Cervical Spinal Cord Morphometrics in Degenerative Cervical Myelopathy: Quantification using Semi-automated Normalized Technique and Correlation with Neurological Dysfunctions.

BACKGROUND CONTEXT: Degenerative cervical myelopathy (DCM) is characterized by spinal cord atrophy. Accurate estimation of spinal cord atrophy is key to the understanding of neurological diseases, including DCM. However, its clinical application is hampered by difficulties in its precise and consistent estimation due to significant variability in spinal cord morphometry along the cervical spine, both within and between individuals. PURPOSE: To characterize morphometrics of the compressed spinal cord in DCM patients. We employed our semi-automated analysis framework that incorporates the Spinal Cord Toolbox (SCT) and a normalization approach to effectively address the challenges posed by cord compression in these patients. Additionally, we examined the clinical relevance of these morphometric measures to enhance our understanding of DCM pathophysiology. STUDY DESIGN: Prospective study. PATIENT SAMPLE: This study investigated 36 DCM patients and 31 healthy controls (HCs). OUTCOME MEASURES: Clinical scores including 9-hole peg test for hand dexterity, hand grip strength, balance, gait speed, modified Japanese Orthopaedic Association (mJOA) score, and imaging-based spinal cord morphometrics. METHOD: Using the generic spine acquisition protocol and our semi-automated analysis pipeline, spinal cord morphometrics, including cross-sectional area (CSA), anterior-posterior (AP) and transverse (RL) diameters, eccentricity, and solidity, were estimated from sagittal T2w magnetic resonance imaging (MRI) images using the Spinal Cord Toolbox (SCT). Normalized metrics were extracted from the C1 to C7 vertebral levels and compared between DCM patients and HC. Morphometric data at regions of maximum spinal cord compression (MSCC) were correlated with the clinical scores. A subset of participants underwent follow-up scans at six months to monitor longitudinal changes in spinal cord atrophy. RESULTS: Spinal cord morphometric data were normalized against the healthy population morphometry (PAM50 database) and extracted for all participants. DCM patients showed a notable reduction in CSA, AP, and RL diameter across all vertebral levels compared to HC. MSCC metrics correlated significantly with clinical scores like dexterity, grip strength, and mJOA scores. Longitudinal analysis indicated a decrease in CSA and worsening clinical scores in DCM patients. CONCLUSION: Our processing pipeline offers a reliable method for assessing spinal cord compression in DCM patients. Normalized spinal cord morphometrics, particularly the CSA could have potential for monitoring DCM disease severity and progression, guiding treatment decisions. Furthermore, to our knowledge our study is the first to apply the generic spinal cord acquisition protocol, ensuring consistent imaging across different MRI scanners and settings. Coupled with our semi-automated analysis pipeline, this protocol is key for the detailed morphometric characterization of compressed spinal cords in patients with DCM, a disease that is both complex and heterogenous. This study was funded by the National Institute of Neurological Disorders and Stroke (NINDS) (K23:NS091430) and (R01: NS129852-01A1).

Post-pandemic paradigm shift toward telemedicine and tele-education; an updated survey of the impact of Covid-19 pandemic on neurosurgery residents in United States.

Background: Several strategies were implemented during the Covid-19 pandemic to enhance residency training and patient care. Objective: This study aims to assess the post-pandemic landscape of neurosurgical training and practice. Method: A survey consisting of 28 questions examining the challenges faced in neurosurgery and the adaptive measures was conducted among US neurosurgery residents from May 2022 to May 2023. Results: This study encompassed 59 neurosurgical residents, predominantly male (72.9%) and in later years of training (66.1%) and were distributed across 25 states. Telemedicine and tele-education were pivotal during the pandemic, with virtual lecture series, standalone lectures, and virtual discussions highly favored. Remote didactic learning increased for nearly half of the residents, while 54.2% resumed in-person instruction. Telemedicine was deemed effective by 86.4% for evaluating neurosurgical patients. Access to teaching environments was restricted for 61.0% of residents, impacting their training. The pandemic significantly influenced elective surgeries, with complete cancellations reported by 42.4%. Reduced faculty engagement was noted by 35.6% of residents, while 47.5% reported a negative impact on the overall resident experience. The majority (76.3%) considered changes to their training reasonable given the global health situation. Conclusions: Strategies implemented during the peak of the pandemic remain crucial in shaping neurosurgery training. Telemedicine has become indispensable, with widespread adoption. Tele-education has also expanded, providing additional learning opportunities. However, traditional didactic courses and hands-on experiences remain essential for comprehensive training. Balancing technology-driven methods with established approaches is crucial for optimizing neurosurgical education and maintaining high-quality patient care.

Early neurological changes in aging cervical spine: insights from PROMIS mobility assessment.

Many studies have shown that the prevalence of degenerative spinal cord compression increases with age. However, most cases at early stages are asymptomatic, and their diagnosis remains challenging. Asymptomatic cervical spinal cord compression (ASCC) patients are more likely to experience annular tears, herniated disks, and later develop symptomatic compression. Asymptomatic individuals do not typically undergo spinal cord imaging; therefore, an assessment test that is both sensitive and specific in diagnosing ASCC may be helpful. It has been demonstrated that the Patient Reported Outcome Measure Information System (PROMIS) mobility test is sensitive in detecting degenerative cervical myelopathy (DCM) symptoms. We investigated the use of the PROMIS mobility test in assessing clinical dysfunction in ASCC. In this study, 51 DCM patients and 42 age-matched healthy control (HC) were enrolled. The degree of cervical spinal cord compression was assessed using the high-resolution cervical spinal cord T2 Weighted (T2w) MRIs, which were available for 14 DCM patients. Measurements of the spinal cords anterior-posterior (AP) diameter at the region(s) that were visibly compressed as well as at different cervical spine levels were used to determine the degree of compression. The age-matched HC cohort had a similar MRI to establish the normal range for AP diameter. Twelve (12) participants in the HC cohort had MRI evidence of cervical spinal cord compression; these individuals were designated as the ASCC cohort. All participants completed the PROMIS mobility, PROMIS pain interference (PI), PROMIS upper extremity (UE), modified Japanese orthopedic association (mJOA), and neck disability index (NDI) scoring scales. We examined the correlation between the AP diameter measurements and the clinical assessment scores to determine their usefulness in the diagnosis of ASCC. Furthermore, we examine the sensitivity and specificity of PROMIS mobility test and mJOA. Compared to the HC group, the participants in the ASCC and DCM cohorts were significantly older (p = 0.006 and p < 0.0001, respectively). Age differences were not observed between ASCC and DCM (p > 0.999). Clinical scores between the ASCC and the HC group were not significantly different using the mJOA (p > 0.99), NDI (p > 0.99), PROMIS UE (p = 0.23), and PROMIS PI (p = 0.82). However, there were significant differences between the ASCC and HC in the PROMIS mobility score (p = 0.01). The spinal cord AP diameter and the PROMIS mobility score showed a significant correlation (r = 0.44, p = 0.002). Decreasing PROMIS mobility was significantly associated with a decrease in cervical spinal cord AP diameter independent of other assessment measures. PROMIS mobility score had a sensitivity of 77.3% and specificity of 79.4% compared to 59.1% and 88.2%, respectively, for mJOA in detecting cervical spinal cord compression. Certain elements of ASCC are not adequately captured with the traditional mJOA and NDI scales used in DCM evaluation. In contrast to other evaluation scales utilized in this investigation, PROMIS mobility score shows a significant association with the AP diameter of the cervical spinal cord, suggesting that it is a sensitive tool for identifying early disability associated with degenerative change in the aging spine. In a comparative analysis of PROMIS mobility test against the standard mJOA, the PROMIS mobility demonstrated higher sensitivity for detecting cervical spinal cord compression. These findings underscore the potential use of PROMIS mobility score in clinical evaluation of the aging spine.

Evaluating a Change in Surgical Antibiotic Prophylaxis in Kidney Transplant Recipients.

The purpose of this study was to retrospectively evaluate if a change in practice from January 2013 to August 2015 affected the rate of surgical-site infections following kidney transplantation at the single academic medical center. More patients were found to have a surgical-site infection when surgical antibiotics were only given intra-operatively despite a lower incidence of risk factors identified in the literature when compared to the cohort who received antibiotics intra-op and post-op for 24 hours.

Process Optimization to Improve Immunosuppressant Drug Testing Turnaround Time.

OBJECTIVES: Timely reporting of immunosuppressant (ISP) drug level results is needed for transplant patient management. This study characterized the local ISP testing process, identified bottlenecks and implemented process improvements to meet turnaround time requirements. METHODS: Laboratory information time stamps, direct observation and discussion with staff were used to construct a value stream map of the ISP testing process to identify process bottlenecks. Improvements were implemented to attain the required turnaround time. RESULTS: Baseline performance of the existing ISP process (seven weeks, n = 272 samples) indicated that only 28% of samples were reported by 2:00 pm Major bottlenecks were identified to be the analytical run schedule, instrument delays, difficulty identifying ISP samples at intake, and difficulty collecting specimens. Process changes resulted in a median of 76% samples reported by 2:00 pm CONCLUSIONS: : Adjusting ISP collection and analysis processes improved the laboratory's ability to meet physician requested result reporting time of 2:00 pm.

Implementation of a patient-focused specialty pharmacy program in an academic healthcare system.

PURPOSE: The development and implementation of a systemwide specialty pharmacy program in an academic healthcare system are described. SUMMARY: Although the system's pharmacy department had developed specialty pharmacy services for patients with certain conditions, it was necessary to expand and standardize those services to meet the needs of all specialty clinics because (1) many of the clinics had experienced an increased volume of prior-authorization requests due to the introduction of new specialty drugs, (2) the dispensing pharmacies were operating at maximum capacity due to the previous decentralization of specialty pharmacy operations, and (3) payers had sent notice that they would require accreditation of the specialty pharmacy program as a condition of participation in their specialty pharmacy networks. To ensure standardization of services and successful preparation for increasing numbers of specialty prescriptions, all specialty pharmacy services were centralized to the healthcare system's Pharmacy Ambulatory Clinical Care Center (PAC(3)). PAC(3) centralized the prior-authorization process to selected specialty clinics. A call center was developed at PAC(3) to provide centralized specialty pharmacy services, including 24-7 patient support, a medication adherence program, home delivery service, and patient education. The program resulted in a 137% increase in specialty pharmacy revenues over a two-year period. PAC(3) processed 1860 prior-authorization cases and enrolled approximately 700 new patients in the specialty pharmacy program within nine months. CONCLUSION: A specialty pharmacy program was established along with operational and infrastructure improvements, resulting in increased revenue, systemwide services, and a fully accredited specialty pharmacy.

Focus on mTOR inhibitors and tacrolimus in renal transplantation: pharmacokinetics, exposure-response relationships, and clinical outcomes.

Mammalian target of rapamycin (mTOR)-inhibitor-containing immunosuppressive regimens have been developed as part of calcineurin inhibitor (CNI) minimization/withdrawal strategies for renal transplant recipients, with the goal of avoiding CNI-associated nephrotoxicity. This review focuses on the pharmacokinetic interactions and exposure-response relationships of mTOR inhibitors and tacrolimus (TAC), the most widely used CNI. We also discuss key randomized clinical studies that have evaluated use of this combination in renal transplantation. Pharmacokinetic studies have shown that mTOR inhibitors, everolimus (EVR) and sirolimus (SRL), have a large intra- and inter-patient variability in drug exposure, and narrow therapeutic windows (trough levels [C0] 3-8 ng/mL and 5-15 ng/mL, respectively). Consequently, routine therapeutic drug monitoring of EVR and SRL is recommended to optimize efficacy and minimize toxicity in individual patients. As there is a good correlation between C0 and area under the curve (AUC), C0 can be used as a convenient and reliable measure of mTOR drug exposure. Clinical data on the use of EVR or SRL in TAC minimization strategies in renal transplantation are limited. Available evidence suggests that treatment with EVR allows early and substantial TAC minimization when used with basiliximab induction and corticosteroids, to achieve good renal function without compromising efficacy or safety. However, data comparing this combination with other regimens are lacking. Results with SRL are more mixed. SRL in combination with reduced TAC has been shown to provide less nephrotoxicity than the SRL/standard TAC combination, with comparable efficacy and safety. However, this approach has been shown to be inferior to other regimens in terms of patient/graft survival and biopsy-proven acute rejection (vs MMF/TAC) as well as renal function (vs MMF/TAC and SRL/MMF). Further studies are needed to define the therapeutic window for TAC when used in combination with mTOR inhibitors, evaluate EVR/reduced TAC versus other regimens, assess long-term outcomes, and determine efficacy and safety in high-risk patients.

Low-dose fluconazole prophylaxis in kidney transplant recipients receiving tacrolimus.

BACKGROUND: The use of prophylactic antifungal therapy is suggested after kidney transplantation. However, efficacy of low-dose (50 mg) oral fluconazole and its effect on tacrolimus trough levels in patients maintained on tacrolimus and mycophenolic acid, with or without corticosteroids, is unknown. METHODS: A retrospective analysis to evaluate efficacy was performed in 305 kidney transplant recipients. An additional analysis to evaluate the fluconazole-tacrolimus drug interaction was performed in 103 patients. Complete tacrolimus area under the curve measurements were also performed in seven patients to further evaluate this drug interaction. RESULTS: The incidence of fungal infections was very low (0.6%, n = 2). The average tacrolimus trough level at the time of discontinuation and one wk after stopping fluconazole was unchanged (11.69 ± 3.18 and 11.15 ± 3.69 ng/mL, p = 0.145, n = 103). Tacrolimus trough levels on and off of fluconazole in a subgroup of patients continued on corticosteroids, was not significantly different (p = 0.952) but was significantly lower after fluconazole discontinuation if corticosteroids were withdrawn (p = 0.037). However, data from complete tacrolimus pharmacokinetics in the corticosteroid withdrawal group demonstrated no clinically significant differences. CONCLUSION: Low-dose, once daily oral fluconazole is effective antifungal prophylaxis after kidney transplantation without significant effects on tacrolimus trough levels or overall exposure.

Factors associated with nonadherence to medication in kidney transplant recipients.

Nonadherence in kidney transplant recipients was evaluated in this report using a questionnaire with five binary questions and one question on a continuous scale. Study participants at the University of Utah Transplant Program (n = 199) were 43.0 ± 14.2 years old; 67% were males, and 81% were White. Two questions that produced heterogeneous outcome were analyzed: 'Do you ever forget to take your medication?' (79% no, 21% yes) and 'Have you ever taken your medications late?' (67% no, 33% yes). Responses to these questions correlated (χ² 65.2, p < 0.001; correlation coefficient 0.57, p < 0.001). We performed a logistic regression analysis to identify factors associated with the combined outcome of forgetting/not taking medications altogether or taking medications off schedule. Higher comorbidity index [odds ratio (OR) 2.19, p < 0.001], living (compared to deceased) donor (OR 2.81, p = 0.005) and full-time employment were associated with forgetting medications or taking them late (OR 3.12, p = 0.01). Recipient age tended to be associated with lower risk of nonadherence, but did not reach statistical significance (OR 0.98 per year of age, p = 0.13). Education level, smoking status, recipient race, dialysis modality, number of medications and the time since first kidney transplantation were not associated with the outcome. In conclusion, renal transplant recipients with greater comorbidity, receiving kidney from a living donor and with full-time employment reported lower levels of medication adherence.

A population-based assessment of the familial component of acute kidney allograft rejection.

BACKGROUND: The genetic determinants of acute kidney transplant rejection (AR) are not well studied, and familial aggregation has never been demonstrated. The goal of this retrospective case-control study was to exploit the unique nature of the Utah Population Database (UPDB) to evaluate if AR or rejection-free survival aggregates in families. METHODS: We identified 891 recipients with genealogy data in the UPDB with at least one year of follow-up, of which 145 (16.1%) had AR and 77 recipients had biopsy-proven rejection graded >or=1A. We compared the genealogical index of familiality (GIF) in cases and controls (i.e. recipients with random assignment of rejection status). RESULTS: We did not find evidence for familial clustering of AR in the entire patient population or in the subgroup with early rejection (n = 52). When the subgroup of recipients with rejection grade >or=1A (n = 77) was analysed separately, we observed increased familial clustering (GIF = 3.02) compared to controls (GIF = 1.96), although the p-value did not reach the level of statistical significance (p = 0.17). Furthermore, we observed an increase in familial clustering in recipients who had a rejection-free course (GIF = 2.45) as compared to controls (GIF = 2.08, p = 0.04). When all recipients were compared to non-transplant controls, they demonstrated a much greater degree of familiality (GIF = 2.03 versus GIF 0.63, p < 0.001). CONCLUSIONS: There is a familial component to rejection-free transplant course and trend to familial aggregation in recipients with AR grade 1A or higher. If a genetic association study is performed, there are families in Utah identified in the current study that can be targeted to increase the power of the test.

No occurrence of de novo HLA antibodies in patients with early corticosteroid withdrawal in a 5-year prospective randomized study.

The purpose of this study was to determine the effect of early corticosteroid cessation on the occurrence of de novo human leukocyte antigen (HLA) antibody posttransplant. Renal transplant recipients (n=37) were randomized to early corticosteroid withdrawal at day 7 posttransplant (n=21 patients), or to chronic steroids (n=16), all in combination with thymoglobulin as induction agent, tacrolimus and mycophenolic acid as maintenance therapy. To establish the time course of HLA antibody appearance, sera collected pretransplant and for up to 5 years posttransplant were screened for the appearance of HLA antibodies. In this 5-year longitudinal study, only one patient in the control group developed a de novo donor-specific HLA antibody. We conclude that renal transplant recipients on steroid withdrawal by the end of week 1 are not at higher risk for developing HLA antibodies compared with a standard steroid regimen up to 5 years posttransplant.

Role of maintenance immunosuppressive regimen in kidney transplant outcome.

Data of long-term immunosuppressive protocol comparison are lacking. The goal of this study was to compare kidney transplant outcome using three common immunosuppressive protocols. A retrospective study was performed of the graft and recipient survival using US Renal Data System data (n = 31,012) between January 1, 1995, and December 31, 1999, with the follow-up through December 31, 2000, on prednisone + cyclosporine + mycophenolate mofetil (PCM; n = 17,108), prednisone + tacrolimus + mycophenolate mofetil (PTM; n = 7225), or prednisone + cyclosporine + azathioprine (PCA; n = 6679). Compared with PCM, there is an increased risk for allograft failure associated with PTM (hazard ratio [HR] 1.09; P < 0.05) and PCA (HR 1.15; P < 0.001). Similar associations were demonstrated in the following subgroups: Early (before 1997) and late (in or after 1997) transplant periods, in living-donor transplants, and in adult and kidney-only recipients. This association also was found between PCA regimen and graft survival in the entire patient population (HR 1.15; P < 0.001) and in the studied subgroups. PCA (HR 1.15; P < 0.005), but not PTM (HR 1.01; P = 0.816), regimen was associated with increased recipient mortality in the entire patient population and in patient subgroups. Secondary outcomes (serum creatinine values at given time points, acute rejection rate, and posttransplantation malignancies) are also discussed. These data suggest that a PCM regimen is associated with lower risk for graft failure compared with a PTM regimen and with lower risk for graft failure and recipient death compared with a PCA regimen.

A retrospective assessment of pre-treatment variables on the response to darbepoetin alfa after renal transplantation.

This retrospective review assesses the efficacy of darbepoetin alfa for treating anemia after renal transplantation. Patients were evaluated over a 12-week period, and efficacy was based on achieving hemoglobin >12 g/dL. Thirty-six patients were analyzed (53% male, 53% cadaveric allografts, median age 42.5 years). Baseline creatinine clearance ranged from approximately 15 to >100 mL/min. Most patients initiated darbepoetin alfa <3 months (50%) or >12 months (44%) after transplantation, 19% were previously receiving recombinant human erythropoietin (rHuEPO), and 47% were on concomitant ACE inhibitors. The majority of patients received either tacrolimus- (53%) or cyclosporine- (44%) based immunosuppression. Overall, 29 (81%) patients achieved the hemoglobin target with a mean time to response of 4.4 weeks. Neither the time to anemia onset, previous rHuEPO therapy, concomitant ACE inhibitor, allograft source, immunosuppressive regimen, nor degree of renal function affected the proportion of patients achieving the hemoglobin target, time to response or darbepoetin alfa dose requirement. Patients with anemia >12 months post-transplantation or on concomitant ACE inhibitors required a significantly longer duration of therapy. No adverse events associated with darbepoetin alfa therapy were detected. These results demonstrate that darbepoetin alfa is a safe and effective treatment for anemia in renal transplant recipients.

Lack of economic benefit with basiliximab induction in living related donor adult renal transplant recipients.

STUDY OBJECTIVE: To assess the effect of basiliximab (BAS) induction therapy on acute rejection rates and overall costs in adult living related donor (LRD) renal transplant recipients. Design. Retrospective chart review and cost-effectiveness analysis of the first 12 months after transplantation. SETTING: University hospital and outpatient renal transplant clinic. PATIENTS: Sixty consecutive adult LRD renal transplant recipients. INTERVENTION: The treatment group received BAS 20 mg intravenously on postoperative days 0 and 4. The control group received no induction agents. Both groups received cyclosporine microemulsion, azathioprine, and corticosteroids for maintenance immunosuppression. MEASUREMENTS AND MAIN RESULTS: Six patients (three in each group) were excluded; three had received muromonab-CD3 as an induction agent and three were lost to follow-up. At 12-months, the frequency of acute rejection episodes was 15% (4/27) in the control group and 22% (6/27) in the BAS group (NS). Renal function, as measured by average serum creatinine level, was similar at months 1, 2, 3, 6, and 12 for both groups. The frequency of infectious complications was similar in both groups. No adverse effects were associated with BAS. Mean initial hospitalization charges were dollar 51,970.01 and dollar 68,093.90 in the control and BAS groups, respectively (p < 0.05). The control group had more readmissions (18 vs 14 in the BAS group), but the average charge/readmission was lower (dollar 10,148.50 vs dollar 21,952.58 in the BAS group; NS). All costs were adjusted to 2000 dollars (US). CONCLUSION: Basiliximab induction therapy did not provide clear clinical efficacy benefit or prove to be cost-effective compared with no induction in LRD recipients.