Risk factors for kyphosis recurrence after implant removal in percutaneous osteosynthesis for post-traumatic thoracolumbar fracture.

PURPOSE: Short-segment minimally invasive percutaneous spinal osteosynthesis has now become one of the treatments of choice to treat thoracolumbar fractures. The question of implant removal once the fracture has healed is still a matter of debate since this procedure can be associated with loss of sagittal correction. Therefore, we analyzed risk factors for kyphosis recurrence after spinal implants removal in patients treated with short-segment minimally invasive percutaneous spinal instrumentation for a thoracolumbar fracture. METHODS: A total of 32 patients who underwent implant removal in percutaneous osteosynthesis for post-traumatic thoracolumbar fracture were enrolled in our study. Patient's medical record, operative report and imaging examinations carried out at the trauma and during the follow-up were analyzed. RESULTS: Every patient experienced fracture union. Vertebral kyphotic angle (VKA) and Cobb angle (CA) improved significantly after stabilization surgery. VKA, CA, upper disk kyphotic angle (UDKA) and lower disk kyphotic angle (LDKA) significantly gradually decreased during follow-up. Traumatic disk injury (p: 0.001), younger age (p: 0.01), canal compromise (p: 0.04) and importance of surgical correction (p < 0.001) were significantly associated with kyphosis recurrence after implant removal. Anterior body augmentation did not affect loss of correction (CA and VKA) during the follow-up period (p: 0.57). CONCLUSION: Despite correction of the fracture after stabilization, we observed a progressive loss of correction over time appearing even before implant removal. Particular attention should be paid to post-traumatic disk damage or canal invasion, to young patients and to surgical overcorrection of the traumatic kyphosis.

Mono-segmental percutaneous screw fixation in the management of AoSpine thoracolumbar type B fracture in patients with ankylosing spondylitis: A new treatment.

PURPOSE: To assess the viability and effectiveness of mono-segmental percutaneous screw fixation in the treatment of unstable type B thoracolumbar fracture due to ankylosing spondylitis. METHODS: We report here all 40 patients treated by mono-segmental screw fixation in this indication, between January 2018 and January 2022, with follow-up at 3 and 9 months. Study variables comprised operating time, length of stay, fusion, stabilization quality, and peri-operative morbidity and mortality. RESULTS: One patient showed early displacement of rods caused by technical error. None of the others showed secondary displacement of rods or screws. Mean age was 73 years (range 18-93), mean hospital stay 4.8 days (range 2-15), mean operative time 52minutes (range 26-95minutes) and mean estimated blood loss 40ml. There were 2 deaths caused by intensive care unit complications. All patients except those in intensive care were verticalized within 24hours after surgery. Parker score was unchanged for each patient before and after surgery and during follow-up. CONCLUSION: Mono-segmental percutaneous screw fixation in the treatment of unstable type B thoracolumbar fracture due to ankylosing spondylitis was safe and effective. This study showed that this surgery reduced length of hospital stay, operative time, blood loss and complications compared to open or extended percutaneous surgery, and allowed fast rehabilitation in this vulnerable population.

Epilepsy surgery for drug-resistant temporal lobe epilepsy in over-50 year-olds: Seizure outcome, surgical complications and neuropsychological outcome.

OBJECTIVE: Surgery is an effective treatment for drug-resistant temporal-lobe epilepsy (TLE), but is still underutilized for older patients because of a perceived higher rate of perioperative complications, cognitive decline and worse seizure outcome. METHODS: We retrospectively screened all patients operated on in our institution for drug-resistant TLE between 2007 and 2019. Data of patients aged ≥50 years versus <50 years at surgery were compared. The primary endpoint was freedom from disabling seizure (Engel I) at 2 years postoperatively. RESULTS: In patients aged ≥50 years (n=19), mean age at surgery was 54.9 years and mean disease duration was 36.6 years. At 2 years postoperatively, rates of Engel I seizure outcome were not significantly different between the two groups (73.9% in the <50 years group versus 94.4% in the ≥50 years group). Although surgical complications were significantly (47.4%) in the older patients, neurological deficit was permanent in only 5.3% of cases. At 1 year postoperatively, neuropsychological outcome did not significantly differ between the two groups. CONCLUSIONS: Patients aged ≥50 years had an excellent seizure outcome at 2 years postoperatively. Early postoperative complications were more frequent in patients aged ≥50 years but were mostly transient. Cognitive outcome was similar to that in younger patients. These findings strongly suggest that age ≥50 years should not be an exclusion criterion for resective epilepsy surgery in patients with drug-resistant TLE.

Promising clinical performance of pretargeted immuno-PET with anti-CEA bispecific antibody and gallium-68-labelled IMP-288 peptide for imaging colorectal cancer metastases: a pilot study.

INTRODUCTION: This pilot study evaluated the imaging performance of pretargeted immunological positron emission tomography (immuno-PET) using an anti-carcinoembryonic antigen (CEA) recombinant bispecific monoclonal antibody (BsMAb), TF2 and the [68Ga]Ga-labelled HSG peptide, IMP288, in patients with metastatic colorectal carcinoma (CRC). PATIENTS AND METHODS: Patients requiring diagnostic workup of CRC metastases or in case of elevated CEA for surveillance were prospectively studied. They had to present with elevated CEA serum titre or positive CEA tumour staining by immunohistochemistry of a previous biopsy or surgical specimen. All patients underwent endoscopic ultrasound (EUS), chest-abdominal-pelvic computed tomography (CT), abdominal magnetic resonance imaging (MRI) and positron emission tomography using [18F]fluorodeoxyglucose (FDG-PET). For immuno-PET, patients received intravenously 120 nmol of TF2 followed 30 h later by 150 MBq of [68Ga]Ga-labelled IMP288, both I.V. The gold standard was histology and imaging after 6-month follow-up. RESULTS: Eleven patients were included. No adverse effects were reported after BsMAb and peptide injections. In a per-patient analysis, immuno-PET was positive in 9/11 patients. On a per-lesion analysis, 12 of 14 lesions were positive with immuno-PET. Median SUVmax, MTV and TLG were 7.65 [3.98-13.94, SD 3.37], 8.63 cm3 [1.98-46.64; SD 14.83] and 37.90 cm3 [8.07-127.5; SD 43.47] respectively for immuno-PET lesions. Based on a per-lesion analysis, the sensitivity, specificity, positive-predictive value and negative-predictive value were, respectively, 82%, 25%, 82% and 25% for the combination of EUS/CT/MRI; 76%, 67%, 87% and 33% for FDG-PET; and 88%, 100%, 100% and 67% for immuno-PET. Immuno-PET had an impact on management in 2 patients. CONCLUSION: This pilot study showed that pretargeted immuno-PET using anti-CEA/anti-IMP288 BsMAb and a [68Ga]Ga-labelled hapten was safe and feasible, with promising diagnostic performance. TRIAL REGISTRATION: ClinicalTrials.gov NCT02587247 Registered 27 October 2015.

Evolution of serum Anti-Müllerian Hormone (AMH) level in young women treated with chemotherapy for breast cancer according to basal AMH level.

OBJECTIVE: Serum AMH level has been shown to decrease in women treated for breast cancer in several studies. However, whether basal AMH status affects AMH dynamics during chemotherapy remains to be clarified. The objective of this study was to compare serum AMH dynamics in young women with either low, normal or high basal serum AMH level at diagnosis, during and after treatment with chemotherapy for breast cancer. STUDY DESIGN: In this secondary analysis of a prospective cohort study, serum AMH was measured during and after chemotherapy in 239 women of reproductive age diagnosed with breast cancer and treated with chemotherapy. The association between AMH dynamics throughout chemotherapy and during follow-up and basal AMH status, i.e. low AMH (<1 µg/l, <7 pmol/l), normal AMH (1-4.9 µg/l, 7-36 pmol/l) and high AMH (≥5 µg/l, >36 pmol/l), was evaluated. Menses occurrence was also recorded. RESULTS: A total of 21 women had low, 154 had normal and 64 had high basal AMH level. Serum AMH rapidly decreased during chemotherapy in all groups, and its variation during chemotherapy and follow-up was not significantly different between the 3 groups. CONCLUSION: No association was found between AMH variation during chemotherapy and follow-up, and basal AMH level at diagnosis. However, women with high basal AMH levels have significantly higher AMH levels throughout chemotherapy and follow-up than women with normal or low basal AMH levels at diagnosis.

Angiogenic factors sFlt-1 and PlGF in preeclampsia: Prediction of risk and prognosis in a high-risk obstetric population.

OBJECTIVES: Despite its simple definition, preeclampsia can have variable and atypical clinical presentations, an unpredictable course, and potential adverse maternal and fetal outcomes. No single test currently predicts risk or prognosis adequately. Scientific advances suggest that an angiogenic imbalance is involved in its pathophysiology. The objective of this study was to investigate the use of sFlt-1, PlGF, and their ratio in predicting preeclampsia. MATERIALS AND METHODS: In a single-center prospective observational study, we measured the angiogenic markers sFlt-1 and PlGF and calculated the sFlt-1/PlGF ratio in patients at risk of preeclampsia at 20 to 37 weeks of gestation. The main outcomes were the occurrence of preeclampsia and the interval before its onset. RESULTS: Of the 67 at risk patients included, 8 (12%) developed preeclampsia. For a sFlt-1/PlGF ratio ≥85, the specificity was 93%. The ratio was significantly higher (ratio=104±30) in women with an onset time less than 5 weeks than in those with later preeclampsia (ratio=10±2), P<0.001. CONCLUSION: In a high-risk population, angiogenic markers appear to be an interesting aid in predicting the onset of preeclampsia with high specificity and in estimating time to onset. However, due to small number of cases of PE, more studies are needed before recommendations to use these markers in daily practice.

Prospective evaluation of serum anti-Müllerian hormone dynamics in 250 women of reproductive age treated with chemotherapy for breast cancer.

AIM: Women of reproductive age with breast cancer generally receive gonadotoxic chemotherapy. Fertility issues are of great concern for them. However, little is known on ovarian damage during chemotherapy and its evolution during long-term follow-up. The aim of this study was to provide a detailed description of serum anti-Müllerian hormone (AMH) evolution during chemotherapy and 24-month follow-up. METHODS: This prospective cohort study was conducted in 250 patients, aged 18-39 years, diagnosed with breast cancer and treated with adjuvant/neoadjuvant chemotherapy. Each patient underwent blood AMH measurement at each chemotherapy cycle, and at 6, 12 and 24 months after chemotherapy. Menses occurrence was also recorded. RESULTS: Mean basal AMH level was 4.19 ± 4.84 ng/mL, and was negatively correlated with age. Serum AMH level rapidly decreased in all patients after each chemotherapy cycle to undetectable levels in most of them, and slowly increased in 45% of the patients during the 24-month follow-up. AMH decrease was significantly associated with age and basal AMH level, but not with cyclophosphamide dose and tamoxifen use. The prevalence of chemotherapy-related amenorrhoea was 92.4% at the end of chemotherapy; women with amenorrhoea being significantly older and having lower basal AMH than women who resumed menses. CONCLUSIONS: Our study confirms rapid and deep ovarian reserve alteration in young women receiving chemotherapy for breast cancer, and shows moderate AMH recovery in some patients. Although AMH cannot alone predict fertility potential, these new data emphasise the need for post-treatment ovarian insufficiency follow-up, strongly support the use of fertility preservation strategies and may provide new tools for improved counselling.

Identification of a novel HLA allele, HLA-B*15:416, in a bone marrow hematopoietic stem cell donor.

The novel HLA-B*15:416 allele differs from HLA-B*15:01:01:01 by a single nucleotide substitution at codon 114.

Anti-müllerian hormone levels and evolution in women of reproductive age with breast cancer treated with chemotherapy.

BACKGROUND: Long-term consequences of cancer treatments in young women, and especially fertility issues, are gaining attention as survival rates increase. Breast cancer is the most frequent malignancy in women of reproductive age. AIM: The purpose of this review is to describe serum anti-müllerian hormone (AMH) level at diagnosis and its evolution during and after chemotherapy in women of reproductive age treated for breast cancer. Second, the impact of taxanes on AMH, the association between AMH and amenorrhea, and the comparison of AMH with other hormonal markers of ovarian reserve were studied. METHODS: A systematic PubMed search was conducted on all articles, published up to April 2016 and related to AMH in women suffering from breast cancer using the following key words: AMH, müllerian-inhibiting substance, ovarian reserve, ovarian function, breast cancer, gonadotoxicity, ovarian toxicity, amenorrhea, chemotherapy, and menopause. RESULTS: AMH levels rapidly fall down to undetectable levels in most women during chemotherapy and generally persist at very low levels in most women after the treatment. Taxanes seem to impact negatively ovarian function, but data on ovarian reserve are scarce. AMH is a predictor of the occurrence of chemotherapy-related amenorrhea and is the most relevant hormonal marker of ovarian reserve. CONCLUSION: Serum AMH is a relevant tool for ovarian reserve assessment and follow-up during treatment in premenopausal women with breast cancer. Further large prospective studies are necessary to determine its predictive interest for post-treatment residual fertility, and eventually use it in fertility preservation counseling before treatment initiation.

Risk factors and outcome of graft failure after HLA matched and mismatched unrelated donor hematopoietic stem cell transplantation: a study on behalf of SFGM-TC and SFHI.

Graft failure remains a severe complication of hematopoietic stem cell transplantation (HSCT). Several risk factors have already been published. In this study, we re-evaluated them in a large cohort who had the benefit of the recent experience in HSCT (2006-2012). Data from 4684 unrelated donor HSCT from 2006 to 2012 were retrospectively collected from centers belonging to the French Society for Stem Cell Transplantation. Among the 2716 patients for whom HLA typing was available, 103 did not engraft leading to a low rate of no engraftment at 3.8%. In univariate analysis, only type of disease and status of disease at transplant for malignant diseases remained significant risk factors (P=0.04 and P<0.0001, respectively). In multivariate analysis, only status of disease was a significant risk factor (P<0.0001). Among the 61 patients who did not engraft and who were mismatched for 1 HLA class I and/or HLA-DP, 5 donor-specific antibodies (DSAs) were detected but only 1 was clearly involved in graft failure, for the others their role was more questionable. Second HSCT exhibited a protective although not statistically significant effect on OS (hazard ratio=0.57 [0.32-1.02]). In conclusion, only one parameter (disease status before graft) remains risk factor for graft failure in this recent cohort.

Is there any impact of HLA-DPB1 disparity in 10/10 HLA-matched unrelated hematopoietic SCT? Results of a French multicentric retrospective study.

We retrospectively analyzed the impact of HLA-DPB1 mismatches in a large cohort of 1342 French patients who underwent 10/10 HLA-matched unrelated HSCT. A significant impact of HLA-DPB1 allelic mismatches (2 vs 0) was observed in severe acute GVHD (aGVHDIII-IV) (risk ratio (RR)=1.73, confidence interval (CI) 95% 1.09-2.73, P=0.019) without impact on OS, TRM, relapse and chronic GVHD (cGVHD). According to the T-cell epitope 3 (TCE3)/TCE4 HLA-DPB1 disparity algorithm, 37.6% and 58.4% pairs had nonpermissive HLA-DPB1, respectively. TCE3 and TCE4 disparities had no statistical impact on OS, TRM, relapse, aGVHD and cGVHD. When TCE3/TCE4 disparities were analyzed in the graft-vs-host or host-vs-graft (HVG) direction, only a significant impact of TCE4 nonpermissive disparities in the HVG direction was observed on relapse (RR=1.34, CI 95% 1.00-1.80, P=0.048). In conclusion, this French retrospective study shows an adverse prognosis of HLA-DPB1 mismatches (2 vs 0) on severe aGVHD and of nonpermissive TCE4 HVG disparities on relapse after HLA-matched 10/10 unrelated HSCT.

Antimicrobial activity of copaíba (Copaifera langsdorffii) oleoresin on bacteria of clinical significance in cutaneous wounds / Atividade antimicrobiana do óleo-resina de copaíba (Copaifera langsdorffii) em bactérias de significância clínica em úlceras cutâneas

The present study was designed to evaluate the in vitro antimicrobial activity of Copaifera langsdorffii oleoresin, which has been used in folk medicine as an anti-inflammatory, antibacterial, healing among others. The oleoresin was tested against Gram-positive (Staphylococcus aureus, Streptococcus pyogenes, Enterococcus faecalis) and Gram-negative (Pseudomonas aeruginosa and Escherichia coli) bacteria related to infections in cutaneous wounds. Antimicrobial activity was determined by the minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) assays. Copaiba oleoresin showed antimicrobial activity only against the Gram-positive bacteria with MIC of 200 µg/mL, 400 µg/mL and 1100 µg/mL for S. aureus, S. pyogenes and E. faecalis, respectively. MBC values were the same as MIC for S. aureus and S. pyogenes and for E. faecalis it was 1200 µg/mL. Considering that infection significantly impairs the wound healing process, we believe that the use of copaiba oleoresin as a component of a topical formulation could be a valuable adjunct in the treatment of infected wounds, mainly in the case of wounds infected by Gram-positive microorganisms.

Este trabalho avaliou a atividade antimicrobiana in vitro do óleo-resina da Copaifera langsdorffii, o qual vem sendo utilizado há muitos anos na medicina tradicional popular, principalmente devido às suas propriedades antiinflamatórias, antibacterianas, cicatrizante entre outras. O óleo-resina foi testado em bactérias Gram-positivas (Staphylococcus aureus, Streptococcus pyogenes, Enterococcus faecalis) e Gram-negativas (Pseudomonas aeruginosa e Escherichia coli) relacionadas com infecções de úlceras cutâneas. A atividade antimicrobiana foi determinada pelos testes da Concentração Inibitória Mínima (CIM) e Concentração Bactericida Mínima (CBM). O óleo-resina apresentou atividade antimicrobiana in vitro apenas para as bactérias Gram-positivas, com valores de CIM de 200 µg/mL, 400 µg/mL e 1100 µg/mL para S. aureus, S. pyogenes e E. faecalis, respectivamente. Os valores de CBM foram os mesmos que os valores de MIC para S. aureus e S. pyogenes. O valor de CBM para o microrganismo E. faecalis foi de 1200 µg/mL. Considerando que a presença de infecção significativamente impede o processo normal de cicatrização de úlceras cutâneas, acreditamos que o óleo-resina de copaíba, utilizado como componente de formulações tópicas, poderia ser um adjunto importante no tratamento de úlceras cutâneas infectadas, principalmente nos casos de infecção por microrganismos Gram-positivos.

Absence of VHL gene alteration and high VEGF expression are associated with tumour aggressiveness and poor survival of renal-cell carcinoma.

BACKGROUND: The von Hippel-Lindau gene (VHL) alteration, a common event in sporadic clear-cell renal-cell carcinoma (CCRCC), leads to highly vascularised tumours. Vascular endothelial growth factor (VEGF) is the major factor involved in angiogenesis, but the prognostic significance of both VHL inactivation and VEGF expression remain controversial. The aims of this study were to analyse the relationship between VHL genetic and epigenetic alterations, VHL expression and VEGF tumour or plasma expression, and to analyse their respective prognostic value in patients with CCRCC. METHODS: A total of 102 patients with CCRCC were prospectively analysed. Alterations in VHL were determined by sequencing, Multiplex Ligation-dependent Probe Amplification (MLPA) and methylation-specific MLPA. Expression of pVHL and VEGF was determined by immunohistochemistry. Plasma VEGF was measured by enzyme-linked immunosorbent assay (ELISA). RESULTS: VHL mutation, deletion and promoter methylation were identified in 70, 76 and 14 cases, respectively. Overall, at least one VHL-gene alteration occurred in 91 cases (89.2%). Both VEGF tumour and plasma expression appeared to be decreased in case of VHL alteration. Median progression-free survival and CCRCC-specific survival were significantly reduced in patients with wild-type VHL or altered VHL and high VEGF expression, which, therefore, represent two markers of tumour aggressiveness in CCRCC. CONCLUSION: Stratifying CCRCCs according to VHL and VEGF status may help tailor therapeutic strategy.

[Contribution of the laboratory in hypoglycemia diagnosis induced by insulin administration in a 2-year-old girl]. / Apport du laboratoire dans le diagnostic d'une hypoglycémie liée à des injections d'insuline chez un enfant de 2 ans.

We report the case of a 2 year-old child presented to the emergency department following a seizure. The child was hypotonic and examination was unremarkable but laboratory tests confirmed a severe hypoglycaemia. The insulin level, inappropriately high for the glycemia and the peptide C undetectable suggested exogenous hyperinsulinism. We conclude that the hypoglycaemia was likely the result of Munchhausen syndrome by proxy. The specificity of two immunoassays used (Elecsys Roche and IRMA CisBio) for the synthetic analogues of insulin explains the discrepancy between the insulin levels obtained but was crucially useful to the approach of the cause of the hypoglycaemia.

Relevance of KIR gene matching in unrelated hematopoietic stem cell transplantations.

The aim of this collaborative study was to evaluate the impact of killer cell immunoglobulin-like receptor (KIR) gene disparities on unrelated hematopoietic stem cell transplantations (HSCT) outcome. To address this question, we have determined the presence or absence of 14 functional KIR genes in HLA-matched (n= 164) or HLA-mismatched (n= 100) donor/recipient pairs and investigated whether KIR gene disparities had an impact on both the occurrence of acute graft-vs-host-disease incidence and overall survival. In a univariate analysis, our preliminary results suggest a detrimental effect of a few KIR gene disparities on patient survival that should be avoided in unrelated HSCT.

[Central hypothyroidism associated with bexarotene therapy]. / Une étiologie d'hypothyroïdie à ne pas méconnaître: l'hypothyroïdie centrale associée au traitement par bexarotène Targretin.

We report the case of a patient with cutaneous T-cell lymphoma treated by bexaroten Targretin, a synthetic retinoid analog with specific affinity for retinoid X receptor. The treatment induced mixed hyperlipidemia and severe central hypothyroidism characterized by reduced TSH and thyroxine serum levels. Only the pituitary thyreotrope function was affected. Targretin therapy can be maintained. Adverse drug events may be managed by fenofibrate Lipanthyl for dyslipidemia and high dose L-thyroxin Lévothyrox requiring serum free thyroxin level measurement for central hypothyroidism.

Caspase-2, a novel lipid sensor under the control of sterol regulatory element binding protein 2.

Caspases play important roles in apoptotic cell death and in some other functions, such as cytokine maturation, inflammation, or differentiation. We show here that the 5'-flanking region of the human CASP-2 gene contains three functional response elements for sterol regulatory element binding proteins (SREBPs), proteins that mediate the transcriptional activation of genes involved in cholesterol, triacylglycerol, and fatty acid synthesis. Exposure of several human cell lines to statins, lipid-lowering drugs that drive SREBP proteolytic activation, induced the CASP-2 gene to an extent similar to that for known targets of SREBP proteins. Adenoviral vector-mediated transfer of active SREBP-2 also induced expression of the CASP-2 gene and the caspase-2 protein and increased the cholesterol and triacylglycerol cellular content. These rises in lipids were strongly impaired following small interfering RNA-mediated silencing of the CASP-2 gene. Taken together, our results identify the human CASP-2 gene as a member of the SREBP-responsive gene battery that senses lipid levels in cells and raise the possibility that caspase-2 participates in the control of cholesterol and triacylglycerol levels.