Postoperative management following osteotomies around the knee: a narrative review.

The present narrative review provides a summary of postoperative therapy modalities and their effectiveness following osteotomies around the knee. The topics that are discussed in the scientific discourse include support of cartilage cell regeneration, pain management, drainage insertion, tourniquet use, pharmacological and mechanical thromboembolism prophylaxis, weight-bearing protocols and bone consolidation. There is evidence for the use of pharmacological thromboembolism prophylaxis and weight-bearing protocols. A standardized postoperative treatment concept following osteotomies around the knee cannot be derived due to lack of evidence for the other topics in current literature.

Surgical Technique and Preliminary Outcomes of Double-Level Osteotomy for Valgus Deformity.

Background: Data are limited regarding the surgical technique or outcomes of double-level osteotomy (DLO) combining medial closing-wedge distal femoral osteotomy and medial closing-wedge high tibial osteotomy in patients with moderate-to-severe valgus deformity. Purpose/Hypothesis: To describe the surgical technique and assess the short-term outcomes and surgical accuracy of DLO in patients with a moderate or severe valgus deformity. It was hypothesized that this technique would result in good clinical outcomes with precise deformity correction. Study Design: Case series; Level of evidence, 4. Methods: Eight patients (mean age, 44.2 ± 10.9 years) with a moderate or severe valgus knee treated with DLO (9 knees; mechanical tibiofemoral angle [mTFA], 10.3°± 3.5°) were included. The mean follow-up was 25.1 ± 11.1 months. Preoperative to postoperative changes in radiographic parameters (mTFA, mechanical lateral distal femoral angle, mechanical medial proximal tibial angle, joint line convergence angle) and clinical scores (Hospital for Special Surgery score, Oxford Knee Score, Lysholm score) were assessed. Surgical accuracy was calculated by subtracting the achieved postoperative correction from the preoperatively planned targeted correction. Results: The mTFA changed significantly from 10.3°± 3.5° preoperatively to -1.8°± 3.4° postoperatively (P < .001); the mechanical lateral distal femoral angle and mechanical medial proximal tibial angle changed significantly by 5.1°± 2.7° and 5.9°± 2.2°, respectively (P < .001 for both); and the posterior distal femoral angle decreased significantly from 85.9°± 3.1° to 84.2°± 2.4° (P < .01). There was no significant difference between pre- and postoperative joint line convergence angles (3.3°± 2.3° to 2.6°± 2.1°). The accuracy of the correction was high: the mTFA achieved postoperatively differed from the mTFA planned preoperatively by a mean of 2.7°± 1.9° (range, 0.6°-6.6°). Significant pre- to postoperative improvement was seen for all outcome scores (Hospital for Special Surgery, from 67 ± 11 to 93 ± 4; Oxford Knee Score, from 29 ± 7 to 43 ± 3; Lysholm, from 41 ± 24 to 89 ± 8; P < .001 for all). Conclusion: High surgical accuracy was achieved, and patients who underwent varus DLO for valgus knees showed improved knee function at short-term follow-up. Varus DLO can be a surgical option to restore the optimal alignment and joint line obliquity in patients with moderate or severe valgus malalignment.

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.

Myeloid cell replacement is neuroprotective in chronic experimental autoimmune encephalomyelitis.

Multiple sclerosis (MS) is an autoimmune disease characterized by demyelination of the central nervous system (CNS). Autologous hematopoietic cell transplantation (HCT) shows promising benefits for relapsing-remitting MS in open-label clinical studies, but the cellular mechanisms underlying its therapeutic effects remain unclear. Using single-nucleus RNA sequencing, we identify a reactive myeloid cell state in chronic experimental autoimmune encephalitis (EAE) associated with neuroprotection and immune suppression. HCT in EAE mice results in an increase of the neuroprotective myeloid state, improvement of neurological deficits, reduced number of demyelinated lesions, decreased number of effector T cells and amelioration of reactive astrogliosis. Enhancing myeloid cell incorporation after a modified HCT further improved these neuroprotective effects. These data suggest that myeloid cell manipulation or replacement may be an effective therapeutic strategy for chronic inflammatory conditions of the CNS.

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.

Salvage Algorithm for Deep Surgical Site Infections after HTO with Unstable Bone Situation Using a Hexapod System - Primary Results.

The incidence of deep surgical site infections following high tibial osteotomy (HTO) ranges between 0.4 to 4.7%. It is a severe complication with a high risk for poor clinical outcome. The aim of this study was to proof that a salvage algorithm for infected HTO with unstable bone situation leads to an infection-free status and bone union of the osteotomy and that correct limb alignment can be restored with good knee function.The study included seven patients with peri-implant infections following HTO. Infections occurred 83 ± 58.9 days (range: 24-191) after HTO. All patients underwent the "RESTORE" algorithm: patients received (1) REmoval of the HTO hardware and extensive debridement; (2) the osteotomy was STabilized with a hexapod external fixator (Taylor Spatial Frame, TSF); (3) the osteotomy gap was Opened; and (4) the alignment was REconstructed using the TSF, aiming for the intended limb alignment of the initial HTO. Patient-reported outcomes were assessed 22-36 months after removal of the TSF.After 24 weeks (range: 11-35), an infection-free status and bone healing were achieved. In all cases, the limb was saved, and the previously targeted mechanical axis of the lower limb was restored. All patients reached full extension of the knee joint and at least 110° of flexion. For KOOS: Symptoms 67.86 ± 18.1, Pain 73.41 ± 16.58, ADL 78.99 ± 21.32, Sports 52.14 ± 25.96, and QoL 41.96 ± 24.66. OKS 35.71 ± 8.8, SF-12 Physical Health 38.89 ± 10.3, and SF-12 Mental Health 46.86 ± 13.76.The "RESTORE" algorithm is a safe and effective salvage procedure. The concept allows for saving the limb and obtaining the previously planned limb alignment. Patient-reported outcome measures showed slightly lowered values than healthy samples, but substantially better values than patients awaiting HTO. Due to the possibility of initial full weight-bearing, the risk of higher morbidity caused by immobilization is minimized.

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.

Classification and Incidence of Heterotopic Ossifications in Relation to NSAID Prophylaxis after Elbow Trauma.

Heterotopic ossification (HO) after elbow trauma can be responsible for significant motion restrictions. The study's primary aim was to develop a new X-ray-based classification for HO of the elbow. This retrospective study analyzed elbow injury radiographs from 138 patients aged 6-85 years (mean 45.9 ± 18) who underwent operative treatment. The new classification was applied at 6 weeks, 12 weeks, and 6 months postoperatively. The severity of HO was graded from 0 to 4 and localization was defined as r (radial), p (posterior), u (ulnar) or a (anterior) by two observers. The patients were categorized based on injury location and use of non-steroidal anti-inflammatory drugs (NSAIDs) for HO prophylaxis. The correlations between the generated data sets were analyzed using Chi-square tests (χ2) with a significance level of p < 0.05. The inter- and intraobserver reliability was assessed using Cohen's Kappa. In 50.7% of the evaluated X-rays, the formation of HO could be detected after 12 weeks, and in 60% after 6 months. The analysis showed a significant correlation between the injury's location and the HO's location after 12 weeks (p = 0.003). The use of an NSAID prophylaxis did not show a significant correlation with the severity of HO. The classification showed nearly perfect inter- (κ = 0.951, p < 0.001) and intrareliability (κ = 0.946, p < 0.001) according to the criteria of Landis and Koch. Based on the presented classification, the dimension and localization of HO in the X-ray image can be described in more detail compared to previously established classifications and, thus, can increase the comparability of results across studies.

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.

Patient perception and satisfaction in awake burr hole trepanation under local anesthesia for evacuation of chronic subdural hematoma.

Evacuation of chronic subdural hematoma (CSDH) will be one of the most common neurosurgical procedures in the future in the increasingly aging societies. Performing cranial surgery on awake patients may place a psychological burden on them. Aim of this study was to evaluate the psychological distress of patients during awake CSDH relief. Patients with awake evacuation of CSDH via burr hole trepanation were included in our monocentric prospective study. Patient perception and satisfaction were measured using standardized surveys 3-5 days and 6 months after surgery. Among other questionnaires, the Hospital Anxiety and Depression and the Impact of Event Scale, were used to quantify patients' stress. A total of 50 patients (mean age 72.9 years (range 51 - 92)) were included. During surgery, 28 patients reported pain (mean 4.1 (SD 3.3)). Postoperatively, 26 patients experienced pain (mean 2.7 (SD 2.6)). Patients' satisfaction with intraoperative communication was reported with a mean of 8.3 (SD 2.1). There was a significant negative correlation between intraoperatively perceived pain and satisfaction with intraoperative communication (p = 0.023). Good intraoperative communication during evacuation of CSDH in awake patients is associated with positive patient perception and correlates with pain reduction.

Postoperative Management of Osteochondral Lesions of the Ankle: A Survey Among German-Speaking Foot and Ankle Surgeons.

OBJECTIVE: To assess the current treatment of osteochondral lesions of the ankle (OCLA) by German-speaking foot and ankle surgeons, focusing on the management of postoperative care and rehabilitation. DESIGN: A questionnaire was created by a panel of 4 experienced foot and ankle surgeons on behalf of the "Clinical Tissue Regeneration" (CTR) working group of the German Society of Orthopaedics and Trauma Surgery (DGOU), and distributed electronically to members of the CTR, participants of the German Cartilage Registry (Knorpelregister DGOU©), and members of 6 German-speaking orthopedics or sports medicine societies. Results were classified depending on the consensus within the answers (agreement ≥75% "strong tendency," 50%-74% "tendency," 25%-49% "weak tendency," <25% "no tendency"). RESULTS: A total of 60 participants returned the questionnaire. The main results are as follows: regarding the frequency of surgical procedures for OCLA, refixation of the fragment, retrograde drilling, and bone marrow stimulation with or without using a matrix were performed by at least 75% of the surgeons and was considered a strong tendency. There was a strong tendency to stabilize the ankle (76.7%) and perform corrective osteotomies (51.7%). In total, 75.5% and 75% of the surgeons performed bone marrow stimulation with and without using a matrix, respectively. Corrective osteotomy and ankle stabilization were performed in 64.5% and 65.2% cases, respectively. Most participants included published recommendations on postoperative rehabilitation and the return to sports activities in their postoperative management. The main surgical procedures were considered the most critical factor in influencing the postoperative management by 81% of the participants (strong tendency). Adjunct surgical procedures such as corrective osteotomy and stabilization of the ankle were considered important by 67.8% of the respondents (tendency). CONCLUSIONS: The management of OCLA varies among German-speaking foot and ankle surgeons. Therefore, guidelines remain essential to standardize the management of OCLA, to achieve improved and stable results. This survey will assist clinicians and patients with rehabilitation to return to sports after treating the ankle's cartilage injury.

Impact of pre-hospital handling and initial time to cranial computed tomography on outcome in aneurysmal subarachnoid hemorrhage patients with out-of-hospital sudden cardiac arrest-a retrospective bi-centric study.

Background: Aneurysmal subarachnoid hemorrhage (SAH) presents occasionally with cardiac arrest (CA). The impact of pre-hospital and emergency room (ER) treatment on outcome remains unclear. Therefore, we investigated the impact of pre-hospital treatment, focusing on lay cardiopulmonary resuscitation (CPR), and ER handling on the outcome of SAH patients with out-of-hospital CA (OHCA). Methods: In this bi-centric retrospective analysis, we reviewed SAH databases for OHCA and CPR from January 2011 to June 2021. Patients were analyzed for general clinical and epidemiological parameters. CPR data were obtained from ambulance reports and information on ER handling from the medical records. Data were correlated with patient survival at hospital discharge as a predefined outcome parameter. Results: Of 1,120 patients with SAH, 45 (4.0%) were identified with OHCA and CPR, 38 of whom provided all required information and were included in this study. Time to resuscitation was significantly shorter with lay resuscitation (5.3 ± 5.2 min vs. 0.3 ± 1.2 min, p = 0.003). Nineteen patients were not initially scheduled for cranial computed tomography (CCT), resulting in a significantly longer time interval to first CCT (mean ± SD: 154 ± 217 min vs. 40 ± 23 min; p < 0.001). Overall survival to discharge was 31.6%. Pre-hospital lay CPR was not associated with higher survival (p = 0.632). However, we observed a shorter time to first CCT in surviving patients (p = 0.065). Conclusions: OHCA in SAH patients is not uncommon. Besides high-quality CPR, time to diagnosis of SAH appears to play an important role. We therefore recommend considering CCT diagnostics as part of the diagnostic algorithm in patients with OHCA.

Long-term Outcomes after Medial Open Wedge High Tibial Osteotomy - A Retrospective Study of 69 Patients.

High tibial osteotomy (HTO) is a widespread option to avoid or delay total knee arthroplasty (TKA). The present study aimed to assess the long-term survival rate and postoperative subjective knee function after isolated medial open wedge HTO in patients with symptomatic medial compartment knee osteoarthritis (OA) and varus malalignment.Sixty-nine patients (48.8 ± 6.7, 35-66 years; preoperative mechanical tibiofemoral angle [mTFA] -5.3 ± 3.4; -14.9-0.0° varus) treated with medial open wedge HTO using a TomoFix plate were included in this retrospective study, with a follow-up of at least 10 years (11.8 ± 1.0 years). The survival rate after HTO was calculated after 5 and 10 years. Subjective knee function was assessed using Hospital for Special Surgery (HSS), Oxford knee, Lequesne, and Lysholm scores.Thirty-three patients underwent conversion to TKA, on average, 7.0 ± 3.4 (1.3-13.7) years after HTO. Five- and ten-year survival rates were 84.1 and 60.9%, respectively. Patients without conversion to TKA showed a Lysholm score of 64.5 (35-92), Lequesne score of 7 (1-13), HSS score of 71 (56-86), and Oxford knee score of 38.5 (25-44) at the last follow-up (more than 10 years). Significantly higher scores were registered at the last follow-up compared to the preoperative state regarding the Lysholm score (preoperative: 43.5 [12-95]; follow-up: 64.5 [35-92]; p < 0.001). The HSS score (preoperative: 69.5 [43-93]; follow-up: 71 [56-86]; p = 0.6941) showed no statistically significant change during the 10-year follow-up period. The Lequesne score was significantly lower than the preoperative score (preoperative: 11.5 [0.5-22]; follow-up: 7 [1-13]; p < 0.001), indicating a lower handicap.The majority of patients with a valgus medial compartmental knee OA treated with HTO with fixation using the TomoFix plate can expect no conversion to TKA for more than 10 years. Furthermore, patients without conversion to TKA after 10 years still had a significantly higher subjective knee function than preoperatively. Further research is needed to identify risk factors for conversion to TKA. This helps to guide surgeons in selecting patients who will benefit most from HTO.

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.

A cell therapy approach to restore microglial Trem2 function in a mouse model of Alzheimer's disease.

Alzheimer's disease (AD) remains one of the grand challenges facing human society. Much controversy exists around the complex and multifaceted pathogenesis of this prevalent disease. Given strong human genetic evidence, there is little doubt, however, that microglia play an important role in preventing degeneration of neurons. For example, loss of function of the microglial gene Trem2 renders microglia dysfunctional and causes an early-onset neurodegenerative syndrome, and Trem2 variants are among the strongest genetic risk factors for AD. Thus, restoring microglial function represents a rational therapeutic approach. Here, we show that systemic hematopoietic cell transplantation followed by enhancement of microglia replacement restores microglial function in a Trem2 mutant mouse model of AD.

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.

Etiology, Classification, Diagnostics, and Conservative Management of Osteochondral Lesions of the Talus. 2023 Recommendations of the Working Group "Clinical Tissue Regeneration" of the German Society of Orthopedics and Traumatology.

METHODS: Peer-reviewed literature was analyzed regarding different topics relevant to osteochondral lesions of the talus (OLTs) treatment. This process concluded with a statement for each topic reflecting the best scientific evidence available for a particular diagnostic or therapeutic concept, including the grade of recommendation. Besides the scientific evidence, all group members rated the statements to identify possible gaps between literature and current clinical practice. CONCLUSION: In patients with minimal symptoms, OLT progression to ankle osteoarthritis is unlikely. Risk factors for progression are the depth of the lesion on MRI, subchondral cyst formation, and the extent of bone marrow edema. Conservative management is the adaptation of activities to the performance of the ankle joint. A follow-up imaging after 12 months helps not to miss any progression. It is impossible to estimate the probability of success of conservative management from initial symptoms and imaging. Cast immobilization is an option in OLTs in children, with a success rate of approximately 50%, although complete healing, estimated from imaging, is rare. In adults, improvement by conservative management ranges between 45% and 59%. Rest and restrictions for sports activities seem to be more successful than immobilization. Intra-articular injections of hyaluronic acid and platelet-rich plasma can improve pain and functional scores for more than 6 months. If 3 months of conservative management does not improve symptoms, surgery can be recommended.

Augmentation of a neuroprotective myeloid state by hematopoietic cell transplantation.

Multiple sclerosis (MS) is an autoimmune disease associated with inflammatory demyelination in the central nervous system (CNS). Autologous hematopoietic cell transplantation (HCT) is under investigation as a promising therapy for treatment-refractory MS. Here we identify a reactive myeloid state in chronic experimental autoimmune encephalitis (EAE) mice and MS patients that is surprisingly associated with neuroprotection and immune suppression. HCT in EAE mice leads to an enhancement of this myeloid state, as well as clinical improvement, reduction of demyelinated lesions, suppression of cytotoxic T cells, and amelioration of reactive astrogliosis reflected in reduced expression of EAE-associated gene signatures in oligodendrocytes and astrocytes. Further enhancement of myeloid cell incorporation into the CNS following a modified HCT protocol results in an even more consistent therapeutic effect corroborated by additional amplification of HCT-induced transcriptional changes, underlining myeloid-derived beneficial effects in the chronic phase of EAE. Replacement or manipulation of CNS myeloid cells thus represents an intriguing therapeutic direction for inflammatory demyelinating disease.

Corticosteroid-Dependent Leukocytosis Masks the Predictive Potential of White Blood Cells for Delayed Cerebral Ischemia and Ventriculoperitoneal Shunt Dependency in Aneurysmatic Subarachnoid Hemorrhage.

A multitude of pathological and inflammatory processes determine the clinical course after aneurysmal subarachnoid hemorrhage (aSAH). However, our understanding of predictive factors and therapeutic consequences is limited. We evaluated the predictive value of clinically relevant factors readily available in the ICU setting, such as white blood cell (WBC) count and CRP, for two of the leading comorbidities, delayed cerebral ischemia (DCI) and ventriculoperitoneal (VP) shunt dependency in aSAH patients with and without corticosteroid treatment. We conducted a retrospective analysis of 484 aSAH patients admitted to our institution over an eight-year period. Relevant clinical factors affecting the risk of DCI and VP shunt dependency were identified and included in a multivariate logistic regression model. Overall, 233/484 (48.1%) patients were treated with corticosteroids. Intriguingly, predictive factors associated with the occurrence of DCI differed significantly depending on the corticosteroid treatment status (dexamethasone group: Hunt and Hess grade (p = 0.002), endovascular treatment (p = 0.016); no-dexamethasone group: acute hydrocephalus (p = 0.018), peripheral leukocyte count 7 days post SAH (WBC at day 7) (p = 0.009)). Similar disparities were found for VP shunt dependency (dexamethasone group: acute hydrocephalus (p = 0.002); no-dexamethasone group: WBC d7 (p = 0.036), CRP peak within 72 h (p = 0.015)). Our study shows that corticosteroid-induced leukocytosis negates the predictive prognostic potential of systemic inflammatory markers for DCI and VP shunt dependency, which has previously been neglected and should be accounted for in future studies.