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Background: Patients with systemic lupus erythematosus (SLE) with inadequate responses to standard therapies have unmet therapeutic needs. The immunomodulatory, proangiogenic, and antifibrotic properties of mesenchymal stromal cells support their use in treating patients with SLE. We aimed to assess the safety of a single intravenous infusion of allogeneic umbilical cord-derived mesenchymal stromal cells in patients with severe SLE., Methods: This prospective, single-centre, open-label, dose-escalation, Bayesian phase 1 study was done at the Saint-Louis University Hospital (Paris, France). Eligible patients were aged 18-70 years, were diagnosed with SLE according to American College of Rheumatology criteria with positive antinuclear antibodies, had a baseline Safety of Estrogens in Lupus Erythematosus National Assessment-SLE Disease Activity Index (SELENA-SLEDAI) score of 6 or more, and had disease that was refractory to first and second line SLE therapies. Patients were to receive a single intravenous infusion of 1 × 10 6 , 2 × 10 6 , or 4 × 10 6 umbilical cord-derived mesenchymal stromal cells per kg (manufactured from a single umbilical cord) in cohorts of five patients per dose, starting at 2 × 10 6 cells per kg. The primary endpoint was the rate of treatment-related severe adverse events (grade ≥3) in the first 10 days after infusion of umbilical cord-derived mesenchymal stromal cells. People with lived experience were involved in study design, patient enrolment, and dissemination of the study findings. This study is registered with ClinicalTrials.gov, NCT03562065, and the EU Clinical Trials Register, EudraCT2017-001400-29., Findings: From May 14, 2019, to March 6, 2023, 29 patients were screened for eligibility, eight of whom were enrolled in the study. Enrolment was terminated early after inclusion of eight patients and no patients received the 1 × 10 6 dose of umbilical cord-derived mesenchymal stromal cells. Seven (88%) of eight participants were cisgender women and one (13%) was a cisgender man. The median age was 35 years (range 26-57) and the median SLE disease duration was 12 years (5-19). All patients received at least 2 × 10 6 cells per kg (range 2 × 10 6 to 4 × 10 6 ). No severe adverse events and three infusion-related adverse events (two grade 1 and one grade 2) occurred in two patients in the first 10 days after infusion. After 12·4 months (range 12-13) of follow-up, no treatment-related severe adverse events and three non-treatment-related severe adverse events occurred in one patient after relapse., Interpretation: Our results suggest that a single infusion of 2 × 10 6 cells per kg or 4 × 10 6 cells per kg of allogeneic umbilical cord-derived mesenchymal stromal cells was safe in patients with severe SLE. Placebo-controlled trials are needed to confirm clinical efficacy and the role of B-cell modifications in clinical benefit., Funding: Fondation du Rein, Alliance Maladies Rares AFM-Téléthon, Direction de la Recherche Clinique et de l'Innovation AP-HP, and ANR eCellFrance., Competing Interests: Declaration of interests MWL is co-founder and part-time chief scientific officer of INmune Bio, a biotech company that holds intellectual property surrounding an alternative umbilical cord-derived mesenchymal stromal cell product, which was not used in this trial. BW is employed part-time by INmune Bio and holds intellectual property surrounding an alternative umbilical cord-derived mesenchymal stromal cell product through University College London (London, UK). All other authors declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.)

We describe and analyze a "care as usual" strategy of a French Comprehensive Cancer Center during the COVID-19 pandemic to manage surgical patients with gynecological cancer. We conducted a retrospective analysis evaluating the surgical activity in our gynecologic oncology department between January 21 and May 12, 2020. We compared the surgical activity and surgical and oncologic outcomes during the pre-lockdown period and the pandemic period. The main objective was to evaluate the impact of the COVID-19 pandemic on surgical activity. The secondary objectives were to analyze the surgical and the oncologic outcomes. We compared the surgical activity during the 8 weeks after the national lockdown (85 procedures) to the surgical activity in the 8 weeks preceding the lockdown (127 procedures). We observed a 33% decrease in activity between the two periods. The clinical and epidemiologic characteristics were similar between the two periods. There were no differences between the surgical approaches ( p = 0.592), the surgical complexity ( p = 0.323), the length of stay ( p = 0.85), and even for the complex procedure ( p = 0.96) and the perioperative ( p = 0.791) and postoperative complication rates ( p = 0.102). We observed a significant decrease in the time of return to intended oncological treatment (RIOT) during the lockdown period with an average of 31.9 days compared to 46.9 days in the pre-lockdown period ( p = 0.003). During the COVID-19 pandemic, "care as usual" represents an acceptable strategy without impairing the oncologic outcome in a Comprehensive Cancer Center with a patient-centered clinical pathway for gynecologic oncologic surgical patients., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Blache, El Hajj, Jauffret, Houvenaeghel, Sabiani, Barrou, Masquin, Le Saout, Mokart, Faucher and Lambaudie.)

Renal cell carcinoma is the third type of urologic cancer and has a poor prognosis with 30% of metastatic patients at diagnosis. The antiangiogenics and targeted immunotherapies led to treatment remodeling emphasizing the role of the tumour microenvironment. However, long-term responses are rare with a high rate of resistance. New strategies are emerging to improve the efficacy and the emerging drugs are under evaluation in ongoing trials. With the different treatment options, there is an urgent need to identify biomarkers in order to predict the efficacy of drugs and to better stratify patients. Owing to the limitations of programmed death-ligand 1 (PD-L1), the most studied immunohistochemistry biomarkers, and of the tumor mutational burden, the identification of more reliable markers is an unmet need. New technologies could help in this purpose.

Background: Bovine paratuberculosis is a contagious disease, caused by Mycobacterium avium subsp. paratuberculosis (MAP), with adverse effects on animal welfare and serious economic consequences. Published results on host genetic resistance to MAP are inconsistent, mainly because of difficulties in characterizing the infection status of cows. The objectives of this study were to identify quantitative trait loci (QTL) for resistance to MAP in Holstein and Normande cows with an accurately defined status for MAP., Results: From MAP-infected herds, cows without clinical signs of disease were subjected to at least four repeated serum ELISA and fecal PCR tests over time to determine both infected and non-infected statuses. Clinical cases were confirmed using PCR. Only cows that had concordant results for all tests were included in further analyses. Positive and control cows were matched within herd according to their birth date to ensure a same level of exposure to MAP. Cows with accurate phenotypes, i.e. unaffected (control) or affected (clinical or non-clinical cases), were genotyped with the Illumina BovineSNP50 BeadChip. Genotypes were imputed to whole-genome sequences using the 1000 Bull Genomes reference population (run6). A genome-wide association study (GWAS) of MAP status of 1644 Holstein and 649 Normande cows, using either two (controls versus cases) or three classes of phenotype (controls, non-clinical and clinical cases), revealed three regions, on Bos taurus (BTA) chromosomes 12, 13, and 23, presenting significant effects in Holstein cows, while only one of those was identified in Normande cows (BTA23). The most significant effect was found on BTA13, in a short 8.5-kb region. Conditional analyses revealed that only one causal variant may be responsible for the effects observed on each chromosome with the ABCC4 (BTA12), CBFA2T2 (BTA13), and IER3 (BTA23) genes as good functional candidates., Conclusions: A sequence-based GWAS on cows for which resistance to MAP was accurately defined, was able to identify candidate variants located in genes that were functionally related to resistance to MAP; these explained up to 28% of the genetic variance of the trait. These results are very encouraging for efforts towards implementation of a breeding strategy aimed at improving resistance to paratuberculosis in Holstein cows.

Renal cell carcinoma encompass distinct diseases with different pathologic features and distinct molecular pathways. Immune checkpoint inhibitors targeting the programmed death receptor ligand 1 (PD-L1)/programmed death receptor 1 (PD-1) pathway alone or in combination have greatly changed clinical management of metastatic renal cell carcinoma, now competing with antiangiogenic drugs in monotherapy for first-line treatment. However, long-term response rates are low, and biomarkers are needed to predict treatment response. Quantification of PD-L1 expression by immunohistochemistry was developed as a promising biomarker in clinical trials, but with many limitations (different antibodies, tumour heterogeneity, specimens, and different thresholds of positivity). Other biomarkers, including tumour mutational burden and molecular signatures, are also developed and discussed in this review.

The delto-pectoral portion of V. Cephalica was dissected 189 times during surgery and 74 times on cadavers. In 8 out of 10 cases the disposition was of the classical type and the diameter was wide enough to allow catheterization with a 3,4 mm catheter. In 2 out of 10 cases the vein was absent or toothin. This anomaly was most often unilateral with a normal disposition on the other side in 2/3 of cases.

Between 1968 and 1978 the authors have performed 35 Chiari's pelvic osteotomies in adults ; 25 cases reviewed after a more than one year follow-up. The operation is a relatively major one, and complications are not uncommon. Carried out in adults for sequelae of hip dislocation in childhood, with or without arthrosis, it relieves pain remarkably well and improves walking distances but has little effect on hip mobility. Pelvic osteotomy may also give satisfactory results in some advanced forms of arthrosis, provided hip mobility remains sufficient (70 degrees flexion or more).

The authors describe a case of accessory soleus muscle they have seen. It caused the development of a painful swelling on the medial side of the lower third of the leg with progressive equinovarus deformity of the foot. The upper attachment of the accessory muscle was in front of the normal muscle and distally was attached to the inner aspect of the calcaneus. The case was treated by transferring the accessory tendon to the tendo Achillis. 7 other cases reported in the literature are discussed in detail.

The depicted procedure minimizes the hazards of aggressive manipulations, and excludes any possibility of so-called "warm ischaemia". The kidneys are flushed out in situ with cool pulsatile perfusion through an aortic cannula. Kidneys, aorta and inferior vena cava are then removed en-bloc without interrupting the perfusion, and preserved in Collins' solution at 4 degrees C. After a 6 to 19 hour storage time, one of the kidneys is transplanted on another dog, while the second one is submitted to histological examination. Nine transplantations were carried out, followed in 7 cases with a most satisfactory diuresis resuming, and with urinary ionic levels, as well as daily urea output, normalization within 48 hours. Histologic examination showed an unaffected glomerular apparatus, but some mild tubular lesions.

Eighteen children aged between zero and seven months have been treated by a method using Scott's harness to maintain the hips in hyperflexion. Twenty one hips were subluxated. In two cases, the method was inadequate and the hips had to be treated by progressive traction. In one case osteochondritis developed. In other cases the treatment was successful. The technical details of this technique are given.

After a brief description of the classification of fractures of lower and of humerus in children, methods are described for the application of different orthopedic and surgical procedures developed over the years. Treatment of supracondylar fractures remains very conventional (Judet's method), experience lacking in the use of contention in strong flexion for these fractures. Emphasis is placed on two points: the need for perfect reduction under all circumstances, since growth will have little impact on correction of residual faults, and the quality and reading of review radiographic images to avoid major mistakes in reduction.

Molecules recognised by the monoclonal antibodies Leu 1 - OKT 1 - Mid 5 (CD5 molecules) were originally shown on human T cells and are equivalent to Lyt-1 molecules in the mouse. These surface molecules are detectable on some human B cells, but are weakly expressed. We have therefore tested the effects of the tumour-promoter, phorbol myristic acetate (PMA) on expression of these molecules on B cells. Sheep red blood cell rosette-depleted lymphoid organ or blood cells from 8 controls and 10 rheumatoid arthritis (RA) patients were examined fresh and cultured with PMA for 48 hours and the cells stained with Leu 1 or Mid 5 by indirect immunofluorescence. Cells were analysed by UV microscopy or flow cytometry. More RA blood B cells were positive for Leu 1 than normals before culture. Following incubation with PMA, the percentage of positive cells increased in all cell populations (1-49% in RA patients and 5-26% in controls). There was no difference in the expression of Leu 1 on Kappa--or lambda--positive cells before and after culture in PMA. Leu 1 positive cells were under-represented in Epstein-Barr virus-driven cell lines.

This study is based on 48 cases of paralysis of the femoral or sciatic nerves complicating hip surgery, mostly total hip arthroplasty. Most of these lesions arose during difficult operations. The diagnosis was clinical and electromyographic, but it was not always made from the outset. The prognosis was better for the cases of paralysis of the femoral or peroneal nerves than for the cases of generalised sciatic paralysis in which the recovery, slower as it was, was only satisfactory in 15 cases out of 26. The treatment was primarily medical and required reeducation. A surgical treatment was considered when the electrical exploration showed no improvement after 6 weeks.

Anatomopathologic study of fractures of lower end of femur in 87 patients demonstrated the frequency of compound lesions in adults, epiphyseal detachment being the most common finding in children. Therapy used resulted in consolidation within a mean period of 4 months. Anatomic results were satisfactory in 87% of cases, 2 of 3 patients recuperating a knee compatible with a normal active life. Complications were rare. The current therapeutic attitude in adults is resolutely surgical, particularly in case of an intra-articular fracture line. In children, treatment remains orthopedic, except for epiphyseal detachments when minimal fixation allows perfect anatomic reduction and avoids secondary growth disorders.

Three cases of Kirner's deformity in siblings are reported. Kirner's deformity consists in a palmar bending of the terminal phalanx of the 5th finger. The deformity is usually bilateral; the condition is congenital but the deformity is recognized in later childhood and has to be classified as osteochondrodysplasia.

The authors report a case of transverse fracture of the second part of the sacrum with neurological signs. Whilst such a lesion would appear very rare, associated involvement of the sacral roots is very common. Recovery of the neurological deficit syndrome is hazardous. A review of the literature fails to provide the basis for a defined programme of management.

The authors have studied fifty-nine patients in whom a total hip prosthesis had been removed for various reasons. In forty-five cases the greater trochanter was inserted into the acetabulum and the position maintained by external fixation. In fourteen cases the prosthesis was simply removed and traction applied for several weeks. Forty-one patients were available for follow up study. The results were identical as regards pain. The residual stability was better in cases of trochantero-pelvic penetration but residual mobility was better after simple removal. The latter procedure should be performed in cases of acetabular destruction, in advanced age or in cases where the insertion of a new prosthesis can be anticipated later. Healing of draining sinuses is related to the extent of tissue excision and the removal of all cement.

A literature review allowed classification of seven cases of Sprengel's deformity based on that described by Rigault et al. This classification into three types as a function of degree of elevation defines each case within the context of associated malformations, and appropriate therapy. Surgery is indicated, employing Woodward's type of operation, for patients with functional and esthetic deficits, particularly in Rigault's type II deformity.

The administration of high doses of sodium penthiobarbital in intensive resuscitation sometimes results in venous and cutaneous lesions in the form of phlebitis associated with major necrosis. Histological analysis demonstrates that these are essentially intimal lesions and the authors suggest various hypotheses to explain the origin of such clinical signs.

Capitellum fractures are exceedingly rare. The five observations reported herein show that the clinical aspect is often discrete, necessitating a detailed radiographic study, especially with the elbow seen in profile. As the spontaneous evolution of this type of fracture presents a poor prognosis, surgical reduction of the fracture is immediately indicated and systematic osteosynthesis guarantees a satisfactory functional result.

The subperiosteal type of chondroma of hand is reputedly rare. Four such cases are reported two in adolescents, one in a child and one in an adult. The chondroma being localized to the phalanges, its most frequent development site. In one patient multiple chondromata were present. The relevant literature and typical characters of these subperiosteal chondromata are reviewed. Radiological images show clearly outlined tumors due to peripheral calcification. Treatment is surgical by block excision through healthy bone, this avoiding recurrence.

A young 15 year old girl presented with a voluminous desmoid tumor of the calf. Three attempts to excise the tumor were only partially successful because of the risk of vascular and nerve damage, and excision was incomplete on each occasion. These tactics appeared to be justified, however, since the tumor had little functional effects and appeared to become stable at the last examination. The tactical surgical problems are discussed, the benign nature of the tumor imposing conservative surgery which is often incomplete, although in certain cases the operation can be combined with a recovery arterial shunt. The various etiopathogenic elements of these tumors are described.

230 shelf operations were carried out between 1961 and 1985 for painful acetabular dysplasia or subluxation of the hip. 208 patients have been followed up for more than one year, with 79 for between 10 and 24 years. Substantial relief of pain was obtained in 88%. The benefits of operation usually continue for many years. Factors which may lead to a poor result are advanced age, dislocation of the hip and the presence of marked osteoarthritic changes. The results have been compared with those obtained for Chiari's osteotomy, and the relative indications for the two procedures are discussed.

Three cases of granulomatous nephropathy are reported. In two patients this was definitely related to a true renal sarcoidosis, while the third case raised the problem of the significance of an "isolated sarcoidosis nodule". The authors discuss the frequency, clinical symptoms, and pathological appearances of these renal lesions which reveal the presence of sarcoidosis, as well as the relationship between renal insufficiency and the parenchymatous lesions observed, and therapy.

The proportion of T Lymphocytes with receptors for interleukin 2 is increased in the blood, the synovial fluid and, in particular, the synovial membrane in rheumatoid arthritis. However, there is no correlation between the percentage in blood and the percentage in the joints. The helper T lymphocytes are proportionately more activated than the suppressor T lymphocytes.

The radiographic results of treatment of unstable thoracolumbar spinal injuries by Harrington rods are reviewed. The loss of initial correction of kyphosis is 8 degrees on average. Correlation between good anatomical reduction and lapse of time before operation, level of instrumentation and solid spinal fusion exists. But, in burst fracture with deficient anterior pilar, the incidence of loss of reduction is important. The influence of Harrington rods on the spine is significant.

Two patients presented with osteoid osteomas of the distal phalanx of a toe. A review of documented cases provided data on the characteristic features of these lesions. Diagnosis and treatment, in all cases, were ensured by excision biopsy, enabling a permanent cure to be obtained with a minimum of mutilation.

Latarjet's operations as single therapy was performed in 52 patients admitted since 1976 with recurrent antero-internal dislocation of shoulder. There were no recurrences but three patients (6%) complained of residual instability. Effectiveness of results depends on use of a perfect technique : the bony ridge playing both an active and passive role should be level with the antero-internal border of the glenoid.

89 cases of sero-negative rheumatoid arthritis (RA) were compared to 127 cases of sero-positive RA. Anti-perinuclear and anti-keratin antibodies were detected less frequently in the first group (51 vs 67% and 28 vs 33%, respectively), while the inverse was found for anti-nuclear antibodies (28 vs 24%). "Light" rheumatoid factors (RF)--IgG, IgM, IgE, IgA and IgD--were detected in 23.6, 21.3, 17.5, 11.3 and 0 per cent of cases of sero-negative R.A. The evolutive state of these cases was less severe. RF agglutinins were detected in 5 out of 12 samples of synovial fluid tested in cases of sero-negative RA.