Seeking Equity; Pathway Programs in Liaison Committee on Medical Education Medical Schools for Minoritized Students.

Objectives: There is a paucity of data on pathway programs that seek to increase underrepresented in medicine (URiM) students in medicine. Therefore, this investigation aimed to describe the status and associations of pathway programs at US medical schools. Methods: From May to July 2021, the authors obtained information by (1) accessing pathway programs listed on the Association of American Medical Colleges (AAMC) website, (2) reviewing websites of US medical schools, (3) calling medical schools to obtain further information. The data retrieved from the medical school websites was compiled into a 27-item checklist based on the maximum number of different items that was extracted from any of the medical school websites. The data included program characteristics, curricula, activities, and outcomes. Each program was assessed on the number of categories of which information was available. Statistical analyses determined significant associations of URiM-focused pathways and other factors. Results: The authors identified 658 pathway programs: 153 (23%) listed on AAMC website and 505 (77%) identified from medical school websites. Only 88 (13%) programs listed outcomes and 143 (22%) had adequate website information. URiM-focused programs (48%) were independently associated with AAMC website listing (adjusted odds ratio [aOR] = 2.62, P = .001), no fees requirement (aOR = 3.33, P = .001), oversight by diversity departments (aOR = 2.05, P = .012), Medical College Admission Test preparations (aOR = 2.70, P = .001), research opportunities (aOR = 1.51, P = .022), and mentoring (aOR = 2.58., P < .001). Programs targeting K1-12 were less likely to offer mentoring, shadowing or research or include URiM students. Programs with outcomes were more likely to be college programs with longer durations and offer research, while programs listed on AAMC website provided more resources. Conclusion: Although pathway programs are available for URiM students, accessibility issues due to inadequate websites information and early exposure are barriers. Most programs have insufficient data on their website, including a lack of outcome data which is detrimental in today's virtual climate. Medical schools should update their websites to ensure that students requiring support to matriculate into medical school have adequate and relevant information to make informed decisions regarding participation.

Enterprise Cybersecurity: Building a Successful Defense Program.

Cybersecurity is no longer an option or an afterthought-it is a strategic asset that every organization must address, especially in healthcare. The impact of modern cyberattacks extends well beyond privacy breaches and damage to brand or reputation; it can also affect the safe delivery of care. In 2017, a global security incident affected National Health Service hospitals in England and Scotland, preventing them from providing services to patients and causing thousands of appointments to be canceled. Such serious cyberattacks are becoming more prevalent, and their impact has dramatically changed from impeding back-office operations to threatening patient safety and the financial viability of healthcare organizations. This era of increased cybersecurity risks has compelled successful organizations to rapidly adapt their information security strategies and develop world-class cyber defense programs.

Performance of a Commercially Available MAL Antibody in the Diagnosis of Primary Mediastinal Large B-Cell Lymphoma.

Myelin and lymphocyte (MAL) protein has been previously reported as a highly specific marker for distinguishing primary mediastinal large B-cell lymphoma (PMBL) from diffuse large B-cell lymphoma, not otherwise specified (DLBCL, NOS). However, there has not been a commercially available MAL antibody for immunohistochemistry. We identified a commercially available MAL monoclonal antibody and evaluated it by immunohistochemistry on 43 cases of PMBL and 63 cases of DLBCL, NOS. We also compared this with a CD200 antibody that was previously reported useful in distinguishing PMBL and DLBCL, NOS. A threshold of 10% positive tumor cells was used to determine positive protein expression. MAL was expressed in 72% cases of PMBL and 0% of cases of DLBCL, NOS (sensitivity=72%, specificity=100%). CD200 was expressed in 81% of PMBL cases and 13% of DLBCL, NOS cases (sensitivity=81%, specificity=87%). To our knowledge, this is the first report on the utility of a commercially available MAL monoclonal antibody in the diagnosis of PMBL. There is a high specificity with good sensitivity in distinguishing PMBL from DLBCL, NOS, similar to previous studies with a noncommercial source. This antibody will likely prove useful in identifying cases of PMBL in routine practice.

Biclonal light chain gammopathy with aberrant CD33 expression in secondary plasma cell leukemia.

Plasma cell leukemia is a rare neoplastic proliferation of circulating plasma cells. Clonal proliferations of plasma cells, such as in plasma cell leukemia or plasma cell myeloma, are typically characterized by production of a monoclonal heavy and/or light chain immunoglobulin. We present a case of a secondary plasma cell leukemia arising from plasma cell myeloma with dual expression of lambda and kappa light chains along with aberrant expression of CD33, CD20, and dim CD56. This case emphasizes the importance of recognizing aberrant immunophenotypes in plasma cell leukemias and represents the first reported case of biclonal light chain expression in a secondary plasma cell leukemia.

The elevated expression of a mismatch repair protein is a predictor for biochemical recurrence after radical prostatectomy.

PURPOSE: The inability to predict clinical outcome of prostate cancer is a major impediment to effective treatment decisions and patient counseling. New markers of recurrence are needed to improve the accuracy of risk assessment and treatment of prostate cancer. Our previous studies identified a mismatch repair protein, PMS2, to be elevated in prostate cancer; here, we investigate the prognostic potential of this marker. We hypothesized that the elevation of PMS2 would correlate with disease outcome. EXPERIMENTAL DESIGN: Retrospective quantitative immunohistochemistry was done to measure PMS2 in high-grade cancers of 166 men treated by radical prostatectomy with a biochemical recurrence rate of 56%. Associations between PMS2 levels, pathologic variables, and biochemical recurrence over time were determined. RESULTS: The mean level of PMS2 protein was consistently higher in both cancer-associated benign epithelium and cancer cells of patients who recurred, compared with nonrecurrent patients. PMS2 was an independent predictor of time-to-recurrence in Cox multivariate analyses and significantly stratified patients based on outcome. PMS2 was able to improve the sensitivity of total percent Gleason 4/5 as a risk factor for recurrence in this cohort. CONCLUSIONS: PMS2 protein levels were shown to be a predictor of time-to-recurrence after surgery. This study is the first to document that the elevation of a mismatch repair protein negatively correlates with prognosis and has implications in patient diagnosis and molecular profiling.

The molecular mechanism of DNA damage recognition by MutS homologs and its consequences for cell death response.

We determined the molecular mechanism of cell death response by MutS homologs in distinction to the repair event. Key protein-DNA contacts differ in the interaction of MutS homologs with cisplatinated versus mismatched DNA. Mutational analyses of protein-DNA contacts, which were predicted by molecular dynamics (MD) simulations, were performed. Mutations in suggested interaction sites can affect repair and cell death response independently, and to different extents. A glutamate residue is identified as the key contact with cisplatin-DNA. Mutation of the residue increases cisplatin resistance due to increased non-specific DNA binding. In contrast, the conserved phenylalanine that is instrumental and indispensable for mismatch recognition during repair is not required for cisplatin cytotoxicity. These differences in protein-DNA interactions are translated into localized conformational changes that affect nucleotide requirements and inter-subunit interactions. Specifically, the ability for ATP binding/hydrolysis has little consequence for the MMR-dependent damage response. As a consequence, intersubunit contacts are altered that most likely affect the interaction with downstream proteins. We here describe the interaction of MutS homologs with DNA damage, as it differs from the interaction with a mismatch, and its structural translation into all other functional regions of the protein as a mechanism to initiate cell death response and concomitantly inhibit repair.

The failure of years of experience with electrocardiographic transmission from paramedics to the hospital emergency department to reduce the delay from door to primary coronary intervention below the 90-minute threshold during acute myocardial infarction.

INTRODUCTION: Emergency medical services (EMS), hospital emergency departments, and cardiologists have taken steps to reduce time to reperfusion therapy by implementation of aggressive acute myocardial infarction treatment and triage protocols. Data indicate that significant myocardial salvage requires reperfusion within 2 hours, and the current American College of Cardiology guideline is 90 minutes after hospital emergency department admission. MATERIALS AND METHODS: To minimize delays in time to reperfusion in an urban-rural North Carolina County, Guilford County EMS and the Moses Cone Hospital have collaborated to implement transmission of EMS electrocardiographs (ECGs) to the emergency department. The study population included 92 patients who were transported by EMS and received primary coronary intervention during the second, third, and fourth years after initiation of this intervention in 1993. RESULTS: The median time from symptom onset to the initial ECG was 77 minutes. There was an additional 23 minutes between the availability of this ECG and the arrival of the patient at the emergency department. In the first year of the intervention, the time from hospital arrival to percutaneous coronary intervention was 80 minutes. In years 2 through 4, they were 93, 85, and 94 minutes, respectively. In 2003, 10 years after the intervention, the time from hospital arrival to percutaneous coronary intervention was 113 minutes. CONCLUSION: Initial gains in the time from hospital arrival to percutaneous coronary intervention, attributed to acquisition of the ECG in the prehospital setting, were not sustained over 10 years.

MSH2 missense mutations alter cisplatin cytotoxicity and promote cisplatin-induced genome instability.

Defects in the mismatch repair protein MSH2 cause tolerance to DNA damage. We report how cancer-derived and polymorphic MSH2 missense mutations affect cisplatin cytotoxicity. The chemotolerance phenotype was compared with the mutator phenotype in a yeast model system. MSH2 missense mutations display a strikingly different effect on cell death and genome instability. A mutator phenotype does not predict chemotolerance or vice versa. MSH2 mutations that were identified in tumors (Y109C) or as genetic variations (L402F) promote tolerance to cisplatin, but leave the initial mutation rate of cells unaltered. A secondary increase in the mutation rate is observed after cisplatin exposure in these strains. The mutation spectrum of cisplatin-resistant mutators identifies persistent cisplatin adduction as the cause for this acquired genome instability. Our results demonstrate that MSH2 missense mutations that were identified in tumors or as polymorphic variations can cause increased cisplatin tolerance independent of an initial mutator phenotype. Cisplatin exposure promotes drug-induced genome instability. From a mechanistical standpoint, these data demonstrate functional separation between MSH2-dependent cisplatin cytotoxicity and repair. From a clinical standpoint, these data provide valuable information on the consequences of point mutations for the success of chemotherapy and the risk for secondary carcinogenesis.