Post-transplant diabetes mellitus (PTDM) worsens outcomes after kidney transplantation, and immunosuppression agents contribute to PTDM. We have previously shown that tacrolimus (TAC) and sirolimus (SIR) cause hyperglycemia in normal rats. While there is little data on the mechanism for immunosuppressant-induced hyperglycemia, we hypothesized that the TAC and SIR-induced changes are reversible. To study this possibility, we compared normal rats treated for 2 weeks with either TAC, SIR, or a combination of TAC and SIR prior to evaluating their response to glucose challenge, with parallel groups also treated for 2 weeks after which treatment was stopped for 4 weeks, prior to studying their response to glucose challenge. Mean daily glucose and growth velocity was decreased in SIR, and TAC+SIR-treated animals compared to controls (P < 0.05). TAC, SIR, and TAC+SIR treatment also resulted in increased glucose response to glucose challenge, compared to controls (P < 0.05). SIR-treated animals also had elevated insulin concentrations in response to glucose challenge, compared to controls (P < 0.05). Insulin content was decreased in TAC and TAC+SIR, and islet apoptosis was also increased after TAC+SIR treatment (P < 0.05). Four weeks after treatments were stopped, all differences resolved between groups. In conclusion, TAC, SIR, and the combination of TAC+SIR-induced changes in glucose and insulin responses to glucose challenge that were accompanied by changes in islet apoptosis and insulin content. These changes were no longer present 4 weeks after cessation of therapy suggesting immunosuppressant-induced changes in glucose metabolism are likely reversible.
OBJECTIVE Sinonasal malignancies that extend to the anterior skull base frequently require neurosurgical intervention. The development of techniques for craniofacial resection revolutionized the management of these neoplasms, but modern and long-term data are lacking, particularly those related to the incorporation of endoscopic techniques and novel adjuvant chemotherapeutics into management schema. The present study was performed to better define the utility of surgical management and to determine factors related to outcome. METHODS Patients who underwent surgery between 1993 and 2020 were included in this retrospective cohort study. Only patients with greater than 6 months of clinical and radiological follow-up were included. Outcome measures included progression, survival, and treatment-related complications. RESULTS Two hundred twenty-five patients were included. The mean clinical follow-up was 6.5 years. The most common histological diagnosis was olfactory neuroblastoma (33%). Overall, metastatic disease and brain invasion were present in 8% and 19% of patients, respectively, at the time of surgery. A lumbar drain was used in 54% of patients. When stratified by decade, higher-stage disease at surgery became more frequent over time (15% of patients had metastatic disease in the 3rd decade of the study period vs 4% in the 1st decade). Despite the inclusion of patients with progressively higher-stage disease, median overall survival (OS) remained stable in each decade at approximately 10 years (p = 0.16). OS was significantly worse in patients with brain invasion (p = 0.006) or metastasis at the time of surgery (p = 0.014). Complications occurred after 28% of operations, but typically resulted in no long-term negative sequelae. Use of a lumbar drain was a significant predictor of complications (p = 0.02). Permanent ophthalmological disabilities were observed after 4% of surgical procedures. One patient died during the perioperative period. Finally, major complications (Clavien-Dindo grade ≥ IIIb) decreased from 27% of patients in the 1st decade to 10% in the 3rd decade (p = 0.007). CONCLUSIONS The surgical management of sinonasal malignancies with anterior skull base involvement is effective and generally safe. Surgical management, however, is only one facet of the overall multimodal management paradigms created to optimize patient outcomes. Survival outcomes have remained stable despite more extensive disease at surgery in patients who have presented in recent decades. The safety of such surgery has improved over time owing to the incorporation of endoscopic surgical techniques and the avoidance of lumbar spinal drainage with open resection.
Background Immunosuppression medications contribute to posttransplant diabetes mellitus in patients and can cause insulin resistance in male rats. Tacrolimus (TAC)-sirolimus (SIR) immunosuppression is also associated with appearance of ovarian cysts in transplant patients. Because insulin resistance is observed in patients with polycystic ovary syndrome, we hypothesized that TAC or SIR may induce reproductive abnormalities. Methods We monitored estrus cycles of adult female rats treated daily with TAC, SIR, and combination of TAC-SIR, or diluent (control) for 4 weeks. Animals were then challenged with oral glucose to determine their glucose and insulin responses, killed, and their blood and tissues, including ovaries and uteri harvested. Results TAC and TAC-SIR treatments increased mean random glucose concentrations (P<0.05). TAC, SIR, and TAC-SIR treatments also increased the glucose response to oral glucose challenge (P<0.05). The insulin response to glucose was significantly higher in rats treated with SIR compared with TAC (P<0.05). TAC, SIR and TAC-SIR treatments reduced number of estrus cycles (P<0.05). The ovaries were smaller after SIR and TAC-SIR treatment compared with controls. The TAC and TAC-SIR treatment groups had fewer preovulatory follicles. Corpora lutea were present in all groups. Ovarian aromatase expression was reduced in the SIR and TAC-SIR treatment groups. A significant (P<0.05) reduction in uterine size was observed in all treatment groups when compared with controls. Conclusion In a model of immunosuppressant-induced hyperglycemia, both TAC and SIR induced reproductive abnormalities in adult female rats, likely through different mechanisms.
The middle fossa approach for the resection of small acoustic neuromas is a viable, but underutilized treatment modality with the goal of hearing preservation. The authors aim to demonstrate this approach and its nuances through this video presentation. A 38-year-old man presented with an incidentally discovered small, intracanalicular acoustic neuroma that was initially observed, but growth was noted. The patient had good hearing, and therefore a hearing preservation approach was offered. A gross-total resection was achieved, and the patient maintained good hearing postoperatively. This video demonstrates relevant anatomy, surgical indications, technical aspects of resection, including reconstruction, and postoperative outcomes. The video can be found here: https://stream.cadmore.media/r10.3171/2021.7.FOCVID21124
BackgroundType of sedation (conscious sedation (CS) or general anesthesia (GA)) during Intra-arterial mechanical thrombectomy (IAMT) for treatment of acute ischemic stroke may affect patient outcomes. Previous studies suggested that CS cohorts have a higher probability of good outcome than GA cohorts. However, CS cohorts had lower initial NIH stroke scores (NIHSS). This study offers an investigation into outcomes after IAMT based on sedation type.MethodsPatients at our institution who underwent IAMT for treatment of acute ischemic stroke caused by anterior circulation occlusion between 2013-2015 were included in the study. Primary endpoint was functional outcome on the modified Rankin Scale (mRS) at 90 days post-IAMT. Secondary endpoints included NIHSS at 48 hours post-IAMT, time from CT scan to puncture and from puncture to initial recanalization, recanalization as defined by the Thrombolysis in Cerebral Ischemia (TICI) score, intensive care and hospital length of stay, and all-cause in-hospital mortality.ResultsThirty nine patients were included in analysis; 17 received GA and 22 received CS. Cohorts were similar in baseline characteristics, including NIHSS. The 90-day mRS was not significantly different between cohorts, as was the case for most secondary endpoints. Successful recanalization was higher in both groups than previously reported and a significantly higher TICI 3 recanalization rate was achieved in the GA cohort.ConclusionsWe show that equal outcomes are possible with either CS or GA if initial NIHSS is comparable. It seems reasonable for neuro-interventionalists to continue practicing using their personal preference for sedation. However, prospective randomized trials are still needed.
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Introduction Clival malignancies pose particular surgical challenges due to complex skull base anatomy and the involvement of vital neurovascular structures. While endoscopic endonasal approached are widely used, the outcomes for clival malignancies remain poorly understood. In this study we assessed the impact of endoscopic and open surgical approaches on PFS, time to initiation of radiotherapy, KPS, and GTR rates for clival malignancies. Methods A retrospective case series for clival malignancies operated between 1993 and 2019 was conducted. Inclusion criteria were age over 18 and a follow-up of at least a 6 months. Statistical analyses were conducted using STATA version 15 statistical software package StataCorp. Results For the whole cohort (113 patients), and for upper and middle lesions, open surgical approaches increased odds of disease progression, compared to EEA (HR 2.10 to HR 2.43), p < 0.05. EEA had a shorter time interval from surgery to initiation of radiotherapy. No difference in 6 and 12 month KPS was found between surgical groups. Patients undergoing open surgery were less likely to achieve GTR for upper clival lesions. Conclusions EEA was found to be associated with increased PFS, for upper and middle clival malignancies. The time to initiation of radiotherapy was shorter for patients undergoing EEA compared to open surgery for patients with middle clival involvement. GTR rates were found to be significantly better with EEA for patients with upper clival malignancies.
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