Management of complications of mega-implants following treatment of primary and periprosthetic fractures of the lower extremities.

In recent years, indications for implanting mega-implants were established in managing major bone defects linked to revision arthroplasty due to loosening, periprosthetic fractures, re-implantation following periprosthetic joint infection, non-union following fractures as well as complex intraarticular primary fractures. This study was conducted to discuss and analyze the strategy of diagnosis and management of complications following the use of mega-implants in treating primary and periprosthetic fractures of the lower extremities. This is a monocentric retrospective study. Patients aged ≥ 18 years who underwent implantation of a megaendoprosthesis due to periprosthetic or primary fractures of the lower extremity between January 2010 and February 2023 were identified from the authors' hospital information system. We identified 96 patients with equal numbers of fractures (71 periprosthetic fractures and 25 primary fractures). 90 cases out of 96 were investigated in this study. The drop-out rate was 6.25% (six cases). The average follow-up period was 22 months (1 to 8 years) with a minimum follow-up of 1 year. The diagnosis of complications was provided on the basis of subjective symptoms, clinical signs, radiological findings and laboratory investigations such as C-reactive protein, leucocyte count and the microbiological findings. The indications for implantations of modular mega-implants of the lower extremities were periprosthetic fractures (65 cases/72.22%) and primary fractures (25 cases/27.78%). Pathological fractures due to malignancy were encountered in 23 cases (25.56%), in one case due to primary tumor (1.11%) and 22 cases due to metastatic lesions (24.44%). Two cases (2.22%) presented with primary intraarticular fractures with severe osteoporosis and primary arthrosis. In all cases with malignancy staging was performed. Regarding localization, proximal femur replacement was encountered in 60 cases (66.67%), followed by distal femur replacement (28 cases/31.11%) and total femur replacement (2 cases/2.22%). The overall complication rate was 23.33% (21 complications in 21 patients). The most common complication was dislocation which was encountered in nine cases (10%), all following proximal femoral replacement (9 cases out of 60, making 15% of cases with proximal femoral replacement). The second most common complication was infection (six cases, 6.67%), followed by four aseptic loosenings (4.44%), further intraoperative periprosthetic fracture in one case (1.11%) and a broken implant in one case (1.11%). We noticed no cases with wear and tear of the polyethylene components and no cases of disconnections of the modular components. Mega-endoprostheses enable versatile management options in the treatment of primary and periprosthetic fractures of the lower extremities. The rate of complications such as loosening, implant failure, dislocation and infection are within an acceptable range in this preliminary analysis. However, implantation of mega-endoprostheses must be strictly indicated due the limited salvage options following surgery.

Randomized Clinical Trials and Observational Tribulations: Providing Clinical Evidence for Personalized Surgical Pain Management Care Models.

Proving clinical superiority of personalized care models in interventional and surgical pain management is challenging. The apparent difficulties may arise from the inability to standardize complex surgical procedures that often involve multiple steps. Ensuring the surgery is performed the same way every time is nearly impossible. Confounding factors, such as the variability of the patient population and selection bias regarding comorbidities and anatomical variations are also difficult to control for. Small sample sizes in study groups comparing iterations of a surgical protocol may amplify bias. It is essentially impossible to conceal the surgical treatment from the surgeon and the operating team. Restrictive inclusion and exclusion criteria may distort the study population to no longer reflect patients seen in daily practice. Hindsight bias is introduced by the inability to effectively blind patient group allocation, which affects clinical result interpretation, particularly if the outcome is already known to the investigators when the outcome analysis is performed (often a long time after the intervention). Randomization is equally problematic, as many patients want to avoid being randomly assigned to a study group, particularly if they perceive their surgeon to be unsure of which treatment will likely render the best clinical outcome for them. Ethical concerns may also exist if the study involves additional and unnecessary risks. Lastly, surgical trials are costly, especially if the tested interventions are complex and require long-term follow-up to assess their benefit. Traditional clinical testing of personalized surgical pain management treatments may be more challenging because individualized solutions tailored to each patient's pain generator can vary extensively. However, high-grade evidence is needed to prompt a protocol change and break with traditional image-based criteria for treatment. In this article, the authors review issues in surgical trials and offer practical solutions.

Durotomy- and Irrigation-Related Serious Adverse Events During Spinal Endoscopy: Illustrative Case Series and International Surgeon Survey.

BACKGROUND: Durotomy during endoscopic spine surgery can cause a patient's neurological or cardiovascular status to deteriorate unexpectedly intra- or postoperatively. There is currently limited literature regarding appropriate fluid management strategies, irrigation-related risk factors, and clinical consequences of incidental durotomy during spinal endoscopy, and no validated irrigation protocol exists for endoscopic spine surgery. Thus, the present article sought to (1) describe 3 cases of durotomy, (2) investigate standard epidural pressure measurements, and (3) survey endoscopic spine surgeons on the incidence of adverse effects believed to result from durotomy. MATERIALS AND METHODS: The authors first reviewed clinical outcomes and analyzed complications in 3 patients with intraoperatively recognized incidental durotomy. Second, the authors conducted a small case series with intraoperative epidural pressure measurements during gravity-assisted irrigated video endoscopy of the lumbar spine. Measurements were conducted on 12 patients with a transducer assembly that was introduced through the endoscopic working channel of the RIWOSpine Panoview Plus and Vertebris endoscope to the decompression site in the spine. Third, the authors conducted a retrospective, multiple-choice survey of endoscopic spine surgeons to better understand the frequency and seriousness of problems they attributed to irrigation fluid escaping from the surgical decompression site into the spinal canal and neural axis. Descriptive and correlative statistical analyses were performed on the surgeons' responses. RESULTS: In the first part of this study, durotomy-related complications during irrigated spinal endoscopy were observed in 3 patients. Postoperative head computed tomographic (CT) images revealed massive blood in the intracranial subarachnoid space, the basal cisterns, the III and IV ventricle, and the lateral ventricles characteristic of an arterial fisher grade IV subarachnoid hemorrhage, and hydrocephalus without evidence of aneurysms or angiomas. Two additional patients developed intraoperative seizures, cardiac arrhythmia, and hypotension. The head CT image in 1 of these 2 patients had intracranial air entrapment.In the second part, epidural pressure measurements in 12 patients who underwent uneventful routine lumbar interlaminar decompression for L4-L5 and L5-S1 disc herniation showed an average epidural pressure of 24.5 mm Hg.In the third part, the online survey was accessed by 766 spine surgeons worldwide and had a response rate of 43.6%. Irrigation-related problems were reported by 38% of responding surgeons. Only 11.8% used irrigation pumps, with 90% running the pump above 40 mm Hg. Headaches (4.5%) and neck pain (4.9%) were observed by nearly a 10th (9.4%) of surgeons. Seizures in combination with headaches, neck and abdominal pain, soft tissue edema, and nerve root injury were reported by another 5 surgeons. One surgeon reported a delirious patient. Another 14 surgeons thought that they had patients with neurological deficits ranging from nerve root injury to cauda equina syndrome related to irrigation fluid. Autonomic dysreflexia associated with hypertension was attributed by 19 of the 244 responding surgeons to the noxious stimulus of escaped irrigation fluid that migrated from the decompression site in the spinal canal. Two of these 19 surgeons reported 1 case associated with a recognized incidental durotomy and another with postoperative paralysis. CONCLUSIONS: Patients should be educated preoperatively about the risk of irrigated spinal endoscopy. Although rare, intracranial blood, hydrocephalus, headaches, neck pain, seizures, and more severe complications, including life-threatening autonomic dysreflexia with hypertension, may arise if irrigation fluid enters the spinal canal or the dural sac and migrates from the endoscopic site along the neural axis rostrally. Experienced endoscopic spine surgeons suspect a correlation between durotomy and irrigation-related extra- and intradural pressure equalization that could be problematic if associated with high volumes of irrigation fluid LEVEL OF EVIDENCE: 3.

The Changing Environment in Postgraduate Education in Orthopedic Surgery and Neurosurgery and Its Impact on Technology-Driven Targeted Interventional and Surgical Pain Management: Perspectives from Europe, Latin America, Asia, and The United States.

Personalized care models are dominating modern medicine. These models are rooted in teaching future physicians the skill set to keep up with innovation. In orthopedic surgery and neurosurgery, education is increasingly influenced by augmented reality, simulation, navigation, robotics, and in some cases, artificial intelligence. The postpandemic learning environment has also changed, emphasizing online learning and skill- and competency-based teaching models incorporating clinical and bench-top research. Attempts to improve work-life balance and minimize physician burnout have led to work-hour restrictions in postgraduate training programs. These restrictions have made it particularly challenging for orthopedic and neurosurgery residents to acquire the knowledge and skill set to meet the requirements for certification. The fast-paced flow of information and the rapid implementation of innovation require higher efficiencies in the modern postgraduate training environment. However, what is taught typically lags several years behind. Examples include minimally invasive tissue-sparing techniques through tubular small-bladed retractor systems, robotic and navigation, endoscopic, patient-specific implants made possible by advances in imaging technology and 3D printing, and regenerative strategies. Currently, the traditional roles of mentee and mentor are being redefined. The future orthopedic surgeons and neurosurgeons involved in personalized surgical pain management will need to be versed in several disciplines ranging from bioengineering, basic research, computer, social and health sciences, clinical study, trial design, public health policy development, and economic accountability. Solutions to the fast-paced innovation cycle in orthopedic surgery and neurosurgery include adaptive learning skills to seize opportunities for innovation with execution and implementation by facilitating translational research and clinical program development across traditional boundaries between clinical and nonclinical specialties. Preparing the future generation of surgeons to have the aptitude to keep up with the rapid technological advances is challenging for postgraduate residency programs and accreditation agencies. However, implementing clinical protocol change when the entrepreneur-investigator surgeon substantiates it with high-grade clinical evidence is at the heart of personalized surgical pain management.

Clinical Consequences of Incidental Durotomy during Full-Endoscopic Lumbar Decompression Surgery in Relation to Intraoperative Epidural Pressure Measurements.

Background: Seizures, neurological deficits, bradycardia, and, in the worst cases, cardiac arrest may occur following incidental durotomy during routine lumbar endoscopy. Therefore, we set out to measure the intraoperative epidural pressure during lumbar endoscopic decompression surgery. Methods: We conducted a retrospective observational cohort study to obtain intraoperative epidural measurements with an epidural catheter-pressure transducer assembly through the spinal endoscope on 15 patients who underwent lumbar endoscopic decompression of symptomatic lumbar herniated discs and spinal stenosis. The endoscopic interlaminar technique was employed. Results: There were six (40.0%) female and nine (60.0%) male patients aged 49.0667 ± 11.31034, ranging from 36 to 72 years, with an average follow-up of 35.15 ± 12.48 months. Three of the fifteen patients had seizures with durotomy and one of these three had intracranial air on their postoperative brain CT. Another patient developed spinal headaches and diplopia on postoperative day one when her deteriorating neurological function was investigated with a brain computed tomography (CT) scan, showing an intraventricular hemorrhage consistent with a Fisher Grade IV subarachnoid hemorrhage. A CT angiogram did not show any abnormalities. Pressure recordings in the epidural space in nine patients ranged from 20 to 29 mm Hg with a mean of 24.33 mm Hg. Conclusion: Most incidental durotomies encountered during lumbar interlaminar endoscopy can be managed without formal repair and supportive care measures. The intradural spread of irrigation fluid and intraoperatively used drugs and air entrapment through an unrecognized durotomy should be suspected if patients deteriorate in the recovery room. Ascending paralysis may cause nausea, vomiting, upper and lower motor neuron symptoms, cranial nerve palsies, hypotension, bradycardia, and respiratory and cardiac arrest. The recovery team should be prepared to manage these complications.

Cartilage repair strategies in the knee according to Dutch Orthopedic Surgeons: a survey study.

BACKGROUND: This study surveyed Dutch orthopedic surgeons on the management of cartilage defects in the knee and the adherence to the recently updated Dutch knee cartilage repair consensus statement (DCS). METHODS: A web-based survey was sent to 192 Dutch knee specialists. RESULTS: The response rate was 60%. Microfracture, debridement and osteochondral autografts are performed by the majority, 93%, 70% and 27% of respondents, respectively. Complex techniques are used by < 7%. Microfracture is mainly considered in defects 1-2 cm2 (by > 80%) but also in 2-3 cm2 (by > 40%). Concomitant procedures, e.g., malalignment corrections, are performed by 89%. Twenty-one percent of surgeons treat patients aged 40-60 years. Microfracture, debridement and autologous chondrocyte implantation are not considered to be highly affected by age > 40 years by any of the respondents (0-3%). Moreover, for the middle-aged there is a large spread in treatments considered. In case of loose bodies, the majority (84%) only performs refixation in the presence of attached bone. CONCLUSION: Small cartilage defects in ideal patients may be well treated by general orthopedic surgeons. The matter becomes complicated in older patients, or in case of larger defects or malalignment. The current study reveals some knowledge gaps for these more complex patients. Referral to tertiary centers might be indicated, as is stated by the DCS, and this centralization should enhance knee joint preservation. Since the data from present study are subjective, registration of all separate cartilage repair cases should fuel objective analysis of clinical practice and adherence to the DCS in the future.

PATHOLOGIC FINDINGS IN GENDER-AFFIRMING MASTECTOMY: A SYSTEMATIC REVIEW.

Following increased cultural awareness, expanded access to care, and decreased stigmatization, the number of transgender individuals seeking gender affirmation surgery such as gender-affirmation mastectomy (GAM) continues to rise. While post-mastectomy breast tissue is often sent for pathologic evaluation, few studies address the utility and standardization of this practice. This literature review evaluates the pathology findings in GAM specimens reported in the medical literature. A systematic review following PRISMA guidelines was performed to evaluate all medical publications related to pathology reports following GAM. The overall type and incidence of benign and malignant breast lesions were analyzed to elucidate which patient characteristics significantly affect the pathology findings. Overall, eight of 488 identified studies met inclusion criteria (1278 patients). The incidence of pre-malignant lesions was 2.42%, including flat epithelial atypia (0.08%), atypical hyperplasia (0.23%), atypical ductal hyperplasia (1.33%), atypical lobular hyperplasia (0.39%), and lobular carcinoma in situ (0.39%).Patient age, hormonal therapy, and family / patient history of breast cancer were inconsistently reported among included studies. Lack of standardized pathologic classification did not permit further statistical analysis. Although patients who undergo GAM are unlikely to have premalignant or malignant findings on breast pathology examination, pathologic evaluation of breast tissue remains common practice. Additional studies, which include a standardized method of pathologic evaluation, are necessary before practice guidelines can be recommended.

Outcomes in Bariatric and Metabolic Surgery: an Updated 5-Year Review.

PURPOSE OF REVIEW: Knowledge regarding postoperative outcomes after bariatric and metabolic surgery continues to evolve. This review highlights key findings in outcomes research over the last 5 years related to weight loss, remission of obesity-related disease, reflux, revisional surgery, robotic-assisted surgical platforms, and adolescent populations. RECENT FINDINGS: Sleeve gastrectomy (SG) and Roux-en-Y gastric bypass (RYGB) produce similar weight loss patterns at 5 years, while duodenal switch (BPD/DS) and related procedures are associated with maximal weight loss overall and optimal resolution of obesity-related comorbidities. Remission of type 2 diabetes mellitus (T2DM) following surgery is more likely in patients who are not insulin dependent prior to surgery. Bariatric and metabolic surgery offers a significant protective effect against coronary artery disease (CAD) and associated interventions in both diabetic and nondiabetic patients, as well as heart failure (HF). Gastroesophageal reflux disease (GERD) and dysphagia following SG are common, and routine endoscopic surveillance for Barrett's esophagus may be of significant utility. Robotic-assisted laparoscopic platforms concur similar outcomes to laparoscopic intervention, with a potential benefit in high BMI patients. Revisional surgery is most commonly performed for weight regain and/or inadequate weight loss following an index procedure, or reflux, and generally characterized by higher postoperative complication rates and longer inpatient lengths of stay (LOS). Surgical intervention in adolescent populations has similar weight loss and postoperative complication profiles to those seen in adult populations, with improved outcomes related to T2DM. Bariatric and metabolic surgery continues to evolve as a treatment for obesity and obesity-related comorbidities. While effective for weight loss and remission of obesity-related disease, SG is associated with high rates of postoperative GERD.

Amino Acid-Functionalized Polyelectrolyte Films as Bioactive Surfaces for Cell Adhesion.

Surfaces were prepared with polyelectrolyte derivatives of poly(styrene- alt-maleic anhydride) (PSMA) functionalized with amino acids of different hydropathy indices, with the aim of evaluating the effect of the chemical functionality of polyelectrolytes on SH-SY5Y neuroblastoma cell adhesion. Functionalizing PSMA derivatives with l-glutamine, l-methionine, and l-tyrosine yielded PSMA-Gln, PSMA-Met, and PSMA-Tyr polyelectrolytes, respectively. We first studied the adsorption behavior of PSMA functionalized with amino acids on silicon wafer surfaces modified with 3-aminopropyltriethoxysilane at pH 4.0 and 7.0 and at low and high ionic strengths. The highest rate of polyelectrolyte adsorption was at pH 4.0 and high ionic strength and was higher with the glutamine and tyrosine films. The advance contact angles (θA) of the polyelectrolyte surfaces showed a moderate effect of ionic strength and pH on polyelectrolyte film wettability, with PSMA-Tyr being slightly more hydrophobic. Atomic force microscopy images of the polyelectrolyte surfaces showed two types of morphology: the well-defined globular nanostructure of PSMA-Met and PSMA-Tyr and densely packed nanofibrous-like structure of PSMA-Gln. The highest level of ionic strength caused a slight decrease in the size of the nanostructure that formed the surface domains, which was reflected in the degree of surface roughness. Cell adhesion assays with the polyelectrolyte film showed that SH-SY5Y neuroblastoma cells cultured on PSMA-Met present a well-extended morphology characterized by a stellate shape, with five or more actin-rich thin processes, whereas SH-SY5Y cells that were seeded on PSMA-Gln and PSMA-Tyr have a round morphology, with fewer and shorter processes. These results indicate that it is possible to modulate the surface characteristics of polyelectrolyte films based on their chemical functionality and environmental parameters such as pH and ionic strength in order to evaluate their effect on cell adhesion. Thus, surfaces prepared from polyelectrolytes functionalized with amino acids are an attractive and simple platform for cell adhesion, which can be used in developing biomaterials with modulated surface properties.

[Pulmonary involvement in rheumatoid arthritis]. / Lungenbeteiligung bei rheumatoider Arthritis.

Pulmonary involvement in patients with rheumatoid arthritis, in particular interstitial lung diseases (RA-ILD) is of great clinical importance. Patients should be asked about symptoms of pulmonary involvement and the lungs should be clinically examined even during the diagnostic procedure and regularly during the course of the disease. Before initiation of a basic pharmacological treatment an X­ray examination of thoracic organs is obligatory. In cases of conspicuous clinical or radiological findings, extended diagnostic procedures with lung function testing (body plethysmography with diffusion measurement) and high resolution computed tomography (CT) should be performed, depending on the findings. The differential diagnosis of interstitial lung alterations in patients with RA is broad and should consider side effects of the basis medication in addition to infectious causes. The optimal pharmacological treatment of RA-ILD is not sufficiently clarified. The value of methotrexate (MTX) has changed because, in contrast to previous assumptions, a better course could be observed under MTX treatment, at least in mild to moderate courses of RA-ILD. In the case of a clinically relevant RA-ILD, tumor necrosis factor (TNF) blockers should be avoided because a dramatic deterioration of pulmonary function has sometimes been observed. Among biological disease-modifying antirheumatic drugs (DMARD), rituximab and abatacept are currently preferred. The role of Janus kinase (JAK) inhibitors in RA-ILD is currently being discussed but limited data are available. Patients with RA-ILD benefit from a close collaboration between pulmonologists and rheumatologists.

[Challenges of primary hip arthroplasty with high hip dislocation]. / Herausforderungen der primären Hüftendoprothetik bei hoher Hüftluxation.

BACKGROUND: Endoprosthetic care of high hip dislocation is a surgical challenge. The hip anatomy is greatly altered in these patients, including a rather flat and small acetabulum with impaired bone quality and a relevant chance of a bony defect of the acetabular roof. Additionally, the front coverage and in some cases even the dorsal coverage of the hip are missing. The proximal femur is characterized with an increased antetorsion, a coxa valga position and an enlarged greater trochanter. The medullary cavity is narrowed, the offset is reduced, and the absolut leg length can be enlarged. Further anatomic variations can have been caused by previous surgeries. AIM OF THE TREATMENT: The goal of the endoprosthetic care is the re-creation of a hip with an anatomic center of rotation, an anatomic offset and equal leg length. TREATMENT: This can be achieved by a medial shift of the acetabular cup. An acetabular osteotomy including central cancellous bone graft or a bony graft to reinforce the acetabular roof might be necessary. In cases in which an anatomic acetabular cup placement is not possible, a more cranial placement can be done. Further strategies that are essential in several cases are shortening or re-orientation osteotomies of the femur, reaming of the medullary cavity and correct implant selection. Additionally, thorough soft tissue management is of main importance. Generally, the surgery should be well prepared preoperatively.

Low-grade infections as a possible cause of arthrofibrosis after total knee arthroplasty.

PURPOSE: Arthrofibrosis after total knee arthroplasty represents a considerable burden for the patient and a therapeutic challenge for the practitioner. One possible cause discussed in the literature is a low-grade infection. This hypothesis should be examined within the scope of this retrospective study. PATIENTS AND METHODS: Nineteen patients with clinical symptoms of arthrofibrosis after primary total knee arthroplasty were examined between January, 1999 and January, 2012. Incorrect positioning was radiologically ruled out. All patients were examined clinically (score of Freeman as well as Blauth and Jäger), radiologically (component and leg alignment, patella height according to Insall and Salvati), microbiologically (culture-based procedures), molecular biologically (PCR) and histologically in the course of an open revision of the prosthesis. RESULTS: According to the score of Freeman et al. (1977), a highly significant improvement in pain (p = 0.007) and in the overall score (p = 0.003) was shown. The knee joint mobility did not change significantly (p = 0.795). PCR was negative in 17 patients. One patient showed a PCR-positive result of the synovial membrane for Corynebacterium spp., while Staphylococcus warneri was detected in the culture. Another patient had a positive result of synovia PCR for Enterococcus cecorum as well as Corynebacterium spp. However, this culture was sterile. In 16 patient samples, no bacterial growth was detectable. Two samples were not evaluable. The main histopathological findings were synovialitis and fibrosis. CONCLUSION: The hypothesis of low-grade-infection-induced arthrofibrosis after total knee arthroplasty could not be confirmed in this study. However, based on this small study population the conclusion needs to be confirmed by new and larger studies, ideally prospectively designed including a control group.

[Bone marrow edema-differential diagnosis of the femoral head necrosis]. / Das Knochenmarködem ­ Differenzialdiagnose zur aseptischen Hüftkopfnekrose.

In patients with hip pain, clinical examination is of only restricted value in the differential diagnosis. Besides a patient's age, their medical history is often helpful in finding the correct diagnosis. Additionally, imaging can give valuable hints for excluding or validating a differential diagnosis. Nowadays, magnetic resonance imaging (MRI) is often used as a primary imaging modality in Germany. These MRIs show a bone marrow edema (BME) in many different pathologies. BME occurs in transitory bone marrow edema and outside of the atraumatic femoral head necrosis, concomitant with coxarthrosis, arthritis, herniation pit, and osteoid osteoma, amongst other conditions. This article describes several frequent differential diagnoses and gives hints on how to find the correct diagnosis.

[Work-life balance : Thoughts of the Young Surgeon representatives of the German Surgical Society]. / Work-Life-Balance : Gedanken des Perspektivforums Junge Chirurgie der Deutschen Gesellschaft für Chirurgie.

Work-life balance is a commonly used term that appears in different contexts and has a different meaning for many colleagues. Unfortunately, however, it is often used as a negative, simplified term to describe the assumed attitude of young surgeons towards work and a medical career, even though this is not universally applicable. As the representatives for Young Surgeons of the German Society of Surgery the aim of this article is to present our thoughts on the issue and associated problems and provide a differentiated outline for discussion.

[Lymphocytic myocarditis in a patient with metastatic clear cell renal cell carcinoma treated with Nivolumab]. / Lymphozytäre Myokarditis unter Nivolumabtherapie bei metastasiertem klarzelligen Nierenzellkarzinom.

Immune checkpoint inhibitors against the PD-1 protein offer a new therapy option for many solid cancers. We report a patient with metastatic renal cell cancer treated with Nivolumab. As a rare immune-mediated adverse event, we describe a fatal lymphocytic myocarditis two weeks after starting immune therapy. The cause of death was first diagnosed at autopsy. This case report underlines the importance and need of clinical autopsies as an instrument of quality assurance and detection of rare therapy-induced adverse effects.

High-dose chemotherapy with autologous haematopoietic stem cell support for relapsed or refractory primary CNS lymphoma: a prospective multicentre trial by the German Cooperative PCNSL study group.

To investigate safety and efficacy of high-dose chemotherapy followed by autologous stem cell transplantation (HCT-ASCT) in relapsed/refractory (r/r) primary central nervous system lymphoma (PCNSL), we conducted a single-arm multicentre study for immunocompetent patients (<66 years) with PCNSL failing high-dose methotrexate)-based chemotherapy. Induction consisted of two courses of rituximab (375 mg/m2), high-dose cytarabine (2 × 3 g/m2) and thiotepa (40 mg/m2) with collection of stem cells in between. Conditioning for HCT-ASCT consisted of rituximab 375 mg/m2, carmustine 400 mg/m2 and thiotepa (4 × 5 mg/kg). Patients commenced HCT-ASCT irrespective of response after induction. Patients not achieving complete remission (CR) after HCT-ASCT received whole-brain radiotherapy. Primary end point was CR after HCT-ASCT. We enrolled 39 patients; median age and Karnofsky performance score are 57 years and 90%, respectively. About 28 patients had relapsed and 8 refractory disease. About 22 patients responded to induction and 32 patients commenced HCT-ASCT. About 22 patients (56.4%) achieved CR after HCT-ASCT. Respective 2-year progression-free survival (PFS) and overall survival (OS) rates were 46.0% (median PFS 12.4 months) and 56.4%; median OS not reached. We recorded four treatment-related deaths. Thiotepa-based HCT-ASCT is an effective treatment option in eligible patients with r/r PCNSL. Comparative studies are needed to further scrutinise the role of HCT-ASCT in the salvage setting.

The Development of a Representative Porcine Early-Onset Scoliosis Model With a Standalone Posterior Spinal Tether.

STUDY DESIGN: In vivo analysis in a porcine model. OBJECTIVES: To develop a porcine experimental scoliosis model representative of early-onset scoliosis (EOS) with the use of a radiopaque ultra-high molecular weight polyethylene (UHMWPE) posterior spinal tether. SUMMARY OF BACKGROUND DATA: Large animal experimental scoliosis models with substantial growth potential are needed to test new fusionless scoliosis correction techniques. Previously described scoliosis models involve rib procedures, which violate the thoracic cage and affect subsequent corrective procedures. Models omitting these rib procedures have experienced difficulties in producing persistent three-dimensional structural deformities representative of EOS. METHODS: Scoliosis was induced in 14 immature pigs using an asymmetric posterior radiopaque UHMWPE spinal tether fixated to an offset device at lumbar and thoracic levels. Radiographs were taken at 2-week intervals, and frontal and sagittal Cobb angles were measured. A tether release was performed at the 10-week follow-up, and the animals were observed for another 10 weeks. RESULTS: Four animals had complications (infections and/or screw breakout) and were excluded from the study. Eight animals developed progressive curves with a mean frontal Cobb angle of 62°. A thoracic lordosis (34°) and a thoracolumbar kyphosis (22°) formed. CT analysis, acquired prior to tether release, showed a mean vertebral rotation of 37° at the apex with a mean vertebral wedge angle of 10°. After tether release, the frontal Cobb angles decreased to 46° at the 20-week follow-up. Sagittal curvature was not substantially affected after tether release. CONCLUSIONS: We describe a large animal scoliosis model, which exhibits a substantial deformity in three planes without the use of rib procedures additional to a posterior spinal tether. The created deformities showed persistence after tether release. With the management of infection and enhancement of instrumentation stability, the creation of a valid model for testing new devices in fusionless scoliosis surgery seems feasible. LEVEL OF EVIDENCE: Level V.

[Three Years Follow-up Study after Refractive Small Incision Lenticule Extraction (SMILE) Using 500 kHz Femtosecond Laser in "Fast Mode"]. / Drei Jahre Nachbeobachtung nach refraktiver Small Incision Lenticule Extraction (SMILE) mit einem 500-kHz-Femtosekundenlaser im "Fast Mode".

Background The aim of this clinical trial was to check the results of laser built-in settings 3 years after ReLEx SMILE for moderate and high myopia in unselected "real life" patients. Patients and Methods 50 myopic eyes of 27 patients were called in for examination after 3 years. 25 of these eyes with a preoperative myopia under - 6D comprised the "moderate myopia subgroup". All surgeries were performed with the 500 kHz VisuMax® femtosecond laser (Carl Zeiss Meditec AG, Jena) in the "fast mode" setting. Results The spherical equivalent (SE) of the entire group changed from - 6.18 D (± 1.91) prior to surgery to - 0.18 D (± 0.39) 3 years later. The preoperative SE in the moderate myopia subgroup changed from - 4.71 D (± 0.94) to - 0.04 D (± 0.23). 14 % of 50 eyes gained one line and 22 % lost one line of CDVA. The regression between month 3 and 36 was 0.07D for the entire group and 0.06 D for the moderate myopia subgroup. There were no late side effects. Primary undercorrection was predominantly seen in eyes over - 6 D. Conclusion ReLEx SMILE shows remarkable stability over the entire range of myopias after 3 years, however primary undercorrection occurs predominantly in eyes of - 6.0 D, which necessitates nomogram adjustment.

[Lymphoma in rheumatic diseases]. / Lymphome bei rheumatischen Erkrankungen.

Various systemic inflammatory diseases, such as rheumatoid arthritis (RA), Sjögren's syndrome and systemic lupus erythematosus (SLE) are associated with an increased risk for the development of lymphomas. Studies on patients with RA and Sjögren's syndrome have shown that there is a clear association of the incidence of lymphoma with the severity and activity of the disease and lymphomas in particular are diseases which preferentially occur in immunosuppressed patients; therefore, knowledge of the different lymphoma subtypes, their prognosis and treatment options are important for rheumatologists. Currently, there is no evidence for an increased risk of lymphoma with the available conventional basis therapies or biologic disease-modifying antirheumatic drugs (DMARDs). The decision on how to treat a patient with previous lymphoma who requires antirheumatic treatment is more difficult as patients with previous malignancies are not included in clinical studies and in registries a bias with respect to patient selection must be taken into consideration. Decisions on the treatment approach, therefore need to be individualized and interdisciplinary management together with the treating hematologist is warranted.

High-dose methotrexate-based immuno-chemotherapy for elderly primary CNS lymphoma patients (PRIMAIN study).

To investigate immuno-chemotherapy for elderly immuno-competent patients (⩾65 years) with newly diagnosed primary central nervous system lymphoma, we conducted a multicentre single-arm trial. One cycle consisted of rituximab (375 mg/m2, days 1, 15, 29), high-dose methotrexate (3 g/m2 days 2, 16, 30), procarbazine (60 mg/m2 days 2-11) and lomustine (110 mg/m2, day 2)-R-MPL protocol. Owing to infectious complications, we omitted lomustine during the study and consecutive patients were treated with the R-MP protocol. Three cycles were scheduled and repeated on day 43. Subsequently, patients commenced 4 weekly maintenance treatment with procarbazine (100 mg for 5 days). Primary end point was complete remission (CR) after 3 cycles. We included 107 patients (69 treated with R-MPL and 38 with R-MP). In all, 38/107 patients achieved CR (35.5%) and 15 (14.0%) achieved partial remission. R-MP was associated with a lower CR rate (31.6%) compared with R-MPL (37.7%), but respective 2-year progression-free survival (All 37.3%; R-MP 34.9%; R-MPL 38.8%) and overall survival (All 47.0%; R-MP 47.7%; R-MPL 46.0%) rates were similar. R-MP was associated with less ⩾grade 3 toxicities compared with R-MPL (71.1% vs 87.0%). R-MP is more feasible while still associated with similar efficacy compared with R-MPL and warrants further improvement in future studies.