[Mediocarpal instability of the wrist]. / Mediokarpale Instabilitäten der Handwurzel.

Typical lesions of the carpal ligaments are mostly found after a fall on the wrist in hyperextension or as complex injuries after severe trauma, e. g. after a fall from a significant height, motorcycle accident or as accompanying lesions in multiple trauma. The typical mechanisms, patterns and diagnostic algorithms are well known for the common ligamentous injuries (e.g. scapholunate, lunotriquetral and perilunate); therefore, consistent diagnostic procedures and adequate therapy are increasingly performed after such lesions, e. g. by early ligament repair or by ligament reconstruction through augmentation. Within appropriate operative treatment, accompanying fractures are also treated and instabilities are addressed by transfixation of joints by Kirschner wires. If followed by immobilization with a cast or stable brace, healing can be achieved in most cases; however, more problems occur if ligamentous lesions or instabilities are not clearly due to a trauma mechanism and more the result of laxity or hypermobile situations due to a congenital predisposition. In such cases, wrist pain is often described and misdiagnosed as the result of overload or tenovaginitis.

[Skeletal tuberculosis of the distal radius during pregnancy]. / Ossäre Tuberkulose am distalen Radius in der Schwangerschaft.

We present a case of a pregnant woman (32nd gestational week) that suffered from a chronic non-healing wound at the distal radius. Skeletal tuberculosis was finally diagnosed and treated successfully with staged surgical therapy combined with appropriate medication. One year after surgical treatment, the outcome of the mother was excellent and the baby did not suffer from any disease related to operative procedures or pharmacotherapy. Operative treatment of skeletal tuberculosis (especially osteoarticular and vertebral tuberculosis) in combination with tuberculostatic therapy during pregnancy and lactation seem to be the appropriate treatment with minimal risk for the child and excellent outcome for the mother.

A kinome-centered CRISPR-Cas9 screen identifies activated BRAF to modulate enzalutamide resistance with potential therapeutic implications in BRAF-mutated prostate cancer.

Resistance to drugs targeting the androgen receptor (AR) signaling axis remains an important challenge in the treatment of prostate cancer patients. Activation of alternative growth pathways is one mechanism used by cancer cells to proliferate despite treatment, conferring drug resistance. Through a kinome-centered CRISPR-Cas9 screen in CWR-R1 prostate cancer cells, we identified activated BRAF signaling as a determinant for enzalutamide resistance. Combined pharmaceutical targeting of AR and MAPK signaling resulted in strong synergistic inhibition of cell proliferation. The association between BRAF activation and enzalutamide resistance was confirmed in two metastatic prostate cancer patients harboring activating mutations in the BRAF gene, as both patients were unresponsive to enzalutamide. Our findings suggest that co-targeting of the MAPK and AR pathways may be effective in patients with an activated MAPK pathway, particularly in patients harboring oncogenic BRAF mutations. These results warrant further investigation of the response to AR inhibitors in BRAF-mutated prostate tumors in clinical settings.

Necrotizing fasciitis: treatment concepts and clinical results.

BACKGROUND: Necrotizing fasciitis is a life-threatening soft tissue infection characterized by a rapid spreading infection of the subcutaneous tissue and in particular the fascia. The management of infected tissues requires a rapid diagnosis, immediate aggressive surgical management and an extended debridement. In some cases early amputations of the affected tissues and maximum intensive care treatment, in case of sepsis, are required. Due to a rising number of cases we aimed to evaluate our patients in a retrospective review. METHOD: All patients diagnosed with necrotizing fasciitis from 2014 to 2016 (21 months) in our level one trauma center were identified. Their charts were reviewed and data were analyzed in terms of demographic and social information, microbiological results, therapeutic course, socio-economic outcome and mortality. RESULTS: We found 15 patients with necrotizing fasciitis. None of these died in the observation period. The mean number of surgical interventions was seven. Two patients underwent limb amputation; diabetes mellitus was assigned with a significant higher risk for amputation. The mean hospitalization was 32 days, including 8 days on intensive care unit. Of the discovered bacteria 93% were sensitive to the initial antibiotic treatment with Ampicillin, Clindamycin and Clont. CONCLUSION: Surgical therapy is indicated if necrotizing fasciitis is suspected. Diabetes mellitus was a clinical predictor of limb amputation in patients with necrotizing fasciitis in our cohort. Aminopenicillin ± sulbactam in combination with clindamycin and/or metronidazole is recommended as initial calculated antibiotic treatment.

Clinical outcome after alternative treatment of scaphoid fractures and nonunions.

PURPOSE: Achieving stable fixation of scaphoid fractures and nonunions continues to be a challenge. Compression screw fixation has been the current standard surgical procedure. However, in some cases, bone healing cannot be achieved and requires further revision. Recent series reintroduced volar plating as valid option for stable fixation. The aim of the study was to review clinical outcome of alternative scaphoid treatment. METHODS: From 2011 to 2014, nine patients with scaphoid fracture were treated by Headless Compression Screw (HCS) and seven patients with scaphoid nonunion by HCS or volar mini condylar plate with bone graft. The average age was 34.4 years and the average time to follow-up was 19.3 months. From 1996 to 1998, 38 patients with scaphoid nonunion were treated using compression screw (S-group) or volar mini condylar plate (P-group) with bone graft. The average age was 39.6 years and the average time to follow-up was 26.2 months. RESULTS: The union rate was 100%. For scaphoid fractures, the mean Modified Mayo Wrist Score (MMWS) was 94.1 and the DASH score 7.4. From 2011 to 2014, the MMWS was 87.9 and the DASH score 7 in scaphoid nonunions. In the period between 1996 and 1998, the MMWS was 67.2 in the P-group and 58.6 in the S-group, and the DASH score 16.8 and 28.2. CONCLUSIONS: Our study demonstrated that appropriate application of the HCS was able to produce very satisfactory results in scaphoid fractures and nonunions. In our opinion, however, the method of scaphoid plate osteosynthesis can achieve a higher degree of stability, particularly rotational stability, in case of multifragmentary avascular scaphoid nonunions.

Tumor suppressor BTG1 promotes PRMT1-mediated ATF4 function in response to cellular stress.

Cancer cells are frequently exposed to physiological stress conditions such as hypoxia and nutrient limitation. Escape from stress-induced apoptosis is one of the mechanisms used by malignant cells to survive unfavorable conditions. B-cell Translocation Gene 1 (BTG1) is a tumor suppressor that is frequently deleted in acute lymphoblastic leukemia and recurrently mutated in diffuse large B cell lymphoma. Moreover, low BTG1 expression levels have been linked to poor outcome in several solid tumors. How loss of BTG1 function contributes to tumor progression is not well understood. Here, using Btg1 knockout mice, we demonstrate that loss of Btg1 provides a survival advantage to primary mouse embryonic fibroblasts (MEFs) under stress conditions. This pro-survival effect involves regulation of Activating Transcription Factor 4 (ATF4), a key mediator of cellular stress responses. We show that BTG1 interacts with ATF4 and positively modulates its activity by recruiting the protein arginine methyl transferase PRMT1 to methylate ATF4 on arginine residue 239. We further extend these findings to B-cell progenitors, by showing that loss of Btg1 expression enhances stress adaptation of mouse bone marrow-derived B cell progenitors. In conclusion, we have identified the BTG1/PRMT1 complex as a new modifier of ATF4 mediated stress responses.

[Outcome after Implantation of the Aptis Total Distal Radioulnar Joint Replacement Prosthesis]. / Ergebnisse nach Implantation der Aptis-Prothese zum Ersatz des distalen Radioulnargelenks.

BACKGROUND: To date, the Aptis distal radioulnar joint (DRUJ) prosthesis by Scheker is the only total, bipolar prosthesis available. In the literature, only few data exist concerning the prosthesis and its surgical technique. Aim of the present study was the evaluation of the medium-term clinical and radiological outcome following implantation of the Aptis DRUJ prosthesis. METHODS AND PATIENTS: 5 patients (4 women and 1 man) with mean age of 40.2 (30-65) years underwent secondary implantation of the Aptisprosthesis between February 2006 and May 2013. The average date of the follow-up was after 36 (24-48) months. Besides the complications, the wrist range of motion (ROM) and the strength in grip were measured. The quality of pain was determined using a visual analogue pain scale from 0-10. In follow-up X-ray controls, bone resorption and bony abnormalities were evaluated. The DASH score as well as the postoperative subjective satisfaction of the patients were recorded. RESULTS: No patient required removal of the prosthesis. Only 1 patient underwent secondary surgery in which debridement of the screw tip over the radius was required. The postoperative range of motion in pronation and supination was measured with 78 (70-90)° and 82 (70-90)°. The average grip strength amounted to 29 (24-32) kg. This represented 85 (76-100)% of the value of the contralateral side. Postoperative pain symptoms on the visual analogue pain scale were measured with 0 points at rest and with 1.2 (0-2) points under strain. Radiological evaluation showed bone resorption at the radial peg in 2 patients, but without evidence of implant loosening. The DASH score was recorded with 37 (13-75) points. All patients were satisfied or very satisfied after the surgical treatment. CONCLUSION: The Aptis prosthesis is a safe and efficient treatment option for previously failed surgery of the DRUJ.

Triplane fractures: do we need cross-sectional imaging?

INTRODUCTION: Diagnosis of Triplane fractures remains difficult in common practice. Aim of the study was the evaluation of the fracture pattern and the benefit of cross-sectional imaging in classification of Triplane-fractures. MATERIAL AND METHODS: A total of 27 pediatric patients treated for ankle fractures were identified from patient charts. Radiographic images of epiphyseal fractures (X-rays and additional cross-sectional imaging) were blinded evaluated by 13 observers to answer a specific questionnaire regarding type or fracture and treatment suggestion. RESULTS: There were seven Triplane-I and eight Triplane-II fractures. The other physeal ankle fracture group consisted of four patients with a Twoplane-fracture, five Salter-and-Harris (SH) II, one SH-III, and two SH-IV fracture. Accuracy of classification improved considerably depending on the experience of the observer in pediatric trauma care. Surgeons specialized in pediatric trauma care classified correctly with conventional X-rays in 48.1 % of all cases presented versus 31.5 % appropriate diagnosis by younger fellows. Accuracy in exact specification of Triplane-fractures was comparable lesser in younger fellows (31.1 vs. 22 %). Cross-sectional imaging improved classification of all fractures in both groups (75.6 % specialized vs. 47.3 % non specialized). Whereas availability of cross-sectional imaging improved treatment recommendation in specialized surgeons this benefit was not detectable for the doctors without specialization. Evaluation of fracture pattern showed a relatively stereotypical fracture pattern in Triplane-II fractures, whereas Triplane-I fractures were more variable. CONCLUSION: The additional information of cross-sectional imaging seems helpful for any physician in finding the right classification of a pediatric ankle fracture. However, the additive information appears especially viable for experienced surgeons to suggest the appropriate treatment.

Intraoperative PEEP-ventilation during PMMA-injection for augmented pedicle screws: improvement of leakage rate in spinal surgery.

BACKGROUND: Within the last two decades the use of polymethylmethacrylate (PMMA) in the treatment of osteoporotic vertebral fractures has been established widely. Several techniques of cement application in spinal surgery have been described. Besides classical vertebroplasty, kyphoplasty and related techniques that reinforce stability of the fractured vertebral body itself, augmentation of pedicle screws became an issue in the past 10 years. Aim of this technique is strengthening of the implant-bone-interface and the prevention of loosening and failure of posterior instrumentation in limited bone quality due to osteoporosis. PMMA use in spinal surgery always bears the risk of cement leakage and cement embolism. There are only few publications dealing with cement leakage in pedicle screw augmentation. We examined our cohort concerning incidence and type of leakage in comparison to the literature. In particular, we evaluated a possible role of intrathoracic pressure during cementation procedure. PATIENTS AND METHODS: In this retrospective study 42 patients were included. Mean age was 74 (57-89) years. 311 fenestrated, augmented screws were analyzed postoperatively concerning leakage and subsequent pulmonary embolism of cement particles. Overall, there was a leakage rate of 38.3 %, and 28.6 % of patients showed pulmonary embolism of PMMA. During surgery, patients were in part ventilated with a positive end-expiratory pressure (PEEP) of 15 cmH2O during cement injection. These individuals showed significantly less leakage locally as well as less PMMA-emboli in the pulmonary circulation in contrast to patients ventilated without increased PEEP. CONCLUSION: PEEP elevation during administration of PMMA via fenestrated pedicle screws is reducing the leakage rate in spinal surgery. These beneficial effects warrant further evaluation in prospective studies.

Cervical spine fractures in the elderly: morbidity and mortality after operative treatment.

PURPOSE: Although there are currently many different strategies and recommendations in the therapy of cervical spine fractures in elderly patients, there are still no generally accepted treatment algorithms. The aim of the present study was to analyze the morbidity, mortality, and outcome of operated cervical spine injuries in the elderly. METHODS: This study presents a retrospective review of 69 patients aged 65 years or older admitted to our level I trauma center with cervical spine injury, who had undergone surgical treatment. The data were acquired by analysis of the hospital inpatient enquiry system and radiological review. RESULTS: The ratio between male and female patients was 37:32. The average age of the patients was 76 years (ranging from 65 to 96 years) for males and 80 years (ranging from 66 to 93 years) for females. Injury to the cervical spine was caused by low-energy trauma in 71 % and high-energy trauma in 29 %, respectively. 55.1 % sustained isolated cervical spine injuries, 39.1 % injuries to two adjacent vertebrae, 2.9 % injuries to three adjacent vertebrae, and 2.9 % an odontoid fracture combined with associated fracture(s) in non-contiguous vertebra(e). Isolated spine injury level was dominated by C2 (47.8 %). The most common site for injuries to two adjacent vertebrae was observed at C6/C7 (14.5 %). The morbidity included cerebral complications, respiratory complications, Clostridium difficile-associated disease, heart failure, and acute renal failure. Operative complications included dislocation/malposition, neurovascular lesions, wound infection, and transient swallowing difficulty. The mortality rate at 3 months was 26.1 %, with an in-hospital mortality of 21.7 %. Age was associated with mortality at 3 months. A cervical fracture-induced neurological deficit was documented in 26.1 %, resulting in a mortality of 44.4 % (8/18). Twenty-seven of 33 patients living at home/nursing home at the time of injury returned to their home/nursing home after their hospitalization. The overall outcome was predominantly related to age and the severity of neurological deficit. CONCLUSIONS: In elderly patients with cervical spine fractures, the hospital course is complicated by medical issues and early mortality rates are significant. Therefore, treatment strategies should be carefully individualized to the patients and their comorbidities.