The spectrum of acute and chronic consequences of neurotrauma in professional and amateur boxing - A call to action is advocated to better understand and prevent this phenomenon.

Introduction: Despite changes in regulations, boxing-related injuries and fatalities are still occurring. The numbers available in the literature regarding mortality and long-term consequences may not accurately represent the actual situation. Indeed, the real extent of this phenomenon remains poorly known. Research question: Delineating the spectrum of acute and chronic consequences of boxing-related traumatic brain injuries (TBI). Material and methods: Narrative review of the literature concerning acute and chronic boxing-related TBI. Keywords such as mortality, boxing, subdural hematoma were used to search in PubMed and Google scholar. An updated analysis of the Velazquez fatalities collection in boxing was undertaken. Results: The Velazquez collection includes 2076 fatalities from 1720 to the present with a death rate of 10 athletes per year. More than half of the deaths (N = 1354, 65.2%) occurred after a knock-out, and nearly 75% happened during professional bouts. In Australia, from 1832 to 2020, 163 fatalities were recorded (75% professional). In Japan, from 1952 to 2016, 38 deaths were recorded with a mean age of 23.9 years. Up to 40% of retired professional boxers in the United States were diagnosed with symptoms of chronic brain injury. Clinical dementia is far more prevalent among professional boxers than in amateurs with an incidence of 20%. Discussion and conclusions: A concerted effort to raise awareness and shed light on boxing-related neuro-trauma is required. Similar considerations can be made for other combat sports or contact sports. A call to action to address this knowledge gap, decrease and prevent this phenomenon is advocated.

Tetraparesis following thoracic spine surgery in a patient with Klippel-Feil syndrome and ABCB4 mutation: a case report.

BACKGROUND: Klippel-Feil syndrome is a rare condition described in 1912 by Maurice Klippel and André Feil. It is defined as a congenital cervical fusion of at least two vertebrae, associated with a classical triad of clinical signs: short neck, low posterior hairline, and limited range of movement. However, Klippel-Feil syndrome manifests with a vast spectrum of phenotypes, ranging from no symptoms to complete triad, with or without other associated malformations. Most commonly, CCF results from sporadic mutations, even though autosomal recessive, autosomal dominant, or even X-linked inheritance can be detected. The ATP-binding cassette subfamily B member 4 is only expressed in the liver and is involved in biliary phospholipid secretion. The clinical spectrum includes various hepatobiliary pathologies, including low phospholipid-associated cholelithiasis, and has never been associated with musculoskeletal anomalies. CASE PRESENTATION: A 55-year-old male Caucasian patient presenting with low phospholipid-associated cholelithiasis syndrome with ATP-binding cassette subfamily B member 4 mutation and liver cirrhosis was referred to our clinic for a liver transplant. A period of 6 months before, the patient underwent a T7-T9 posterior fixation for a T8 osteoporotic fracture. Postoperatively, he was tetraparetic, whereas he was neurologically intact before the operation. At admission to our hospital, he was still tetraparetic and presented with clinical signs of cervical myelopathy. Moreover, he suffered a limitation of cervical range of motion in all directions, short neck, and low posterior hairline. Imaging showed multiple cervical and thoracic vertebral bodies fusion, as well as cervical spine stenosis. Based on the available data, we diagnosed a type 3 Klippel-Feil syndrome according to Samartzis' classification. CONCLUSIONS: The heterogeneity of KFS and the various potential hereditary links that are known indicate that it is important to highlight all potential cases related to known genetic defects. At present, no association between ATP-binding cassette subfamily B member 4 mutation and congenital cervical fusions has been reported. The other important clinical focus of this case is the appearance of spontaneous tetraparesis after thoracic spine surgery. This mechanism remains unclear, but considering different spinal anatomy it might have been due to difficult intubation and patient's positioning during his previous operation.

Posterior spine fusion in a Jehovah's Witness patient with severe rigid idiopathic scoliosis - A case report.

Introduction: Early onset scoliosis (EOS) represent a challenge for spine surgeons. The selection of the best treatment is complex. Some patients, such as Jehovah's Witnesses who refuse blood transfusions, are at high risk of complication when surgical treatment is required because blood loss is a major cause of morbidity and postoperative transfusion rates. Research question: Describe blood-saving techniques that allowed an extensive and invasive surgical procedure in a Jehovah's Witness patient. Material and method: 17-year-old Jehovah's Witness girl with severe 120° Cobb Lenke 1A idiopathic scoliosis started as EOS was prepared with 4 cycles of recombinant human erythropoietin, iron and folic acid supplementation that brought her hemoglobin level from 13.6 g/dl to 16.2 g/dl. In the first surgical time, a temporary rod was implanted. Spine dissection using bipolar sealer and a special electrocautery that operates at lower temperatures than traditional ones was performed. Facetectomies and multilevel Ponte osteotomies was performed using an ultrasonic bone scalpel. The second surgical time, the definitive rods were placed, and the correction of the deformity was achieved using the rod link reducer technique. Results: A good correction of the main curve in the coronal plane is achieve. The Hb nadir was 7.2 g/dl four days after the second operation. The postoperative course was uneventful. Discussion and conclusion: The integration of modern and traditional preoperative, intraoperative, and postoperative blood sparing techniques allowed us to perform an extensive and invasive surgical procedure in a Jehovah's Witness girl with a severe idiopathic scoliosis.

The Impact of Controlled Ovarian Stimulation on Serum Oxidative Stress Markers in Infertile Women with Endometriosis Undergoing ICSI.

Endometriosis-related infertility is associated with oxidative stress (OS). The present study aims to compare serum OS markers of infertile women with endometriosis and controls during the follicular phase of the natural cycle (D1), after pituitary downregulation using a GnRH agonist (D2), after controlled ovarian stimulation (COS) on the day of human chorionic gonadotropin administration (D3), and on the day of oocyte retrieval (D4). One hundred and eight serum samples (58 controls and 35 early and 18 advanced endometriosis cases) were collected at these four timepoints. OS markers were compared among the groups and timepoints using a linear regression model with mixed effects and a post-test using orthogonal contrasts. The significance was set at 5%. We observed altered OS markers in the endometriosis patients during the D1, D2, D3, and D4 timepoints compared to the controls. The evidence of systemic OS in infertile patients with endometriosis during COS suggests the mobilization of potent antioxidants in an attempt to protect the oocyte from oxidative damage, especially on the day of oocyte retrieval.

Transcriptomic analysis of cumulus cells shows altered pathways in patients with minimal and mild endometriosis.

Endometriosis is a chronic inflammatory disorder that is highly associated with infertility. This association seems to be related to oocyte impairment, mainly in the initial stages of endometriosis (minimal and mild), where no distortions or adhesions are present. Nonetheless, invasive oocyte analyses are not routinely feasible; thus, indirect assessment of oocyte quality is highly desirable, and, in this context, cumulus cells (CCs) may be more suitable targets of analysis. CCs are crucial in oocyte development and could be used as an index of oocyte quality. Therefore, this prospective case-control study aimed to shed light on the infertility mechanisms of endometriosis I/II by analyzing the CCs' mRNA transcription profile (women with endometriosis I/II, n = 9) compared to controls (women with tubal abnormalities or male factor, n = 9). The transcriptomic analyses of CCs from patients with minimal and mild endometriosis revealed 26 differentially expressed genes compared to the controls. The enrichment analysis evidenced some altered molecular processes: Cytokine-cytokine receptor interactions, Chemokine signaling, TNF signaling, NOD-like receptor signaling, NF-kappa B signaling, and inflammatory response. With the exception of CXCL12, all enriched genes were downregulated in CCs from patients with endometriosis. These findings provide a significant achievement in the field of reproductive biology, directing future studies to discover biomarkers of oocyte quality in endometriosis.

Screening of Variants in the Transcript Profile of Eutopic Endometrium from Infertile Women with Endometriosis during the Implantation Window.

OBJECTIVE: Abnormalities in the eutopic endometrium of women with endometriosis may be related to disease-associated infertility. Although previous RNA-sequencing analysis did not show differential expression in endometrial transcripts of endometriosis patients, other molecular alterations could impact protein synthesis and endometrial receptivity. Our aim was to screen for functional mutations in the transcripts of eutopic endometria of infertile women with endometriosis and controls during the implantation window. METHODS: Data from RNA-Sequencing of endometrial biopsies collected during the implantation window from 17 patients (6 infertile women with endometriosis, 6 infertile controls, 5 fertile controls) were analyzed for variant discovery and identification of functional mutations. A targeted study of the alterations found was performed to understand the data into disease's context. RESULTS: None of the variants identified was common to other samples within the same group, and no mutation was repeated among patients with endometriosis, infertile and fertile controls. In the endometriosis group, nine predicted deleterious mutations were identified, but only one was previously associated to a clinical condition with no endometrial impact. When crossing the mutated genes with the descriptors endometriosis and/or endometrium, the gene CMKLR1 was associated either with inflammatory response in endometriosis or with endometrial processes for pregnancy establishment. CONCLUSION: Despite no pattern of mutation having been found, we ponder the small sample size and the analysis on RNA-sequencing data. Considering the purpose of the study of screening and the importance of the CMKLR1 gene on endometrial modulation, it could be a candidate gene for powered further studies evaluating mutations in eutopic endometria from endometriosis patients.

OBJETIVO: Anormalidades no endométrio eutópico de mulheres com endometriose podem estar relacionadas à infertilidade associada à doença. Embora a análise prévia de sequenciamento de RNA não tenha evidenciado expressão diferencial em transcritos endometriais de pacientes com endometriose, outras alterações moleculares poderiam afetar a síntese de proteínas e a receptividade endometrial. Nosso objetivo foi rastrear mutações funcionais em transcritos de endométrios eutópicos de mulheres inférteis com endometriose e de controles durante a janela de implantação. MéTODOS: Os dados do sequenciamento de RNA de biópsias endometriais coletados durante a janela de implantação de 17 pacientes (6 mulheres inférteis com endometriose, 6 controles inférteis, 5 controles férteis) foram analisados para a descoberta de variantes e a identificação de mutações funcionais. Um estudo direcionado das alterações encontradas foi realizado para compreender os dados no contexto da doença. RESULTADOS: Nenhuma das variantes identificadas foi comum a outras amostras dentro do mesmo grupo, assim como nenhuma mutação se repetiu entre pacientes com endometriose, controles inférteis e férteis. No grupo de endometriose, foram identificadas nove mutações deletérias preditas, mas apenas uma foi previamente associada a uma condição clínica sem impacto endometrial. Ao cruzar os genes mutados com os descritores endometriose e/ou endométrio, o gene CMKLR1 foi associado a resposta inflamatória na endometriose e a processos endometriais para estabelecimento da gravidez. CONCLUSãO: Apesar de nenhum padrão de mutação ter sido encontrado, ponderamos o pequeno tamanho da amostra e a análise dos dados de sequenciamento de RNA. Considerando o objetivo do estudo de triagem e a importância do gene CMKLR1 na modulação endometrial, este poderia ser um gene candidato para estudos adicionais que avaliem mutações no endométrio eutópico de pacientes com endometriose.

Predictors of Survival in Subtotally Resected WHO Grade I Skull Base Meningiomas.

BACKGROUND: Although gross total resection (GTR) is the goal in meningioma surgery, this can sometimes be difficult to achieve in skull base meningiomas. We analyzed clinical outcomes and predictors of survival for subtotally resected benign meningiomas. METHODS: A total of 212 consecutive patients who underwent subtotal resection (STR) for benign skull base meningioma between 1990-2010 were investigated. RESULTS: Median age was 57.7 [IQR 18.8] years, median preoperative Karnofsky performance status (KPS) was 80.0 [IQR 20.0], 75 patients (35.4%) had posterior fossa meningioma. After a median follow-up of 6.2 [IQR 7.9] years, retreatment (either radiotherapy or repeated surgery) rate was 16% at 1-year, 27% at 3-years, 34% at 5-years, and 38% at 10-years. Ten patients (4.7%) died perioperatively, 9 (3.5%) had postoperative hematomas, and 2 (0.8%) had postoperative infections. Neurological outcome at final visit was improved/stable in 122 patients (70%). Multivariable analysis identified advanced age and preoperative KPS < 70 as negative predictors for overall survival (OS). Patients who underwent retreatment had no significant reduction of OS. CONCLUSIONS: Advanced age and preoperative KPS were independent predictors of OS. Retreatments did not prolong nor shorten the OS. Clinical outcomes in STR skull base meningiomas were generally worse compared to cohorts with high rates of GTR.

Predictors of Survival in Atypical Meningiomas.

INTRODUCTION: Predictors of survival and progression of disease in atypical meningiomas are less well documented in the literature compared to benign meningiomas. Higher grade meningiomas tend to recur often and one of the most critical aspects is how to best deal with relapses. METHODS: A total of 77 consecutive patients who underwent craniotomy for atypical meningioma between 1990-2010 at Oslo University Hospital (OUH) were reviewed. RESULTS: Median age at surgery was 62.21 [interquartile range (IQR): 22.87] years. Fifty-one patients (66.2%) had neurological deficits at presentation. Fifty-four patients (70.1%) underwent gross total resection (GTR). Thirty-nine patients (50.7%) had improved/stable neurological outcomes at 6-12 months. Twenty-two patients (28.6%) underwent retreatment, of whom 20 (26.0%) were subjected to resection followed by adjuvant radiotherapy. Overall survival (OS) was significantly longer in patients <65 years (p < 0.001), with preoperative Karnofsky performance scale (KPS) score of ≥ 70 (p = 0.006), and who required no retreatment (p = 0.033). GTR significantly prolonged the retreatment-free survival rate (p < 0.001). STR carried almost a six-fold greater risk of neurological outcome deterioration (p = 0.044). CONCLUSIONS: GTR significantly prolonged retreatment-free survival but had no significant impact on OS. STR was a significant risk factor for deteriorated neurological outcome. Age, preoperative KPS, and retreatment were all strong predictors of OS. Median time-to-retreatment (TTR) did not shorten significantly throughout repeated surgeries.

Altered transcriptome in cumulus cells of infertile women with advanced endometriosis with and without endometrioma.

RESEARCH QUESTION: Is the transcriptome of cumulus cells of infertile women with advanced endometriosis (EIII/IV), with and without endometrioma, altered? DESIGN: In this prospective case-control study, next-generation RNA sequencing was used to compare the transcript profile of cumulus cells among infertile patients undergoing ovarian stimulation for intracytoplasmic sperm injection with EIII/IV, with (n = 9) and without endometrioma (n = 9), and controls (n = 9). An in-silico enrichment analysis was conducted to establish the possibly altered pathways in cumulus cells of patients with endometriosis. RESULTS: Most of the differentially expressed genes (DEG) were found when cumulus cells from women with EIII/IV with endometrioma were compared with controls (DEG, n = 461). In women with EIII/IV without endometrioma, only 66 DEG were verified compared with controls. The enrichment analysis showed that some DEG in cumulus cells of endometriosis are involved in important pathways for the oocyte competence acquisition, such as oxidative phosphorylation, metabolism, mitochondrial function, acetylation and steroid biosynthesis. No DEG were found when cumulus cells from women with EIII/IV with and without endometrioma were compared. CONCLUSION: RNA sequencing results suggest that cumulus cells of infertile women with EIII/IV have an altered transcriptome, regardless of endometrioma. The present findings offer a better understanding of the genes and molecular mechanisms that may be involved in endometriosis-related infertility, mostly in the oocyte competence acquisition process.

miR-532-3p: a possible altered miRNA in cumulus cells of infertile women with advanced endometriosis.

RESEARCH QUESTION: Is the profile of microRNA (miRNA) altered in cumulus cells of infertile women with early (EI/II) and advanced (EIII/IV) endometriosis? DESIGN: In this prospective case-control study, a miRNA profile including 754 targets was evaluated in samples of cumulus cells from infertile women with endometriosis (5 EI/II, 5 EIII/IV) and infertile controls (5, male and/or tubal factor) undergoing ovarian stimulation for intracytoplasmic sperm injection, using TaqMan® Array Human MicroRNA Cards A and B. The groups were compared with Kruskal-Wallis test, followed by Benjamini-Hochberg correction and Dunn's post hoc test. An in silico enrichment analysis was performed to list the possibly altered pathways in which the altered miRNA target genes are involved. RESULTS: Only the miRNA miR-532-3p showed significant differences among the analysed groups, being down-regulated in the EIII/IV group compared with the infertile control group, as well as compared with the EI/II group. The enrichment analysis showed that some genes regulated by this miRNA are involved in important pathways for the acquisition of oocyte competence, such as the oxytocin, calcium, Wnt, FoxO, ErbB and Ras signalling pathways, as well as the oocyte meiosis pathway. CONCLUSION: The present findings bring new perspectives to understanding the follicular microenvironment of infertile women with different stages of endometriosis. It is suggested that the dysregulation of miR-532-3p may be a potential mechanism involved in the aetiopathogenesis of endometriosis-related infertility. Further studies are needed to evaluate these pathways in cumulus cells of infertile women with the disease, as well as their impact on the acquisition of oocyte competence.