14.9 and MCID of 11.1 established in this study can assist clinicians and researchers in the interpretation of within-group changes (MIC) and differences between groups (MCID) at 1 year after TKA.

The ceiling effects of patient reported outcome measures for total knee arthroplasty.

BACKGROUND: Patient reported outcome measurements (PROMs) that exhibit a substantial ceiling effect show clustering of participant's scores towards the upper limit of a scale and consequently have low discriminatory power among high end scores. This study aimed to compare ceiling effects at 1 and 2 years postoperatively across commonly usedPROMs for TKA. HYPOTHESIS: We hypothesized, that the analyzed PROMs differ substantially in regards to their ceiling effect. PATIENTS AND METHODS: Patients that underwent a primary unilateral TKA and completed pre-operative and post-operative questionnaires were included in the analysis. Participants completed the KOOS, KOOS-12, KOOS-JR, KOOS-PS, WOMAC and OKS preoperatively, and completed the KOOS, KOOS-12, KOOS-JR, KOOS-PS, WOMAC,OKS and FJS postoperatively at 1 and 2 years. RESULTS: 1-year and 2-year follow-up data was available for 380 and 193 patients, respectively. The preoperative mean age was 68.0 (8.5) and mean BMI was 31.4kg/m2 (6.6), with a male to female ratio of 49.6% to 50.4%. At 1 year postoperatively, a ceiling effect was seen for the Pain and ADL subscales of the KOOS and the KOOS JR. The KOOS Pain, Symptoms, ADL and QoL subscales, the WOMAC Total and KOOS JR exhibited a ceiling effect at 2 years postoperatively. We found 9.0% and 14.8% of patients achieving a maximum score in the FJS at 1 and 2 years, respectively, indicating the absence of a substantial ceiling effect. CONCLUSION: The PROMs studied differ substantially with regards to their ceiling effect and consequently their ability to detect differences between well performing groups. The KOOS Pain, Symptoms, ADL and QoL subscales, the WOMAC Total and KOOS JR exhibited a substantial ceiling effect at 2 years postoperatively. We recommend using PROMs like the FJS and KOOS-12 with a more evenly distribution of scores across the scale when studying well performing cohorts. LEVEL OF EVIDENCE: III.

The KOOS-12 shortform shows no ceiling effect, good responsiveness and construct validity compared to standard outcome measures after total knee arthroplasty.

PURPOSE: To investigate the validity, responsiveness and ceiling effect of the recently introduced KOOS-12 and compare its performance to the KOOS, OKS, WOMAC and UCLA activity scales. METHODS: Patients from an independent multicentre study examining a medially stabilized knee system prospectively completed the KOOS, OKS, WOMAC and UCLA preoperatively and at 1 year postoperatively. KOOS-12 scores were calculated from the full length KOOS data. Construct validity was assessed using Spearman's correlation analysis. The ceiling effect was evaluated by calculating the percentage of patients with a maximum score. If the percentage exceeded 15%, a ceiling effect was considered to be present. Responsiveness was evaluated by performing paired t tests on the changes in measures and calculation of Cohen's d. RESULTS: A ceiling effect was present for the KOOS Pain, ADL and QoL subscales and the KOOS-JR at 1 year postoperatively. No ceiling effect was observed for the KOOS-12. Correlation of the KOOS-12 was low (0.3 < r < 0.5) with the UCLA, moderate (0.5 < r < 0.7) with the KOOS symptoms, sports and WOMAC stiffness subscales and high (r > 0.7) with all other scores and subscales. Effect size of the UCLA activity scale was moderate (Cohen's d 0.2-0.8) whereas effect sizes of all other outcome measures were large (d > 0.8). CONCLUSION: The KOOS-12 does not exhibit a ceiling effect, has good convergent construct validity and is responsive to changes in pain, function, QoL and knee impact between preoperatively and 1 year postoperatively. LEVEL OF EVIDENCE: Diagnostic level III.

The PROMISE study protocol: a multicenter prospective study of process optimization with interdisciplinary and cross-sectoral care for German patients receiving hip and knee endoprostheses.

Background and purpose - Knee and hip replacement are common and increasing procedures, and an optimized care process that could be implemented in different settings would be useful. The PROMISE trial investigates whether a new care process works equally in different German settings and how the results compare with current non-standardized care.Patients and methods - This multi-center prospective mixed-method study includes 2,000 German patients receiving arthritis-related hip or knee endoprostheses. An interdisciplinary and cross-sectoral care process was developed and implemented in 3 German hospitals with different levels of care, and corresponding rehabilitation centers were included to bridge the gap after acute care.Duration and outcome - The PROMISE trial recruited patients between May 2018 and March 2020. Follow-up will end in February 2021. Assessments are performed at: examination on clinical indication, 1 week before surgery, on the day of surgery, at the end of hospitalization, end of the rehabilitation program, and 3 months, 6 months, and 12 months after surgery. Outcomes include patient-reported outcomes, medical examination findings, and routinely collected data regarding the surgery and complications. Guideline-based interviews are conducted with selected patients and care partners. The primary endpoint is the presence of chronic pain at 12 months after surgery. Secondary endpoints are the number of recognized pre-existing conditions, physical activity at 12 months after surgery, use of medical services, quality of life, and interactions between care partners.Trial registration - The trial is registered with the German Clinical Trials Register (https://www.drks.de; DRKS00013972; March 23, 2018).

Comparison of time and dose dependent gene expression and affected pathways in primary human fibroblasts after exposure to ionizing radiation.

BACKGROUND: Exposure to ionizing radiation induces complex stress responses in cells, which can lead to adverse health effects such as cancer. Although a variety of studies investigated gene expression and affected pathways in human fibroblasts after exposure to ionizing radiation, the understanding of underlying mechanisms and biological effects is still incomplete due to different experimental settings and small sample sizes. Therefore, this study aims to identify the time point with the highest number of differentially expressed genes and corresponding pathways in primary human fibroblasts after irradiation at two preselected time points. METHODS: Fibroblasts from skin biopsies of 15 cell donors were exposed to a high (2Gy) and a low (0.05Gy) dose of X-rays. RNA was extracted and sequenced 2 h and 4 h after exposure. Differentially expressed genes with an adjusted p-value < 0.05 were flagged and used for pathway analyses including prediction of upstream and downstream effects. Principal component analyses were used to examine the effect of two different sequencing runs on quality metrics and variation in expression and alignment and for explorative analysis of the radiation dose and time point of analysis. RESULTS: More genes were differentially expressed 4 h after exposure to low and high doses of radiation than after 2 h. In experiments with high dose irradiation and RNA sequencing after 4 h, inactivation of the FAT10 cancer signaling pathway and activation of gluconeogenesis I, glycolysis I, and prostanoid biosynthesis was observed taking p-value (< 0.05) and (in) activating z-score (≥2.00 or ≤ - 2.00) into account. Two hours after high dose irradiation, inactivation of small cell lung cancer signaling was observed. For low dose irradiation experiments, we did not detect any significant (p < 0.05 and z-score ≥ 2.00 or ≤ - 2.00) activated or inactivated pathways for both time points. CONCLUSIONS: Compared to 2 h after irradiation, a higher number of differentially expressed genes were found 4 h after exposure to low and high dose ionizing radiation. Differences in gene expression were related to signal transduction pathways of the DNA damage response after 2 h and to metabolic pathways, that might implicate cellular senescence, after 4 h. The time point 4 h will be used to conduct further irradiation experiments in a larger sample.

Spontaneous and Radiation-Induced Chromosome Aberrations in Primary Fibroblasts of Patients With Pediatric First and Second Neoplasms.

The purpose of the present study was to investigate whether former childhood cancer patients who developed a subsequent secondary primary neoplasm (SPN) are characterized by elevated spontaneous chromosomal instability or cellular and chromosomal radiation sensitivity as surrogate markers of compromised DNA repair compared to childhood cancer patients with a first primary neoplasm (FPN) only or tumor-free controls. Primary skin fibroblasts were obtained in a nested case-control study including 23 patients with a pediatric FPN, 22 matched patients with a pediatric FPN and an SPN, and 22 matched tumor-free donors. Clonogenic cell survival and cytogenetic aberrations in Giemsa-stained first metaphases were assessed after X-irradiation in G1 or on prematurely condensed chromosomes of cells irradiated and analyzed in G2. Fluorescence in situ hybridization was applied to investigate spontaneous transmissible aberrations in selected donors. No significant difference in clonogenic survival or the average yield of spontaneous or radiation-induced aberrations was found between the study populations. However, two donors with an SPN showed striking spontaneous chromosomal instability occurring as high rates of numerical and structural aberrations or non-clonal and clonal translocations. No correlation was found between radiation sensitivity and a susceptibility to a pediatric FPN or a treatment-associated SPN. Together, the results of this unique case-control study show genomic stability and normal radiation sensitivity in normal somatic cells of donors with an early and high intrinsic or therapy-associated tumor risk. These findings provide valuable information for future studies on the etiology of sporadic childhood cancer and therapy-related SPN as well as for the establishment of predictive biomarkers based on altered DNA repair processes.

Venous thromboembolism in patients hospitalized for knee joint replacement surgery.

Patients undergoing knee joint replacement (KJR) are at high risk of postoperative venous thromboembolism (VTE), but data on the time trends of VTE rate in this population are sparse. In this analysis of the German nationwide inpatient sample, we included all hospitalizations for elective primary KJR in Germany 2005-2016. Overall, 1,804,496 hospitalized patients with elective primary KJR (65.1% women, 70.0 years [IQR 63.0-76.0]) were included in the analysis. During hospitalization, VTE was documented in 23,297 (1.3%) patients. Total numbers of primary KJR increased from 129,832 in 2005 to 167,881 in 2016 (ß-(slope)-estimate 1,978 [95% CI 1,951 to 2,004], P < 0.001). In-hospital VTE decreased from 2,429 (1.9% of all hospitalizations for KJR) to 1,548 (0.9%) cases (ß-estimate - 0.77 [95% CI - 0.81 to - 0.72], P < 0.001), and in-hospital death rate from 0.14% (184 deaths) to 0.09% (146 deaths) (ß-estimate - 0.44 deaths per year [95% CI - 0.59 to - 0.30], P < 0.001). Infections during hospitalization were associated with a higher VTE risk. VTE events were independently associated with in-hospital death (OR 20.86 [95% CI 18.78-23.15], P < 0.001). Annual number of KJR performed in Germany increased by almost 30% between 2005 and 2016. In parallel, in-hospital VTE rates decreased from 1.9 to 0.9%. Perioperative infections were associated with higher risk for VTE. Patients who developed VTE had a 21-fold increased risk of in-hospital death.

Increased postoperative dexamethasone and gabapentin reduces opioid consumption after total knee arthroplasty.

PURPOSE: Dexamethasone and gabapentin are used in multimodal pain management protocols to reduce postoperative pain after total knee arthroplasty. For both analgesic adjuvants, the optimal dose regimen to reduce opioid usage is still unclear. METHODS: The opioid consumption of patients undergoing primary TKA before and after a change of the analgesic adjuvant medication in our protocol (old protocol: 4 mg of dexamethasone daily for 2 days, 600 mg gabapentin daily for 1 week; new protocol: 10 mg dexamethasone daily for 2 days, 300 mg gabapentin every 8 h for 1 week) were retrospectively compared. All surgeries were performed under spinal anesthesia. Peri- and postoperative pain medication remained unchanged. RESULTS: A total of 186 patients who received TKA between 11/29/2016 and 06/09/2017 were screened. Six patients who received general anesthesia, 4 patients who underwent simultaneous bilateral TKA, and 16 patients with ongoing opioid consumption at the time of surgery were excluded, leaving 80 patients in each group. Opioid consumption within 24 h [morphine equivalents in mg: mean 50.5, standard deviation (SD) 30.0 (old) vs. 39.8, SD 24.2 (new); P = 0.0470], cumulative consumption over 48 h (97.3, SD 64.4 vs. 70.4, SD 51.2; P = 0.0040) and cumulative consumption over 72 h (108.1, SD 79.5 vs. 82.5, SD 72.6; P = 0.0080), were all significantly lower in the new protocol. CONCLUSION: Increased postoperative administration of dexamethasone and gabapentin after TKA is associated with lower opioid consumption. Within the first 48 h, up to about 25% of opioids can be spared, comparing high-dose to low-dose protocols. LEVEL OF EVIDENCE: Therapeutic Level III.

HDAC inhibitor-loaded bone cement for advanced local treatment of osteosarcoma and chondrosarcoma.

UNLABELLED: The treatment of osteosarcoma, especially wide resection, is challenging. An additional local drug therapy after resection using anti-neoplastic bone cement (Polymethylmethacrylate (PMMA)) could help improve the outcome of therapy. In this study, we evaluated the effects of PMMA loaded with valproic acid (VPA) and suberoylanilide hydroxamic acid (SAHA) on the cell activity of a SaOs-2 cell culture, as well as the elution rate of the drugs out of the bone cement. MATERIALS AND METHODS: In our experiments, we used the SaOs-2 osteosarcoma and the SW1353 chondrosarcoma cell line. Bone cement clots (5 g) were prepared and loaded with different drug concentrations of VPA (25 mg and 50 mg) and SAHA (1 mg, 2.5 mg and 5 mg). Two control groups were established, one with a native cement clot, the other with human mesenchymal stem cells, in order to evaluate toxicity on non tumor-cells. Cell activity was measured using an Alamar Blue assay on days 1, 2, 3, 4 and 7. The cement clots were additionally examined in a material testing unit for biomechanical and structural changes. RESULTS: Tumor cells showed a significant and complete reduction of activity under therapy with VPA and SAHA. Drug release of VPA was extensive between days 0 and 3 and decreased progressively to day 7. Cumulative drug concentration in the medium continuously increased. Biomechanical testing of the cement clots showed no differences in stability and architecture compared to the control group. SaOs-2 and SW1353 cells with medium from native cement clots without drug therapy presented a cell activity of 100% in all groups and during all measurements. Human mesenchymal stem cells were not significantly affected during therapy with VPA and low concentrations of SAHA. In contrast, cell activity of human mesenchymal stem cells was significantly reduced under therapy with higher concentrations of SAHA, with an approximately linear decrease between days 0-3 and a rapidly decreasing activity between days 4-7. CONCLUSION: A local cytotoxic therapy in the treatment of osteosarcoma and chondrosarcoma might improve the rate of metastasis and survival of patients. Our results present an encouraging approach to loading PMMA with anti-neoplastic drugs.

Minimally invasive surgery for achalasia in patients >40 years: more favorable than anticipated.

PURPOSE: The efficacy of Heller myotomy in patients >40 years-a significant predictor suggesting a favorable response to pneumatic dilation-has been questioned. The aim of our study was to evaluate the results obtained in patients aged <40 and >40 years undergoing minimally invasive surgery (MIS) for achalasia. METHODS: In January 2008, we established the MIS technique for achalasia in our clinic. In the following period from January 2008 to March 2011, 74 patients underwent primary laparoscopic myotomy for achalasia. The procedure was accomplished with an anterior 180° semifundoplication according to Dor in all patients. The Eckardt score and the Gastrointestinal Quality of Life Index (GQLI) served as outcome measures. RESULTS: The median age of patients was 45.5 years (range, 18-85 years) with a median duration of preoperative achalasia symptoms of 57 months (range, 2-468 months). There were no conversions to open surgery and-except for one patient with a sterile pleural effusion-no postoperative complications. At a median follow-up of 12 months, the preoperative Eckardt score of 7.0 (range, 3-12) was found to be significantly decreased to a median of 2 (range, 0-6; P < 0.001). With regard to patients <40 and >40 years, the postoperative Eckardt score obtained in the older patient population was not significantly lower (P = 0.074). There was no statistically significant difference between the two groups with respect to the postoperative GQLI (P = 0.860). Neither gender nor preoperative Botox injection or pneumatic dilation inserted a significant influence on the postoperative clinical outcome (P > 0.05). CONCLUSIONS: Laparoscopic Heller myotomy for achalasia is associated with a high success rate as the primary therapeutic option and after failure of endoscopic therapy. It can be performed safely and with favorable outcomes also in patients >40 years. However, the long-term durability of the procedure remains to be established.