Outcomes using linear accelerator stereotactic radiosurgery for the treatment of trigeminal neuralgia: A single-center, retrospective study.

Background: Linear accelerator (LINAC)-based stereotactic radiosurgery (SRS) treatment of trigeminal neuralgia (TN) may have similar efficacy to Gamma Knife SRS (GK-SRS), but the preponderance of data comes from patients treated with GK-SRS. Our objective was to analyze the outcomes for LINAC-based treatment of TN in patients at our institution. Methods: We retrospectively analyzed data for patients who underwent LINAC-based SRS for TN from 2006 to 2018. Data were collected from the patients' medical records. Nonparametric statistics were used for the analysis. Results: Of the 41 patients treated with LINAC-based SRS (typically 90 Gy dosed using a 4 mm collimator for one fraction) during that time, follow-up data of >3 weeks post-SRS were available for 32 patients. The median pretreatment Barrow Neurological Institute (BNI) pain score was 5 (range 4-5). The follow-up period ranged from 0.9 to 113.2 months (median 5 months). There was significant improvement in postradiation BNI pain score (P < 0.001), with 23 (72%) patients who improved to a BNI pain score of 1-3. One patient had bothersome hypoesthesia postradiation. Approximately 38% of patients who had initial pain control had recurrence of symptoms (BNI > 3). Survival analysis showed a median time to pain recurrence of 30 months. There was no relationship between prior microvascular decompression (MVD) surgery and change in BNI pain score pre- to posttreatment. Conclusion: The results demonstrate that LINAC-based SRS is an effective means to treat TN. Prior MVD surgery did not affect efficacy of SRS in lowering the BNI score from pre- to posttreatment in this patient cohort.

SM-COLSARSPROT: Highly Immunogenic Supramutational Synthetic Peptides Covering the World's Population.

Fifty ~20-amino acid (aa)-long peptides were selected from functionally relevant SARS-CoV-2 S, M, and E proteins for trial B-21 and another 53 common ones, plus some new ones derived from the virus' main genetic variants for complementary trial C-21. Peptide selection was based on tremendous SARS-CoV-2 genetic variability for analysing them concerning vast human immunogenetic polymorphism for developing the first supramutational, Colombian SARS-protection (SM-COLSARSPROT), peptide mixture. Specific physicochemical rules were followed, i.e., aa predilection for polyproline type II left-handed (PPIIL) formation, replacing ß-branched, aromatic aa, short-chain backbone H-bond-forming residues, π-π interactions (n→π* and π-CH), aa interaction with π systems, and molecular fragments able to interact with them, disrupting PPIIL propensity formation. All these modified structures had PPIIL formation propensity to enable target peptide interaction with human leukocyte antigen-DRß1* (HLA-DRß1*) molecules to mediate antigen presentation and induce an appropriate immune response. Such modified peptides were designed for human use; however, they induced high antibody titres against S, M, and E parental mutant peptides and neutralising antibodies when suitably modified and chemically synthesised for immunising 61 major histocompatibility complex class II (MHCII) DNA genotyped Aotus monkeys (matched with their corresponding HLA-DRß1* molecules), predicted to cover 77.5% to 83.1% of the world's population. Such chemically synthesised peptide mixture represents an extremely pure, stable, reliable, and cheap vaccine for COVID-19 pandemic control, providing a new approach for a logical, rational, and soundly established methodology for other vaccine development.

The Effect of Hospital Transfer on Patient Outcomes After Rehabilitation for Spinal Injury.

OBJECTIVE: Spine fractures, including associated spinal cord injury, account for 3%-6% of all skeletal fractures annually in the United States. Patients who undergo interhospital transfer after injury may have a greater likelihood of nonroutine disposition, longer hospital stay, and higher cost. We evaluated the effects of patient transfer on functional outcomes after spine trauma. METHODS: Patients were treated after acute traumatic spine injury at a rehabilitation hospital in 2011-2017. Compared patients were those directly admitted to the tertiary hospital or transferred from a community hospital. RESULTS: A total of 188 patients (mean age 46.1 ± 18.6 years, 77.1% men) were evaluated, including 130 (69.1%) directly admitted and 58 (30.9%) transferred patients. The most common levels of injury were at C5 (19.1%) and C6 (12.2%), and most injuries were American Spinal Injury Association injury severity score grade D (33.2%) or grade A (32.1%). No statistical difference in age, injury pattern, timing from injury to surgery, or rehabilitation length of stay was seen between admitted and transferred patients. A significant improvement in ambulation distances was seen at discharge for directly admitted compared with transferred patients (447.7 ± 724.9 vs. 159.9 ± 359.5 feet; P = 0.005). However, no significant difference primary outcomes, namely American Spinal Injury Association injury severity score distribution (P = 0.2) or Functional Independence Measures (Δ30.9 ± 15.9 vs. 30.1 ± 17.1; P = 0.7), were seen between admitted and transferred patients at time of rehabilitation discharge. CONCLUSIONS: Interhospital transfer status did not diminish time to rehabilitation after injury or reduce functional recovery, suggesting early surgical treatment in community settings may have merit prior to transfer.

Cost Analysis of Inpatient Rehabilitation after Spinal Injury: A Retrospective Cohort Analysis.

Objective The lifetime direct and indirect costs of spinal injury and spinal cord injury (SCI) increase as the severity of injury worsens. Despite the potential for substantial improvement in function with acute rehabilitation, the factors affecting its cost have not yet been evaluated. We used a proprietary hospital database to evaluate the direct costs of rehabilitation after spine injury. Methods A single-center, retrospective cohort cost analysis of patients with acute, traumatic spine injury treated at a tertiary facility from 2011 to 2017 was performed. Results In the 190 patients (mean age 46.1 ± 18.6 years, 76.3% males) identified, American Spinal Injury Association impairment scores on admission were 32.1% A, 14.7% B, 14.7% C, 33.2% D, and 1.1% E. Surgical treatment was performed in 179 (94.2%) cases. Most injuries were in the cervical spine (53.2%). A mean improvement of Functional Impairment Score of 30.7 ± 16.2 was seen after acute rehabilitation. Costs for care comprised facility (86.5%), pharmacy (9.2%), supplies (2.0%), laboratory (1.5%), and imaging (0.8%) categories. Injury level, injury severity, and prior inpatient surgical treatment did not affect the cost of rehabilitation. Higher injury severity (p = 0.0001, one-way ANOVA) and spinal level of injury (p = 0.001, one-way ANOVA) were associated with higher length of rehabilitation stay in univariate analysis. However, length of rehabilitation stay was the strongest independent predictor of higher-than-median cost (risk ratio = 1.56, 95% CI 1.21-2.0, p = 0.001) after adjusting for other factors. Conclusions Spine injury has a high upfront cost of care, with greater need for rehabilitation substantially affecting cost. Improving the efficacy of rehabilitation to reduce length of stay may be effective in reducing cost.

Distinctive Structure of the EphA3/Ephrin-A5 Complex Reveals a Dual Mode of Eph Receptor Interaction for Ephrin-A5.

The Eph receptor tyrosine kinase/ephrin ligand system regulates a wide spectrum of physiological processes, while its dysregulation has been implicated in cancer progression. The human EphA3 receptor is widely upregulated in the tumor microenvironment and is highly expressed in some types of cancer cells. Furthermore, EphA3 is among the most highly mutated genes in lung cancer and it is also frequently mutated in other cancers. We report the structure of the ligand-binding domain of the EphA3 receptor in complex with its preferred ligand, ephrin-A5. The structure of the complex reveals a pronounced tilt of the ephrin-A5 ligand compared to its orientation when bound to the EphA2 and EphB2 receptors and similar to its orientation when bound to EphA4. This tilt brings an additional area of ephrin-A5 into contact with regions of EphA3 outside the ephrin-binding pocket thereby enlarging the size of the interface, which is consistent with the high binding affinity of ephrin-A5 for EphA3. This large variation in the tilt of ephrin-A5 bound to different Eph receptors has not been previously observed for other ephrins.