Urinary bother, Urinalysis, and Two-Year Efficacy Follow-Up Results of Phase I Trial of Intravesical Bacillus Calmette-Guérin Combined with Intravenous Pembrolizumab in Recurrent or Persistent High-Grade Non-Muscle-Invasive Bladder Cancer after Previous Bacillus Calmette-Guérin Treatment.

OBJECTIVE: To report urinary bother, urinalysis changes, disease-free survival (DFS), and overall survival (OS) over 2 years for subjects enrolled in a phase I dose-escalation trial (NCT02324582) of intravesical Bacillus Calmette-Guérin (BCG) in combination with systemic pembrolizumab for recurrent or persistent high-grade non-muscle invasive bladder cancer (HGNMIBC). METHODS: Eighteen patients consented to the study. Five were screen failures. Clinical activity was determined using cystoscopy and cytology with a biopsy of suspicious lesions. Urinalysis and International Prostate symptom score were assessed at pre-treatment, Week 10 (during combined BCG and pembrolizumab treatment), and 3 and 6 months from treatment completion. IPSS was analyzed using a mixed-model repeated measures analysis. A Chi-square test was used to compare urinalysis results at each interval. RESULTS: The pathologic disease stage after restaging transurethral resection and before treatment was pTa in 6 (46.2%), CIS in 6 (46.2%), and pT1 in 1 (7.7%). There was no increase in reported urinary bother throughout treatment. Quality of life measurements demonstrated no change in subjective burden. On urinalysis, we did not observe significant differences at 3 months compared to baseline evaluation. At 12 months, the DFS and OS were 69.23% and 92.31%, respectively. At 24 months, the DFS and OS were 38.46% and 92.31%, respectively. CONCLUSIONS: Treatment with BCG combined with intravenous pembrolizumab is not showing increased urinary bother or adverse urinalysis changes. Two-year response data is promising and await confirmation in the phase III study (Keynote 676).

Potential tools for predicting response to chemotherapy in OC: Assessment of immune dysbiosis, participant's self-rated health and microbial dynamics.

Epithelial ovarian cancer (OC) is the deadliest female reproductive cancer; an estimated 13,270 women will die from OC in 2023. Platinum-based chemotherapy resistance mechanisms contribute to poor OC 5-year survival rates. Peripheral inflammation is linked to various disease states and we previously identified unique peritoneal microbial features predictive of OC. We hypothesized that unique peripheral immune profiles and peritoneal microbial features may be predictive of disease-free interval (time to recurrence) and response to chemotherapy in participants with OC. We also investigated self-rated health (SRH) scores in the context of peripheral inflammation as a potential screening tool for OC. Blood and peritoneal fluid were collected from participants with OC or a benign adnexal mass (BPM). Lymphocyte populations were analyzed using Fluorescence Activated Cell Sorting, serum cytokine levels were analyzed using the Human Th17 Magnetic Bead Panel assay and peritoneal fluid microbial features were analyzed using Next Generation Sequencing (NGS). Participants completed a standardized questionnaire on self-rated physical and emotional health. Participants were classified into three chemotherapy response categories: platinum-refractory, platinum-resistant or platinum-sensitive. A significant positive correlation was found between elevated inflammatory status on the day of surgery and longer disease-free interval. SRH measures did not correlate with immune status in participants with OC or a BPM. We identified a correlation between peritoneal microbial features and chemotherapy response. We conclude that immune dysbiosis may be useful in predicting OC recurrence. The immune findings reported here set the framework for additional studies utilizing immune profiles to predict platinum-based chemotherapy responsiveness in OC.

Quality of life following treatment with intra-arterial cisplatin with concurrent radiation and erlotinib for locally advanced head and neck cancer.

OBJECTIVES: Studies that focus on the feasibility of using erlotinib plus chemoradiation to treat locally advanced head and neck cancer have given hints of improved survival outcomes compared to chemoradiation alone. However, the influence of this treatment regimen on the quality of life of the patients has not been documented. We conducted a study of this triple combination and now have documented follow-up survival data as well as long-term quality of life (QoL) measures. METHODS: Three sets of QoL questionnaires were given to patients with a diagnosis of head and neck cancer at two time points, pre- and post-treatment, to assess differences in quality of life after receiving chemotherapy with intra-arterial (IA) cisplatin (150 mg/m2), concomitant radiation (70 Gy), and oral erlotinib (150 mg/day). Additionally, patients were followed for a total of 5 years. RESULTS: Treatment had a detrimental effect on appearance, taste, and saliva domain scores in their QoL questionnaires. Nonetheless, fewer patients reported pain and anxiety. SIGNIFICANCE OF RESULTS: The combination of erlotinib with chemoradiation produced similar adverse effects on the QoL scores of patients with head and neck cancer as compared to chemoradiation alone.

Impact of cytotoxic chemotherapy on aldo-keto reductase family 1 member B10 expression.

OBJECTIVE: Aldo-keto reductase family 1 member B10 (AKR1B10) is a protein that is produced and secreted by a significant number of breast cancers. However, a potential confounder to the use of AKR1B10 as a tumor marker is its elevation in patients given cytotoxic chemotherapy. We therefore conducted a prospective study to analyze AKR1B10 levels in patients with breast cancer receiving neoadjuvant cytotoxic chemotherapy. METHODS: The study enrolled 10 patients from November 2015 to July 2017. All patients had locally advanced, but non-metastatic, breast cancer, and they received neoadjuvant chemotherapy followed by surgery. Serum AKR1B10 levels and tumor imaging were assessed before, during, and after chemotherapy. RESULTS: No increase in serum AKR1B10 levels was noted in patients receiving chemotherapy whose levels were elevated at diagnosis. CONCLUSION: The findings are complex, but the overall data suggest that AKR1B10 is suitable as a tumor marker in patients with elevated levels at the time of diagnosis.

Documented Penicillin Allergies Should Not Preclude Use of Preoperative Cefazolin in Hip and Knee Arthroplasty.

INTRODUCTION: Perioperative cefazolin administration for total joint arthroplasty is a first-line antibiotic recommended by the American Academy of Orthopaedic Surgeons (AAOS) guidelines for the prevention of periprosthetic joint infections (PJIs). We aim to analyze the clinical viability of giving patients with a documented penicillin allergy (PA) a perioperative full-strength cefazolin "test dose" under anesthesia. METHODS: This is a retrospective chart review of 2,451 total joint arthroplasties from a high-volume arthroplasty orthopaedic surgeon over a 5-year period from January 2013 through December 2017. This surgeon routinely gave patients with a documented PA a full-strength cefazolin test dose while under anesthesia instead of administrating a second-line antibiotic. The primary outcomes examined were allergic reaction and postoperative infection. RESULTS: Cefazolin was given to 87.1% of all patients (1,990) and 46.0% of patients with a PA (143). The total rate of allergic reactions among all patients was 0.5% (11). Only one patient with a documented PA who received cefazolin had an allergic reaction. The reaction was not severe and did not require any additional treatment. In patients who had no reported allergies and received cefazolin, 0.3% (6) had an allergic reaction. There was no statistically significant difference in the rate of allergic reaction when comparing patients with and without a PA (P = 0.95). Patients receiving cefazolin had an overall PJI rate of 2.9% (57) versus those patients receiving antibiotics other than cefazolin who sustained a 5.5% PJI rate (16), which was statistically significant (P = 0.02). CONCLUSION: This study found that utilization of a full-strength test dose of cefazolin in patients with a documented PA is a feasible, safe, and effective way of increasing the rate of cefazolin administration and thus mitigating the risk of PJIs.

The Impact of COVID-19 on Emergency Medicine Rotations.

Introduction The impact of modifications in curriculum and clinical rotations made secondary to the COVID-19 pandemic on medical education has yet to be fully investigated. We observed differences in the types of patients seen by medical students that may have resulted from clinical disruptions due to the COVID-19 pandemic. We then evaluated what impact these disruptions had on the students' clinical competency. Methods We obtained patient logbooks of third-year medical students (M3) and fourth-year sub-interns (M4) from the first three emergency medicine (EM) rotation blocks of the 2019-2020 (Y19) and 2020-2021 (Y20) academic years. We then reviewed and categorized the chief complaints seen and procedures in which they participated. A robust t-test was used to detect differences in chief complaints and procedures. Finally, we looked for objective differences using the chi-square test in clinical performance between the class of 2021 (Class21) and the class of 2022 (Class22), as assessed by performance on our institution's clinical competency examination. Results Overall, students saw a 25.3% decrease in average number of patient encounters. Statistically significant decreased average numbers of infectious (-28.3%, p=0.013); musculoskeletal (-22.2%, p=0.018); gastrointestinal (GI) (-24.6%, p<0.01); genitourinary (GU) (-33.2%, p<0.01); head, eyes, ears, nose, throat (HEENT) (-31.1%, p<0.01); trauma (-33.0%, p<0.01); and respiratory (-45.4%, p<0.001) complaints were observed. Both M3s and M4s encountered significantly less GU (-25.6%, p=0.048; -41.7%, p=0.016) and trauma (-29.1%, p=0.023; -33.2%, p=0.032) complaints in Y20. M4s saw significantly less GI complaints (-42.6%, p<0.001) in Y20, whereas M3s encountered significantly less psychiatric and HEENT complaints (-30.3%, p=0.046; -34.6%, p=0.013). Both classes saw significantly less respiratory complaints in Y20 but more so for M4s (-65.3%, p<0.001) than for M3s (-27.9%, p=0.033). There were no significant differences in average number of procedures between years. We did not observe any differences in overall clinical performance between the two selected classes. While class of 2021 scored a significantly higher average on a case of fatigue (p=0.0004) and class of 2022 on a case of abdominal pain (p<0.0001), there were no significant differences in the primary chief complaints that would be attributed to COVID-19, such as dyspnea. Conclusion Modifications made to curricula and clinical rotations due to the COVID-19 pandemic led to students encountering less patients overall, with significant decreases in multiple chief complaint types compared to Y19 but no significant change in procedure numbers. Notably, there was no major impact seen on clinical competency providing a positive argument for considering innovative teaching and learning methods.

The Student You Know: Orthopedic Surgery Home Program Match Rates and Geographic Relationships Before and After COVID-19.

OBJECTIVE: In March 2020, COVID-19 was declared a pandemic by the World Health Organization. This led to the outright cancellation of away rotations and in person residency interviews for the class of 2021. This study aims to identify the geographic relationships in the orthopedic match and further explore COVID-19's effect on these geographic relationships. Furthermore, we aim to compare the home program match rates before and after COVID-19. SETTING: Southern Illinois University School of Medicine, Department of Orthopedic Surgery (tertiary, university-based). DESIGN AND PARTICIPANTS: Residency websites and social media sites were used to record basic residency information as well as each resident's year, matriculated medical school, and matriculated medical school geographic data. This information was used to evaluate the proportion of orthopedic residents from "home program" medical schools and evaluate the geographic relationship of matched orthopedic residents. 202 Orthopedic residencies were initially identified and 134 allopathic and nonmilitary residency programs met the inclusion criteria. In all, 3253 of the 3931 (82.7%) current U.S orthopedic residents were included in the analysis. RESULTS: In the 4 orthopedic surgery residency classes before the pandemic (2017-2020), 21.8% of residency slots were filled by home program students. During the pandemic match cycle (2021), this number jumped to 28.2% (p < 0.0006). The increase was observed consistently across residency subgroup analysis: class size, doximity rank, and doximity research rank. Correspondingly, there was a statistically significant increase from 34.7% (2017-2020) to 39.3% (2021) (p = 0.0318) in residencies matching with same state medical students. Regional trends stayed consistent. Our study showed that residency programs matched applicants who went to same region medical schools during the 2020 to 2021 cycle at nearly the exact same rate as they did pre-pandemic (63.6%, up from 63.3%). CONCLUSIONS: Our study demonstrates that despite widespread virtual away rotations and virtual open houses, residency programs showed an increased preference for their home program students. This trend was significant and widespread, highlighting the generalized nationwide hesitation of both residency programs and students on the virtual interview process.

Consequences of Structural Urbanism: Urban-Rural Differences in Cancer Patients' Use and Perceived Importance of Supportive Care Services from a 2017-2018 Midwestern Survey.

BACKGROUND: Structural inequities, in part, undergird urban-rural differences in cancer care. The current study aims to understand the potential consequences of structural inequities on rural and urban cancer patients' access to and perceived importance of supportive cancer care resources. METHODS: We used data collected from November 2017 to May 2018 from a larger cross-sectional needs assessment about patients' support needs, use of services, and perceptions at a Midwestern United States cancer center. Oncology patients received a study packet during their outpatient clinic visit, and interested patients consented and completed the questionnaires. RESULTS: Among the sample of 326 patients, 27% of the sample was rural. In adjusted logistic regression models, rural patients were less likely to report using any secondary support services (15% vs. 27%; OR = 0.43, 95%CI [0.22, 0.85], p = 0.02) and less likely than urban counterparts to perceive secondary support services as very important (51% vs. 64%; OR = 0.57, 95%CI [0.33, 0.94], p = 0.03). CONCLUSION: Structural inequities likely have implications on the reduced access to and importance of supportive care services observed for rural cancer patients. To eliminate persistent urban-rural disparities in cancer care, rural residents must have programs and policies that address cancer care and structural inequities.

AKR1B10 as a Potential Novel Serum Biomarker for Breast Cancer: A Pilot Study.

Background: Aldo-keto reductase 1B10 (AKR1B10) is a secretory protein that is upregulated in breast cancer. Objective: This case-controlled pilot study evaluated the serum level of AKR1B10 in healthy women and patients with a localized or metastatic breast cancer. Methods: AKR1B10 levels were measured by ELISA and IHC in several patient cohorts. Results: Our data showed that serum AKR1B10 was significantly elevated in patients with localized (6.72 ± 0.92 ng/ml) or metastatic (7.79 ± 1.13 ng/ml) disease compared to cancer-free healthy women (1.69 ± 0.17 ng/ml) (p<0.001); the serum AKR1B10 was correlated with its expression in tumor tissues, but not with the tumor burden, molecular subtypes or histological stages. After surgical removal of primary tumors, the serum AKR1B10 was rapidly decreased within 3 days and plateaued at a level similar to that of healthy controls in most patients. ROC curve analysis suggested the optimal diagnostic cut-off value of serum AKR1B10 at 3.456 ng/ml with AUC 0.9045 ± 0.0337 (95% CI 0.8384 - 0.9706), sensitivity 84.75% (95% CI 73.01% to 92.78%), and specificity 93.88% (95% CI 83.13% to 98.72%). Conclusions: These data indicate the potential value of serum AKR1B10 as a biomarker of breast cancer.

Comparison of Using Intraoperative Computed Tomography-Based 3-Dimensional Navigation and Fluoroscopy in Anterior Cervical Diskectomy and Fusion for Cervical Spondylosis.

OBJECTIVE: Anterior cervical diskectomy and fusion (ACDF) is a highly successful procedure to treat spinal cord or nerve root compression; however, complications can still occur. With advancements in imaging, 3-dimensional (3D) reconstruction allows real-time instrument tracking in a surgical field relative to the patient's anatomy. Here, we compare plate positioning and short-term outcomes when using 3D navigation to fluoroscopy in ACDF for degenerative spine disease. METHODS: All ACDFs for cervical spondylosis performed by 6 surgeons at a single center between 2010 and 2018 were included. ACDFs were divided into those performed using 3D navigation or fluoroscopy. Records were assessed for patient demographics, American Society of Anesthesiology score, number of operated interspaces, operative time, length of stay, perioperative complications, and 90-day readmissions. Postoperative images were reviewed for lateral and angular plate deviations. RESULTS: A total of 193 ACDFs performed with 3D navigation and 728 performed with fluoroscopy were included. After controlling for demographics and surgical characteristics, using 3D navigation was associated with less lateral plate deviation (P = 0.048) and longer operative times per interspace (P < 0.001) but was not associated with angular plate deviation (P = 0.724), length of stay (P = 0.393), perioperative complications (P = 0.844), and 90-day readmissions (P = 0.539). CONCLUSIONS: Using 3D navigation in ACDF for degenerative disease is associated with slightly more midline plate positioning and comparable short-term outcomes as using fluoroscopy and can be a suitable alternative. Advantages of using this technology, such as improved visualization of anatomy, should be weighed against disadvantages, such as increased operative time, on a per-patient basis.

A Blended Approach to Learning in an Obstetrics and Gynecology Residency Program: Proof of Concept.

PROBLEM: Graduate medical education programs are expected to educate residents to be able to manage critically ill patients. Most obstetrics and gynecology (OB/GYN) graduate medical education programs provide education primarily in a didactic format in a traditional face-to-face setting. Busy clinical responsibilities tend to limit resident engagement during these educational sessions. The revision of the training paradigm to a more learner-centered approach is suggested. INTERVENTION: A blended learning education program was designed and implemented to facilitate the teaching and learning of obstetric emergencies, specifically diabetic ketoacidosis and acute-onset severe hypertension in pregnancy. The program incorporated tools to foster a community of inquiry. Multimedia presentations were also utilized as the main modality to provide instruction. The blended learning course was designed in accordance with the cognitive theory of multimedia learning. CONTEXT: This intervention was carried out in the Department of Obstetrics and Gynecology, Southern Illinois University. All 15 OB/GYN residents were enrolled in this course as part of their educational curriculum. First, face-to-face instructions were given in detail about the blended learning process, course content, and online website. The residents were then assigned tasks related to completing the online component of the course, including watching multimedia presentations, reading the resources placed online, and participating in online asynchronous discussions. The course culminated with a face-to-face session to clarify misconceptions. Pre- and postcourse quizzes were administered to the residents to assess their retention and understanding. OUTCOME: Objective analysis demonstrated significant improvements in retention and understanding after participating in the course. The blended learning format was well received by the residents. Resident perception of social presence in the asynchronous online discussions was demonstrative of low scores relating to peer-to-peer interaction. The multimedia presentations and the availability of learning resources were well received. LESSONS LEARNED: Outcomes of this study suggest that blended learning is a viable tool to support teaching and learning of obstetric emergencies in an OB/GYN residency program.

Cell-free stem cell-derived extract formulation for treatment of knee osteoarthritis: study protocol for a preliminary non-randomized, open-label, multi-center feasibility and safety study.

BACKGROUND: Musculoskeletal conditions are highly prevalent, and knee OA is most common. Current treatment modalities have limitations and either fail to solve the underlying pathophysiology or are highly invasive. To address these limitations, attention has focused on the use of biologics. The efficacy of these devices is attributed to presence of growth factors (GFs), cytokines (CKs), and extracellular vesicles (EVs). With this in mind, we formulated a novel cell-free stem cell-derived extract (CCM) from human progenitor endothelial stem cells (hPESCs). A preliminary study demonstrated the presence of essential components of regenerative medicine, namely GFs, CKs, and EVs, including exosomes, in CCM. The proposed study aims to evaluate the safety and efficacy of intraarticular injection of the novel cell-free stem cell-derived extract (CCM) for the treatment of knee OA. METHODS AND ANALYSIS: This is a non-randomized, open-label, multi-center, prospective study in which the safety and efficacy of intraarticular CCM in patients suffering from grade II/III knee OA will be evaluated. Up to 20 patients with grade II/III OA who meet the inclusion and exclusion criteria will be consented and screened to recruit 12 patients to receive treatment. The study will be conducted at up to 2 sites within the USA, and the 12 participants will be followed for 24 months. The study participants will be monitored for adverse reactions and assessed using Numeric Pain Rating Scale (NPRS), Patient-Reported Outcomes Measurement Information System (PROMIS) Score, Knee Injury and Osteoarthritis Outcome Score Jr. (KOOS Jr.), 36-ietm short form survey (SF-36), Single Assessment Numeric Evaluation (SANE), physical exams, plain radiography, and magnetic resonance imaging (MRI) with Magnetic Resonance Observation of Cartilage Repair Tissue (MOCART) score for improvements in pain, function, satisfaction, and cartilage regeneration. DISCUSSION: This prospective study will provide valuable information into the safety and efficacy of intraarticular administration of cell-free stem cell-derived extract (CCM) in patients suffering with grade II/III knee OA. The outcomes from this initial study of novel CCM will lay the foundation for a larger randomized, placebo-controlled, multi-center clinical trial of intraarticular CCM for symptomatic knee OA. TRIAL REGISTRATION: Registered on July 21, 2021. ClinicalTrials.gov NCT04971798.

Evaluation of immediate and short-term efficacy of DualStim therapy with and without intracavernosal umbilical cord-derived Wharton's jelly in patients with erectile dysfunction: Study protocol for a randomized controlled trial.

INTRODUCTION: Erectile dysfunction (ED) affects a significant portion of the United States population and causes negative psychological burdens that affects men and their partner's quality of life and satisfaction. Extracorporeal shock therapy (ESWT) utilizing focused ESWT and radial ESWT in Low-intensity shock wave therapy has been used to treat ED with some success. Wharton's Jelly (WJ) is a biologic substance with large amounts of stem cells, growth factors, cytokines and extracellular components. The use of combined focused and radial ESWT (DualStim therapy) with injected WJ have potential uses in ED that may have advantages over current treatments. MATERIALS: A randomized, single-blinded, controlled clinical trial will be conducted to evaluate the efficacy and safety of DualStim therapy and intracavernosal injection of WJ in moderate to severe ED. A total of 60 patients with moderate to severe ED will be enrolled and treated with DualStim therapy with intracavernosal injection of WJ or saline for a period of 7 weeks. The International Index of Erectile Function - Erectile Function score will be used to gauge the treatment related changes in relation to the subject's baseline. The scores will be recorded at baseline and compared to follow-ups 1,3 and 6 months post-treatment. Any adverse events or severe adverse events will be recorded in the corresponding case report forms. Sexual Encounter Profile, as well as the Global Assessment Questionnaire and the Erection Hardness Score will be used to determine the sexual activity improvement from baseline leading to optimal penetration at follow-ups 1,3 and 6 months post-treatment. DISCUSSION: This clinical trial is one of the first studies to determine the immediate and short-term efficacy of DualStim therapy, with and without intracavernosal injection of formulated umbilical cord-derived WJ to improve and/or restore erectile function in patients with moderate to severe ED. This study will also provide insight into the safety and efficacy of WJ. We anticipate clinically significant improvement in patients suffering from moderate and severe ED treated with DualStim therapy with WJ compared to their baseline and DualStim with saline.

Developing a Novel, At-Home Procedure Curriculum for Fourth-Year Medical Students in Response to the COVID-19 Pandemic.

The coronavirus disease 2019 (COVID-19) pandemic provided our institution a unique opportunity to develop a new procedural curriculum for our fourth-year, emergency medicine-bound medical students. A significant portion of our ED's fourth-year elective has traditionally been centered in our simulation center, using high-fidelity simulation models to practice important emergency medicine procedures. Due to the pandemic, the simulation center was unavailable for our use, and this new curriculum was created in an effort to fill this gap in procedural education.

Safety and efficacy of umbilical cord-derived Wharton's jelly compared to hyaluronic acid and saline for knee osteoarthritis: study protocol for a randomized, controlled, single-blind, multi-center trial.

BACKGROUND: Osteoarthritis (OA) is the most common joint disorder in the United States of America (USA) with a fast-rising prevalence. Current treatment modalities are limited, and total knee replacement surgeries have shown disadvantages, especially for grade II/III OA. The interest in the use of biologics, including umbilical cord (UC)-derived Wharton's jelly (WJ), has grown in recent years. The results from a preliminary study demonstrated the presence of essential components of regenerative medicine, namely growth factors, cytokines, hyaluronic acid (HA), and extracellular vesicles, including exosomes, in WJ. The proposed study aims to evaluate the safety and efficacy of intra-articular injection of UC-derived WJ for the treatment of knee OA symptoms. METHODS: A randomized, controlled, single-blind, multi-center, prospective study will be conducted in which the safety and efficacy of intra-articular administration of UC-derived WJ are compared to HA (control) and saline (placebo control) in patients suffering from grade II/III knee OA. A total of 168 participants with grade II or III knee OA on the KL scale will be recruited across 53 sites in the USA with 56 participants in each arm and followed for 1 year post-injection. Patient satisfaction, Numeric Pain Rating Scale, Knee Injury and Osteoarthritis Outcome Score, 36-Item Short Form Survey (SF-36), and 7-point Likert Scale will be used to assess the participants. Physical exams, X-rays, and MRI with Magnetic Resonance Observation of Cartilage Repair Tissue score will be used to assess improvement in associated anatomy. DISCUSSION: The study results will provide valuable information into the safety and efficacy of intra-articular administration of Wharton's jelly for grade II/III knee osteoarthritis. The results of this study will also add to the treatment options available for grade II/III OA as well as help facilitate the development of a more focused treatment strategy for patients. TRIAL REGISTRATION: ClinicalTrials.gov, NCT04711304 . Registered on January 15, 2021.

Phase I trial of intravesical Bacillus Calmette-Guérin combined with intravenous pembrolizumab in recurrent or persistent high-grade non-muscle-invasive bladder cancer after previous Bacillus Calmette-Guérin treatment.

OBJECTIVES: We conducted the first phase I dose-escalation trial (NCT02324582) of intravesical Bacillus Calmette-Guérin (BCG) in combination with systemic pembrolizumab in patients with high-grade non-muscle-invasive bladder cancer (HGNMIBC) who had persistent or recurrent disease after prior intravesical therapy with BCG. The primary endpoint was the safety of this combination. The secondary endpoint was clinical activity at three months following BCG treatment. METHODS: Eighteen patients were consented for the study, five of which were screen failures. Six doses of pembrolizumab were administered every 3 weeks over 16 weeks concurrently with six weekly doses of BCG beginning at week 7. Patient safety was evaluated from the time of consent through 30 days following pembrolizumab treatment. Clinical activity was determined using cystoscopy and biopsy of suspicious lesions. RESULTS: Treatment-related adverse events included one grade 4 adverse event (AEs) (adrenal insufficiency). There were nine grade 3 AEs (chest discomfort, pulmonary embolism, arthritis, wrist edema, injection site reaction, bilateral wrist pain, cardiomyopathy, hypokalemia, urinary tract infection). There were 49 grade 1 and 30 grade 2 AEs (88% of AEs). Eleven patients finished the treatment, and two patients died during the study. Of 13 patients treated, nine patients (69%) had no evidence of disease at 3 months following BCG treatment. CONCLUSIONS: We report for the first time that combining BCG and pembrolizumab in treating HGNMIBC is safe allowing complete treatment of most patients. A phase III trial has opened to test the efficacy of this combination in HGNMIBC (KEYNOTE-676).

Utility of Head Computed Tomography Scans Before Outpatient Follow-up for Low-Risk Mild Traumatic Brain Injury.

BACKGROUND: Neurosurgeons are frequently consulted for traumatic brain injuries (TBIs) resulting in intracranial hemorrhage (ICH). After inpatient confirmation of hemorrhage stability, outpatient head computed tomography (CT) is often performed to assess for hemorrhage resolution. Our objective was to assess the practice patterns and clinical utility of routine outpatient head CT scans for patients with mild TBI (mTBI). MATERIALS AND METHODS: A retrospective review was performed on all adult mTBI patients with ICH who presented to a level I trauma center over a 4-year period. A combination of the patient's initial clinical evaluation and CT findings was used to identify mTBI patients at low risk for neurologic deterioration and neurosurgical intervention. Findings from the outpatient follow-up clinical evaluation and head CT were assessed. Patients without outpatient follow-up within 3 months were excluded. RESULTS: Forty-nine patients met inclusion criteria for the study. Thirty-two had an outpatient head CT before their follow-up appointment. Twenty-one patients had at least 1 neurologic finding at the earliest follow-up appointment. All patients except those with a subdural hematoma (SDH) had smaller or resolving ICH on outpatient CT scans. Seven patients with an SDH had unchanged or expanded hemorrhage on outpatient imaging, 2 of whom had traumatic brain injury-related hospitalizations and 1 of whom underwent neurosurgical intervention due to an enlarging SDH. CONCLUSIONS: Routine outpatient head CT scans before follow-up for low-risk mTBI patients without an SDH appears to have limited clinical utility. In low-risk mTBI patients with an SDH, obtaining an outpatient head CT is reasonable to monitor for resolution.

Addressing Unmet Basic Needs to Improve Colposcopy Adherence Among Women With Abnormal Cervical Cancer Screening.

OBJECTIVES: The aims of the study were to identify unmet basic needs (BNs) among women referred to colposcopy, to assess patient acceptability/satisfaction with assistance from a navigator to address unmet BNs, and to estimate adherence to colposcopy. METHODS: Women were recruited between September 2017 and January 2019 from 2 academic colposcopy centers, one serving a rural and one an urban area. Basic needs were assessed by phone before colposcopy appointments and considered unmet if unlikely to resolve in 1 month. Colposcopy adherence prestudy and poststudy implementation was abstracted over 4-6 months from administrative records. After a lead-in phase of 25 patients at each site, a BN navigator was offered to new participants with 1 or more unmet BNs. Primary outcome was adherence to initial appointment. RESULTS: Among 100 women, 59% had 1 or more unmet BNs, with similar prevalence between urban and rural sites. Adherence to initial colposcopy was 83% overall, 72% at the rural clinic, and 94% at the urban clinic (p = .006). These adherence rates were improved from 4 months before study launch (30/59 [51%] rural clinic and 68/137 [50%] urban clinic). Although acceptability of BN navigation was greater than 96% and women felt that it helped them get to their colposcopy visit, having a navigator was not associated with adherence. Women reporting no unmet BNs had the lowest adherence compared with women with 1 or more unmet BNs, regardless of navigator assistance (p = .03). CONCLUSIONS: Disadvantaged women who need colposcopy have unmet BNs and value navigator assistance for initial appointments. However, when appointment scheduling includes telephone reminders and inquiring about BNs, a navigator may not add value.

Assessing the efficacy of mild traumatic brain injury management.

OBJECTIVE: Intracranial hemorrhage (ICH) is frequently found on computed tomography (CT) after mild traumatic brain injury (mTBI) prompting transfer to centers with neurosurgical coverage and repeat imaging to confirm hemorrhage stability. Studies suggest routine repeat imaging has little utility in patients with minimal ICH, no anticoagulant/antiplatelet use, and no neurological decline. Additionally, it is unclear which mTBI patients benefit from transfer for neurosurgery consultation. The authors sought to assess the clinical utility and cost effectiveness of routine repeat head CTs and transfer to tertiary centers in patients with low-risk, mTBI. METHODS: Retrospective evaluation of patients receiving a neurosurgical consultation for TBI during a 4-year period was performed at a level 1 trauma center. Patients were stratified according to risk for neurosurgical intervention based on their initial clinical evaluation and head CT. Only patients with low-risk, mTBI were included. RESULTS: Of 531 patients, 119 met inclusion criteria. Eighty-eight (74.0 %) received two or more CTs. Direct cost of repeat imaging was $273,374. Thirty-seven (31.1 %) were transferred to our facility from hospitals without neurosurgical coverage, costing $61,384. No patient had neurosurgical intervention or mTBI-related in-hospital mortality despite enlarging ICH on repeat CT in three patients. Two patients had mTBI related 30-day readmission for seizure without ICH expansion. CONCLUSION: Routine repeat head CT or transfer of low-risk, mTBI patients to a tertiary center did not result in neurosurgical intervention. Serial neurological examinations may be a safe, cost-effective alternative to repeat imaging for select mTBI patients. A large prospective analysis is warranted for further evaluation.