Patient Characteristics Impact Performance of AI Algorithm in Interpreting Negative Screening Digital Breast Tomosynthesis Studies.

Background Artificial intelligence (AI) is increasingly used to manage radiologists' workloads. The impact of patient characteristics on AI performance has not been well studied. Purpose To understand the impact of patient characteristics (race and ethnicity, age, and breast density) on the performance of an AI algorithm interpreting negative screening digital breast tomosynthesis (DBT) examinations. Materials and Methods This retrospective cohort study identified negative screening DBT examinations from an academic institution from January 1, 2016, to December 31, 2019. All examinations had 2 years of follow-up without a diagnosis of atypia or breast malignancy and were therefore considered true negatives. A subset of unique patients was randomly selected to provide a broad distribution of race and ethnicity. DBT studies in this final cohort were interpreted by a U.S. Food and Drug Administration-approved AI algorithm, which generated case scores (malignancy certainty) and risk scores (1-year subsequent malignancy risk) for each mammogram. Positive examinations were classified based on vendor-provided thresholds for both scores. Multivariable logistic regression was used to understand relationships between the scores and patient characteristics. Results A total of 4855 patients (median age, 54 years [IQR, 46-63 years]) were included: 27% (1316 of 4855) White, 26% (1261 of 4855) Black, 28% (1351 of 4855) Asian, and 19% (927 of 4855) Hispanic patients. False-positive case scores were significantly more likely in Black patients (odds ratio [OR] = 1.5 [95% CI: 1.2, 1.8]) and less likely in Asian patients (OR = 0.7 [95% CI: 0.5, 0.9]) compared with White patients, and more likely in older patients (71-80 years; OR = 1.9 [95% CI: 1.5, 2.5]) and less likely in younger patients (41-50 years; OR = 0.6 [95% CI: 0.5, 0.7]) compared with patients aged 51-60 years. False-positive risk scores were more likely in Black patients (OR = 1.5 [95% CI: 1.0, 2.0]), patients aged 61-70 years (OR = 3.5 [95% CI: 2.4, 5.1]), and patients with extremely dense breasts (OR = 2.8 [95% CI: 1.3, 5.8]) compared with White patients, patients aged 51-60 years, and patients with fatty density breasts, respectively. Conclusion Patient characteristics influenced the case and risk scores of a Food and Drug Administration-approved AI algorithm analyzing negative screening DBT examinations. © RSNA, 2024.

The (±)-5-Aza[1.0]triblattane Skeleton via Azetine Cycloaddition.

The first synthesis of the 5-aza[1.0]triblattane skeleton was achieved through a [4 + 2] cycloaddition approach using a suitably protected azetine and cyclopentadiene. A series of azetines were synthesized to explore both stability and suitable N-protection. The key step following cycloaddition utilized a noninitiated protonated aminyl radical cyclization to install the final 5-azatriblattane bond, but it was found to be considerably more unstable than the 6-aza isomer under acidic conditions.

9-Azahomocubane.

Homocubane, a highly strained cage hydrocarbon, contains two very different positions for the introduction of a nitrogen atom into the skeleton, e. g., a position 1 exchange results in a tertiary amine whereas position 9 yields a secondary amine. Herein reported is the synthesis of 9-azahomocubane along with associated structural characterization, physical property analysis and chemical reactivity. Not only is 9-azahomocubane readily synthesized, and found to be stable as predicted, the basicity of the secondary amine was observed to be significantly lower than the structurally related azabicyclo[2.2.1]heptane, although similar to 1-azahomocubane.

seco-1-Azacubane-2-carboxylic Acid: Derivative Scope and Comparative Biological Evaluation.

The unusual and sterically constrained amino acid, seco-1-azacubane-2-carboxylic acid, was incorporated into a range of bioactive chemical templates, including enalaprilat, perindoprilat, endomorphin-2 and isoniazid, and subjected to biological testing. The endomorphin-2 derivative displayed increased activity at the δ opioid receptor, but a loss in activity was observed in the other cases, although human normal cell line evaluation suggests limited cytotoxic effects.

What Matters Most: The Documented Goals, Values and Motivators of Advanced Cancer Patients.

BACKGROUND: Goals of care conversations are essential to delivery of goal concordant care. Infrequent and inconsistent goals of care documentation potentially limit delivery of goal concordant care. METHODS: At Kaiser Permanente San Francisco Cancer Center, a standardized documentation template was designed and implemented to increase goals of care documentation by oncologists. The centralized, prompt-based template included value clarification of the goals and values of advanced cancer patients beyond treatment preferences. Documented conversations using the template during the initial pilot period were reviewed to characterization the clinical context in which conversations were recorded. Common goals and motivators were also identified. RESULTS: A total of 178 advanced cancer patients had at least 1 documented conversation by a medical oncologist using the goals of care template. Oncologists consistently documented within the template goals of therapy and motivating factors in decision making. The most frequently documented goals of care were "Avoiding Pain and Suffering," "Physical Independence," and "Living as Long as Possible." The least recorded goal was "Comfort Focused Treatment Only." CONCLUSIONS: Review of oncologist documented goals of care conversations using a prompt-based template allowed for characterization of the clinical context, therapy goals and motivators of advanced cancer patients. Communication of goals of care conversations by oncologists using a standardized prompt-based template within a centralized location has the potential to improve delivery of goal concordant care.

Aeromonas caviae-Associated Severe Bloody Diarrhea.

Aeromonas species are capable of inducing severe infections in both immunocompetent and immunocompromised individuals. Gastroenteritis is the most common infection associated with Aeromonas species in humans. We report a rare case of Aeromonas caviae severe gastroenteritis and bloody diarrhea that led to the development of sepsis in a 45-year-old female with no history of immunocompromising conditions. This patient required extensive medical support which included blood transfusions and antibiotics. Fortunately, with appropriate diagnostic measures and targeted antibiotic therapy, her symptoms resolved. Aeromonas species are becoming increasingly frequent among the pathogens isolated from patients suffering from gastroenteritis. As such, it is becoming increasingly important for clinicians to consider this pathogen when working up their patients for diarrhea.

Arc1 : a regulator of triglyceride homeostasis in male Drosophila.

Achieving metabolic homeostasis is necessary for survival, and many genes are required to control organismal metabolism. A genetic screen in Drosophila larvae identified putative fat storage genes including Arc1 . Arc1 has been shown to act in neurons to regulate larval lipid storage; however, whether Arc1 functions to regulate adult metabolism is unknown. Arc1 esm18 males store more fat than controls while both groups eat similar amounts. Arc1 esm18 flies express more brummer lipase and less of the glycolytic enzyme triose phosphate isomerase, which may contribute to excess fat observed in these mutants. These results suggest that Arc1 regulates adult Drosophila lipid homeostasis.

seco-1-Azacubane-2-carboxylic acid-Amide Bond Comparison to Proline.

seco-1-Azacubane-2-carboxylic acid, an unusual and sterically constrained amino acid, was found to undergo amide bond formation at both the N- and C-termini using proline based bioactive molecule templates as a concept platform.

Current use of the National Surgical Quality Improvement Program surgical risk calculator in academic surgery: a mixed-methods study.

Background: This study aims to quantitatively assess use of the NSQIP surgical risk calculator (NSRC) in contemporary surgical practice and to identify barriers to use and potential interventions that might increase use. Materials and methods: We performed a cross-sectional study of surgeons at seven institutions. The primary outcomes were self-reported application of the calculator in general clinical practice and specific clinical scenarios as well as reported barriers to use. Results: In our sample of 99 surgeons (49.7% response rate), 73.7% reported use of the NSRC in the past month. Approximately half (51.9%) of respondents reported infrequent NSRC use (<20% of preoperative discussions), while 14.3% used it in ≥40% of preoperative assessments. Reported use was higher in nonelective cases (30.2% vs 11.1%) and in patients who were ≥65 years old (37.1% vs 13.0%), functionally dependent (41.2% vs 6.6%), or with surrogate consent (39.9% vs 20.4%). NSRC use was not associated with training status or years in practice. Respondents identified a lack of influence on the decision to pursue surgery as well as concerns regarding the calculator's accuracy as barriers to use. Surgeons suggested improving integration to workflow and better education as strategies to increase NSRC use. Conclusions: Many surgeons reported use of the NSRC, but few used it frequently. Surgeons reported more frequent use in nonelective cases and frail patients, suggesting the calculator is of greater utility for high-risk patients. Surgeons raised concerns about perceived accuracy and suggested additional education as well as integration of the calculator into the electronic health record.

Five-year mortality after traumatic central cord syndrome in Wales.

Aims: Traumatic central cord syndrome (CCS) typically follows a hyperextension injury and results in motor impairment affecting the upper limbs more than the lower, with occasional sensory impairment and urinary retention. Current evidence on mortality and long-term outcomes is limited. The primary aim of this study was to assess the five-year mortality of CCS, and to determine any difference in mortality between management groups or age. Methods: Patients aged ≥ 18 years with a traumatic CCS between January 2012 and December 2017 in Wales were identified. Patient demographics and data about injury, management, and outcome were collected. Statistical analysis was performed to assess mortality and between-group differences. Results: A total of 65 patients were identified (66.2% male (n = 43), mean age 63.9 years (SD 15.9)). At a minimum of five years' follow-up, 32.3% of CCS patients (n = 21) had died, of whom six (9.2%) had died within 31 days of their injury. Overall, 69.2% of patients (n = 45) had been managed conservatively. There was no significant difference in age between conservatively and surgically managed patients (p = 0.062). Kaplan-Meier analysis revealed no significant difference in mortality between patients managed conservatively and those managed surgically (p = 0.819). However, there was a significant difference in mortality between the different age groups (< 50 years vs 50 to 70 years vs > 70 years; p = 0.001). At five years' follow-up, 55.6% of the patient group aged > 70 years at time of injury had died (n = 15). Respiratory failure was the most common cause of death (n = 9; 42.9%). Conclusion: Almost one-third of patients with a traumatic CCS in Wales had died within five years of their injury. The type of management did not significantly affect mortality but their age at the time of injury did. Further work to assess the long-term functional outcomes of surviving patients is needed to generate more reliable prognostic information.

Alcohol withdrawal syndrome in trauma patients: a study using the Trauma Quality Program Participant User File.

Objective: To identify the rates and possible predictors of alcohol withdrawal syndrome (AWS) among adult trauma patients. Methods: This is a retrospective review of all adult patients (18 years or older) included in the 2017 and 2018 American College of Surgeons Trauma Quality Program Participant User File (PUF). The main outcomes were rates and predictors of AWS. Results: 1 677 351 adult patients were included in the analysis. AWS was reported in 11 056 (0.7%). The rate increased to 0.9% in patients admitted for more than 2 days and 1.1% in those admitted for more than 3 days. Patients with AWS were more likely to be male (82.7% vs. 60.7%, p<0.001), have a history of alcohol use disorder (AUD) (70.3% vs. 5.6%, p<0.001) and have a positive blood alcohol concentration (BAC) on admission (68.2% vs. 28.6%, p<0.001). In a multivariable logistic regression, history of AUD (OR 12.9, 95% CI 12.1 to 13.7), cirrhosis (OR 2.1, 95% CI 1.9 to 2.3), positive toxicology screen for barbiturates (OR 2.1, 95% CI 1.6 to 2.7), tricyclic antidepressants (OR 2.2, 95% CI 1.5 to 3.1) or alcohol (OR 2.5, 95% CI 2.4 to 2.7), and Abbreviated Injury Scale head score of ≥3 (OR 1.7, 95% CI 1.6 to 1.8) were the strongest predictors for AWS. Conversely, only 2.7% of patients with a positive BAC on admission, 7.6% with a history of AUD and 4.9% with cirrhosis developed AWS. Conclusion: AWS after trauma was an uncommon occurrence in the patients in the PUF, even in higher-risk patient populations. Level of evidence: IV: retrospective study with more than one negative criterion.

1-Azahomocubane.

Highly strained cage hydrocarbons have long stood as fundamental molecules to explore the limits of chemical stability and reactivity, probe physical properties, and more recently as bioactive molecules and in materials discovery. Interestingly, the nitrogenous congeners have attracted much less attention. Previously absent from the literature, azahomocubanes, offer an opportunity to investigate the effects of a nitrogen atom when incorporated into a highly constrained polycyclic environment. Herein disclosed is the synthesis of 1-azahomocubane, accompanied by comprehensive structural characterization, physical property analysis and chemical reactivity. These data support the conclusion that nitrogen is remarkably well tolerated in a highly strained environment.

Seasonal temperatures in West Antarctica during the Holocene.

The recovery of long-term climate proxy records with seasonal resolution is rare because of natural smoothing processes, discontinuities and limitations in measurement resolution. Yet insolation forcing, a primary driver of multimillennial-scale climate change, acts through seasonal variations with direct impacts on seasonal climate1. Whether the sensitivity of seasonal climate to insolation matches theoretical predictions has not been assessed over long timescales. Here, we analyse a continuous record of water-isotope ratios from the West Antarctic Ice Sheet Divide ice core to reveal summer and winter temperature changes through the last 11,000 years. Summer temperatures in West Antarctica increased through the early-to-mid-Holocene, reached a peak 4,100 years ago and then decreased to the present. Climate model simulations show that these variations primarily reflect changes in maximum summer insolation, confirming the general connection between seasonal insolation and warming and demonstrating the importance of insolation intensity rather than seasonally integrated insolation or season duration2,3. Winter temperatures varied less overall, consistent with predictions from insolation forcing, but also fluctuated in the early Holocene, probably owing to changes in meridional heat transport. The magnitudes of summer and winter temperature changes constrain the lowering of the West Antarctic Ice Sheet surface since the early Holocene to less than 162 m and probably less than 58 m, consistent with geological constraints elsewhere in West Antarctica4-7.

Massive Left Ventricular Thrombus Causing Bilateral Posterior Cerebral Artery Stroke: A Case Report and Review of Literature.

Left ventricular thrombus (LVT) is a major complication of acute myocardial infarction (MI). Here, we describe the case of a 36-year-old female with a history of acute anterior MI six years prior to hospitalization, who presented with bilateral vision loss due to a bilateral embolic posterior cerebral artery (PCA) stroke in the setting of a 5.7 x 1.7 cm LVT. She underwent bilateral PCA thrombectomy, which led to improvement of her symptoms. Her LVT was managed non-surgically with apixaban and clopidogrel. Her case highlights the need for more medical education about LVT, as quick initiation of anticoagulation is essential in improving outcomes. We review the existing literature to explain the pathogenesis, diagnosis, and treatment of LVT.

Venous Thromboembolism and Thymic Hyperplasia in the Setting of Silent Graves' Disease.

Venous thromboembolism is a common, yet serious life-threatening condition that has many well-recognized associations which include but are not limited to pregnancy, polycythemia, trauma, immobility, and malignancy. The pathophysiology behind the pro-coagulant effects of hyperthyroidism has been well established; however, there are no current guidelines regarding deep venous thrombosis (DVT) surveillance in patients with hyperthyroidism. In this report, we discuss the case of a 36-year-old female with no significant past medical history (PMH) with the exception of a 15 pack-year smoking history, who presented to us with an extensive, rapidly-progressing lower extremity DVT. Despite aggressive treatment measures, she developed a pulmonary embolus in the hospital. During her stay, she was diagnosed with Graves' disease by hormone profile and thyroid-stimulating hormone receptor (TSH-R) antibody positivity. Additionally, an incidental thymic mass, likely thymic hyperplasia, was found on imaging and presumed to be associated with Graves' disease. This case study reports a difficult-to-treat venous thromboembolism in the setting of Graves' disease along with a review of current literature and pathophysiology on the subject.

Differential requirements for the Eps15 homology domain proteins EHD4 and EHD2 in the regulation of mammalian ciliogenesis.

The endocytic protein EHD1 controls primary ciliogenesis by facilitating fusion of the ciliary vesicle and by removal of CP110 from the mother centriole. EHD3, the closest EHD1 paralog, has a similar regulatory role, but initial evidence suggested that the other two more distal paralogs, EHD2 and EHD4 may be dispensable for ciliogenesis. Herein, we define a novel role for EHD4, but not EHD2, in regulating primary ciliogenesis. To better understand the mechanisms and differential functions of the EHD proteins in ciliogenesis, we first demonstrated a requirement for EHD1 ATP-binding to promote ciliogenesis. We then identified two sequence motifs that are entirely conserved between EH domains of EHD1, EHD3 and EHD4, but display key amino acid differences within the EHD2 EH domain. Substitution of either P446 or E470 in EHD1 with the aligning S451 or W475 residues from EHD2 was sufficient to prevent rescue of ciliogenesis in EHD1-depleted cells upon reintroduction of EHD1. Overall, our data enhance the current understanding of the EHD paralogs in ciliogenesis, demonstrate a need for ATP-binding and identify conserved sequences in the EH domains of EHD1, EHD3 and EHD4 that regulate EHD1 binding to proteins and its ability to rescue ciliogenesis in EHD1-depleted cells.

The (±)-6-Aza[1.0]triblattane Skeleton: Contraction beyond the Wilder-Culberson Ring System.

Synthesis of the 6-aza[1.0]triblattane skeleton and the unexpected construction of the 7-azatetracyclo[4.2.1.02,5.03,7]nonane framework are reported, as inspired by the Wilder-Culberson 1-aza[1.1]triblattane ring system. The key steps to assess the 6-aza[1.0]triblattane include accessing the 1,6-cycloaddition product from reaction of chlorosulfonyl isocyanate with cyclohept-1,3,5-triene followed by intramolecular electrocyclization and aminium radical cyclization.

Case report of congenital intestinal malrotation in an adult discovered three months status-post appendectomy.

INTRODUCTION AND IMPORTANCE: Intestinal malrotation is a congenital anomaly primarily diagnosed in children, with limited cases reported in adults. Prompt recognition is necessary to prevent life-threatening complications including bowel ischemia and death. We present a rare case of adult intestinal malrotation highlighting difficulty in diagnosis and surgical management. CASE PRESENTATION: A 37-year-old Caucasian woman presented with a 3-day history of worsening diffuse abdominal pain, three months status-post laparoscopic appendectomy. CT scan with contrast of the abdomen and pelvis demonstrated small bowel mesenteric swirling and descending duodenal transition point. Differential diagnosis included intestinal malrotation versus small bowel obstruction. Pre-operatively, the patient expressed frustration with years of abdominal pain and lack of improvement. Treatment with open surgical small bowel detorsion and ligation of the Ladd's bands was performed, after initial laparoscopic intervention was complicated by enterotomy. The patient recovered well post-operatively with final diagnosis of intestinal malrotation with midgut volvulus. Discharge home was delayed due to polysubstance withdrawal. Post-operatively, the patient reported immediate relief of symptoms which persisted at 2-week and 2-month follow-ups. CLINICAL DISCUSSION: Few reports of congenital malrotation diagnosed in adulthood are reported. This highlights the importance of evaluating all patients for malrotation when the appendix is found outside of the normal positioning in the RLQ, as surgical correction of malrotation is of utmost importance in such patients. CONCLUSION: Clinicians should consider intestinal malrotation in adults with recurrent vague abdominal symptoms. To our knowledge, this is the first report of congenital malrotation discovered in an adult after prior appendectomy.

Understanding the Presentation of Terminal Ileitis.

Our patient is a 47-year-old African American female with a past medical history of recurrent episodes of small bowel obstruction. She presented to the emergency department with symptoms of nausea, vomiting, and abdominal pain. Upon further evaluation, imaging showed obstruction at the terminal ileum. Based on the holistic clinical presentation, we initially thought that this patient was experiencing symptoms of early onset Crohn's disease. Gastroenterology evaluated the patient and was uncertain of the formal diagnosis. Colonoscopy and biopsy were not pathognomonic for Crohn's disease, suggesting that there may be a component of terminal ileitis or another inflammatory bowel disease process. This case exemplifies the degree to which these inflammatory bowel disease processes frequently overlap.

Transoral Gunshot Injury Resulting in Mechanical Block to Cervical Rotation: A Case Report.

CASE: We report a case of self-inflicted transoral gunshot injury in a 24-year-old man resulting in mechanical block to cervical rotation. Anterior surgical removal of the pellet was successful with the patient experiencing no early or long-term functional deficits. CONCLUSION: Given the rarity of a cervical spine injury from gunshot wound without long-term complications, this unique case supports the role of early operative management in such injuries.