Immune microenvironment of basal cell carcinoma and tumor regression following combined PD-1/LAG-3 blockade.

Systemic treatment options for patients with locally advanced or metastatic basal cell carcinoma (BCC) are limited, particularly when tumors are refractory to anti-programmed cell death protein-1 (PD-1). A better understanding of immune checkpoint expression within the BCC tumor microenvironment may inform combinatorial treatment strategies to optimize response rates. CD3, PD-1, programmed death ligand-1 (PD-L1), lymphocyte activation gene 3 (LAG-3), and T-cell immunoglobulin domain and mucin domain 3 (TIM-3)+ cell densities within the tumor microenvironment of 34 archival, histologically aggressive BCCs were assessed. Tumor infiltrating lymphocyte (TIL) expression of PD-1, PD-L1, and LAG-3, and to a lesser degree TIM-3, correlated with increasing CD3+ T-cell densities (Pearson's r=0.89, 0.72, 0.87, and 0.63, respectively). 100% of BCCs (34/34) demonstrated LAG-3 and PD-1 expression in >1% TIL; and the correlation between PD-1 and LAG-3 densities was high (Pearson's r=0.89). LAG-3 was expressed at ~50% of the level of PD-1. Additionally, we present a patient with locally-advanced BCC who experienced stable disease during and after 45 weeks of first-line anti-PD-1 (nivolumab), followed by a partial response after the addition of anti-LAG-3 (relatlimab). Longitudinal biopsies throughout the treatment course showed a graduated increase in LAG-3 expression after anti-PD-1 therapy, lending support for coordinated immunosuppression and suggesting LAG-3 as a co-target for combination therapy to augment the clinical impact of anti-PD-(L)1.

AuduBon-Bons: Bite-Sized Learning for Residents in the Ambulatory Obstetrics and Gynecology Clinic.

Background: While most medical education happens in the inpatient setting, the vast majority of medicine is practiced in the outpatient setting. Graduates from our obstetrics and gynecology (OB/GYN) program consistently report lower confidence and comfort in the ambulatory, as opposed to inpatient, setting. Objective: To describe and evaluate a novel curriculum, delivered in an ambulatory clinic covering ambulatory care topics, and to assess its feasibility in a single site OB/GYN residency program. Methods: We created an ambulatory curriculum, comprising short modules delivered in the ambulatory clinic during the first 15 minutes of every half-day clinic session. Modules were delivered using a flipped classroom format with pre-session assignments during the 2019-2020 academic year. Outcomes were residents' pre- and post-session comfort and confidence and module developers' time to create the curriculum. Time tracking was performed. Results: On average, 11 residents were present for the teaching session weekly. Twenty-four residents and 6 faculty were eligible to complete pre- and post-session surveys. For every weekly session, the average resident comfort level and the average resident confidence level with the module's topic increased from the pre-module survey to the post-module survey. Residents completed pre-module assignments 64.8% (236 of 364) of the time, and of residents who completed the pre-work, 89.4% (211 of 236) reported it was useful. Average survey completion rate was 70.5% (1398 of 1984). Conclusions: We showed that it is feasible to create and implement an ambulatory curriculum for residents in OB/GYN, and this curriculum increased resident's comfort and confidence with ambulatory practice.

Socioeconomic deprivation predicts outcome following radial head and neck fractures.

INTRODUCTION: There is increasing evidence demonstrating an association between fracture epidemiology and socioeconomic status. However, the influence of socioeconomic deprivation on fracture outcome has not been documented before. The aim of this study was to determine if socioeconomic deprivation influenced the short-term outcome following a fracture of the radial head or neck. METHODS: We identified from a prospective database all patients who sustained a radial head or neck fracture over an 18-month period. The primary outcome measure for this study was the patient-reported short musculoskeletal function assessment (SMFA). The Index of Multiple Deprivation (IMD) was used to quantify deprivation, and any correlation with functional outcome was determined. Multivariate regression analysis was used to determine the influence of deprivation on outcome once other significant demographic and fracture characteristics had been accounted for. RESULTS: There were 200 patients in the study cohort, of which 107 (53.5%) were female and the mean age was 44 years (16-83). At a mean follow-up of 6 months the median SMFA score was 0.54 (0-55.4). The SMFA was found to be influenced by the IMD, with increasing deprivation associated with a poorer outcome (p=0.006). On multivariate analysis, the AO fracture classification, compensation and increasing deprivation were the only independent predictors of outcome (all p<0.05). CONCLUSIONS: We have a shown a clear correlation between functional outcome and socioeconomic status, with the most deprived patients reporting a poorer outcome. Future work should be aimed at determining which aspects of deprivation influence patient outcome, with modifiable factors targeted in future health-care planning.

Radial shortening following a fracture of the proximal radius.

BACKGROUND AND PURPOSE: The Essex-Lopresti lesion is thought to be rare, with a varying degree of disruption to forearm stability probable. We describe the range of radial shortening that occurs following a fracture of the proximal radius, as well as the short-term outcome in these patients. PATIENTS AND METHODS: Over an 18-month period, we prospectively assessed all patients with a radiographically confirmed proximal radial fracture. Patients noted to have ipsilateral wrist pain at initial presentation underwent bilateral radiography to determine whether there was disruption of the distal radio-ulnar joint suggestive of an Essex-Lopresti lesion. Outcome was assessed after a mean of 6 (1.5-12) months using clinical and radiographic results, including the Mayo elbow score (MES) and the short musculoskeletal function assessment (SMFA) questionnaire. One patient with a Mason type-I fracture was lost to follow-up after initial presentation. RESULTS: 60 patients had ipsilateral wrist pain at the initial assessment of 237 proximal radial fractures. Radial shortening of ≥ 2mm (range: 2-4mm) was seen in 22 patients (mean age 48 (19-79) years, 16 females). The most frequent mechanism of injury was a fall from standing height (10/22). 21 fractures were classified as being Mason type-I or type-II, all of which were managed nonoperatively. One Mason type-III fracture underwent acute radial head replacement. Functional outcome was assessed in 21 patients. We found an excellent or good MES in 18 of the 20 patients with a Mason type-I or type-II injury. INTERPRETATION: The incidence of the Essex-Lopresti lesion type is possibly under-reported as there is a spectrum of injuries, and subtle disruptions often go unidentified. A full assessment of all patients with a proximal radial fracture is required in order to identify these injuries, and the index of suspicion is raised as the complexity of the fracture increases.

Radial head and neck fractures: functional results and predictors of outcome.

BACKGROUND: The purpose of this study was to determine the functional outcomes and predictive factors of radial head and neck fractures. METHODS: Over an 18-month period, we performed a prospective study of 237 consecutive patients with a radiographically confirmed proximal radial fracture (156 radial head and 81 radial neck). Follow-up was carried out over a 1-year period using clinical and radiologic assessment, including the Mayo Elbow Score (MES). Multivariate regression analysis was used to determine significant predictors of outcome according to the MES. RESULTS: Of the 237 patients enrolled in the study, 201 (84.8%) attended for review, with a mean age of 44 years (range, 16-83 years; standard deviation, 17.3). One hundred eighty-seven (93%) patients achieved excellent or good MESs. The mean MES for Mason type-I (n = 103) and type-II (n = 82) fractures was excellent, with only two patients undergoing surgical intervention. For Mason type-III (n = 11) and type-IV (n = 5) fractures, the flexion arc, forearm rotation arc, and MES in the nonoperatively treated patients were not significantly different (all p ≥ 0.05) from those managed operatively. Regression analysis revealed that increasing age, increasing fracture complexity according to the AO-OTA classification, increasing radiographic comminution, and operative treatment choice were independently significant predictors of a poorer outcome (all p < 0.05). CONCLUSIONS: A majority of radial head and neck fractures can be treated nonoperatively, achieving excellent or good results. Age, fracture classification, radiographic comminution, and treatment choice are important factors that determine recovery.

Elevated intramuscular compartment pressures do not influence outcome after tibial fracture.

BACKGROUND: Although the importance of monitoring differential compartment pressures (Delta P) after tibial fractures has been established, many surgeons continue to use intramuscular pressures in diagnosing compartment syndrome, despite the limitations of this strategy. The cited reason for this is concern over leaving high intramuscular pressures untreated. METHODS: One hundred one patients with tibial fractures with satisfactory Delta P were studied. Forty-one patients had elevated intramuscular pressures of over 30 mm Hg for more than 6 hours continuously. These patients were compared with a control group of 60 patients who had pressures of less than 30 mm Hg throughout. Outcome was measured prospectively in terms of muscular power and return to function over the year after injury. RESULTS: No significant differences were found. CONCLUSION: Provided Delta P remains satisfactory, patients with elevated intramuscular pressures after tibial fracture do not have a greater incidence of complications than those with low pressures. These patients can therefore be observed safely.