Does adding exercise or physical activity to pharmacological osteoporosis therapy in patients with increased fracture risk improve bone mineral density and lower fracture risk? A systematic review and meta-analysis.

This prospectively registered systematic review and meta-analysis examines whether exercise (EX) training has an additive effect to osteoanabolic and/or antiresorptive pharmacological therapy (PT) in people with osteoporosis on bone mineral density (BMD), bone turnover markers (BTMs), fracture healing, and fractures. Four databases (inception to 6 May 2022), 5 trial registries, and reference lists were searched. Included were randomized controlled trials comparing the effect of EX + PT vs. PT with regard to BMD, BTM, fracture healing, and fractures. Risk of bias was assessed using the Cochrane RoB2 and certainty of evidence by the GRADE approach. Random-effects meta-analysis with Hartung-Knapp-Sidik-Jonkman adjustment was used to estimate standardized mean differences and 95% confidence intervals. Out of 2593 records, five RCTs with 530 participants were included. Meta-analysis showed with very low certainty evidence and wide confidence intervals that EX + PT compared to PT had larger effect sizes for BMD at 12 months at the hip (SMD [95%CI]: 0.18 [- 1.71; 2.06], n = 3 studies), tibia (0.25 [- 4.85; 5.34], n = 2), lumbar spine (0.20 [- 1.15; 1.55], n = 4), and forearm (0.05 [- 0.35; 0.46], n = 3), but not femoral neck (- 0.03 [- 1.80; 1.75], n = 3). Furthermore, no improvement was revealed for BTM such as bone ALP (- 0.68 [- 5.88; 4.53], n = 3), PINP (- 0.74 [- 10.42; 8.93], n = 2), and CTX-I (- 0.69 [- 9.61; 8.23], n = 2), but with very wide confidence intervals. Three potentially relevant ongoing trials were identified via registries. No data were found for fracture healing or fracture outcomes. It remains unclear whether EX has an additive impact to PT in people with osteoporosis. High-quality, adequately powered, targetted RCTs are required. PROTOCOL REGISTRATION: PROSPERO CRD42022336132.

Acute myeloid leukemia-induced functional inhibition of healthy CD34+ hematopoietic stem and progenitor cells.

Acute myeloid leukemia (AML) is characterized by an expansion of leukemic cells and a simultaneous reduction of normal hematopoietic precursors in the bone marrow (BM) resulting in hematopoietic insufficiency, but the underlying mechanisms are poorly understood in humans. Assuming that leukemic cells functionally inhibit healthy CD34+ hematopoietic stem and progenitor cells (HSPC) via humoral factors, we exposed healthy BM-derived CD34+ HSPC to cell-free supernatants derived from AML cell lines as well as from 24 newly diagnosed AML patients. Exposure to AML-derived supernatants significantly inhibited proliferation, cell cycling, colony formation, and differentiation of healthy CD34+ HSPC. RNA sequencing of healthy CD34+ HSPC after exposure to leukemic conditions revealed a specific signature of genes related to proliferation, cell-cycle regulation, and differentiation, thereby reflecting their functional inhibition on a molecular level. Experiments with paired patient samples showed that these inhibitory effects are markedly related to the immunomagnetically enriched CD34+ leukemic cell population. Using PCR, ELISA, and RNA sequencing, we detected overexpression of TGFß1 in leukemic cells on the transcriptional and protein level and, correspondingly, a molecular signature related to TGFß1 signaling in healthy CD34+ HSPC. This inhibitory effect of TGFß1 on healthy hematopoiesis was functionally corrobated and could be pharmacologically reverted by SD208, an inhibitor of TGFß receptor 1 signaling. Overall, these data indicate that leukemic cells induce functional inhibition of healthy CD34+ HSPC, at least in part, through TGFß1, suggesting that blockage of this pathway may improve hematopoiesis in AML.

The influence of obesity on functional outcomes and patient satisfaction 8 weeks after total knee arthroplasty: results of the prospective FInGK study.

OBJECTIVES: To investigate obese versus non-obese subjects´ knee joint function, stiffness, pain, expectations, and outcome satisfaction before and two months after total knee arthroplasty (TKA). METHODS: This study is a secondary analysis of data retrieved via a prospective single-centre cohort study investigating knee joint function and health care services utilization in patients undergoing TKA (FInGK Study). For the primary study, elective TKA patients were consecutively recruited between December 2019 and May 2021. Preoperative expectations, Western Ontario and McMasters Universities Osteoarthritis Index (WOMAC), surgery outcome satisfaction, and sociodemographic variables were assessed via self-reported questionnaires. In the current study, obese (Body Mass Index (BMI) ≥ 30 kg/m²) versus non-obese (BMI < 30 kg/m²) subjects' data were exploratively compared before and two months after TKA. Multivariable logistic regression assessed factors associated with TKA satisfaction two months postoperatively. Linear regression evaluated factors associated with higher WOMAC change two months postoperatively. RESULTS: A total of 241 subjects participated (response: 85.2%). Eighty-seven were non-obese (mean age: 70.7 years, 63.2% female) and 154 were obese (mean age: 67.1 years, 57.8% female). Obese subjects reported inferior pre- and postoperative pain and knee joint function compared to non-obese subjects. Yet, WOMAC scores of obese and non-obese subjects significantly improved from preoperative means of 52.6 and 46.8 to 32.3 and 24.4 after surgery, respectively. The only significant TKA satisfaction predictor was subjects' smoking status. Non-obesity and worse preoperative WOMAC scores were predictive of higher WOMAC change scores after two months. CONCLUSION: Both obese and non-obese subjects reported significant symptom improvements. However, as obese subjects' short-term outcomes were still inferior, more research on TKA rehabilitation measures adapted to the needs of this growing patient group is warranted to maximize their benefits from TKA.

Vitamin D Deficiency: The Missing Etiological Factor in the Development of Juvenile Osteochondrosis Dissecans?

BACKGROUND: Vitamin D deficiency can result in rickets and hypocalcemia during infant and childhood growth. There is an increasing interest in the role of vitamin D with regards to childhood bone health. Osteochondrosis dissecans (OD) is a common disease affecting different joints. To date, the exact etiology of OD still remains unclear. The aim of this study was to evaluate a possible association of vitamin D deficiency and juvenile OD. METHODS: A retrospective chart review of the years 2010 to 2015 of all orthopaedic patients with an initial diagnosis of juvenile OD admitted to undergo operative treatment of the OD was performed. Patient demographics, medical history, information on sports activity (if available) and serum vitamin D (25-OH-D) level on admission date were obtained. For statistical comparison, we measured baseline prevalence of vitamin D insufficiency in age-matched orthopaedic patients presenting at the department of pediatric orthopaedics. RESULTS: A total of 80 patients were included in this study. Overall, 97.5% (n=78) of tested patients in the OD group had serum vitamin D levels below the recommended threshold of 30 ng/mL (mean value of 10.1 ng/mL (±6.7 ng/mL)). Over 60% (n=49) were vitamin D deficient, 29 patients (37%) showed serum levels below 10 ng/mL corresponding to a severe vitamin D deficiency. Of note, only 2 patients (2.5%) reached serum vitamin D levels above the recommended threshold of 30 ng/mL. No statistical difference was found in respect to sports activity level before onset of the symptoms (P=0.09). Statistical analysis found a significant difference in vitamin D levels between patients with OD and patients without an OD (P=0.026). CONCLUSIONS: We found an unexpected high prevalence of vitamin D deficiency in juveniles diagnosed with OD presenting with significant lower mean 25-OH-D level compared with a control group. These results suggest that vitamin D deficiency is potentially associated with the development of OD. Thus, vitamin D deficiency might be an important cofactor in the multifactorial development of juvenile OD. For this reason, supplementation of vitamin D might not only be a potential additional therapy but also be a possible preventative factor in patients with juvenile OD. However, future prospective studies are needed to confirm this preliminary data. LEVEL OF EVIDENCE: Level III-this is a case-control study.

[Influence of frequently prescribed drugs on bone healing]. / Beeinflussung der Knochenheilung durch häufig verordnete Medikamente.

BACKGROUND: Bone healing after fractures is influenced by many different factors. Besides patient-related factors, such as age, gender and other comorbidities, other drugs taken also have a relevant impact on bone healing. OBJECTIVE: The aim of the study was to give an overview of the effects of frequently used drugs on fracture healing, with the exception of specific osteoporosis drugs and hormones. MATERIAL AND METHODS: This overview is based on a medline search with the search string of each pharmacological agent. RESULTS: Frequently used pharmacological substances were identified, for example corticosteroids, antihypertensive drugs, diuretics, antidepressive drugs, antiepileptics, statins, antibiotics, nonsteroidal anti-inflammatory drugs, anticoagulants and others. Except for antihypertensive drugs, thiazide diuretics and statins, which have osteoprotective effects and stimulate bone healing, all other drugs have negative effects on fracture healing in preclinical and animal studies. Clinical data are scarce. CONCLUSION: Data for the effects of the abovementioned pharmacological substances could be found mostly in preclinical studies. The effects of these agents on bone healing in humans has currently not been studied or published. Therefore, the use of these drugs should be discussed carefully in cases with a compromised fracture healing.

[Importance of osteoporosis-related fractures for patients]. / Bedeutung osteoporosebedingter Frakturen für den Patienten.

BACKGROUND: Osteoporosis is a common disease that affects both women and men. Due to a reduced bone mineral density and increasing age, the risk for atraumatic fractures increases. These fractures cause pain due to the fracture itself and also have far-reaching sequelae in nearly all areas of life of patients. OBJECTIVE: The aim of this article is to summarize the consequences of osteoporotic fractures from the patient's point of view and to highlight the consequences of osteoporosis for the patient. The necessity for timely diagnostics and treatment after a fracture event is explained. MATERIAL AND METHODS: For each term a literature search was performed using key topic-related terms and the results are presented as a narrative review. RESULTS: Various areas of importance for patients were identified. A direct assessment of the patient's point of view was not feasible using a literature search; however, studies with surveys of patients could be identified and therefore, the patient's point of view could be integrated. Areas of interest that could be identified in the literature were pain, psychological well-being, cognitive abilities, mortality and long-term need for nursing. CONCLUSION: The effects of osteoporosis and fractures are multifactorial and often severe for the patient. The measures for prevention of osteoporotic fractures should be consistently implemented in the daily clinical routine and the necessary diagnostics and treatment should be rapidly initiated.

[Establishment of fracture liaison services in Germany]. / Etablierung von Frakturnetzwerken in Deutschland.

BACKGROUND: Osteoporosis results in fragility fractures that are associated with a high morbidity and mortality as well as an increased risk for subsequent fragility fractures. Thus, the first fragility fracture should be the last. To achieve this goal patients need treatment of osteoporosis according to the prevailing clinical guidelines. OBJECTIVE: This article presents the current clinical care situation of patients with a manifest osteoporosis in Germany and the accompanying risks. As a possible solution the concept of a fracture liaison service (FLS) as a new intersectoral care concept is presented and options for the establishment of FLS in Germany are provided. MATERIAL AND METHODS: A literature search (PubMed) was conducted using key terms. The practical experiences of the authors in the context of establishing an FLS were also considered. RESULTS: Compared to other countries, in Germany only a minority of patients receive treatment for osteoporosis after fragility fractures. To improve the care situation an intersectoral FLS provides a coordinated referral of patients with fragility fractures from inpatient care in hospitals to specialists in private practice. This enables the strict identification and treatment of high-risk patients according to the prevailing clinical guidelines. In Germany, different options exist to structure an FLS under consideration of the local circumstances. CONCLUSION: In Germany, FLS should be established nationwide and according to uniform standards. This would significantly improve the quality of clinical care of patients with manifest osteoporosis.

No improvement in reducing outliers in coronal axis alignment with patient-specific instrumentation.

PURPOSE AND HYPOTHESIS: Patient-specific instrumentation (PSI) uses 3D preoperative imaging to produce individualized cutting blocks specific to patients' anatomy and according to the preoperative plan with the aim to reduce the number of mechanical leg alignment (MLA) outliers, to improve implant positioning and to decrease surgery time. The primary purpose of this study was to investigate the efficacy of a specific PSI in comparison with standard instrumentation (SI) in reducing the number of MLA outliers. It was hypothesized that the number of MLA outliers would be significantly lower in the PSI group. METHODS: A multicenter randomized controlled trial was implemented. There were 59 patients in the PSI group and 66 in the SI group. The absolute number of outliers outside the ± 3° target neutral MLA was compared between the groups with a Chi-square test. As secondary outcomes, the Knee Society Score (KSS) and the Knee Injury and Osteoarthritis Outcome Score (KOOS) were compared between the groups preoperatively and at 90-day follow-up. RESULTS: There were 15 (26.3%) MLA outliers in the PSI group and 8 (12.3%) in the SI group. The number of outliers was not independent from the group ( X2 (1) = 3.8, p = 0.04; Relative risk = 1.5). Preoperatively, there were no significant differences between the groups when comparing their KSS and KOOS sub-scores. At 90 days postoperatively, the patients in the SI group showed better KOOS-Quality of Life (KOSS-QOL) in comparison with the PSI group (p < 0.0001). CONCLUSION: The use of PSI did not significantly reduce the number of MLA outliers in comparison with SI. There were no differences when comparing the achieved mean MLA of both groups. LEVEL OF EVIDENCE: Level I, prospective randomized controlled trial.

[Update of the German S3 guideline on atraumatic femoral head necrosis in adults]. / Update S3-Leitlinie Atraumatische Femurkopfnekrose des Erwachsenen.

The update of the German S3 guideline on atraumatic femoral head necrosis in adults aims to provide an overview of diagnosis and treatment. All clinical studies, systematic reviews, and meta-analyses published in German or English between 01.05.2013 and 30.04.2017 were included. Of 427 studies, 28 were suitable for analysis. Risk factors are corticosteroids, chemotherapy, kidney transplants, hemoglobinopathies, and alcoholism. Differential diagnoses are for example bone marrow edema, insufficiency fracture, and destructive arthropathy. Radiography should be performed upon clinical suspicion. In patients with normal radiography findings but persistent complaints, magnetic resonance imaging (ARCO classification) is the method of choice. Computed tomography (CT) can be used to confirm/exclude articular surface collapse. A subchondral sclerosis zone >30% in CT indicates a better prognosis. Left untreated, a subchondral fracture will develop within 2 years. The risk of disease development in the opposite side is high during the first 2 years, but unlikely thereafter. In conservative therapy, iloprost and alendronate can be used in a curative approach, the latter for small, primarily medial necrosis. Conservative therapy alone as well as other drug-based and physical approaches are not suitable for treatment. No particular joint-preserving surgery can currently be recommended. Core decompression should be performed in early stages with <30% necrosis. From ARCO stage IIIc or in stage IV, the indication for total hip arthroplasty should be checked. Results after total hip arthroplasty are comparable with those after coxarthrosis, although the revision rate is higher due to the relatively young age of patients. Statements on the effectiveness of cell-based therapies such as expanded stem cells or bone marrow aspirates cannot currently be made.

High Prevalence of Vitamin D Deficiency in Patients with Bone Tumors.

The aim of this study was to evaluate the prevalence of vitamin D deficiency in patients with different types of bone tumors and to elucidate whether or not there are differences in prediagnostic vitamin D levels in patients with malignant compared to benign bone tumors. Prediagnostic serum 25(OH)D levels of 105 consecutive patients that presented with bone tumors and tumor-like lesions to two Orthopedic Level I University Centers in Germany between 2011 and 2016 were measured on admission. We found an alarming and widespread rate of vitamin D deficiency in patients with bone tumors. Specifically, 83% of all patients had low vitamin D levels with a mean 25(OH)D level of 19.82 ng/ml. Notably, patients diagnosed with malignant bone tumors had significantly lower vitamin D levels compared to patients with benign bone lesions (p = 0.0008). In conclusion, it is essential to assess vitamin D levels in patients with tumors involving bone. In addition, there might be an association between vitamin D deficiency and the onset or course of primary malignant bone tumors.

Is there an association between low serum 25-OH-D levels and the length of hospital stay in orthopaedic patients after arthroplasty?

BACKGROUND: The purpose of this observational study was to evaluate serum levels of 25-OH-D in patients scheduled to undergo elective hip or knee arthroplasty. We hypothesised that 25-OH-D level is an independent risk factor for length of stay in orthopaedic patients after elective hip or knee arthoplasty. MATERIALS AND METHODS: 25-OH-D levels were measured in 1083 patients admitted to an orthopaedic surgery department to undergo elective hip or knee arthroplasty. Comparisons were performed using Chi square or Student's t test, followed by univariate and multiple linear regression analysis examining the correlation between the length of stay in the orthopaedic department and 25-OH-D level while adjusting for possible confounders. RESULTS: Overall, 86 % of patients had insufficient serum levels of 25-OH-D, and over 60 % were vitamin D deficient. The mean length of stay was 13.2 ± 8.3 days. In patients with hypovitaminosis D, the length of stay was significantly longer compared to patients with normal serum 25-OH-D levels (15.6 ± 7.2 compared to 11.3 ± 7.9 days, P = 0.014). In univariate analyses, serum 25-OH-D level was inversely related to the length of stay in our orthopaedic department compared to patients with normal vitamin D levels (r = -0.16; P = 0.008). In multivariate analyses, the length of stay remained significantly associated with low 25-OH-D levels (P = 0.002), indicating that low vitamin D levels increase the length of stay. CONCLUSIONS: We found a high frequency of hypovitaminosis D among orthopaedic patients scheduled to undergo elective arthroplastic surgery. Low vitamin D levels showed a significant inverse association to the length of stay in our orthopaedic department. Patients with vitamin D levels in the target range were hospitalised 4.3 days less than patients with hypovitaminosis D. Level 3 of evidence according to "The Oxford 2011 levels of evidence".

In-vivo analysis of epicutaneous pressure distribution beneath a femoral tourniquet--an observational study.

BACKGROUND: Compression of the tissue beneath tourniquets used in limb surgery is associated with varying degrees of soft tissue damage. The interaction between fluids and applied pressure seems to play an important role in the appearance of skin lesions. The extent of the transfer of force between the tourniquet and the skin, however, has yet to be studied. The aim of the present study was to quantify in-vivo the transfer of pressure between a tourniquet and the skin of the thigh. METHODS: Pressure under the tourniquet was measured using sensors in 25 consecutive patients over the course of elective surgical procedures. Linear mixed modeling was used to assess the homogeneity of the distribution of pressure around the circumference of the limb, variation in pressure values over time, and the influence of limb circumference and the Body-Mass-Index (BMI) on pressure transfer. RESULTS: Mean pressure on the skin was significantly lower than the inner pressure of the cuff (5.95%, 20.5 ± 9.36 mmHg, p < 0.01). There was a discrete, but significant (p < 0.001) increase in pressure within the first twenty minutes after inflation. Sensors located in the area of overlap of the cuff registered significantly higher pressure values (p < 0.01). BMI and leg circumference had no influence on the transfer of pressure to the surface of the skin (p = 0.88 and p = 0.51). CONCLUSIONS: Pressure transfer around the circumference of the limb was distributed inhomogeneously. The measurement series revealed a global pressure drop compared to the initial pressure of the cuff. No relationship could be demonstrated between the pressure transferred to the skin and the BMI or limb circumference.

Vitamin D insufficiency in the elderly orthopaedic patient: an epidemic phenomenon.

PURPOSE: The purpose of this observational study was to evaluate serum levels of 25-OH-D of elderly patients presenting with orthopaedic illness. Furthermore, we enquired about potential confounders and risk factors of hypovitaminosis D in comorbidities and daily medication of the elderly. METHODS: Vitamin D levels in 1,083 patients aged >70 years and admitted to an orthopaedic surgery department were measured. Univariate and multivariate analyses were used to assess risk factors for insufficient vitamin D levels. RESULTS: Overall, 86 % of patients had insufficient serum levels of 25-OH-D and >60 % were vitamin D deficient. Serum vitamin D levels were lower during winter and months with fewer sunshine hours. Patients presenting with obesity, hypertension and osteoporosis were more likely to have low vitamin D levels. CONCLUSIONS: We found a high prevalence of hypovitaminosis D in elderly, nonhospitalized orthopaedic patients. Given the well-known effects of vitamin D on bone metabolism and muscle health, as well as its nonskeletal effects, vitamin D insufficiency may have a negative impact.

Is there an association between periprosthetic joint infection and low vitamin D levels?

PURPOSE: Vitamin D is increasingly being recognized as an important mediator of immune function and may have a preventive role in the pathogenesis of periprosthetic joint infection. To the best of our knowledge, no other study has examined possible associations between periprosthetic joint infection and vitamin D deficiency. We investigated the rate of vitamin D deficiency in patients treated for periprosthetic joint infection and whether vitamin D deficiency is independent of other risk factors for vitamin D deficiency in patients with periprosthetic joint infection. METHODS: Serum 25-hydroxyvitamin D (25OHD) levels of every patient scheduled to receive a total prosthesis either of the hip, knee, or shoulder in the orthopaedic department of the Johannes-Guttenberg-University Hospital in Mainz, Germany (109 patients), were measured after admission. Furthermore, serum 25OHD levels were measured for every patient presenting with periprosthetic joint infection (n = 50) or aseptic loosening of the prosthesis (n = 31) scheduled to undergo revision surgery. The prevalence of normal (> 30 ng/ml), insufficient (20-30 ng/ml), and deficient (<20 ng/ml) 25OHD levels was determined. RESULTS: All tested patient subgroups showed low vitamin D levels. Statistical analysis found no significant difference in vitamin D levels comparing patients with prosthesis and patients with aseptic prosthesis loosening (p = 0.58). Significant differences in 25OHD levels were found comparing patients with periprosthetic joint infection and patients scheduled for primary arthroplasty (p < 0.001). In addition, we found a significant difference (p < 0,001) in 25OHD levels of patients with periprosthetic joint infection compared with patients with aseptic prosthesis loosening. CONCLUSION: We found a high frequency of vitamin D deficiency in patients being treated by primary arthroplasty and those with aseptic joint prosthetic loosening and periprosthetic joint infection. Vitamin D deficiency was severe in patients with periprosthetic joint infection.

Uncemented femoral revision arthroplasty using a modular tapered, fluted titanium stem: 5- to 16-year results of 163 cases.

BACKGROUND AND PURPOSE: Due to the relative lack of reports on the medium- to long-term clinical and radiographic results of modular femoral cementless revision, we conducted this study to evaluate the medium- to long-term results of uncemented femoral stem revisions using the modular MRP-TITAN stem with distal diaphyseal fixation in a consecutive patient series. PATIENTS AND METHODS: We retrospectively analyzed 163 femoral stem revisions performed between 1993 and 2001 with a mean follow-up of 10 (5-16) years. Clinical assessment included the Harris hip score (HHS) with reference to comorbidities and femoral defect sizes classified by Charnley and Paprosky. Intraoperative and postoperative complications were analyzed and the failure rate of the MRP stem for any reason was examined. RESULTS: Mean HHS improved up to the last follow-up (37 (SD 24) vs. 79 (SD 19); p<0.001). 99 cases (61%) had extensive bone defects (Paprosky IIB-III). Radiographic evaluation showed stable stem anchorage in 151 cases (93%) at the last follow-up. 10 implants (6%) failed for various reasons. Neither a breakage of a stem nor loosening of the morse taper junction was recorded. Kaplan-Meier survival analysis revealed a 10-year survival probability of 97% (95% CI: 95-100). INTERPRETATION: This is one of the largest medium- to long-term analyses of cementless modular revision stems with distal diaphyseal anchorage. The modular MRP-TITAN was reliable, with a Kaplan-Meier survival probability of 97% at 10 years.

Stromal alterations in patients with monoclonal gammopathy of undetermined significance, smoldering myeloma, and multiple myeloma.

ABSTRACT: The hallmark of multiple myeloma (MM) is a clonal plasma cell infiltration in the bone marrow accompanied by myelosuppression and osteolysis. Premalignant stages such as monoclonal gammopathy of undetermined significance (MGUS) and asymptomatic stages such as smoldering myeloma (SMM) can progress to MM. Mesenchymal stromal cells (MSCs) are an integral component of the bone marrow microenvironment and play an important role in osteoblast differentiation and hematopoietic support. Although stromal alterations have been reported in MM contributing to hematopoietic insufficiency and osteolysis, it is not clear whether alterations in MSC already occur in MGUS or SMM. In this study, we analyzed MSCs from MGUS, SMM, and MM regarding their properties and functionality and performed messenger RNA sequencing to find underlying molecular signatures in different disease stages. A high number of senescent cells and a reduced osteogenic differentiation capacity and hematopoietic support were already present in MGUS MSC. As shown by RNA sequencing, there was a broad spectrum of differentially expressed genes including genes of the BMP/TGF-signaling pathway, detected already in MGUS and that clearly increases in patients with SMM and MM. Our data may help to block these signaling pathways in the future to hinder progression to MM.

Overlapping Stromal Alterations in Myeloid and Lymphoid Neoplasms.

Myeloid and lymphoid neoplasms share the characteristics of potential bone marrow infiltration as a primary or secondary effect, which readily leads to hematopoietic insufficiency. The mechanisms by which clonal malignant cells inhibit normal hematopoietic stem and progenitor cells (HSPCs) in the bone marrow (BM) have not been unraveled so far. Given the pivotal role of mesenchymal stromal cells (MSCs) in the regulation of hematopoiesis in the BM niche it is assumed that MSCs also play a relevant role in the pathogenesis of hematological neoplasms. We aimed to identify overlapping mechanisms in MSCs derived from myeloid and lymphoid neoplasms contributing to disease progression and suppression of HSPCs to develop interventions that target these mechanisms. MSCs derived from healthy donors (n = 44) and patients diagnosed with myeloproliferative neoplasia (n = 11), myelodysplastic syndromes (n = 16), or acute myeloid leukemia (n = 25) and B-Non-Hodgkin lymphoma (n = 9) with BM infiltration and acute lymphoblastic leukemia (n = 9) were analyzed for their functionality and by RNA sequencing. A reduced growth and differentiation capacity of MSCs was found in all entities. RNA sequencing distinguished both groups but clearly showed overlapping differentially expressed genes, including major players in the BMP/TGF and WNT-signaling pathway which are crucial for growth, osteogenesis, and hematopoiesis. Functional alterations in healthy MSCs were inducible by exposure to supernatants from malignant cells, implicating the involvement of these factors in disease progression. Overall, we were able to identify overlapping factors that pose potential future therapeutic targets.

Preventing long-term disability in CIDP: the role of timely diagnosis and treatment monitoring in a multicenter CIDP cohort.

BACKGROUND: Chronic inflammatory demyelinating polyneuropathy (CIDP) is an inflammatory disease affecting the peripheral nerves and the most frequent autoimmune polyneuropathy. Given the lack of established biomarkers or risk factors for the development of CIDP and patients' treatment response, this research effort seeks to identify potential clinical factors that may influence disease progression and overall treatment efficacy. METHODS: In this multicenter, retrospective analysis, we have screened 197 CIDP patients who presented to the University Hospitals in Düsseldorf, Berlin, Cologne, Essen, Magdeburg and Munich between 2018 and 2022. We utilized the respective hospital information system and examined baseline data with clinical examination, medical letters, laboratory results, antibody status, nerve conduction studies, imaging and biopsy findings. Aside from clinical baseline data, we analyzed treatment outcomes using the Standard of Care (SOC) definition, as well as a comparison of an early (within the first 12 months after manifestation) versus late (more than 12 months after manifestation) onset of therapy. RESULTS: In terms of treatment, most patients received intravenous immunoglobulin (56%) or prednisolone (39%) as their first therapy. Patients who started their initial treatment later experienced a worsening disease course, as reflected by a significant deterioration in their Inflammatory Neuropathy Cause and Treatment (INCAT) leg disability score. SOC-refractory patients had worse clinical outcomes than SOC-responders. Associated factors for SOC-refractory status included the presence of fatigue as a symptom and alcohol dependence. CONCLUSION: Timely diagnosis, prompt initiation of treatment and careful monitoring of treatment response are essential for the prevention of long-term disability in CIDP and suggest a "hit hard and early" treatment paradigm.

Computer-assisted fluoroscopic navigation of percutaneous spinal interventions.

PURPOSE: Percutaneous spine procedures may occasionally be difficult and subject to complications. Navigation using a dynamic reference base (DRB) may ease the procedure. Yet, besides other shortcomings, its fixation demands additional incisions and thereby defies the percutaneous character of the procedure. METHODS: A new concept of atraumatic referencing was invented including a special epiDRB. The accuracy of navigated needle placement in soft tissue and bone was experimentally scrutinised. Axial and pin-point deviations from the planned trajectory were investigated with a CT-based 3D computer system. Clinical evaluation in a series of ten patients was also done. RESULTS: The new epiDRB proved convenient and reliable. Its fixation to the skin with adhesive foil provided a stable reference for navigation that improves the workflow of percutaneous interventions, reduces radiation exposure and helps avoid complications. CONCLUSIONS: Percutaneous spine interventions can be safely and accurately navigated using epiDRB with minimal trauma or radiation exposure and without additional skin incisions.

Is there an epidemic vitamin D deficiency in German orthopaedic patients?

BACKGROUND: Vitamin D plays an essential role in bone health and muscle function. Some studies have shown a widespread rate of vitamin D deficiency in the general population, but few have reported on the vitamin D status of orthopaedic patients. QUESTIONS/PURPOSES: We investigated (1) the extent of hypovitaminosis D in orthopaedic patients, (2) seasonal variations in vitamin D levels, and (3) possible risk factors for insufficient vitamin D levels. METHODS: Vitamin D levels in 1119 patients consecutively admitted to an orthopaedic surgery department in 2011 were measured. To investigate the correlation between climate factors and vitamin D levels, the sunshine hours for each month in 2011 were collected by Deutscher Wetterdienst (the German weather service) in the region where most tested patients lived. The prevalence of normal (> 30 ng/mL), insufficient (20-30 ng/mL), and deficient (< 20 ng/mL) 25-hydroxyvitamin D levels was determined. Univariate and multivariate analyses were used to assess risk factors for insufficient vitamin D levels. RESULTS: Overall, 84% of patients had insufficient levels of vitamin D and 60% were vitamin D deficient. Only 15% were in the target range of 30 to 60 ng/mL. The prevalence of low vitamin D levels was greater during winter and months with fewer sunshine hours. Vitamin D levels did not vary according to age, sex, and disease. Individuals with obesity, hypertension, and osteoporosis were more likely to have low vitamin D levels compared with their healthy counterparts. CONCLUSIONS: There is an alarmingly high rate of hypovitaminosis D and vitamin D deficiency among orthopaedic patients in this region of Germany, whose latitude (50° N) is approximately the same as those of Vancouver (49°, 15' N) and Paris (48°, 51' N). Given the well-known effects on bone metabolism and muscle health, low vitamin D levels may negatively affect patients. Screening and treating hypovitaminosis D appears to be important in this patient population.