FOXG1 targets BMP repressors and cell cycle inhibitors in human neural progenitor cells.

FOXG1 is a critical transcription factor in human brain where loss-of-function mutations cause a severe neurodevelopmental disorder, while increased FOXG1 expression is frequently observed in glioblastoma. FOXG1 is an inhibitor of cell patterning and an activator of cell proliferation in chordate model organisms but different mechanisms have been proposed as to how this occurs. To identify genomic targets of FOXG1 in human neural progenitor cells (NPCs), we engineered a cleavable reporter construct in endogenous FOXG1 and performed chromatin immunoprecipitation (ChIP) sequencing. We also performed deep RNA sequencing of NPCs from two females with loss-of-function mutations in FOXG1 and their healthy biological mothers. Integrative analyses of RNA and ChIP sequencing data showed that cell cycle regulation and Bone Morphogenic Protein (BMP) repression gene ontology categories were over-represented as FOXG1 targets. Using engineered brain cell lines, we show that FOXG1 specifically activates SMAD7 and represses CDKN1B. Activation of SMAD7 which inhibits BMP signaling may be one way that FOXG1 patterns the forebrain, while repression of cell cycle regulators such as CDKN1B may be one way that FOXG1 expands the NPC pool to ensure proper brain size. Our data reveal novel mechanisms on how FOXG1 may control forebrain patterning and cell proliferation in human brain development.

Outcomes of patients with early stage mucinous ovarian carcinoma: a Dutch population-based cohort study comparing expansile and infiltrative subtypes.

OBJECTIVE: This study aimed to assess the outcomes of patients with early stage mucinous ovarian carcinoma based on subtype (expansile vs infiltrative). METHODS: We retrospectively analyzed all surgically treated patients with mucinous ovarian carcinoma in the Netherlands (2015-2020), using data from national registries. Subtypes were determined, with any ambiguities resolved by a dedicated gynecologic pathologist. Patients with International Federation of Gynecology and Obstetrics (FIGO) stage I were categorized into full staging, fertility-sparing, or partial stagings. Outcomes were overall survival and recurrence free survival, and recurrence rates. RESULTS: Among 409 identified patients, 257 (63%) had expansile and 152 (37%) had infiltrative tumors. Patients with expansile tumors had FIGO stage I more frequently (n=243, 95% vs n=116, 76%, p<0.001). For FIGO stage I disease, patients with expansile and infiltrative tumors underwent similar proportions of partial (n=165, 68% vs n=78, 67%), full (n=32, 13% vs n=23, 20%), and fertility-sparing stagings (n=46, 19% vs n=15, 13%) (p=0.139). Patients with expansile FIGO stage I received less adjuvant chemotherapy (n=11, 5% vs n=24, 21%, p<0.001), exhibited better overall and recurrence free survival (p=0.006, p=0.012), and fewer recurrences (n=13, 5% vs n=16, 14%, p=0.011). Survival and recurrence rates were similar across the expansile extent of staging groups. Patients undergoing fertility-sparing staging for infiltrative tumors had more recurrences compared with full or partial stagings, while recurrence free survival was similar across these groups. Full staging correlated with better overall survival in infiltrative FIGO stage I (p=0.022). CONCLUSIONS: While most patients with FIGO stage I underwent partial staging, those with expansile had better outcomes than those with infiltrative tumors. Full staging was associated with improved overall survival in infiltrative, but not in expansile FIGO stage I. These results provide insight for tailored surgical approaches.

Exploring global barriers to optimal ovarian cancer care: thematic analysis.

OBJECTIVE: To explore the barriers to ovarian cancer care, as reported in the open ended responses of a global expert opinion survey, highlighting areas for improvement in global ovarian cancer care. Potential solutions to overcome these barriers are proposed. METHODS: Data from the expert opinion survey, designed to assess the organization of ovarian cancer care worldwide, were analyzed. The survey was distributed across a global network of physicians. We examined free text, open ended responses concerning the barriers to ovarian cancer care. A qualitative thematic analysis was conducted to identify, analyze, and report meaningful patterns within the data. RESULTS: A total of 1059 physicians from 115 countries completed the survey, with 438 physicians from 93 countries commenting on the barriers to ovarian cancer care. Thematic analysis gave five major themes, regardless of income category or location: societal factors, inadequate resources in hospital, economic barriers, organization of the specialty, and need for early detection. Suggested solutions include accessible resource stratified guidelines, multidisciplinary teamwork, public education, and development of gynecological oncology training pathways internationally. CONCLUSIONS: This analysis provides an international perspective on the main barriers to optimal ovarian cancer care. The themes derived from our analysis highlight key target areas to focus efforts to reduce inequalities in global care. Future regional analysis involving local representatives will enable country specific recommendations to improve the quality of care and ultimately to work towards closing the care gap.

Higher conversion rate to knee arthroplasty in female patients following medial open-wedge high tibial osteotomy.

PURPOSE: Most studies about medial open-wedge high tibial osteotomy (HTO) reported outcomes without focusing on gender differences. Therefore, the study compared the long-term survival rate and postoperative subjective knee function after HTO in female versus male patients with symptomatic medial compartment knee osteoarthritis. METHODS: The data of three cohorts with long-term outcomes were analysed (n = 245; 32% females; age: 49 ± 7 years; Kellgren Lawrence Grade I 6.1%, II 32.7%, III 42.4%; IV 18.8%). The minimum follow-up was at least 6 years or an earlier conversion to total knee arthroplasty (TKA). The gender-specific survival rate after HTO was calculated after 5 and 10 years and compared using Kaplan-Meier analysis and the logrank test. Baseline characteristics and subjective knee function (International Knee Documentation Committee [IKDC]/Lysholm) were analysed between both genders. RESULTS: Forty of 78 (51.3%) women and 41 of 167 men (24.5%) underwent TKA. HTO survival in females was significantly lower (p = 0.0010). The 5- and 10-year survival rates were 85.9% and 62.6% for females and 93.4% and 77.7% for males. In females and males, from preoperative to the last follow-up, the IKDC (43 ± 15 to 58 ± 17; 47 ± 14 to 67 ± 18) and the Lysholm (42 ± 18 to 72 ± 18; 55 ± 22 to 77 ± 23) improved significantly (all p < 0.0001). Females had significantly lower preoperative and postoperative IKDC (p = 0.0438; p = 0.0035) and Lysholm scores (p = 0.0002; p = 0.0323). But the absolute improvements of the IKDC and Lysholm were not significantly different between genders. CONCLUSIONS: Females had higher conversion rates to TKA and lower knee function at the last follow-up. However, preoperative knee function was lower in females and the absolute improvement following HTO was similar for both genders. In general, females benefit from HTO to treat medial knee arthritis, and TKA could be postponed for half of female patients for more than 10 years. However, surgeons must be aware of the described inferior outcomes in females for realistic patient expectation management. LEVEL OF EVIDENCE: Level II.

Early prediction of ventricular peritoneal shunt dependency in aneurysmal subarachnoid haemorrhage patients by recurrent neural network-based machine learning using routine intensive care unit data.

Aneurysmal subarachnoid haemorrhage (aSAH) can lead to complications such as acute hydrocephalic congestion. Treatment of this acute condition often includes establishing an external ventricular drainage (EVD). However, chronic hydrocephalus develops in some patients, who then require placement of a permanent ventriculoperitoneal (VP) shunt. The aim of this study was to employ recurrent neural network (RNN)-based machine learning techniques to identify patients who require VP shunt placement at an early stage. This retrospective single-centre study included all patients who were diagnosed with aSAH and treated in the intensive care unit (ICU) between November 2010 and May 2020 (n = 602). More than 120 parameters were analysed, including routine neurocritical care data, vital signs and blood gas analyses. Various machine learning techniques, including RNNs and gradient boosting machines, were evaluated for their ability to predict VP shunt dependency. VP-shunt dependency could be predicted using an RNN after just one day of ICU stay, with an AUC-ROC of 0.77 (CI: 0.75-0.79). The accuracy of the prediction improved after four days of observation (Day 4: AUC-ROC 0.81, CI: 0.79-0.84). At that point, the accuracy of the prediction was 76% (CI: 75.98-83.09%), with a sensitivity of 85% (CI: 83-88%) and a specificity of 74% (CI: 71-78%). RNN-based machine learning has the potential to predict VP shunt dependency on Day 4 after ictus in aSAH patients using routine data collected in the ICU. The use of machine learning may allow early identification of patients with specific therapeutic needs and accelerate the execution of required procedures.

A recurrent machine learning model predicts intracranial hypertension in neurointensive care patients.

The evolution of intracranial pressure (ICP) of critically ill patients admitted to a neurointensive care unit (ICU) is difficult to predict. Besides the underlying disease and compromised intracranial space, ICP is affected by a multitude of factors, many of which are monitored on the ICU, but the complexity of the resulting patterns limits their clinical use. This paves the way for new machine learning techniques to assist clinical management of patients undergoing invasive ICP monitoring independent of the underlying disease. An institutional cohort (ICP-ICU) of patients with invasive ICP monitoring (n = 1346) was used to train recurrent machine learning models to predict the occurrence of ICP increases of ≥22 mmHg over a long (>2 h) time period in the upcoming hours. External validation was performed on patients undergoing invasive ICP measurement in two publicly available datasets [Medical Information Mart for Intensive Care (MIMIC, n = 998) and eICU Collaborative Research Database (n = 1634)]. Different distances (1-24 h) between prediction time point and upcoming critical phase were evaluated, demonstrating a decrease in performance but still robust AUC-ROC with larger distances (24 h AUC-ROC: ICP-ICU 0.826 ± 0.0071, MIMIC 0.836 ± 0.0063, eICU 0.779 ± 0.0046, 1 h AUC-ROC: ICP-ICU 0.982 ± 0.0008, MIMIC 0.965 ± 0.0010, eICU 0.941 ± 0.0025). The model operates on sparse hourly data and is stable in handling variable input lengths and missingness through its nature of recurrence and internal memory. Calculation of gradient-based feature importance revealed individual underlying decisions for our long short time memory-based model and thereby provided improved clinical interpretability. Recurrent machine learning models have the potential to be an effective tool for the prediction of ICP increases with high translational potential.

Case-mix adjustment to compare hospital performances regarding complications after cytoreductive surgery for ovarian cancer: a nationwide population-based study.

OBJECTIVE: Complication rates after cytoreductive surgery are important quality indicators for hospitals that treat patients with advanced-stage ovarian cancer. Case-mix factors are patient and tumor characteristics that may influence hospital outcomes such as the complication rates. Currently, no case-mix adjustment model exists for complications after cytoreductive surgery; therefore, it is unclear whether hospitals are being compared correctly. This study aims to develop the first case-mix adjustment model for complications after surgery for advanced-stage ovarian cancer, enabling an accurate comparison between hospitals. METHODS: This population-based study included all patients undergoing cytoreductive surgery for advanced-stage ovarian cancer registered in the Netherlands in 2017-2019. Case-mix variables were identified and assessed using logistic regressions. The primary outcome was the composite outcome measure 'complicated course'. Patients had a complicated course when at least one of the following criteria were met: (1) any complication combined with a prolonged length of hospital stay; (2) complication requiring reintervention; (3) any complication with a prolonged length of stay in the intensive care unit; or (4) 30-day mortality or in-hospital mortality during admission following surgery. Inter-hospital variation was analyzed using univariable and multivariable logistic regressions and visualized using funnel plots. RESULTS: A total of 1822 patients were included, of which 10.7% (n=195) had a complicated course. Comorbidity and tumor stage had a significant impact on complicated course rates in multivariable logistic regression. Inter-hospital variation was not significant for case-mix factors. Complicated course rates ranged between 2.2% and 29.1%, and case-mix adjusted observed/expected ratios ranged from 0.20 to 2.67 between hospitals. Three hospitals performed outside the confidence intervals for complicated course rates. These hospitals remained outliers after case-mix adjustment. CONCLUSION: There is variation between hospitals regarding complicated course rates after cytoreductive surgery for ovarian cancer in the Netherlands. While comorbidity and tumor stage significantly affected the complicated course rates, adjusting for case-mix factors did not significantly affect hospital outcomes. The limited impact of case-mix adjustment could be a result of the Dutch centralized healthcare model.

Exploring international differences in ovarian cancer care: a survey report on global patterns of care, current practices, and barriers.

OBJECTIVE: Although global disparities in survival rates for patients with ovarian cancer have been described, variation in care has not been assessed globally. This study aimed to evaluate global ovarian cancer care and barriers to care. METHODS: A survey was developed by international ovarian cancer specialists and was distributed through networks and organizational partners of the International Gynecologic Cancer Society, the Society of Gynecologic Oncology, and the European Society of Gynecological Oncology. Respondents received questions about care organization. Outcomes were stratified by World Bank Income category and analyzed using descriptive statistics and logistic regressions. RESULTS: A total of 1059 responses were received from 115 countries. Respondents were gynecological cancer surgeons (83%, n=887), obstetricians/gynecologists (8%, n=80), and other specialists (9%, n=92). Income category breakdown was as follows: high-income countries (46%), upper-middle-income countries (29%), and lower-middle/low-income countries (25%). Variation in care organization was observed across income categories. Respondents from lower-middle/low-income countries reported significantly less frequently that extensive resections were routinely performed during cytoreductive surgery. Furthermore, these countries had significantly fewer regional networks, cancer registries, quality registries, and patient advocacy groups. However, there is also scope for improvement in these components in upper-middle/high-income countries. The main barriers to optimal care for the entire group were patient co-morbidities, advanced presentation, and social factors (travel distance, support systems). High-income respondents stated that the main barriers were lack of surgical time/staff and patient preferences. Middle/low-income respondents additionally experienced treatment costs and lack of access to radiology/pathology/genetic services as main barriers. Lack of access to systemic agents was reported by one-third of lower-middle/low-income respondents. CONCLUSIONS: The current survey report highlights global disparities in the organization of ovarian cancer care. The main barriers to optimal care are experienced across all income categories, while additional barriers are specific to income levels. Taking action is crucial to improve global care and strive towards diminishing survival disparities and closing the care gap.

Work intensity and quality of life can be restored following double-level osteotomy in varus knee osteoarthritis.

PURPOSE: The purpose of this study was to assess changes in health-related quality of life (HRQL) and work intensity following double-level knee osteotomy (DLO). It was hypothesized that postoperative HRQL would be comparable to that of the general population and that work intensity can be restored in the short term. METHODS: Twenty-four patients (28 varus knees; mechanical tibiofemoral angle: -11.0 ± 3.0° (-6.0 to -17.0), age: 49.1 ± 9.5 (31-65) years) who underwent DLO were included. The duration the patients were unable to work was evaluated. HRQL was measured with the SF-36 questionnaire, which consists of a physical (PCS) and mental component summary score (MCS). The pre- to postoperative changes in the PCS and MCS were analysed. The PCS and MCS were also compared to those of the general population, who has a reference score value of 50 points. The work intensity measured with the REFA classification and the Tegner activity scale were assessed preoperatively and at the final postoperative follow-up examination (18.0 ± 10.0 (5-43) months). RESULTS: The duration that the patients were unable to work was 12.2 ± 4.4 (6-20) weeks. The PCS improved from 32.1 ± 11.3 (14.5-53.3) preoperatively to 54.6 ± 8.5 (25.2-63.7) (p < 0.001) at the final follow-up, and the MCS improved from 53.9 ± 11.1 (17.1-67.7) to 57.2 ± 3.1 (47.3-61.7) (n.s). The preoperative PCS was significantly lower than the reference score of the general population (p < 0.001), whereas the preoperative MCS was similar between the two groups (n.s.). At follow-up, no significant differences were observed between the PCS and the MCS of the patient group and those of the general population. Five patients who were unable to work prior to surgery due to knee symptoms returned to work with moderate (four patients) or even very heavy (one patient) workloads. The Tegner activity scale increased significantly from a median of 2.0 (0.0-5.0) to 4.0 (2.0-7.0) (p < 0.001). CONCLUSION: Our results demonstrate an improvement in quality of life and return to working activity following DLO in the short term. The HRQL can be improved by DLO in patients with varus knee osteoarthritis to the level of the general population. These results can assist surgeons in discussing realistic expectations when considering patients for DLO. LEVEL OF EVIDENCE: Study type: therapeutic, IV.

Diffusion tensor imaging changes in patients with glioma-associated seizures.

INTRODUCTION: Structural white matter changes associated with certain epilepsy subtypes have been demonstrated using diffusion tensor imaging (DTI). This observational study aims to identify potential water diffusion abnormalities in glioma patients with associated seizures. METHODS: Two cohorts from two centers were analyzed independently: (A) Prospectively recruited patients diagnosed with glioma who received preoperative DTI to measure mean diffusivity (MD) and fractional anisotropy (FA) in regions-of-interest (ROIs) including the marginal tumor zone (TU), adjacent peritumoral white matter as well as distant ipsilateral and contralateral white matter and cortex. Data were compared between patients with and without seizures and tested for statistical significance. (B) A retrospective cohort using an alternative technical approach sampling ROIs in contrast enhancement, necrosis, non-enhancing tumor, marginal non-enhancing tumor zone, peritumoral tissue, edema and non-tumorous tissue. RESULTS: (A) The prospective study cohort consisted of 23 patients with 12 (52.2%) presenting with a history of seizures. There were no significant seizure-associated differences in MD or FA for non-tumor white matter or cortical areas. MD-TU was significantly lower in patients with seizures (p = 0.005). (B) In the retrospective cohort consisting of 46 patients with a seizure incidence of 50.0%, significantly decreased normalized values of MD were observed for non-enhancing tumor regions of non-glioblastoma multiforme (GBM) cases in patients with seizures (p = 0.022). CONCLUSION: DTI analyses in glioma patients demonstrated seizure-associated diffusion restrictions in certain tumor-related areas. No other structural abnormalities in adjacent or distant white matter or cortical regions were detected.

Hyperoxia is Dose-Dependently Associated with an Increase of Unfavorable Outcomes in Ventilated Patients with Aneurysmal Subarachnoid Hemorrhage: A Retrospective Cohort Study.

BACKGROUND: Adequate oxygenation in patients with aneurysmal subarachnoid hemorrhage (SAH) is imperative. However, hyperoxia increases formation of reactive oxygen species and may be associated with a dose-dependent toxicity. We postulated a threshold for arterial partial pressure of oxygen (paO2) above which toxicity effects precipitate and sought to study the effects on 30-day mortality, favorable outcome at discharge and at 3 months, and delayed cerebral ischemia. METHODS: In this retrospective single-center cohort study, patients with SAH and mechanical ventilation > 72 h were included. Oxygen integrals were calculated above the following thresholds: 80, 100, 120, and 150 mm Hg and time-weighted mean paO2. All calculations were done from admission to end of day 1, day 3, and day 14. We conducted multivariable logistic regression analyses adjusted for age, sex, duration of ventilation, and Hunt and Hess grade. Time-weighted mean paO2 was categorized by quartiles. Favorable outcome was defined as Glasgow Outcome Scale scores of 4 and 5. RESULTS: From November 2010 to February 2021, 282 of 549 patients fulfilled the inclusion criteria. Odds ratios for 30-day mortality increased dose dependently and were as follows: 1.07 (95% confidence interval [CI] 1.03-1.11; p = 0.001) for each 1 mm Hg per day above 80 mm Hg; 1.16 (95% CI 1.07-1.27), above 100 mm Hg; 1.36 (95% CI 1.15-1.61), above 120 mm Hg; and 1.59 (95% CI 1.22-2.08), above 150 mm Hg (all p < 0.001) at day 14. For favorable outcome at 3 months, odds ratios were 0.96 (95% CI 0.92-0.99) for each 1 mm Hg per day above 80 mm Hg; 0.90 (95% CI 0.84-0.98), above 100 mm Hg; 0.83 (95% CI 0.72-0.97), above 120 mm Hg; and 0.77 (95% CI 0.61-0.97), above 150 mm Hg (all p < 0.05). For time-weighted mean paO2, lowest 30-day mortality and highest favorable outcome at 3 months were found in the second quartile (78-85 mm Hg). Thirty-day mortality increased above 93 mm Hg (fourth quartile), with an odds ratio of 3.4 (95% CI 1.4-8.4, p = 0.007). Odds ratios for favorable outcome at 3 months were 0.28 (95% CI 0.12-0.69), 0.27 (95% CI 0.11-0.67), and 0.24 (95% CI 0.10-0.59) for the first, third, and fourth quartiles, respectively (all p < 0.01). No significant association was found at day 1 and day 3, for favorable outcome at discharge, or for delayed cerebral ischemia. CONCLUSIONS: Integrals above the defined paO2 thresholds were dose-dependently associated with an increase in mortality in ventilated patients with SAH. When we considered time-weighted mean paO2, unfavorable outcomes and 30-day mortality were more frequent both below and above a certain range. Unfavorable outcomes increased in paO2 ranges usually defined as normoxia. This emphasizes the necessity to further characterize oxygenation thresholds in ventilated patients with SAH in prospective clinical studies.

Overweight patients benefit from high tibial osteotomy to the same extent as patients with normal weights but show inferior mid-term results.

PURPOSE: The purpose of this prospective study was to analyze the impact of obesity on the clinical and radiological outcomes 6 years after open-wedge high tibial osteotomy (HTO). METHODS: A total of 120 prospectively recorded patients with medial compartment osteoarthritis underwent open-wedge HTO between 2008 and 2011. The study cohort was frequently examined over a minimum of a 6-year follow-up. The cohort was divided into three groups according to body mass index (BMI): normal weight patients (BMI < 25 kg/m2), pre-obese patients (BMI 25-30 kg/m2) and obese patients (BMI > 30 kg/m2). Clinical and functional outcomes (Oxford Knee Score, Hospital for Special Surgery Score, Lequesne Score, Tegner Activity Scale), subjective health-related quality of life (SF-36), change in mechanical limb alignment (mTFA) as well as conversion to unicompartmental or total knee arthroplasty (TKA) were evaluated. To compare clinical scoring between the groups, univariate variance analysis was applied. Changes in outcome variables over time were analyzed with dependent t tests. RESULTS: From 120 patients, 85 were followed-up over a 6.7-year period on average (6-11.8 years) after HTO. The mean BMI was 28.6 ± 4.6 kg/m2. Each group showed a significant pre- to postoperative increase in all recorded scores (p < 0.05). In absolute terms, both mental and clinical scores of overweight patients did not reach the peak values of the normal weighted population during the period of observation. There was a conversion to TKA in 10.5% after an average of 50.1 ± 25.0 months following surgery. A total of five complications occurred without significant differences (BMI < 25: n = 1, BMI 25-30: n = 2, BMI > 30: n = 2; n.s.). There was a mean pre- to postoperative (six weeks after surgery) correction difference of 6.9° ± 3.2° (mTFA) with higher loss of correction over time in overweight patients. CONCLUSION: In terms of clinical outcome and health-related quality of life, overweight patients may receive a benefit from open-wedge HTO to the same extent as patients with normal weights and show similar complication rates. However, they have inferior preoperative clinical and functional results and mid-term results after open-wedge HTO compared to patients with normal weights. LEVEL OF EVIDENCE: Level III.

Increased tibial tubercle-trochlear groove and patellar height indicate a higher risk of recurrent patellar dislocation following medial reefing.

PURPOSE: Identifying anatomical risk factors on recurrent dislocation after medial reefing is important for deciding surgical treatment. The present study aimed to retrospectively analyze the preoperative magnetic resonance imaging (MRI)-based parameters of patients treated with medial reefing and whether these parameters lead to a higher risk of recurrent dislocation. METHODS: Fifty-five patients (18.6 ± 6.6 years) who underwent medial reefing after primary traumatic patellar dislocation (84% with medial patellofemoral ligament [MPFL] rupture) were included. Patients were followed up for at least 24 months postoperatively (3.8 ± 1.2 years) to assess the incidence of recurrent patellar dislocation. In patients without recurrent dislocation, the Kujala and subjective IKDC scores were assessed. Moreover, the tibial tubercle-trochlear groove (TT-TG), sulcus angle, patellar tilt, patellar shift, and lateral trochlea index (LTI) were measured. The patellar height was measured using the Caton-Dechamps (CDI), Blackburne-Peel (BPI), and Insall-Salvati index (ISI). The cohort was subclassified into two groups with and without recurrent dislocation. Differences between groups were analyzed with respect to the MRI parameters. RESULTS: Forty percent had a pathological sulcus angle of > 145°, 7.2% had an LTI of < 11°, 47.3% had a patellar tilt of > 20°, and 36.4% had a TT-TG of ≥ 16 mm. Increased patellar height was observed in 34.5, 65.5, and 34.5% of the patients as per CDI, BPI, and ISI, respectively. Nineteen (34.5%) patients suffered from recurrent dislocation. Compared with patients without recurrent dislocation, those with recurrent dislocation had a significantly lower LTI (p = 0.0467). All other parameters were not significantly different between the groups. Risk factor analysis showed higher odds ratios (OR > 2), although not statistically significant, for MPFL rupture (OR 2.05 [95% confidence interval 0.38-11.03], LTI (6.6 [0.6-68.1]), TT-TG (2.9 [0.9-9.2]), and patellar height according to ISI (2.3 [0.7-7.5]) and CDI (2.3 [0.7-7.5])). Patients without recurrent dislocation had a Kujala score of 93.7 ± 12.1 (42-100) points and an IKDC score of 90.6 ± 11.7 (55.2-100) points. CONCLUSION: Anatomical, MRI-based parameters should be considered before indicating medial reefing. A ruptured MPFL, an LTI < 11°, a TT-TG ≥ 16 mm, a patellar tilt > 20 mm, and an increased patellar height according to ISI and CDI were found to be associated, although not significantly, with a higher risk (OR > 2) of recurrent patellar dislocation after medial reefing. Thorough preoperative analysis is crucial to reduce the risk of recurrent dislocation in young patient cohorts. LEVEL OF EVIDENCE: Level IV.

Preexisting and treated concomitant ankle instability does not compromise patient-reported outcomes of solitary osteochondral lesions of the talus treated with matrix-induced bone marrow stimulation in the first postoperative year: data from the German Cartilage Registry (KnorpelRegister DGOU).

PURPOSE: The purpose of this study was to compare the subjective ankle function within the first year following matrix-induced bone marrow stimulation (M-BMS) of patients with a solitary osteochondral lesion of the talus (OCLT) with and without concomitant chronic ankle instability (CAI). METHODS: Data from the German Cartilage Registry (KnorpelRegister DGOU) for 78 patients with a solitary OCLT and a follow-up of at least 6 months were included. All patients received M-BMS for OCLT treatment. The cohort was subdivided into patients with OCLT without CAI treated with M-BMS alone (n = 40) and patients with OCLT and CAI treated with M-BMS and additional ankle stabilisation (n = 38). The Foot and Ankle Ability Measure (FAAM), the Foot and Ankle Outcome Score (FAOS), and the Numeric Rating Scale for Pain (NRS) were used to assess patient-reported outcomes (median (minimum-maximum)). RESULTS: From preoperatively to 12 months postoperatively, patients with OCLT without CAI treated with M-BMS alone had a significant improvement of all subscales in the FAAM [activity of daily living 64.3 (10-100) to 88.1 (39-100); sports 34.4 (0-100) to 65.6 (13-94), functional activities of daily life 50 (0-90) to 80 (30-100), functional sports 30 (0-100) to 70 (5-100)] and FAOS [pain 61.1 (8-94) to 86.1 (50-100), symptoms 60.7 (18-96) to 76.8 (29-100), activities of daily living 72.1 (24-100) to 91.9 (68-100), sport/recreational activities 30.0 (0-70) to 62.5 (0-95), quality of life 31.3 (6-50) to 46.9 (19-100)]. Within the first year, patients with OCLT and CAI treated with M-BMS and ankle stabilisation also showed significant improvement in the FAAM [activity of daily living 68.8 (5-99) to 90.5 (45-100); sports 32.8 (0-87.5) to 64.1 (0-94), functional activities of daily life 62.5 (25-100) to 80 (60-90), functional sports 30 (0-100) to 67.5 (0.95)] and the FAOS [pain 66.7 (28-92) to 87.5 (47-100), symptoms 57.1 (29-96) to 78.6 (50-100), activities of daily living 80.1 (25-100) to 98.5 (59-100), sport/recreational activities 35.0 (0-100) to 70.0 (0-100), quality of life 25.0 (0-75) to 50.0 (19-94)]. The pain level decreased significantly in both groups. No significant difference was found between both groups regarding the subscales of FAAM, FAOS and the NRS 1 year postoperatively. CONCLUSION: Improvements in subjective ankle function, daily life activities and sports activities were observed within the first year following M-BMS. Our results suggest that preexisting and treated ankle instability did not compromise subjective outcome in patients treated with M-BMS in the first postoperative year. LEVEL OF EVIDENCE: Level IV.

Os acromiale: prevalence and associated patient-related factors-a population-based study of three thousand and fifty participants.

PURPOSE: The presence of os acromiale is of clinical relevance before performing shoulder surgery but ethnic differences and little information regarding associated factors seem to be present. Population-based studies to clarify these topics are essential so the purpose of this study was to assess the prevalence, anatomy, and associations of os acromiale in a general adult population. METHODS: Both shoulders of 3050 participants from the population-based Study of Health in Pomerania (SHIP) were assessed on magnetic resonance imaging (MRI). Associations with the os acromiale were calculated for sex, age, body height, body weight, and heavy mechanical oscillations on the upper extremity. RESULTS: In total, 1.9% (58/3050) had an os acromiale, while 21 were unilateral left, 23 were unilateral right, and 14 were bilateral. Sixty-eight meso-acromions, three pre-acromions, and one meta-acromion were detected. Os acromiale were more frequent in men (right side: p = 0.037, left side: p = 0.005). Overall, no differences in sides (p = 0.808), to participants' age (right: p = 0.993, left: p = 0.499), body height (right side: p = 0.241, left side: p = 0.154), and the exposure to heavy mechanical oscillations on the upper extremity (right: p = 0.054, left: p = 0.117) were detected. CONCLUSION: Our results support the genetic theory for the aetiology of the os acromiale due to the lower prevalence of the os acromiale in north-eastern Germany compared to the worldwide prevalence (1.9 to 7%) and the lacking association to lifestyle, age, gender, or sides. Additionally, it is important to be aware of possible os acromiale before surgery.

Influenza A Virus NS1 Protein Structural Flexibility Analysis According to Its Structural Polymorphism Using Computational Approaches.

Influenza A viruses are highly contagious RNA viruses that cause respiratory tract infections in humans and animals. Their non-structural protein NS1, a homodimer of two 230-residue chains, is the main viral factor in counteracting the antiviral defenses of the host cell. Its RNA-binding domain is an obligate dimer that is connected to each of the two effector domains by a highly flexible unstructured linker region of ten amino acids. The flexibility of NS1 is a key property that allows its effector domains and its RNA binding domain to interact with several protein partners or RNAs. The three-dimensional structures of full-length NS1 dimers revealed that the effector domains could adopt three distinct conformations as regards their mutual interactions and their orientation relative to the RNA binding domain (closed, semi-open and open). The origin of this structural polymorphism is currently being investigated and several hypotheses are proposed, among which one posits that it is a strain-specific property. In the present study, we explored through computational molecular modeling the dynamic and flexibility properties of NS1 from three important influenza virus A strains belonging to three distinct subtypes (H1N1, H6N6, H5N1), for which at least one conformation is available in the Protein Data Bank. In order to verify whether NS1 is stable in three forms for the three strains, we constructed homology models if the corresponding forms were not available in the Protein Data Bank. Molecular dynamics simulations were performed in order to predict the stability over time of the three distinct sequence variants of NS1, in each of their three distinct conformations. Our results favor the co-existence of three stable structural forms, regardless of the strain, but also suggest that the length of the linker, along with the presence of specific amino acids, modulate the dynamic properties and the flexibility of NS1.

Influence of axial limb rotation on radiographic lower limb alignment: a systematic review.

INTRODUCTION: The influence of limb malrotation on long-leg radiographs (LLR) is frequently discussed in literature. This systematic review aimed to describe the influence of limb rotation on alignment measurements alone and in combination with knee flexion, and determine its clinical impact. MATERIALS AND METHODS: A literature search was conducted in June 2021 using the databases MEDLINE, Cochrane, Web of Science (Clarivate Analytics), and Embase. The search term ((radiograph OR X-ray) AND (position OR rotation) AND limb alignment) was used. Database query, record screening, and study inclusion and exclusion were performed by two reviewers independently. Experimental studies (using either specimens or synthetic bones) or clinical studies (prospective or retrospective using radiographs of patients) analyzing the influence of limb rotation on anatomic and mechanical limb alignment measurements were included. Characteristics and results of the included studies were summarized, simplified, and grouped for comparison to answer the research question. Studies were compared descriptively, and no meta-analysis was performed. RESULTS: A total of 22 studies were included showing large heterogeneity, comprising studies with cadavers, patients, and synthetic bones. Most studies (7 out of 8) reported that external rotation (ER) causes less apparent valgus and leads to more varus and internal rotation (IR) causes more valgus and leads to less varus. However, there is no consensus on the extent of rotation influencing alignment measures. Studies reported about an average change of > 2° (n = 4) and < 2° (n = 4) hip-knee-ankle angle (HKA) between 15°IR and 15°ER. There is a consensus that the impact of rotation on mechanical alignment is higher if additional sagittal knee angulation, such as knee flexion, is present. All five studies analyzing the influence of rotation combined with knee flexion (5°-15°) showed an HKA change of > 2° between 15°IR and 15°ER. CONCLUSION: Malrotation is frequently present on LLR, possibly influencing the measured alignment especially in knees with extension deficit. Surgeons must consider this when measuring and treating deformities (high tibial osteotomy or total knee arthroplasties), and analyzing surgical outcomes. Especially in patients with osteoarthritis with knee extension deficits or postoperative swelling, the effect of malrotation is significantly greater.

Distance from the magnification device contributes to differences in lower leg length measured in patients with TSF correction.

INTRODUCTION: In absence of deformity or injury of the contralateral leg, the contralateral leg length is used to plan limb lengthening. Length variability on long-leg weight-bearing radiographs (LLR) can lead to inaccurate deformity correction. The aim of the study was to (1) examine the variability of the measured limb length on LLR and (2) to examine the influence of the position of the magnification device. MATERIALS AND METHODS: The limb lengths of 38 patients during deformity correction with a taylor-spatial-frame were measured retrospectively on 7.3 ± 2.6 (4-13) LLR per patient. The measured length of the untreated limb between LLR were used to determine length variability between LLR in each patient. To answer the secondary aim, we took LLR from a 90 cm validation distance. A magnification device was placed in different positions: at the middle of the 90 cm distance (z-position), 5 cm anterior and 5 cm posterior from the z-position, at the bottom and top of the validation distance as well as 5 cm medial and 15 cm lateral from the z-position. RESULTS: The measured length variability ranged within a patient from 10 to 50 mm. 76% of patients had a measured limb length difference of ≥ 2 cm between taken LLR. Compared to length measurement of the 90 cm test object with the magnification device in the z-position (90.1 cm), positioning the device 5 cm anterior led to smaller (88.6 cm) and 5 cm posterior led to larger measurements (91.7 cm). The measured length with the magnification device at the bottom, top, medial or lateral (90.4; 89.9; 90.2; 89.8 cm) to the object differed not relevantly. CONCLUSIONS: High variability of limb length between different LLR within one patient was observed. This can result from different positions of the magnification device in the sagittal plane. These small changes in positioning the device should be avoided to achieve accurate deformity correction and bone lengthening. This should be considered for all length and size measurements on radiographs.

Rotation osteotomy of the distal femur influences coronal femoral alignment and the ischiofemoral space.

INTRODUCTION: Despite the fact that osteotomies around the knee represent well-established treatment options for the redistribution of loads and forces within and around the knee joint, unforeseen effects of these osteotomies on the remaining planes and adjacent joints are still to be defined. It was, therefore, the aim of this study to determine the influence of a distal femoral rotation osteotomy on the coronal limb alignment and on the ischiofemoral space of the hip joint. MATERIALS AND METHODS: Long-leg standing radiographs and CT-based torsional measurements of 27 patients undergoing supracondylar rotational osteotomies of the femur between 2012 and 2019 were obtained and utilized for the purpose of this study. Postoperative radiographs were obtained after union at the osteotomy site. The hip-knee-ankle angle (HKA), the mechanical lateral distal femur angle (mLDFA), and the ischiofemoral space were measured. Comparison between means was performed using the Wilcoxon-Mann-Whitney test. RESULTS: Twenty-seven patients underwent isolated supracondylar external rotation osteotomy to reduce the overall antetorsion of the femur. The osteotomy resulted in a 2.4° ± 1.4° mean increase in HKA and 2.4 mm ± 1.7 mm increase in the ischiofemoral space (p < 0.001). CONCLUSION: Supracondylar external rotation osteotomy of the femur leads to valgisation of the coronal limb alignment and increases the ischiofemoral space. This is resultant to the reorientation of the femoral antecurvature and the femoral neck. When planning a rotational osteotomy of the lower limb, this should be appreciated and may also aid in the decision regarding osteotomy site.

Does the socio-demographic profile of patients limit access to bariatric surgery?

PURPOSE: Surgery remains the only treatment allowing for a significant and sustainable weight loss in case of severe obesity. Patients undergo a specific multidisciplinary preparation and selection before the operation. This study aims to correlate the psychosocial profile with the likelihood of undergoing bariatric surgery in patients enrolled in the preparation program of a Swiss reference center. METHODS: All patients referred to an obesity center between January 1, 2016, and June 30, 2017, seeking a first bariatric procedure were included. Socio-demographic data, BMI, preoperative psychological and dietary evaluations were collected. Usually, the preoperative process lasts 1 year. Patients who left the preparation or who had not undergone surgery after more than 2 years of follow-up were considered withdrawers. Surgery completion predictors were reviewed with bivariate analysis and socio-demographic clusters established using the K-means method. RESULTS: Out of a total of 221 patients, 99 (45%) patients had not undergone bariatric surgery 2 years after their first consultation. The patients were divided into four distinct socio-demographic clusters, among which a particularly deprived one. Criteria such as unfavorable psychological (p < 0.001) and dietary (p < 0.001) evaluations, and male gender (p < 0.05) were significantly associated with non-operation, unlike socio-demographic indicators and clusters (p > 0.1). CONCLUSION: Almost half of the patients starting a bariatric program are not operated on, which is related to an unfavorable psychological or dietary evaluation and to the male gender. This study also demonstrates that a significant share of patients combines several factors of social deprivation, without influencing the likelihood of surgery completion. LEVEL OF EVIDENCE: Level V: Descriptive study.