The impact of socioeconomic determinants on the access to care and survival in patients with spinal chordomas- a national cancer database analysis.

PURPOSE: Chordomas are rare malignant neoplasms primarily treated surgically. Disparities related to race and socioeconomic status, may affect patient outcomes. This study aims to identify prognostic factors for access to care and survival in patients with spinal chordomas. METHODS: The NCDB database was queried between the years 2004 and 2017. Kaplan-Meier curves were constructed to compare survival probabilities among different groups, based on race and socioeconomic determinents. RESULTS: 1769 patients were identified, with 87% being White, 5% Hispanic, 4% Black, and Asian each. The mean age was 61.3 years. Most patients received care at academic/research centers and lived in a large metropolitan area, with no difference between races. A significantly higher percentage of Black patients did not undergo surgery (p < 0.001), with no statistically significant difference in survival between races (p = 0.97). A higher survival probability was seen in patients with other government insurances (p < 0.0001), in higher income quartiles (p < 0.0001), in metropolitan areas (p = 0.023), and at an academic/research center (p < 0.0001). A lower survival probability was seen in patients who are uninsured, in rural areas, and at community cancer programs (p < 0.0001). CONCLUSION: This study highlights disparities in access to surgical intervention for patients with spinal chordomas, especially among Black individuals. It emphasizes the significant impact of insurance status and income on access to surgical care and highlights geographical and institutional variations in survival rates. Addressing socioeconomic differences is crucial for fostering equity in neurosurgical outcomes.

Takotsubo Cardiomyopathy Complicating Diabetic Ketoacidosis, Hypothermia and Hypernatremia in a Comatose Patient.

Takotsubo cardiomyopathy (TCM) is a transient wall motion abnormality of the left ventricular apex associated with emotional or physical stress. In the setting of diabetic ketoacidosis (DKA), it is thought to be caused by the compound effect of a catecholamine surge and the noxious effect of acidosis and ketones leading to myocardial stunning. In this report, the first of its kind in the Middle East, we describe the case of a 71-year-old comatose patient, who was being treated for DKA and hypernatremia and was incidentally diagnosed with TCM. We also review 15 case reports of DKA-induced TCM published to date in the literature, many of which had an atypical presentation and good outcomes. Furthermore, we discuss possible risk factors for TCM in our case and supporting literature. It is recommended to maintain increased vigilance and attempt early identification of such conditions in acutely ill patients to prevent life-threatening complications.

Role of nucleobase-specific interactions in binding and bending of DNA by human male sex-determination factor SRY.

Y-chromosome-encoded master transcription factor SRY functions in the embryogenesis of therian mammals to initiate male development. Through interactions of its conserved high mobility-group (HMG) box within a widened DNA minor groove, SRY and related Sox factors induce sharp bends at specific DNA target sites. Here, we present the crystal structure of the SRY HMG domain bound to a DNA site containing consensus element 5'-ATTGTT. The structure contains three complexes in the asymmetric unit; in each complex, SRY forms 10 hydrogen bonds with minor-groove base atoms in 5'-CATTGT/ACAATG-3', shifting the recognition sequence by one base pair (italics). These nucleobase interactions involve conserved residues Arg7, Asn10, and Tyr74 on one side of intercalated Ile13 (the cantilever side chain), and Arg20, Asn32 and Ser36 on the other. Unlike the less-bent NMR structure, DNA bend angles of the distinct box-DNA complexes range from 69-84°, similar to those observed in homologous Sox domain-DNA structures. Electrophoretic studies indicate that respective substitutions of Asn32, Ser36 or Tyr74 by Ala exhibit slightly attenuated specific DNA-binding affinity and bend angles (70-73°) relative to WT (79°). By contrast, respective substitutions of Arg7, Asn10 or Arg20 by Ala markedly impaired DNA-binding affinity in association with much smaller DNA bend angles (53-65°). In a rodent cell-based model of the embryonic gonadal ridge, full-length SRY variants bearing these respective, Ala substitutions exhibited significantly decreased transcriptional activation of SRY's principal target gene (Sox9). Together, our findings suggest that nucleobase-specific hydrogen bonds by SRY are critical for specific DNA binding, bending, and transcriptional activation.

Proton versus photon adjuvant radiotherapy: a multicenter comparative evaluation of recurrence following spinal chordoma resection.

OBJECTIVE: Chordomas are rare tumors of the skull base and spine believed to arise from the vestiges of the embryonic notochord. These tumors are locally aggressive and frequently recur following resection and adjuvant radiotherapy. Proton therapy has been introduced as a tissue-sparing option because of the higher level of precision that proton-beam techniques offer compared with traditional photon radiotherapy. This study aimed to compare recurrence in patients with chordomas receiving proton versus photon radiotherapy following resection by applying tree-based machine learning models. METHODS: The clinical records of all patients treated with resection followed by adjuvant proton or photon radiotherapy for chordoma at Mayo Clinic were reviewed. Patient demographics, type of surgery and radiotherapy, tumor recurrence, and other variables were extracted. Decision tree classifiers were trained and tested to predict long-term recurrence based on unseen data using an 80/20 split. RESULTS: Fifty-three patients with a mean ± SD age of 55.2 ± 13.4 years receiving surgery and adjuvant proton or photon therapy to treat chordoma were identified; most patients were male. Gross-total resection was achieved in 54.7% of cases. Proton therapy was the most common adjuvant radiotherapy (84.9%), followed by conventional or external-beam radiation therapy (9.4%) and stereotactic radiosurgery (5.7%). Patients receiving proton therapy exhibited a 40% likelihood of having recurrence, significantly lower than the 88% likelihood observed in those treated with nonproton therapy. This was confirmed on logistic regression analysis adjusted for extent of tumor resection and tumor location, which revealed that proton adjuvant radiotherapy was associated with a decreased risk of recurrence (OR 0.1, 95% CI 0.01-0.71; p = 0.047) compared with photon therapy. The decision tree algorithm predicted recurrence with an accuracy of 90% (95% CI 55.5%-99.8%), with the lowest risk of recurrence observed in patients receiving gross-total resection with adjuvant proton therapy (23%). CONCLUSIONS: Following resection, adjuvant proton therapy was associated with a lower risk of chordoma recurrence compared with photon therapy. The described machine learning models were able to predict tumor progression based on the extent of tumor resection and adjuvant radiotherapy modality used.

Two-Stage Resection of a Giant Trigeminal Schwannoma in a Non-Neurofibromatosis Type 2 Pediatric Patient: A Case Report, Systematic Review, and Intraoperative Video.

BACKGROUND: Trigeminal schwannoma is an uncommon tumor in pediatric patients. Several surgical approaches have been described in the literature. METHODS: The case of an 11-year-old boy with a giant dumbbell-shaped trigeminal schwannoma removed through a 2-stage approach was presented with an intraoperative video. Using PubMed and Scopus, the literature on trigeminal schwannoma in pediatric patients was searched according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. RESULTS: The search strategy yielded 312 titles, of which 13 were included in the review. Cases of trigeminal schwannoma were described, with a highly variable clinical presentation and anatomical arrangement in cranial fossae. Two-stage approaches were reported, although most studies described single-stage approaches. Common postoperative outcomes were a range of disturbances of cranial nerve V. CONCLUSIONS: The surgical approach varies based on the tumor conformation. However, a 2-stage pterional subtemporal and semisitting retrosigmoid approach is a safe, practical, and effective strategy for the removal of dumbbell-shaped trigeminal schwannoma in a pediatric patient.

Cerebral Amyloid Angiopathy and Atrial Fibrillation: An up to Date Case Report.

Concurrent Cerebral Amyloid Angiopathy (CAA) and Atrial Fibrillation are becoming an increasingly common dilemma in clinical practice due to the aging population and the comorbidities associated with it. In such patients, the physician must appreciate and strike the difficult balance between the risk of ischemic strokes from atrial fibrillation on one hand, and that of intracerebral hemorrhage from coexisting CAA on the other. Anticoagulation is necessary for the former but potentially deleterious for the latter. In this case report, we present the case of a 67-year-old woman with a long history of atrial fibrillation on rivaroxaban who recently began to experience recurrent transient neurological deficits that were later diagnosed as amyloid spells related to concomitant CAA. While there is no clear-cut consensus in published literature on how to best manage these patients regarding the use of anticoagulation, it is recommended to involve a multidisciplinary team for optimal management of these patients.

Crystal structures of a dodecameric multicopper oxidase from Marinithermus hydrothermalis.

Multicopper oxidases (MCOs) represent a diverse family of enzymes that catalyze the oxidation of either an organic or a metal substrate with concomitant reduction of dioxygen to water. These enzymes contain variable numbers of cupredoxin domains, two, three or six per subunit, and rely on four copper ions, a single type I copper and three additional copper ions organized in a trinuclear cluster (TNC), with one type II and two type III copper ions, to catalyze the reaction. Here, two crystal structures and the enzymatic characterization of Marinithermus hydrothermalis MCO, a two-domain enzyme, are reported. This enzyme decolorizes Congo Red dye at 70°C in the presence of high halide concentrations and may therefore be useful in the detoxification of industrial waste that contains dyes. In two distinct crystal structures, MhMCO forms the trimers seen in other two-domain MCOs, but differs from these enzymes in that four trimers interact to create a dodecamer. This dodecamer of MhMCO forms a closed ball-like structure and has implications for the sequestration of bound divalent metal ions as well as substrate accessibility. In each subunit of the dodecameric structures, a Trp residue, Trp351, located between the type I and TNC sites exists in two distinct conformations, consistent with a potential role in facilitating electron transfer in the enzyme.

Cardiac Screening to Mitigate the Risk of Sudden Cardiac Death in Middle Eastern and African Competitive Athletes. A Systematic Review.

OBJECTIVE: The study aims to review the literature regarding abnormalities predisposing to Sudden Cardiac Death (SCD) in young Middle Eastern and African competitive athletes between the years 2009-2019 and aims to assess cardiac pre-participation screening methods. METHODS: A PubMed search was performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The search targeted articles that reported the prevalence of cardiac abnormalities found in Middle Eastern and African athletes, and it also focused on comparing cardiac screening methods for assessment of athletes. RESULTS: our studies fell within the inclusion criteria and were included in the study. Results identified a shortage in the literature regarding prevalence rates of SCD in the Middle East and Africa. Additionally, there seems to be a lack of ethnicity-specific cardiac pre-participation screening programs in the region. Nevertheless, the prevalence of SCD-related abnormalities (HCM, ARVC, etc …) ranged from 0.47 to 4.29%. Included studies conveyed only male athletes with no reports on the female athletic population. CONCLUSION: The present study highlights a need to develop an efficient cardiac pre-participation screening program specific to Arab and African athletes due to their high false-positive rates in contrast to Caucasian athletes. Significant evidence proves that an adequate cardiac screening program can prevent SCD in young competitive athletes. Therefore, it is imperative that future studies highlight the prevalence of abnormalities directly related to SCD in order to create a valid screening program that can be implemented in the region to mitigate the risk of shocking events.