Upper-limb neurovascular compression, pectoralis minor and quadrilateral space syndromes: A narrative review of current literature.

Pectoralis minor syndrome (PMS) and quadrilateral space syndrome (QSS) are uncommon neurovascular compression disorders affecting the upper extremity. PMS involves compression under the pectoralis minor muscle, and QSS results from compression in the quadrilateral space-both are classically observed in overhead-motion athletes. Diagnosing PMS and QSS may be challenging due to variable presentations and similarities with other, more common, upper-limb pathologies. Although there is no gold standard diagnostic, local analgesic muscle-block response in a patient with the appropriate clinical context is often all that is required for an accurate diagnosis after excluding more common etiologies. Treatment ranges from conservative physical therapy to decompressive surgery, which is reserved for refractory cases or severe, acute vascular presentations. Decompression generally yields favorable outcomes, with most patients experiencing significant relief and restored baseline function. In conclusion, PMS and QSS, although rare, can cause debilitating upper-extremity symptoms; accurate diagnosis and appropriate treatment offer excellent outcomes, alleviating pain and disability.

Structural basis of paralog-specific KDM2A/B nucleosome recognition.

The nucleosome acidic patch is a major interaction hub for chromatin, providing a platform for enzymes to dock and orient for nucleosome-targeted activities. To define the molecular basis of acidic patch recognition proteome wide, we performed an amino acid resolution acidic patch interactome screen. We discovered that the histone H3 lysine 36 (H3K36) demethylase KDM2A, but not its closely related paralog, KDM2B, requires the acidic patch for nucleosome binding. Despite fundamental roles in transcriptional repression in health and disease, the molecular mechanisms governing nucleosome substrate specificity of KDM2A/B, or any related JumonjiC (JmjC) domain lysine demethylase, remain unclear. We used a covalent conjugate between H3K36 and a demethylase inhibitor to solve cryogenic electron microscopy structures of KDM2A and KDM2B trapped in action on a nucleosome substrate. Our structures show that KDM2-nucleosome binding is paralog specific and facilitated by dynamic nucleosomal DNA unwrapping and histone charge shielding that mobilize the H3K36 sequence for demethylation.

The Effect of Angioembolization Versus Open Exploration for Moderate to Severe Blunt Liver Injuries on Mortality.

INTRODUCTION: Blunt liver injury is common and is associated with a high morbidity and mortality. More severe injuries often require either angioembolization or open operative repair, depending on patient factors and facility capacity. We sought to describe patient outcomes based on intervention type. METHODS: We analyzed the National Trauma Data Bank (2017-2019) using ICD-10 codes to identify adult patients with blunt liver injury and their interventions. AIS (Abbreviated Injury Scale) scores were used to group patients based on liver injury severity (AIS 2-6). Logistic regression modeling was used to estimate the adjusted odds ratio of death based on intervention type, excluding patients with severe injury. RESULTS: Of 2,848,592 trauma patients, 50,250 patients had a blunt liver injury. Among patients with AIS 3/4/5 injury, 1,140 had angioembolization, 1,529 had an open repair, and 188 had both angioembolization and open repair. In comparison with no intervention and adjusted for age, sex, shock index, ISS, and transfusion total (first four hours), angioembolization was associated with a significant decrease in the odds of mortality for patients with an AIS 4 (OR 0.68, 95% CI 0.47, 0.99) and AIS 5 injury (OR 0.39, 95% CI 0.24, 0.64). In patients with an AIS 5 injury, open repair had an increased odds of mortality at OR 1.99 (95% CI 1.47, 2.69). CONCLUSION: In an analysis of a national trauma database, patients with a moderate to severe injury (AIS 4 or 5), angioembolization was associated with a significant reduction in the adjusted odds of mortality compared to open repair and should be considered when clinically appropriate.

Comparison of Male and Female Surgeons' Experiences With Gender Across 5 Qualitative/Quantitative Domains.

Importance: A growing body of literature has been developed with the goal of attempting to understand the experiences of female surgeons. While it has helped to address inequities and promote important programmatic improvements, work remains to be done. Objective: To explore how practicing male and female surgeons' experiences with gender compare across 5 qualitative/quantitative domains: career aspirations, gender-based discrimination, mentor-mentee relationships, perceived barriers, and recommendations for change. Design, Setting, and Participants: This national concurrent mixed-methods survey of Fellows of the American College of Surgeons (FACS) compared differences between male and female FACS. Differences between female FACS and female members of the Association of Women Surgeons (AWS) were also explored. A randomly selected 3:1 sample of US-based male and female FACS was surveyed between January and June 2020. Female AWS members were surveyed in May 2020. Exposure: Self-reported gender. Main Outcomes and Measures: Self-reported experiences with career aspirations (quantitative), gender-based discrimination (quantitative), mentor-mentee relationships (quantitative), perceived barriers (qualitative), and recommendations for change (qualitative). Results: A total of 2860 male FACS (response rate: 38.1% [2860 of 7500]) and 1070 female FACS (response rate: 42.8% [1070 of 2500]) were included, in addition to 536 female AWS members. Demographic characteristics were similar between randomly selected male and female FACS, with the notable exception that female FACS were less likely to be married (720 [67.3%] vs 2561 [89.5%]; nonresponse-weighted P < .001) and have children (660 [61.7%] vs 2600 [90.9%]; P < .001). Compared with female FACS, female AWS members were more likely to be younger and hold additional graduate degrees (320 [59.7%] were married; 238 [44.4%] had children). FACS of both genders acknowledged positive and negative aspects of dealing with gender in a professional setting, including shared experiences of gender-based harassment, discrimination, and blame. Female FACS were less likely to have had gender-concordant mentors. They were more likely to emphasize the importance of gender when determining career aspirations and prioritizing future mentor-mentee relationships. Moving forward, female FACS emphasized the importance of avoiding competition among female surgeons. They encouraged male surgeons to acknowledge gender bias and admit their potential role. Male FACS encouraged male and female surgeons to treat everyone the same. Conclusions and Relevance: Experiences with gender are not limited to supportive female surgeons. The results of this study emphasize the importance of recognizing the voices of all stakeholders involved when striving to promote workforce diversity and the related need to develop quality improvement/surgical education initiatives that enhance inclusion through open, honest discourse.

The Effects of Histone H2B Ubiquitylations on the Nucleosome Structure and Internucleosomal Interactions.

Eukaryotic gene compaction takes place at multiple levels to package DNA to chromatin and chromosomes. Two of the most fundamental levels of DNA packaging are at the nucleosome and dinucleosome stacks. The nucleosome is the basic gene-packing unit and is composed of DNA wrapped around a histone core. Nucleosomes stack with one another for further compaction of DNA. The first stacking step leads to dinucleosome formation, which is driven by internucleosomal interactions between various parts of two nucleosomes. Histone proteins are rich targets for post-translational modifications, some of which affect the structure of the nucleosome and the interactions between nucleosomes. These effects are often implicated in the regulation of various genomic transactions. In particular, histone H2B ubiquitylation has been associated with facilitated transcription and hexasome formation. Here, we employed semi-synthetically ubiquitylated histone H2B and single-molecule FRET to investigate the effects of H2B ubiquitylations at lysine 34 (H2BK34) and lysine 120 (H2BK120) on the structure of the nucleosome and the interactions between two nucleosomes. Our results suggest that H2BK34 ubiquitylation widens the DNA gyre gap in the nucleosome and stabilizes long- and short-range internucleosomal interactions while H2BK120 ubiquitylation does not affect the nucleosome structure or internucleosomal interactions. These results suggest potential roles for H2B ubiquitylations in facilitated transcription and hexasome formation while maintaining the structural integrity of chromatin.

DOT1L activity in leukemia cells requires interaction with ubiquitylated H2B that promotes productive nucleosome binding.

DOT1L methylates histone H3 lysine 79 during transcriptional elongation and is stimulated by ubiquitylation of histone H2B lysine 120 (H2BK120ub) in a classical trans-histone crosstalk pathway. Aberrant genomic localization of DOT1L is implicated in mixed lineage leukemia (MLL)-rearranged leukemias, an aggressive subset of leukemias that lacks effective targeted treatments. Despite recent atomic structures of DOT1L in complex with H2BK120ub nucleosomes, fundamental questions remain as to how DOT1L-ubiquitin and DOT1L-nucleosome acidic patch interactions observed in these structures contribute to nucleosome binding and methylation by DOT1L. Here, we combine bulk and single-molecule biophysical measurements with cancer cell biology to show that ubiquitin and cofactor binding drive conformational changes to stimulate DOT1L activity. Using structure-guided mutations, we demonstrate that ubiquitin and nucleosome acidic patch binding by DOT1L are required for cell proliferation in the MV4; 11 leukemia model, providing proof of principle for MLL targeted therapeutic strategies.

Cultural Competence, Safety, Humility, and Dexterity in Surgery.

PURPOSE OF REVIEW: As the United States' population diversifies, urgent action is required to identify, dismantle, and eradicate persistent health disparities. The surgical community must recognize how patients' values, beliefs, and behaviors are influenced by race, ethnicity, nationality, language, gender, socioeconomic status, physical and mental ability, sexual orientation, and occupation. RECENT FINDINGS: Lately, health disparities have been highlighted during the COVID-19 pandemic. Surgery is no exception, with notable disparities occurring in pediatric, vascular, trauma, and cardiac surgery. In response, numerous curricula and training programs are being designed to increase cultural competence and safety among surgeons. SUMMARY: Cultural competence, safety, humility, and dexterity are required to improve healthcare experiences and outcomes for minorities. Various opportunities exist to enhance cultural competency and can be implemented at the medical student, resident, attending, management, and leadership levels.

Multimodal analgesia reduces opioid requirements in trauma patients with rib fractures.

BACKGROUND: Rib fractures are common in trauma patients and are associated with significant morbidity and mortality. Adequate analgesia is essential to avoid the complications associated with rib fractures. Opioids are frequently used for analgesia in these patients. This study compared the effect of a multimodal pain regimen (MMPR) on inpatient opioid use and outpatient opioid prescribing practices in adult trauma patients with rib fractures. STUDY DESIGN: A pre-post cohort study of adult trauma patients with rib fractures was conducted at a Level I trauma center before (PRE) and after (POST) implementation of an MMPR. Patients on long-acting opioids before admission and those on continuous opioid infusions were excluded. Primary outcomes were oral opioid administration during the first 5 days of hospitalization and opioids prescribed at discharge. Opioid data were converted to morphine milligram equivalents (MMEs). RESULTS: Six hundred fifty-three patients met inclusion criteria (323 PRE, 330 POST). There was a significant reduction in the daily MME during the second through fifth days of hospitalization; and the average inpatient MME over the first five inpatient days (23 MME PRE vs. 17 MME POST, p = 0.0087). There was a significant reduction in the total outpatient MME prescribed upon discharge (322 MME PRE vs. 225 MME POST, p = 0.006). CONCLUSION: The implementation of an MMPR in patients with rib fractures resulted in significant reduction in inpatient opioid consumption and was associated with a reduction in the quantity of opiates prescribed at discharge. LEVEL OF EVIDENCE: Therapeutic/Care Management; level IV.

Hypoglycemia unawareness is associated with reduced adherence to therapeutic decisions in patients with type 1 diabetes: evidence from a clinical audit.

OBJECTIVE: Hypoglycemia unawareness increases severe hypoglycemia risk. Hypoglycemia avoidance restores awareness, but it is difficult to sustain. We compared adherence to treatment changes by awareness status. RESEARCH DESIGN AND METHODS: Case notes of 90 type 1 diabetic patients were analyzed retrospectively, identifying awareness status and insulin regimens over four visits. The proportion of patients adhering to advice and percent advice taken were calculated. RESULTS: A total of 31 patients with hypoglycemia awareness and 19 patients with hypoglycemia unawareness were identified, with insulin regimens available in 23 and 13, respectively. Patients with hypoglycemia unawareness were older (P = 0.001) and had longer diabetes duration (P = 0.002) and lower A1C (P = 0.007). More patients with hypoglycemia unawareness reported severe hypoglycemia (P = 0.002) and fewer were adherent (53.8 vs. 87.0%, P = 0.046), with lower adherence scores (42.5 +/- 24.7 vs. 75.3 +/- 27.5%, P = 0.001). CONCLUSIONS: Reduced adherence to changes in insulin regimen in hypoglycemia unawareness is compatible with habituation to hypoglycemic stress. Therapies aimed at reversing repetitive harmful behaviors may be useful to restore hypoglycemia awareness and protection from severe hypoglycemia.