The role of immune checkpoint inhibition in triple negative breast cancer.

INTRODUCTION: Immunotherapy has revolutionized cancer treatment, including TNBC, which has limited options of treatment and poor prognosis. ICIs studied in TNBC include pembrolizumab, nivolumab, atezolizumab, and durvalumab. Initial studies exploring ICI monotherapy demonstrated promising yet limited responses. Subsequent studies, KEYNOTE 522 and KEYNOTE 355, which combined ICI with chemotherapy, have resulted in the FDA approval of pembrolizumab in the early-stage and metastatic setting, respectively. AREAS COVERED: This article provides a comprehensive review of the role of ICI in the treatment of TNBC. We reviewed the trials that have evaluated ICI monotherapy, dual therapy, ICI in combination with chemotherapy, targeted therapy, vaccines and radiation. Additionally, we reviewed potential biomarkers of response and immune-related adverse events (irAEs). A literature search was conducted via PubMed and ClinicalTrials.gov as of 5 June 2023. EXPERT OPINION: Various approaches combining immunotherapy with chemotherapy, targeted therapy, vaccines and radiation have been assessed. Pembrolizumab remains the only ICI approved in both the early stage and mTNBC. The role of adjuvant pembrolizumab in those who achieved pCR after neoadjuvant therapy is being investigated. Combining ICI with PARP inhibitors and radiation shows promise. More research is needed in identifying predictors of response. Monitoring of irAEs remains crucial.

The therapeutic effectiveness of fluoroscopically guided intra-articular sacroiliac joint injections in patients with sacroiliac joint dysfunction, an observational study.

Objective: The goal of this project is to evaluate the therapeutic effectiveness of fluoroscopically guided intra-articular sacroiliac (SI) joint injections in patients with diagnosed SI joint dysfunction. Patient reported outcomes related to pain and quality of life measures were evaluated. Design: This is a retrospective observational study of patients receiving intra-articular SI joint injections under a single provider at the Cleveland Clinic from September 2013 to April 2019. Three hundred fifty-one patients received injections and were administered patient reported outcomes (PROs) including the Numeric Rating Scale, Patient Health Questionnaire, Pain Disability Questionnaire, EuroQol-5 Dimensions Questionnaire, and PROMIS-GH Physical and Mental Health at baseline and approximately 1-, 3-, 6-, 12-, and 24-month time points during follow-up appointments. The primary outcome measure was the percentage of patients receiving their first injection who achieved minimal clinically important difference (MCID) in these PROs at each follow-up time point. Secondary outcomes were the percentage of patients achieving MCID in each PRO for each injection analyzed (including patients who received repeat injections) and average change in these PROs at each time point for first and all injections. Results: A total of 351 patients were included in the analysis, with varying time points of follow-up. The average patient age was 52.3 (±14.9) years with 74.9% female and 59.0% white. For first time injections, the MCID was achieved for Numeric Rating Scale in 60.6%, 42.1%, 47.5%, and 32.5% of patients at 1-, 3-, 6-, and 12-month follow-up, respectively. There was significant improvement in PROMIS-GH Physical Health at 3-month, 6-month, and 1-year follow-up. There was no significant improvement in PROMIS-GH Mental Health at any follow-up time points. Conclusions: Fluoroscopically guided intra-articular SI joint injection for SI joint dysfunction is effective in providing therapeutic pain relief exceeding MCID values in greater than 60% of patients at 1 month and greater than 40% at 3- and 6- months after injection. However, while this intervention may provide significant pain relief and improvement in function, it may not address the psychosocial aspect of chronic pain to the same extent.

Benefit of pain and function after cervical transforaminal epidural steroid injections, an observational study.

Objective: To evaluate the improvement of pain and function after cervical transforaminal epidural steroid injections (CTFESI) for radicular pain. Design: This is a retrospective observational study of patients receiving fluoroscopically-guided cervical transforaminal epidural steroid injections under a single provider at a tertiary referral center from December 2013 to December 2020. Primary outcome measures were Numeric Rating Scale (NRS), patient reported percent of pain relief, the Patient Health Questionnaire, the Patient Reported Outcome Measurement Information System (PROMIS) Global Health Physical and Mental Health score, and the Pain Disability Questionnaire. Results: A total of 219 individual patients underwent 261 CTFESI and were included in the analyses. The average subject age was 51.9 years (SD = 11.3) and 50.9 % were male. Following the intervention, average pain relief by NRS at 3 months, 6 months, 1 year, and 2 years was -4.07, -3.82, -4.20, and -4.45, respectively. The average functional improvement with PROMIS-GH physical at 3-months, 6-months, 1- year, and 2-years was 2.23, 2.35, 3.15, and 3.29, respectively. Conclusions: Our results suggest that patients with cervical radiculopathy report significant pain relief and functional improvement following CTFESI. They can also report clinically important improvement in their health-related quality of life.

Eye Dynamics and Engineering Network Consortium: Baseline Characteristics of a Randomized Trial in Healthy Adults.

PURPOSE: To improve understanding of intraocular pressure (IOP) and its variance, this project identifies systemic and ocular characteristics of healthy eyes of adult volunteers including IOP variation, ocular biometrics, and aqueous humor dynamics (AHDs). These data serve as baseline controls for further studies from the Eye Dynamics and Engineering Network (EDEN) Consortium. DESIGN: Multicenter open-label clinical trial in healthy adults randomized to 1 week treatment with 2 approved glaucoma drugs in a crossover design. PARTICIPANTS: Among 135 healthy participants, 122 participants (aged 55.2 ± 8.8 years; 92 females, 30 males) completed the protocol. METHODS: Participants from the University of Michigan, Mayo Clinic, and University of Nebraska Medical Center underwent measurements of ocular biometrics, AHD, and IOP using 4 tonometers. Intraocular pressure data during 3 study visits without glaucoma medications were used in the analysis. The PhenX Toolkit survey acquired standardized data on medical history, surgical history, medications, smoking and alcohol exposures, and physical measures. MAIN OUTCOME MEASURES: The variability of IOP measurements within eyes was assessed as visit-to-visit IOP variation, within-visit IOP variation, and within-visit positional IOP variation. The concordance (or correlation) between eyes was also assessed. RESULTS: Average positional change of > 4.7 mmHg was detected with a range of 0.5-11.0 mmHg. Pearson correlation of IOP between eyes within a visit was 0.87 (95% confidence interval [CI], 0.82-0.91) for Goldmann applanation tonometry, 0.91 (95% CI, 0.88-0.94) for Icare rebound tonometry, and 0.91 (95% CI, 0.88-0.94) for pneumatonometry. There was a 4% to 12% asymmetric fluctuation of 3 mmHg or more between eyes between visits using rebound tonometry, 9% with Goldmann applanation tonometry, and 3% to 4% by pneumotonometry. The coefficient of variation between visits for the same eye ranged from 11.2% to 12.9% for pneumatonometry, from 13.6% to 17.4% for rebound tonometry, and 15.8% to 16.2% for Goldmann applanation tonometry. CONCLUSIONS: The current study from the EDEN Consortium describes measurement methods and data analyses with emphasis on IOP variability. Future papers will focus on changes in ocular biometrics and AHD with timolol or latanoprost treatment. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.

Lupus Cerebellitis Presenting With Ataxia: A Case Report.

We report a case of a woman with a history of systemic lupus erythematosus who developed persistent ataxia and was diagnosis with lupus cerebellitis. Magnetic resonance imaging of the brain showed T2/FLAIR signal hyperintensity within the cerebellar vermis without mass effect. The patient's condition improved with pulse IV methylprednisolone. This case highlights unique imaging findings within the cerebellum, our diagnostic and treatment regimen, and compares this case to previous literature on similar cases.

Effect of Timolol on Aqueous Humor Outflow Facility in Healthy Human Eyes.

PURPOSE: Hyposecretion of aqueous humor has been postulated to adversely affect the health of the trabecular meshwork and outflow resistance. However, the effect of medications that reduce aqueous humor production on outflow facility in living human eyes is unclear. This study evaluated the effect of timolol, an aqueous humor flow suppressant, on outflow facility in healthy eyes. DESIGN: Prospective, before-and-after study. METHODS: In a multicenter study, 113 healthy participants over 40 years of age were included. Intraocular pressure (IOP) was measured with the participant in the sitting position by using a pneumatonometer. The outflow facility was measured with the participant in the supine position by 2-minute pneumatonography. After participants self-administered drops of timolol 0.5% for 1 week, twice daily in each eye, both measurements were repeated. RESULTS: Mean IOP decreased from 15.1 ± 3.0 mm Hg at baseline to 12.4 ± 2.4 mm Hg (P < 0.001) after 1 week of timolol use. Mean outflow facility decreased from 0.23 ± 0.08 µL/min/mm Hg at baseline to 0.18 ± 0.08 µL/min/mm Hg (P < 0.001) after timolol. The change in outflow facility was negatively correlated with baseline outflow facility (r = -0.51; P < 0.001). CONCLUSIONS: Timolol reduces outflow facility in healthy human eyes, and this effect is greater in eyes with higher baseline outflow facility. This phenomenon may be related to reduced aqueous humor flow, but the precise mechanism remains to be determined.