Citations

OBJECTIVE The objective of this study was to describe the quantitative features of intraoperative electromyographic recordings obtained from cranial nerve III, IV, and VI neuromonitoring using 25-mm intraorbital electrodes, in the larger context of demonstrating the practicality of this technique during neurosurgical cases. METHODS A 25-mm-long shaft-insulated intraorbital needle electrode is routinely used at the authors’ institution for extraocular muscle (EOM) electromyographic monitoring of the inferior rectus, superior oblique, and/or lateral rectus muscles when their function is at risk. Cases monitored between January 1, 2021, and December 31, 2022, were reviewed for patient demographics, tumor location and pathology, EOMs monitored, pre- and postoperative examination, and complications from electrode placement. Compound muscle action potentials on triggered electromyography, as well as neurotonic discharges on free-run electromyography, were described quantitatively. RESULTS There were 141 cases in 139 patients reviewed during the 24-month time span, with 278 EOMs monitored (inferior rectus/superior oblique/lateral rectus muscles 68/68/142). Triggered electromyography yielded biphasic or triphasic compound muscle action potentials from EOMs with a mean onset latency of 1.51 msec (range 0.94–3.22 msec), mean maximal peak-to-trough amplitude of 1073.93 μV (range 76.75–7796.29 μV), and high specificity for the channel in nearly all cases. Neurotonic discharges were recorded in 30 of the 278 EOMs (with all 3 muscles represented) and associated with a greater incidence of new or worsened ophthalmoparesis (OR 4.62, 95% CI 1.3–16.4). There were 2 cases of small periorbital ecchymosis attributed to needle placement; additionally, 1 case of needle-related intraorbital hematoma occurred after the review period. CONCLUSIONS The 25-mm shaft-insulated intraorbital electrode facilitates robust and consistent electromyographic recordings of EOMs that are advantageous over existing techniques. Combined with the relative ease of needle placement and low rate of complications, the technique is practical for neuromonitoring during craniotomies.

Abstract Background Hereditary transthyretin amyloidosis (ATTRv) is an inherited, progressive, and fatal disease still largely underdiagnosed. Mutations in the transthyretin (TTR) gene cause the TTR protein to destabilize, misfold, aggregate, and deposit in body tissues, which makes ATTRv a disease with heterogeneous clinical phenotype. Objective To describe the long-term efficacy and safety of inotersen therapy in patients with ATTRv peripheral neuropathy (ATTRv-PN). Methods Patients who completed the NEURO-TTR pivotal study and the NEURO-TTR OLE open-label extension study migrated to the present study and were followed-up for at least 18 more months to an average of 67 months and up to 76 months since day 1 of the inotersen therapy (D1–first dose of inotersen). Disease progression was evaluated by standard measures. Results Ten ATTRv-PN patients with Val30Met mutation were included. The mean disease duration on D1 was of 3 years, and the mean age of the patients was of 46.8 years. During an additional 18-month follow up, neurological function, based on the Neuropathy Impairment Score and the Polyneuropathy Disability Score, functionality aspects (Karnofsky Performance Status), and nutritional and cardiac aspects were maintained. No new safety signs have been noted. Conclusion The treatment with inotersen was effective and well tolerated for the average of 67 months and up to 76 months. Our results are consistent with those of larger phase-III trials.

OBJECTIVE Chronic subdural hematoma (CSDH) is a prevalent neurosurgical condition, particularly among the elderly. Various treatment options exist, but recurrence rates remain high. This systematic review and meta-analysis aims to assess the efficacy and safety of tranexamic acid (TXA) in the management of CSDH. METHODS The authors conducted a comprehensive literature search adhering to the 2020 PRISMA guidelines, involving three primary databases (Scopus, PubMed, and Web of Science) that were searched for articles compiled from inception until October 20, 2023. The primary outcome was recurrence of CSDH, and secondary outcomes included complications and SDH volume following TXA treatment. The mean difference and odds ratios with 95% confidence intervals were calculated using the random-effects model. RESULTS A total of 5 studies, involving 643 patients in the TXA group and 736 patients in the non-TXA group, met the inclusion criteria. The meta-analysis revealed that TXA use led to a significantly lower CSDH recurrence (OR 0.35, 95% CI 0.23–0.53; p < 0.01) without increasing complications (OR 1.84, 95% CI 0.43–7.95; p = 0.42). Additionally, TXA users had a significantly lower CSDH volume compared to the non-TXA group at 3-month follow-up (mean difference −4.56, 95% CI −8.76 to −0.36; p = 0.03). CONCLUSIONS The findings suggest that TXA might be a promising agent for reducing the risk of CSDH recurrence without elevating the risk of complications. However, these results should be interpreted cautiously due to the limited number of studies included and the methodological heterogeneity. Further large-scale randomized controlled trials are needed to confirm these findings.

PURPOSE KRAS is the most commonly mutated driver oncogene in non–small cell lung cancer (NSCLC). Sotorasib and adagrasib, KRAS G12C inhibitors, have been granted accelerated US approval; however, hepatotoxicity is a common side effect with higher rates in patients treated with sotorasib proximal to checkpoint inhibitor (CPI) therapy. The aim of this study was to assess the feasibility and safety of adagrasib after discontinuation of sotorasib because of treatment-related grade 3 hepatotoxicity through real-world and clinical cases. METHODS Medical records from five patients treated in real-world settings were retrospectively reviewed. Patients had locally advanced or metastatic KRAS G12C -mutated NSCLC and received adagrasib after sotorasib in the absence of extracranial disease progression. Additional data were collected for 12 patients with KRAS G12C -mutated NSCLC enrolled in a phase Ib cohort of the KRYSTAL-1 study and previously treated with sotorasib. The end points associated with both drugs included timing and severity of hepatotoxicity, best overall response, and duration of therapy. RESULTS All patients were treated with CPIs followed by sotorasib (initiated 0-64 days after CPI). All five real-world patients experienced hepatotoxicity with sotorasib that led to treatment discontinuation, whereas none experienced treatment-related hepatotoxicity with subsequent adagrasib treatment. Three patients from KRYSTAL-1 transitioned from sotorasib to adagrasib because of hepatotoxicity; one experienced grade 3 ALT elevation on adagrasib that resolved with therapy interruption and dose reduction. CONCLUSION Adagrasib may have a distinct hepatotoxicity profile from sotorasib and is more easily combined with CPIs either sequentially or concurrently. These differences may be used to inform clinical decisions regarding an initial KRAS G12C inhibitor for patients who recently discontinued a CPI or experience hepatotoxicity on sotorasib.

The transplantation of engineered cells that secrete therapeutic proteins presents a promising method for addressing a range of chronic diseases. However, hydrogels used to encase and protect non-autologous cells from immune rejection often suffer from poor mechanical properties, insufficient oxygenation, and fibrotic encapsulation. Here, we introduce a composite encapsulation system comprising an oxygen-permeable silicone cryogel skeleton, a hydrogel matrix, and a fibrosis-resistant polymer coating. Cryogel skeletons enhance the fracture toughness of conventional alginate hydrogels by 23-fold and oxygen diffusion by 2.8-fold, effectively mitigating both implant fracture and hypoxia of encapsulated cells. Composite implants containing xenogeneic cells engineered to secrete erythropoietin significantly outperform unsupported alginate implants in therapeutic delivery over 8 weeks in immunocompetent mice. By improving mechanical resiliency and sustaining denser cell populations, silicone cryogel skeletons enable more durable and miniaturized therapeutic implants.

Background. Microvascular inflammation (MVI) is a key feature of antibody-mediated rejection (AMR) among patients with HLA donor-specific antibody (DSA), but MVI at AMR thresholds (Banff glomerulitis [g] + peritubular capillaritis [ptc] score ≥ 2) without DSA has been increasingly recognized. We aimed to determine the incidence of MVI among highly sensitized kidney transplant recipients without DSA. Methods. We performed a single-center, retrospective, matched cohort study comparing outcomes of kidney transplant recipients with cPRA ≥90% with preexisting DSA (n = 49), cPRA ≥90% without preexisting DSA (n = 47), and matched controls with cPRA = 0 without preexisting DSA (n = 49). Controls were matched by age, donor type, and transplant date. Indication and surveillance biopsies combined with annual de novo DSA screening were obtained. Results. Kidney transplant recipients with a cPRA ≥90% and no evidence of preexisting or de novo DSA had a higher incidence of MVI (glomerulitis + peritubular capillaritis ≥ 2) than patients with cPRA = 0 [35% (17/49) versus 12% (6/49), P = 0.0003] over a median (interquartile range) follow-up of 5 (4–6) y posttransplant. Among this cPRA ≥90% group without DSA, MVI persisted in 54% of cases on follow-up biopsy (7/13), and 24% (4/13) of cases developed transplant glomerulopathy (Banff cg score > 0). Conclusions. Highly sensitized transplant recipients have a high incidence of persistent and progressive MVI, even without DSA. The mechanisms underlying these histologic features needs to be elucidated, but this information is important to consider when making decisions about transplantation among highly sensitized individuals.

Introduction and importance: Cor triatriatum sinister (CTS) is an uncommon heterogeneous congenital cardiac defect that may manifest in adulthood when symptomatic blockage manifests due to a change in hemodynamic physiology or when a condition such as atrial fibrillation (AF) arises. The incidence of cor triatriatum with cardiomyopathy and congenital heart illness ranges from 0.1 to 0.4%. Case presentation: The Department of Cardiology examined a 10-year-old girl for a diastolic murmur. The patient’s medical history was ordinary, and no previously known co-morbid illnesses were present. Pneumonia was the patient’s original medical condition. A cardiac murmur was also discovered during the physical examination, and the patient was forwarded for more research. Physical examination revealed just a diastolic murmur, which was noteworthy. The patient’s care plan includes routine echocardiographic monitoring. Since the deformity was not clinically significant, surgical repair was not advised. Clinical discussion: It is unclear what caused this flaw. A full, incomplete, or fenestrated septum may be the result of the common pulmonary vein failing to merge with the left atrium during embryonic development. The existence of a fibromuscular membrane, which separates the left atrium (LA) into two chambers—the proximal chamber receiving the pulmonary veins (PVs) and the distal chamber contains the mitral valves and LA appendages defines the disease. Conclusion: The diagnostic procedure should be carried out in the optimal settings, however, in cases of frail health systems, employing accessible alternatives might help the early diagnosis. Early referral to a cardiologist is required in case of CTS suspicion.

Case: A 51-year-old man and 64-year-old woman with bilateral cruciate-retaining total knee arthroplasties (CR-TKAs) who sustained unilateral periprosthetic distal femur fractures above their CR-TKA and experienced knee instability secondary to an iatrogenic posterior-cruciate-ligament (posterior cruciate ligament [PCL]) injury from retrograde intramedullary nailing. Both patients recovered knee stability after undergoing revision surgery. Conclusion: Many CR-TKA designs have sufficient medial-lateral intercondylar distance to place a retrograde nail, femoral components with a relatively posterior transition from the trochlear groove to the intercondylar box will necessitate a nail starting point closer to the PCL origin. This may contribute to iatrogenic postoperative knee instability for patients with CR-TKA designs.

Background Rather than considering carotid stenting and endarterectomy to be rival procedures, they ought to be seen as complementary, with some patients more suited to one procedure over another. The respective patient populations best suited for optimal outcomes with stenting and endarterectomy differ substantially. Hence, the CREST‐2 (Carotid Revascularization, Endarterectomy Versus Stent Trial‐2) ( study was designed as 2 separate 2‐arm randomized trials run in parallel. One trial compares intensive medical management with and without stenting; the other, intensive medical management with and without endarterectomy. Each trial has a recruitment target of 1240 patients with ≥70% asymptomatic carotid stenosis, randomized 1:1 in each arm. To ensure patient safety and give stenting the best possible chance of demonstrating net benefits in stroke prevention, CREST‐2 adopted a rigorous procedure for evaluating, monitoring, and approving operators to enroll in the trial. The CREST‐2 Registry was established to allow for recent experience for applicant stent operators. Methods The CREST‐2 Registry is a prospective, multicenter, short‐term observational study of carotid stenting allowing use of multiple devices. Results The registry enrolled its first patient in September 2014, and as of October 2, 2023, a total of 9830 patients have been treated by 207 different stent operators from 103 different clinical centers. In this mixed cohort of asymptomatic (61.1% of the cohort) and symptomatic (38.9%) patients, the 30‐day stroke rate is 1.8% and the combined 30‐day stroke or death rate is 2.6%. At its peak in March 2016, the registry achieved an enrollment rate of 142 cases/month. As of October 20, 2023, a total of 104 patients remain to be enrolled in the CREST‐2 stenting trial. Conclusion The registry has facilitated assembly of a high‐performing team of stent operators for the CREST‐2 trial. With continued support of the many operators, we anticipate completing enrollment by the summer of 2024.