MarrowQuant 2.0: A Digital Pathology Workflow Assisting Bone Marrow Evaluation in Experimental and Clinical Hematology.

Bone marrow (BM) cellularity assessment is a crucial step in the evaluation of BM trephine biopsies for hematologic and nonhematologic disorders. Clinical assessment is based on a semiquantitative visual estimation of the hematopoietic and adipocytic components by hematopathologists, which does not provide quantitative information on other stromal compartments. In this study, we developed and validated MarrowQuant 2.0, an efficient, user-friendly digital hematopathology workflow integrated within QuPath software, which serves as BM quantifier for 5 mutually exclusive compartments (bone, hematopoietic, adipocytic, and interstitial/microvasculature areas and other) and derives the cellularity of human BM trephine biopsies. Instance segmentation of individual adipocytes is realized through the adaptation of the machine-learning-based algorithm StarDist. We calculated BM compartments and adipocyte size distributions of hematoxylin and eosin images obtained from 250 bone specimens, from control subjects and patients with acute myeloid leukemia or myelodysplastic syndrome, at diagnosis and follow-up, and measured the agreement of cellularity estimates by MarrowQuant 2.0 against visual scores from 4 hematopathologists. The algorithm was capable of robust BM compartment segmentation with an average mask accuracy of 86%, maximal for bone (99%), hematopoietic (92%), and adipocyte (98%) areas. MarrowQuant 2.0 cellularity score and hematopathologist estimations were highly correlated (R2 = 0.92-0.98, intraclass correlation coefficient [ICC] = 0.98; interobserver ICC = 0.96). BM compartment segmentation quantitatively confirmed the reciprocity of the hematopoietic and adipocytic compartments. MarrowQuant 2.0 performance was additionally tested for cellularity assessment of specimens prospectively collected from clinical routine diagnosis. After special consideration for the choice of the cellularity equation in specimens with expanded stroma, performance was similar in this setting (R2 = 0.86, n = 42). Thus, we conclude that these validation experiments establish MarrowQuant 2.0 as a reliable tool for BM cellularity assessment. We expect this workflow will serve as a clinical research tool to explore novel biomarkers related to BM stromal components and may contribute to further validation of future digitalized diagnostic hematopathology workstreams.

[Diagnosis and management of tenosynovial giant cell tumor]. / Diagnostic et prise en charge de la tumeur à cellules géantes ténosynoviale.

Tenosynovial giant cell tumor is a benign condition that originates from synovial cells within joints, tendon sheaths, or bursae and may present either in localized (benign) or diffuse (locally aggressive) forms. Currently, the primary treatment approach is surgical, yielding satisfactory results with low recurrence rates in the localized forms, whereas the diffuse type displays high recurrence rates. In parallel, clinical trials are underway to explore pharmaceutical treatment options for the advanced diffuse type. This article aims at consolidating current knowledge about diagnosis and management of this rare tumor, additionally proposing a brief overview of novel therapeutic approaches.

La tumeur à cellules géantes ténosynoviale, bénigne, prend son origine dans les cellules synoviales des articulations, des gaines tendineuses ou des bourses et se présente dans une forme soit localisée (bénigne), soit diffuse (localement agressive). Le traitement principal est chirurgical, offrant des résultats satisfaisants à long terme, avec un faible risque de récidive dans la forme localisée, alors que le taux de récidives est élevé dans la forme diffuse. Parallèlement, des essais cliniques sont en cours pour explorer des options de traitement systémique pour les formes diffuses sévères. Cet article rappelle les connaissances actuelles pour le diagnostic et la prise en charge de cette tumeur rare. De plus, nous proposons un aperçu succinct des nouvelles approches thérapeutiques.

Image-guided percutaneous cryoablation of unresectable sacrococcygeal chordoma: Feasibility and outcome in a selected group of patients with long term follow-up.

BACKGROUND: Chordoma is a rare malignant tumor of the axial skeleton. Percutaneous cryoablation (PCA) is a minimally invasive technique that allows freezing of tumors under imaging control. The purpose of our retrospective study was to investigate the outcome of PCA in a selected cohort of patients with sacrococcygeal chordoma, with a minimum of 5 years follow-up. MATERIALS AND METHODS: Four patients were treated in 10 sessions. The mean follow-up was 57.3 months. We evaluated the feasibility, the procedure-related complications, the impact on pain control and oncological outcomes. RESULTS: Freezing of 100% of the tumor volume was possible in 60%. Pain control was not reliably evaluable. Local recurrence occurred in 90% of the treated lesions; the mean time to progression was 8.1 months (range 1.5-16). At last follow-up, one patient had died of the disease, one of another cause and one was receiving the best supportive care. The only patient alive without the disease had received additional carbon-ion radiotherapy. The 5-year survival rate after index PCA was 50%. CONCLUSION: Complete freezing of the tumor was technically challenging, mainly due to the complex local anatomy. Recurrence occurred in 90% of the lesions treated. PCA should be considered with caution in the curative management of sacrococcygeal chordoma.

Lymphatic Leaks of the Thigh and Inguinal Region: Combined Plastic Surgery Approaches for an Effective Treatment Algorithm.

BACKGROUND: Surgical procedures interfering with the draining nodes in the inguinal region carry the intrinsic risk of lymphatic complications. Lesions of the inguinal lymphatic network can lead to lymphocele or lymphocutaneous fistulas and can eventually be associated to limb lymphedema with consequent high morbidity. OBJECTIVES: This article describes a new surgical algorithm based on wound properties to properly address lymphatic complications of the inguinal area. Based on our experience, surgical solutions ranged from selective lymphatic vessel ligation to microsurgical lymphatic fistula treatment and free tissue transfer. METHODS: Fourteen consecutive patients underwent surgery in our department following failed attempts to address persistent lymphatic leaks. Patient characteristics such as smoking, previous surgeries, comorbidities, and wound properties were considered. Identification of the leak was performed using blue patent dye and indocyanine green fluorescence. Surgical reconstruction occurred, according to our algorithm. RESULTS: Lymphatic leaks were visualized in 11 of 14 patients. Direct closure of the wound after leak ligation could be performed in 4 of 14 patients. Multilymphatic into vein anastomosis was performed in 3 of 14 patients, and the remaining patients benefited from flap surgery based on the wound defects. All 14 patients had successful outcomes (100%) with early drain removal (average, 6 [SD, 6] days) and definitive wound healing 2 weeks postoperatively. After a mean follow-up of 12 (SD, 2.9) months, no clinical infection, lymphatic complication, or wound breakdown occurred. One patient had a partial recurrence that did not require surgical intervention. CONCLUSIONS: A stepwise approach, combining lymphatic surgery principles and plastic surgery flap techniques, can lead to an effective treatment algorithm where surgical options are wound tailored to guarantee the best functional outcomes.

Acute leg compartment syndrome after CT-guided core needle biopsy of a giant cell tumor of the proximal fibula.

Imaging-guided percutaneous core needle biopsy (CNB) is the preferred diagnostic method for bone and soft tissue tumors. In less than 1% of cases, complications are clinically significant and include mainly haema-toma and bleeding. We present a case of acute compartment syndrome (ACS) following CNB of the proximal fibula. A 26-year-old female patient was referred to our sarcoma center with a suspicion of giant cell tumor (GCT) of the proximal fibula. The CT-guided CNB under local anesthesia had caused transient severe pain irradiating to the foot, rapidly subsiding after correction of the needle trajectory. The patient was discharged on the same day without residual symptoms. She presented at the emergency department 48 hours later with severe leg pain and swelling. Compartment pressure was elevated. Urgent fasciotomies were performed, revealing muscle edema, without significant haematoma. Postoperatively, paresthesia improved progressively and the patient regained a normal neurologic status within 4 months. Pathologic analysis confirmed the diagnosis of GCT, which was resected after neoadjuvant denosumab therapy. At the 2-year follow up visit, the patient still presented pain at exertion, but had no objective neurological sequela. ACS is not a well-known complication of CNB in the diagnosis of bone tumors. This rare complication might be diagnosed too late, or even missed, due to pre-existing pain, which can sometimes be severe in GCT, and to the usually short post-procedure surveillance in an outpatient procedure.

Carbon/PEEK nails: a case-control study of 22 cases.

BACKGROUND: Interest around carbon/PEEK plates and nails has been raising. The elastic modulus close to the bone, the high load-carrying capacity and radiolucency make CFR/PEEK materials a potential breakthrough. In the literature, there are abundant data about CFR/PEEK plates in the treatment of proximal humerus, distal radius and distal fibula fractures. In patients affected by bone metastasis, CFR/PEEK nails were proved effective and safe with 12 months of follow-up. Very little is known about performances of CFR/PEEK nails in patients affected by other pathologies. PURPOSES: The aim of the study was to evaluate safety and efficacy of CFR/PEEK nails in the treatment of various pathological conditions. It was also investigated whatever radiolucency of this nails could lead to a more objective evaluation of bone callus or disease site. PATIENTS AND METHODS: In the study group were included 20 patients (22 bone segments) who underwent CFR/PEEK nail implantation (eight humerus, one tibia, nine femur and four knee arthrodesis). They were affected by pathological fractures, and in four cases, they required an arthrodesis of the knee. They were retrospectively evaluated considering nail failures and bone callus or disease progression (RUSH scores). Mean follow-up time was 11 months (min 6.8-max 20.3). In the control group were included patients treated with titanium nails in the same institution for the same pathologies. An interclass correlation coefficient (ICC) analysis was performed in both groups considering RUSH scores by two expert surgeon from two institution to assess whether radiolucency could lead to a more objective evaluation of disease or bone callus site. RESULTS: The ICC of mean values between RUSH scores was 0.882 (IC 95%: 0.702-0.953) in the CFR/PEEK group, while it was 0.778 (IC 95%: 0.41-0.91) in the titanium group. Observers' evaluation showed a significantly higher obscuration by titanium nails than by CFR/PEEK nails. No osteosynthesis failures were reported in both groups. CONCLUSIONS: Our results confirm the safety of CFR/PEEK nails in the short-medium term. The radiolucency of these materials led our observers to perform more objective evaluations of bone callus formation or disease progression compared to the titanium group given the higher ICC. LEVEL OF EVIDENCE: III Case-control therapeutic study.

Total clavicle reconstruction with free peroneal graft for the surgical management of chronic nonbacterial osteomyelitis of the clavicle: a case report.

BACKGROUND: Chronic nonbacterial osteomyelitis (CNO) is a rare chronic autoinflammatory syndrome affecting mainly children and young adults. The natural history of the disease is marked by recurrent pain as the mainstay of inflammatory outbreaks. Typical radiographic findings are osteosclerosis and hyperostosis of the medial clavicle, sternum and first rib. Compression of the brachial plexus is exceedingly rare and one of the few surgical indications. Literature on total clavicle reconstruction is scarce. While claviclectomy alone has been associated with fair functional and cosmetic outcomes, several reconstruction techniques with autograft, allograft or even cement ("Oklahoma prosthesis") have been reported with the aim of achieving better pain control, cosmetic outcome and protecting the brachial plexus and subclavian vessels. We herewith report a unique case of complicated CNO of the clavicle treated with total clavicle reconstruction using a free peroneal graft. CASE PRESENTATION: A 21-year-old female patient presented with CNO of her left clavicle, associated with recurrent, progressive and debilitating pain as well as limited range of motion. In recent years, she started complaining of paresthesia, weakness and pain radiating to her left arm during arm abduction. The clavicle diameter reached 6 cm on computed tomography, with direct compression of the brachial plexus and subclavian vessels. Following surgical biopsy for diagnosis confirmation, she further developed a chronic cutaneous fistula. Therefore, a two-stage total clavicle reconstruction using a vascularized peroneal graft stabilized by ligamentous reconstruction was performed. At two-year follow-up, complete pain relief and improvement of her left shoulder Constant-Murley score were observed, along with satisfactory cosmetic outcome. CONCLUSIONS: This case illustrates a rarely described complication of CNO with direct compression of the brachial plexus and subclavian vessels, and chronic cutaneous fistula. To our knowledge, there is no consensus regarding the optimal management of this rare condition in this context. Advantages and complications of clavicle reconstruction should be carefully discussed with patients due to limited evidence of superior clinical outcome and potential local and donor-site complications. While in our case the outcomes met the patient's satisfaction, it remains an isolated case and further reports are awaited to help surgeons and patients in their decision process.

[Surgical treatment of proximal femur metastases]. / Traitement chirurgical des métastases du fémur proximal.

Aging of the population results in an increase of the incidence of cancer and bone metastases. The proximal femur is one of the most frequent locations of bone metastases. A pathological fracture has a major impact on the quality of life and potentially on survival. In case of impending fracture, prophylactic fixation is therefore strongly recommended. The management of metastases of the proximal femur depends on multiple parameters, life expectancy and fracture risk being the most important ones. If survival is estimated to be less than 6 weeks, surgery is generally not indicated. Beyond 6 weeks, surgical indication essentially depends on location of the metastases on the proximal femur and the presence of a fracture.

L'augmentation de l'espérance de vie s'accompagne d'une croissance de l'incidence des cancers et des métastases osseuses. Le fémur proximal est un des sites les plus fréquents de métastases osseuses. Une fracture pathologique dans cette localisation a un impact majeur sur la qualité de vie et potentiellement sur la survie du patient. Un traitement chirurgical prophylactique est ainsi recommandé en cas de risque de fracture imminente. La prise en charge des métastases fémorales proximales se décide en fonction de multiples paramètres, dont la survie théorique et le risque de fracture sont les plus importants. Si la survie est estimée à moins de 6 semaines, une chirurgie n'est en général pas indiquée. Au-delà, l'indication chirurgicale dépend essentiellement de la localisation des lésions et de la présence d'une fracture associée.

[Hypersensitivity to metal : myth or reality ?] / Allergie aux implants orthopédiques : mythe ou réalité ?

So-called metal allergy is a new interesting subject in orthopedics. Two different ways of thinking prevail in the literature. In the German orthopaedic literature, the diagnosis of metal allergy is often described and considered a real pathology, while we can find a more skeptical approach to this entity in Anglo-Saxons literature. Being an exclusion diagnostic, without any universal consensus on how to diagnose or on the treatment, the aim of this article is to clarify what we know about metal allergy today.

La notion d'allergie aux métaux, en réalité une hypersensibilité retardée (type IV), est un sujet émergent dans la littérature orthopédique. Nos collègues allemands s'y intéressent particulièrement, contrairement aux Anglais qui restent plus réservés. Restant un diagnostic d'exclusion, sans aucune ligne de conduite universelle, tant sur le plan diagnostique que thérapeutique, il nous paraît essentiel de faire le point sur cette entité.

[Sarcoma centres : a necessary tool in the management of patients and for research.] / Centre des sarcomes : un nouvel outil pour améliorer la prise en charge du patient et soutenir la recherche.

Sarcomas are rare diseases, the treatment of which requires an appropriate technical plateform and a broad spectrum of multidisciplinary specialists. Many are initially treated by unplanned excision, and then referred to specialized centres. Secondary treatments may lead to higher complication rates and local recurrence, with lower functional outcome, life quality and possibly overall survival. In order to improve the accessibility for referral to a specialist centre, the coordination of clinical and research activities, and the quality of the management of sarcomas in general, Lausanne University Hospital (CHUV) has opened a Sarcoma centre on October 1st 2016. The objective of the present paper is to illustrate the concept and provide useful clinical recommendations.

Les sarcomes sont des maladies rares, dont la prise en charge multidisciplinaire nécessite un plateau technique important. Ils font souvent l'objet d'une excision initiale accidentelle, nécessitant une reprise en milieu spécialisé, avec un risque majoré de complications et de récidive locale, un impact sur la fonction, voire la survie. La prise en charge des sarcomes est réservée aux centres de référence, où il est souvent difficile pour le praticien de trouver un interlocuteur à qui adresser un patient ou demander un avis. Pour les cliniciens et les chercheurs, il est souvent compliqué de coordonner les activités. Pour en améliorer la prise en charge globale, le CHUV a donc créé un centre des sarcomes, inauguré le 1er octobre 2016. Le présent article a pour but d'illustrer cette problématique et de rappeler quelques données cliniques utiles.

Multidisciplinary approach of lumbo-sacral chordoma: From oncological treatment to reconstructive surgery.

Lumbo-sacral chordoma is a rare, slow-growing tumor, arising from embryonic nothocordal remnants. Wide en bloc excision with clear margins remains mandatory to achieve satisfactory recurrence rates and disease-free survival. No chemotherapy has been demonstrated to be effective and radiotherapy is only marginally effective. Tyrosine kinase receptor inhibitors have showed encouraging results in locally advanced and metastatic chordoma. Reconstructive surgery may become very complex. Multidisciplinary approach in tertiary hospitals is always necessary.

MDCT arthrography of the hip: value of the adaptive statistical iterative reconstruction technique and potential for radiation dose reduction.

OBJECTIVE: The purpose of this article is to assess the effect of the adaptive statistical iterative reconstruction (ASIR) technique on image quality in hip MDCT arthrography and to evaluate its potential for reducing radiation dose. SUBJECTS AND METHODS: Thirty-seven patients examined with hip MDCT arthrography were prospectively randomized into three different protocols: one with a regular dose (volume CT dose index [CTDIvol], 38.4 mGy) and two with a reduced dose (CTDIvol, 24.6 or 15.4 mGy). Images were reconstructed using filtered back projection (FBP) and four increasing percentages of ASIR (30%, 50%, 70%, and 90%). Image noise and contrast-to-noise ratio (CNR) were measured. Two musculoskeletal radiologists independently evaluated several anatomic structures and image quality parameters using a 4-point scale. They also jointly assessed acetabular labrum tears and articular cartilage lesions. RESULTS: With decreasing radiation dose level, image noise statistically significantly increased (p=0.0009) and CNR statistically significantly decreased (p=0.001). We also found a statistically significant reduction in noise (p=0.0001) and increase in CNR (p≤0.003) with increasing percentage of ASIR; in addition, we noted statistically significant increases in image quality scores for the labrum and cartilage, subchondral bone, overall diagnostic quality (up to 50% ASIR), and subjective noise (p≤0.04), and statistically significant reductions for the trabecular bone and muscles (p≤0.03). Regardless of the radiation dose level, there were no statistically significant differences in the detection and characterization of labral tears (n=24; p=1) and cartilage lesions (n=40; p≥0.89) depending on the ASIR percentage. CONCLUSION: The use of up to 50% ASIR in hip MDCT arthrography helps to reduce radiation dose by approximately 35-60%, while maintaining diagnostic image quality comparable to that of a regular-dose protocol using FBP.

Multiple non-ossifying fibromas as a cause of pathological femoral fracture in Jaffe-Campanacci syndrome.

BACKGROUND: Jaffe-Campanacci is a rare syndrome characterised by the association of café-au-lait spots, axillary freckles, multiple non-ossifying fibromas of the long bones and jaw, as well as some features of type 1 neurofibromatosis. There are less than 30 reported cases, and a genetic profile has not yet been determined. Furthermore, it has not been clarified whether it is a subtype of type 1 neurofibromatosis or a separate syndrome. The risk of pathological fracture is over 50%, due to substantial cortical thinning of the weight-bearing bones. CASE PRESENTATION: A 17-year-old female patient, known for type 1 neurofibromatosis, presented with a low-energy distal femoral fracture due to disseminated large non-ossifying fibromas. Investigations revealed all of the distinctive signs of Jaffe-Campanacci syndrome. Both her distal femurs and proximal tibias exhibited multiple non-ossifying fibromas. The fracture was treated by open reduction and internal plate fixation. Some of the bony lesions were biopsied to confirm the diagnosis. The fracture healed eventless, as did the lesions biopsied or involved in the fracture. The other ones healed after curettage and bone grafting performed at the time of plate removal. CONCLUSION: Jaffe-Campanacci is a rare syndrome having unclear interactions with type 1 neurofibromatosis, which still needs to be characterised genetically. It is associated with a high risk of pathological fracture, due to the presence of multiple large non-ossifying fibromas of the long bones, with an expected normal healing time. Curettage and bone grafting promote healing of the lesions and should be considered to prevent pathological fracture. We agree with other authors that all patients with newly-diagnosed type 1 neurofibromatosis should undergo an osseous screening to detect disseminated non-ossifying fibromas, and evaluate the inherent risk of pathological fracture.

Comparisons of preoperative three-dimensional planning and surgical reconstruction in primary cementless total hip arthroplasty.

Reconstruction of important parameters such as femoral offset and torsion is inaccurate, when templating is based on plain x-rays. We evaluate intraoperative reproducibility of pre-operative CT-based 3D-templating in a consecutive series of 50 patients undergoing primary cementless THA through an anterior approach. Pre-operative planning was compared to a postoperative CT scan by image fusion. The implant size was correctly predicted in 100% of the stems, 94% of the cups and 88% of the heads (length). The difference between the planned and the postoperative leg length was 0.3 + 2.3 mm. Values for overall offset, femoral anteversion, cup inclination and anteversion were 1.4 mm ± 3.1, 0.6° ± 3.3°, -0.4° ± 5° and 6.9° ± 11.4°, respectively. This planning allows accurate implant size prediction. Stem position and cup inclination are accurately reproducible.

[Tumors of the musculoskeletal system: from the "lumps" to multidisciplinary care]. / Tumeurs de l'appareil locomoteur: de la simple "bosse" a la prise en charge multidisciplinaire.

Management of musculoskeletal tumours usually begins with the appearance of a lump or bump, or the onset of unspecific symptoms. A poor initial work-up, a faulty biopsy or an inadequate resection may have a severe impact on the prognosis, including re-interventions, amputation, local recurrence or systemic spread of the disease. The patient with a suspicious lesion should be referred to a "sarcoma centers" where a planned and well-performed diagnostic work-up will allow a precise diagnosis in terms of histology and staging. After a multidisciplinary discussion of the case, an accurate treatment plan is established. Such an approach allows an adequate patient management, often with a positive impact on the survival and functional outcome.

Lymphatic flow through (LyFT) ALT flap: an original solution to reconstruct soft tissue loss with lymphatic leakage or lower limb lymphedema.

INTRODUCTION: The lympho-venous shunt using the distal vein of ALT flap pedicle allowed at the same time the coverage of the inguinal defects and to perform lymphovenous shunt into a run-in vein of the descending branch of the lateral circumflex femoral pedicle, draining the lymph through the flap pedicle. Surgical technique, complications and final outcomes (both clinical and lymphoscintigraphic) are reported. METHODS: Five patients (45.8 y.o.[22-70]) with groin soft tissue loss with lymphatic leakage or lower limb lymphedema, benefited of the described technique. The ALT flap was used to cover the defect and, at the same time, we could perform a lymphovenous shunt between afferent lymphatics to the thigh and the descending branch of the lateral circumflex femoral pedicle, distal to the perforator nourishing the flap. Clinical and lymphoscintigraphic assessment of the limbs, cease of lymphorrhea or cellulitis/lymphangitis episodes, eventual downstaging of physiologic/physical therapy were recorded. LYMphatic Quality Of Life in leg (LYMQoLLeg) and patient satisfaction were evaluated. RESULTS: Average flap size was 88.8cm2 (range 84-126). The mean number of multi-lymphovenous anastomosis (MLVA) performed was 1.8 (range 1-3) per patient with 1-3 lymphatics shunted into each vein. Only one hemato-seroma requiring surgical revision. Mean improvement of perometer values was 48.2% (range 27.7-67.7) with an average follow-up of 13.6 months (range 12-17). Lymphoscintigraphy showed disappearing of the lymphatic leak and lymphedema with a high satisfaction of LYMQoL score. DISCUSSION: The combination of pedicle flap with lympho-venous bypass as lymphatic derivation concept, improving the chronic morbidity scenarios of lymphatic complications.

Prosthetic fitting associated with better survival at 5 years after above-knee amputation due to vascular insufficiency.

BACKGROUND: Individuals requiring non-traumatic Gritti-Stokes amputation or mid-thigh amputation usually have multiple comorbidities that place them at high risk of mortality. OBJECTIVE: To determine survival rate 5 years after Gritti-Stokes and mid-thigh amputation in individuals with vascular insufficiency and to identify the predictors of survival. METHODS: We conducted a retrospective observational study including all individuals with vascular insufficiency who underwent amputation from September 2007 to December 2015 in our University Hospital. The indication for amputation was limb necrosis in 86% of cases, infection in 10%, and complications with the stump (discomfort, neuroma or scar dehiscence) in 4%. Medical records were analysed to determine factors and comorbidities. The date of death was retrieved from the national death registry at a minimum of 5 years after amputation. Cox proportional-hazard regression was used to estimate associations between factors and post-amputation survival with hazard ratios (HR) and 95% confidence intervals (CIs). RESULTS: We included 126 people with vascular insufficiency (83 men), mean age was 70 years [20; 97]; eighty-nine participants (71%) died during the study period. Survival rate was 68% at 1 year, 48% at 3 years and 37% at 5 years. Survival was associated with prosthetic fitting (HR 0.306 [95% CI 0.180; 0.521], p<0.001) and length of stay (HR 0.992 [95% CI 0.987; 0.997], p = 0.003). Conversely, limb necrosis was associated with a lower survival rate (HR 3.801 [95% CI 1.615; 8.949], p = 0.002). In a secondary multivariable analysis, Gritti-Stokes amputation was the only factor positively associated with prosthetic fitting (odds ratio 7.407 [95% CI 2.439; 22.489], p<0.001). CONCLUSIONS: The survival rate at 5 years after Gritti-Stokes and mid-thigh amputation in people with vascular insufficiency was 37%. Prosthetic fitting was independently associated with better survival, and Gritti-Stokes amputation was the only factor positively related to prosthetic fitting.

Influence of smoking on the healing of conservatively treated displaced midshaft clavicle fractures.

Aims: Tobacco, in addition to being one of the greatest public health threats facing our world, is believed to have deleterious effects on bone metabolism and especially on bone healing. It has been described in the literature that patients who smoke are approximately twice as likely to develop a nonunion following a non-specific bone fracture. For clavicle fractures, this risk is unclear, as is the impact that such a complication might have on the initial management of these fractures. Methods: A systematic review and meta-analysis were performed for conservatively treated displaced midshaft clavicle fractures. Embase, PubMed, and Cochrane Central Register of Controlled Trials (via Cochrane Library) were searched from inception to 12 May 2022, with supplementary searches in Open Grey, ClinicalTrials.gov, ProQuest Dissertations & Theses, and Google Scholar. The searches were performed without limits for publication date or languages. Results: The meta-analysis included eight studies, 2,285 observations, and 304 events (nonunion). The random effects model predicted a pooled risk ratio (RR) of 3.68 (95% confidence interval 1.87 to 7.23), which can be considered significant (p = 0.003). It indicates that smoking more than triples the risk of nonunion when a fracture is treated conservatively. Conclusion: Smoking confers a RR of 3.68 for developing a nonunion in patients with a displaced middle third clavicle fracture treated conservatively. We know that most patients with pseudarthrosis will have pain and a poor functional outcome. Therefore, patients should be informed of the significantly higher risks of nonunion and offered smoking cessation efforts and counselling. Moreover, surgery should be considered for any patient who smokes with this type of fracture.

Induction of mitochondrial recycling reverts age-associated decline of the hematopoietic and immune systems.

Aging compromises hematopoietic and immune system functions, making older adults especially susceptible to hematopoietic failure, infections and tumor development, and thus representing an important medical target for a broad range of diseases. During aging, hematopoietic stem cells (HSCs) lose their blood reconstitution capability and commit preferentially toward the myeloid lineage (myeloid bias)1,2. These processes are accompanied by an aberrant accumulation of mitochondria in HSCs3. The administration of the mitochondrial modulator urolithin A corrects mitochondrial function in HSCs and completely restores the blood reconstitution capability of 'old' HSCs. Moreover, urolithin A-supplemented food restores lymphoid compartments, boosts HSC function and improves the immune response against viral infection in old mice. Altogether our results demonstrate that boosting mitochondrial recycling reverts the aging phenotype in the hematopoietic and immune systems.

[Total hip arthroplasty through anterior "minimal invasive" approach]. / Prothèse totale de la hanche par voie antérieure "mini-invasive".

Total hip replacement has seen a tremendous development and has become one of the most successful surgical interventions in orthopaedics. While during the first decades of development of total hip arthroplasty the fixation of the implant into the bone was the main concern, the focus has shifted towards surgical technique and soft tissue handling. In order to avoid permanent soft tissue damage, muscular dysfunction and concerns in regards to cosmetics, minimal invasive and anatomic approaches have been developed. We here provide a short overview on various methods of total hip replacements and we describe our technique through a minimal invasive direct anterior approach. While muscle and nerve damage is minimal, this technique allows for a rapid rehabilitation and is associated with an excellent functional outcome and a minimal risk for dislocation.