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OBJECTIVE The study objective was to create a novel milestones evaluation form for neurosurgery sub-interns and assess its potential as a quantitative and standardized performance assessment to compare potential residency applicants. In this pilot study, the authors aimed to determine the form’s interrater reliability, relationship to percentile assignments in the neurosurgery standardized letter of recommendation (SLOR), ability to quantitatively differentiate tiers of students, and ease of use. METHODS Medical student milestones were either adapted from the resident Neurological Surgery Milestones or created de novo to evaluate a student’s medical knowledge, procedural aptitude, professionalism, interpersonal and communication skills, and evidence-based practice and improvement. Four milestone levels were defined, corresponding to estimated 3rd-year medical student through 2nd-year resident levels. Faculty and resident evaluations as well as student self-evaluations were completed for 35 sub-interns across 8 programs. A cumulative milestone score (CMS) was computed for each student. Student CMSs were compared both within and between programs. Interrater reliability was determined with Kendall’s coefficient of concordance (Kendall’s W). Student CMSs were compared against their percentile assignments in the SLOR using analysis of variance with post hoc testing. CMS-derived percentile rankings were assigned to quantitatively distinguish tiers of students. Students and faculty were surveyed on the form’s usefulness. RESULTS The average faculty rating overall was 3.20, similar to the estimated competency level of an intern. Student and faculty ratings were similar, whereas resident ratings were lower (p < 0.001). Students were rated most highly in coachability and feedback (3.49 and 3.67, respectively) and lowest in bedside procedural aptitude (2.90 and 2.85, respectively) in both faculty and self-evaluations. The median CMS was 26.5 (IQR 21.75–29.75, range 14–32) with only 2 students (5.7%) achieving the highest rating of 32. Programs that evaluated the most students differentiated the highest-performing students from the lowest by at least 13 points. A program with 3 faculty raters demonstrated scoring agreement across 5 students (p = 0.024). The CMS differed significantly between SLOR percentile assignments, despite 25% of students being assigned to the top fifth percentile. CMS-driven percentile assignment significantly differentiated the bottom, middle, and top third of students (p < 0.001). Faculty and students strongly endorsed the milestones form. CONCLUSIONS The medical student milestones form was well received and differentiated neurosurgery sub-interns both within and across programs. This form has potential as a replacement for numerical Step 1 scoring as a standardized, quantitative performance assessment for neurosurgery residency applicants.

The rate of surgical site infection (SSI) following elective spine surgery ranges from 0.5%‒10%. Published reports suggest a higher SSI rate in non-elective spine surgery such as spine trauma; however, there is a paucity of large database studies examining this issue.The objective of this study was to investigate the incidence and risk factors of SSI in patients undergoing spine surgery for thoracic and lumbar fractures in a large population database.This is a retrospective study utilizing the PearlDiver Patient Claims Database.Patients undergoing spine surgery for thoracic and lumbar fractures between 2015-2020 were identified in the PearlDiver Patient Claims Database using ICD-10 codes. Patients were excluded who had another surgery either 14 days before or 21 days after the index spine surgery, or pathologic fracture.Rate of surgical site infection.Clinical data collected from the PearlDiver database based on ICD-10 codes included gender, age, diabetes, smoking status, obesity, Elixhauser Comorbidity Index (ECI), Charlson Comorbidity Index (CCI), and SSI. Univariate analysis was used to assess the association of potential risk factors and SSI. Multivariable analysis was used to identify independent risk factors of SSI. The authors have no conflicts of interest or funding sources to declare.A total of 11,401 patients undergoing spine surgery for thoracic and lumbar fractures met inclusion criteria, and 1,065 patients were excluded. 860 patients developed SSI (7.5%). Risk factors significantly associated with SSI in univariate analysis included diabetes (OR 1.50; 95% CI, 1.30‒1.73; p.001), obesity (OR 1.66; 95% CI, 1.44‒1.92; p.001), increased age (p.001), ECI (p.001), and CCI (p.001). On multivariable analysis, obesity and ECI were independently associated with SSI (p.001 and p.001, respectively).Non-elective surgery for thoracic and lumbar fractures is associated with a 7.5% risk of SSI. Obesity and ECI are independent predictors of SSI in this population. Limitations include the reliance on accurate insurance coding which may not fully capture all SSI, and in particular superficial SSI. These findings provide a broad overview of the risk of SSI in this population at a national level and may also help counsel patients regarding risk.

Supplementary Materials from Evaluation of current methods used to analyze the expression profiles of ATP-binding cassette transporters yields an improved drug-discovery database

The development of multidrug resistance (MDR) to chemotherapy remains a major challenge in the treatment of cancer. Resistance exists against every effective anticancer drug and can develop by multiple mechanisms. These mechanisms can act individually or synergistically, leading to MDR, in which the cell becomes resistant to a variety of structurally and mechanistically unrelated drugs in addition to the drug initially administered. Although extensive work has been done to characterize MDR mechanisms in vitro, the translation of this knowledge to the clinic has not been successful. Therefore, identifying genes and mechanisms critical to the development of MDR in vivo and establishing a reliable method for analyzing highly homologous genes from small amounts of tissue is fundamental to achieving any significant enhancement in our understanding of MDR mechanisms and could lead to treatments designed to circumvent it. In this study, we use a previously established database that allows the identification of lead compounds in the early stages of drug discovery that are not ATP-binding cassette (ABC) transporter substrates. We believe this can serve as a model for appraising the accuracy and sensitivity of current methods used to analyze the expression profiles of ABC transporters. We found two platforms to be superior methods for the analysis of expression profiles of highly homologous gene superfamilies. This study also led to an improved database by revealing previously unidentified substrates for ABCB1, ABCC1, and ABCG2, transporters that contribute to MDR. [Mol Cancer Ther 2009;8(7):2057–66]

OBJECTIVE To comply with the removal of the 88-hour week exemption and to support additional operative experience during junior residency, Oregon Health & Science University (OHSU) switched from a night-float call schedule to a modified 24-hour call schedule on July 1, 2019. This study compared the volumes of clinical, procedural, and operative cases experienced by postgraduate year 2 (PGY-2) and PGY-3 residents under these systems. METHODS The authors retrospectively studied billing and related clinical records, call schedules, and Accreditation Council for Graduate Medical Education case logs for PGY-2 and PGY-3 residents at OHSU, a tertiary academic health center, for the first 4 months of the academic years from 2017 to 2020. The authors analyzed the volumes of new patient consultations, bedside procedures, and operative procedures performed by each PGY-2 and PGY-3 resident during these years, comparing the volumes experienced under each call system. RESULTS Changing from a PGY-2 resident–focused night-float call system to a 24-hour call system that was more evenly distributed between PGY-2 and PGY-3 residents resulted in decreased volume of new patient consultations, increased volume of operative procedures, and no change in volume of bedside procedures for PGY-2 residents. PGY-3 residents experienced a decrease in operative procedure volume under the 24-hour call system. CONCLUSIONS Transition from a night-float system to a 24-hour call system altered the distribution of clinical and procedural experiences between PGY-2 and PGY-3 residents. Further research is necessary to understand the impact of these changes on educational outcomes, quality and safety of patient care, and resident satisfaction.

Introduction Pilocytic astrocytoma is a classically benign tumor that most often affects pediatric patients. Rarely, it occurs during adulthood. We present a case series and systematic literature review of adult pilocytic astrocytoma (APA) to examine the clinical presentation, extent of resection, and recurrence rate associated with this tumor in this population. Materials and Methods Our institutional records were retrospectively reviewed for cases of pilocytic astrocytoma in adults. A PubMed search identified English-language studies of pathology-proven APA. A meta-analysis was performed to determine the relationship between extent of tumor resection and recurrence. Results Forty-six patients with APA were diagnosed at our institution (mean age 33.6 ± 13.3; 24 [52%] female). Twenty-four patients (52%) underwent gross total resection, 11 (24%) subtotal resection, 4 (9%) near total resection, 4 (9%) observation after biopsy, and 3 (6%) radiotherapy alone. Tumors recurred or progressed in 6 (13%) patients, of whom 4 were treated by STR and 2 were treated by radiotherapy alone. Thirty-nine (95%) patients were still alive at last follow-up. A systematic literature review identified 415 patients with APA in 38 studies. Including our case series, 7 studies reported extent of resection, follow-up, and recurrence. Of 254 patients with a weighted mean follow-up of 77.7 ± 49.6 (31–250) months, 129 (51%) were treated with gross total resection, and 125 (49%) underwent subtotal resection. Tumor recurred in 79 (31%) patients, 22 (27%) after gross total resection and 57 (73%) after subtotal resection (P Conclusions Pilocytic astrocytoma rarely presents during adulthood. Overall, prognosis is favorable and survival rates are high. APA recurrence is more likely after STR, and the goal of surgery should always be GTR when feasible.

Spinal deformity can be defined as malalignment of the spine in the coronal, sagittal, and/or axial planes. It is a common condition with a great clinical impact on health-related quality of life and the cost of care. Appropriate management may encompass a wide range of options including nonoperative care, limited decompression, limited fusion, and complex spinal realignment. Complex spinal realignment involves application of a broad spectrum of techniques for deformity correction and is often characterized by significant variability in surgical approach between providers. The presence of variability reflects an absence of an evidence-based approach to care and the need for guiding principles. The purpose of this chapter is to describe the impact of spinal deformity on health status and to detail principles of deformity correction that can guide clinicians in selecting appropriate surgical plans to maximize patient benefit while minimizing the risks and costs of care.

Although in vitro models have been a cornerstone of anti-cancer drug development, their direct applicability to clinical cancer research has been uncertain. Using a state-of-the-art Taqman-based quantitative RT-PCR assay, we investigated the multidrug resistance (MDR) transcriptome of six cancer types, in established cancer cell lines (grown in monolayer, 3D scaffold, or in xenograft) and clinical samples, either containing >75% tumor cells or microdissected. The MDR transcriptome was determined a priori based on an extensive curation of the literature published during the last three decades, which led to the enumeration of 380 genes. No correlation was found between clinical samples and established cancer cell lines. As expected, we found up-regulation of genes that would facilitate survival across all cultured cancer cell lines evaluated. More troubling, however, were data showing that all of the cell lines, grown either in vitro or in vivo, bear more resemblance to each other, regardless of the tissue of origin, than to the clinical samples they are supposed to model. Although cultured cells can be used to study many aspects of cancer biology and response of cells to drugs, this study emphasizes the necessity for new in vitro cancer models and the use of primary tumor models in which gene expression can be manipulated and small molecules tested in a setting that more closely mimics the in vivo cancer microenvironment so as to avoid radical changes in gene expression profiles brought on by extended periods of cell culture.

Background Wide-necked anterior communicating artery aneurysms represent a subset of lesions with challenging endovascular treatment despite new endoluminal and intrasaccular devices. Objective To assess the long-term clinical and angiographic outcomes of stent-assisted embolization for wide-necked anterior communicating artery aneurysms. Methods Between March 2008 and March 2014, 32 patients with unruptured wide-necked AComm aneurysms were treated using stent-assisted embolization. The Glasgow Outcome Scale was reviewed at the time of discharge and at latest follow-up. Ischemic and hemorrhagic events were also recorded and analyzed. Aneurysm occlusion was evaluated post-intervention and on subsequent follow-up evaluations. Results Successful stent deployment was achieved in all cases, but in 1 patient the coils could not be contained inside the aneurysm, and the procedure was aborted without complications. The distal segment of the stent was positioned in the ipsilateral A2 in 16 patients, in the contralateral A2 in 15 patients, and in the contralateral A1 in 1 patient. There were no periprocedural thromboembolic or hemorrhagic complications. The rate of major complications was 6%. One patient developed intracranial hemorrhage related to antiplatelet therapy and another had ischemic events due to in-stent stenosis. Angiographic follow-up was available for 26 aneurysms and during a mean follow-up of 22 months, 81% of the lesions were completely occluded and 8% had a small residual neck. The retreatment rate for residual aneurysms was 3%. Conclusion Our long-term results suggest that stent-assisted embolization for anterior communicating artery aneurysms may be considered an excellent treatment option with an adequate combination of safety profile and effectiveness.

BACKGROUND AND IMPORTANCE: Intracranial dural arteriovenous fistulas (DAVFs) are acquired abnormal communications between dural arteries and veins. Risk factors for development include sinus thrombosis and hypercoagulability, such as occurs in heritable thrombophilias. While there have been reports of other types of vascular anomalies (such as cavernous and arteriovenous malformations) occurring in families, to our knowledge there have been no reports of familial intracranial DAVFs. We describe the first 2 cases of intracranial DAVFs occurring in first-degree relatives. CLINICAL PRESENTATION: A 66-year-old woman presented with an 18-month history of bilateral pulsatile tinnitus. Neurological examination was significant for a prominent pulsatile bruit over the left mastoid region. Laboratory studies demonstrated heterozygosity for Prothrombin G20210A mutation. Imaging disclosed a large left Type I Borden DAVF involving the distal transverse-sigmoid sinus junction. She underwent uncomplicated stereotactic radiosurgery to the fistula that led to complete resolution of her tinnitus and the fistula. A 73-year-old woman, the sister of the previous patient, presented with a 24-month history of pulsatile tinnitus affecting the left ear. Laboratory studies demonstrated heterozygosity for the Prothrombin G20210A mutation. Imaging revealed a left Type I Borden DAVF involving the left transverse and sigmoid sinuses. The patient's symptoms resolved spontaneously without treatment. Repeat imaging revealed interval involution of the fistula. CONCLUSION: We describe 2 sisters who were heterozygous for Prothrombin G20210A mutation and found to have DAVFs. Clinicians should be aware of the potential for these fistulas to congregate in first-degree relatives via heritable thrombophilias such as the Prothrombin G20210A mutation.

The development of multidrug resistance (MDR) to chemotherapy remains a major challenge in the treatment of cancer. Resistance exists against every effective anticancer drug and can develop by multiple mechanisms. These mechanisms can act individually or synergistically, leading to MDR, in which the cell becomes resistant to a variety of structurally and mechanistically unrelated drugs in addition to the drug initially administered. Although extensive work has been done to characterize MDR mechanisms in vitro, the translation of this knowledge to the clinic has not been successful. Therefore, identifying genes and mechanisms critical to the development of MDR in vivo and establishing a reliable method for analyzing highly homologous genes from small amounts of tissue is fundamental to achieving any significant enhancement in our understanding of MDR mechanisms and could lead to treatments designed to circumvent it. In this study, we use a previously established database that allows the identification of lead compounds in the early stages of drug discovery that are not ATP-binding cassette (ABC) transporter substrates. We believe this can serve as a model for appraising the accuracy and sensitivity of current methods used to analyze the expression profiles of ABC transporters. We found two platforms to be superior methods for the analysis of expression profiles of highly homologous gene superfamilies. This study also led to an improved database by revealing previously unidentified substrates for ABCB1, ABCC1, and ABCG2, transporters that contribute to MDR. [Mol Cancer Ther 2009;8(7):2057–66]

Background: Current guidelines offer numerous options for initiating therapy in patients with untreated, advanced stage follicular lymphoma (FL). Selecting among these options that include watchful waiting, single-agent and combination chemotherapy, monoclonal antibodies, and radioimmunotherapy, remains challenging. Recent data suggest that chemotherapy combined with a monoclonal antibody may alter patterns of relapse and overall survival for pts with FL (Fisher, Blood 2004). While rituximab (R) chemotherapy combinations have become commonly used for untreated pts with FL, to date, the optimal first-line therapy remains undefined. To address this issue, we updated a systematic literature review and performed a meta-analysis of first-line therapy for untreated FL that examined the effect of various chemotherapy regimens combined with R on response rates and survival in patients with untreated FL. Methods: The comprehensive systematic review included searches the Cochrane Central Register of Controlled Trials (Cochrane Library Issue 1, 2003), MEDLINE (1/1996–6/2006), EMBASE (1/1980–7/2006), American Society of Hematology Annual Meeting abstracts (2002–2005), and American Society of Clinical Oncology Annual Meeting abstracts (1995–2006). Each database was searched using combinations of the term follicular lymphoma and the terms for medications and treatment regimens. Inclusion criteria for studies were as follows: 1) Inclusion of patients with untreated stage III/IV FL grades 1, 2, or 3; 2) Intervention with chemotherapy and/or immunotherapy, radioimmunotherapy, or watchful waiting; 3) Reporting in English of the following treatment outcome measures specifically for patients with FL: CR/CR-unconfirmed, overall response rate (OR), and at least one form of survival data. Abstracts subsequently published as papers were excluded. Extracted data included pre-treatment disease status, treatment regimen, median follow-up time, progression free survival, overall survival, CR and OR. The following treatment strategies from peer-review publications were analyzed: single agent R, R-CVP, R-CHOP, and fludarabine-combinations with R (R-Fcom). In meta-analyses of selected studies, we utilized the Mantel-Haenszel (fixed effects model) and DerSimonain and Laird (random effects) methods to calculate the risk difference comparing treatment regimens’ CR/CRu to the spontaneous CR in patients undergoing watchful waiting (4.6%; Ardeshna et al. Lancet, 2003). Results: In total, over 3135 abstracts were reviewed to identify 11 studies meeting the inclusion criteria for this analysis. These studies included data from 3144 patients. Only one study presenting CR data for R-CVP (36%, 95% confidence interval: 28%–44%) met inclusion criteria. The meta-analyses estimated the CR rate associated with single-agent R to be 30% (95% CI: 20%–40%), R-CHOP to be 62% (30%–94%), and R-Fcom to be 85% (76%–94%) (random effects; see Figure). Conclusions: R-CHOP and R-fludarabine combinations appear to produce the highest CR rates for untreated pts with FL. Meta-analysis can aid clinicians in therapeutic decision making as they weight the risks and benefits of various regimens for newly diagnosed pts. Figure Figure

Background:Although advanced stage follicular lymphoma (FL) is considered incurable with standard therapy, and early institution of therapy has not demonstrated benefits over watchful waiting, novel strategies such as lymphoma vaccines and maintenance rituximab(R) provide opportunities for achieving prolonged disease-free intervals. Promoting the benefits of these strategies will depend upon improving the complete response rate(CR) with initial treatment. To date, the optimal first-line therapy remains undefined. To address this issue, we conducted a systematic literature review and meta-analyses comparing first-line chemotherapy regimens for FL. Methods:We searched the Cochrane Central Register of Controlled Trials (Cochrane Library Issue 1, 2003), MEDLINE (1/1966–6/2005), EMBASE (1/1980–7/2005), American Society of Hematology Annual Meeting abstracts (2002–2004), and American Society of Clinical Oncology Annual Meeting abstracts (1995–2005). Each search used combinations of the term follicular lymphoma and terms for medications and treatment regimens. Criteria for including studies were: Inclusion of patients with untreated stage III/IV FL; Intervention with chemotherapy and/or immunotherapy, radioimmunotherapy, or watchful waiting; Reporting in English of the following treatment outcome measures for patients with FL: CR/CR-unconfirmed, overall response rate (OR), and at least one form of survival data. Extracted data included pre-treatment disease status, treatment regimen, median follow-up time, progression free survival, overall survival, CR and OR. The following treatment strategies from peer-review publications were analyzed: single-agent fludarabine(F), fludarabine-combinations(F-com), single-agent alkylators(A), alkylator-combinations (without anthracycline), and anthracycline-combinations. In meta-analyses of selected studies, we utilized the Mantel-Haenszel (fixed effects model) and DerSimonain and Laird (random effects) methods to calculate the risk difference comparing treatment regimens’ CR/CRu to the spontaneous CR in patients undergoing watchful waiting (4.6%; Ardeshna et al. Lancet, 2003). Results:Over 1800 abstracts were reviewed yielding 37 reported treatments that met inclusion criteria and included 2709 patients. The benefits of initial chemotherapy for achieving CR are shown in Figure 1. Single-agent F and A had similar benefits, as did F-com and CHOP. Substantial heterogeneity existed among other alkylator and anthracycline combinations limiting their ability to be combined using meta-analysis. Overall, chemotherapy provided a 49% improvement in the chances of attaining CR (95% CI:41%–57%). Meta-analyses of single agent R and RCHOP showed CR of 26% (95% CI:18%–34%) and 74% (95% CI:65%–83%) respectively (Figure 1B). Insufficient numbers of studies met inclusion criteria to examine the benefits of adding R to other regimens. Conclusions:CHOP and F-com provide the greatest likelihood of achieving CR in untreated FL. This benefit is even greater in CHOP patients who receive R. Selection of an initial regimen for patients with FL will depend on patient-specific factors and future plans for other therapies. Figure Figure

Background:Numerous treatment options are available to patients with relapsed follicular lymphoma(FL), ranging from watchful waiting to transplantation. At present, the optimal therapy for this patient population remains undefined. Single agent rituximab(R) and radioimmunotherapy(RIT) with anti-CD20 antibody linked to iodine-131 (I131 Tositumomab) or to yttrium-90 (Y90-ibritumomab tiuxetan) have emerged as well tolerated treatments for relapsed FL and other indolent B-cell non-Hodgkin’s lymphomas(NHL). In phase II and III trials, RIT has demonstrated higher rates of complete response(CR) and overall response(OR) in patients with relapsed FL. To quantify the benefit of RIT and compare this to R, We conducted a systematic review of the literature and a meta-analysis of selected studies. Methods:As part of a broader review, we searched the Cochrane Central Register of Controlled Trials (Cochrane Library Issue 1, 2003), MEDLINE (1/1966-6/2005), EMBASE (1/1980-7/2005), American Society of Hematology Annual Meeting abstracts (2002–2004), and American Society of Clinical Oncology Annual Meeting abstracts (1995–2005). Each database was searched using combinations of the term follicular lymphoma and the terms for medications and treatment regimens. Inclusion criteria for studies were as follows: 1)Inclusion of patients with relapsed FL; 2)Treatment with RIT targeted at the CD20 antigen; 3)Original reporting in English of the following treatment outcome measures for patients with FL and/or other indolent NHL: CR/CR-unconfirmed, OR, and at least one form of survival data. Extracted data included pre-treatment disease status, patient characteristics, treatment regimen, progression free survival, overall survival, CR and OR. We utilized the Mantel-Haenszel (fixed effects model) and DerSimonain and Laird (random effects) methods to calculate the risk difference comparing the rates of CR/CRu and OR with RIT to those observed with conjugated CD20 antibody. For randomized trials of RIT the comparator in analyses was the control group from the trial. For other trials, response rates with RIT were compared to those observed with R in relapsed FL (McLaughlin, JCO 1998). Results:Over 1800 records were reviewed with 10 articles meeting inclusion criteria with 245 patients. Nearly all studies of RIT were multi-institutional, accrued patients between 1995 and 2002, had a median patient age >50 years, and had 48%–68% male patients. Three studies did not specify the number of patients with indolent NHL by histological class. In the remainder, 65%–100% of patients had FL grade 1 or 2. The percentage of patients with FL grade 3 or transformed NHL ranged in studies from 0 to 25%. In comparison to unconjugated CD20 antibody, overall, RIT improved CR by 30% (95% CI:24%–37%) and improved OR by 42% (95% CI:35%–49%). I131- and Y90-based RIT had overlapping benefits. Conclusions:As suggested by the individual trials, RIT can improve the likelihood of response and CR compared with R. Selecting appropriate patients for RIT will require consideration of patient factors as well as future treatment options such as transplantation and maintenance therapy that may extend the benefits of these improved response rates. Figure Figure