Faculty Bibliography

The optimal treatment of patients with diffuse large B-cell lymphoma (DLBCL) or Hodgkin lymphoma (HL) with preexisting cardiomyopathy is uncertain. An anonymous, electronic survey was distributed by e-mail to three US lymphoma cooperative groups, two community hospitals, and twelve academic medical systems, and distributed at one international lymphoma meeting. Fifty hematology-oncology providers caring for patients with lymphoma were included. In response to a vignette of a 67-yo with Stage III DLBCL with LVEF of 40-45%, 15 (30%) would use non-anthracycline regimens, 13 (26%) R-CHOP with liposomal doxorubicin instead of doxorubicin, 11 (22%) R-CHOP without modification and 6 (12%) R-CHOP with a continuous doxorubicin infusion. In a second vignette of a patient with HL in remission after frontline treatment with doxorubicin cumulative dose 300 mg/m², 16 (32%) would order an echocardiogram after treatment. There was substantial variability in preferred treatment regimens with preexisting cardiomyopathy and in cardiac monitoring after anthracycline.

OBJECTIVE:Preeclampsia remains one of the leading causes of perinatal mortality worldwide. Little is known of the modifiable risk factors that can be identified and addressed early in pregnancy to reduce the risk of preeclampsia and its associated adverse outcomes. We sought to determine if there is a synergistic effect of pre-pregnancy body-mass index and obstructive sleep apnea on the risk of preeclampsia. STUDY DESIGN/METHODS:We conducted a retrospective cohort study of singleton pregnancies delivered in Kaiser Permanente Southern California hospitals between January 1, 2010, and December 31, 2020 (n=342,349). Preeclampsia and sleep apnea were ascertained using clinical diagnosis codes. Body-mass index in kg/m2 measured during prenatal care visits was categorized as normal (18.5 to 24.9), overweight (25 to 29.9), and obese (≥30). Multivariable logistic regression was used to estimate adjusted relative risks (adjusted RR) and 95% confidence intervals (CI). RESULTS:Compared to normal weight in a pregnancy, overweight (adjusted RR: 1.6; 95% CI: 1.5, 1.7) and obese body mass index (adjusted RR: 2.5; 95% CI: 2.4, 2.6) were associated with an increased risk of preeclampsia. Independent of pre-pregnancy body-mass index, a pregnancy with obstructive sleep apnea was associated with an increased risk of preeclampsia (adjusted RR: 2.2; 95% CI: 1.8, 2.6). Compared to normal weight without the diagnosis of obstructive sleep apnea in a pregnancy, overweight (adjusted RR: 4.6; 95% CI: 2.9, 7.4) and obese body mass index (adjusted RR: 3.8; 95% CI: 3.2, 4.6) with the diagnosis of obstructive sleep apnea were associated with an increased risk of preeclampsia. CONCLUSIONS:Obstructive sleep apnea and elevated body-mass index have independent and additive relationship with preeclampsia. Overweight women at-risk of preeclampsia should be advised of a higher likelihood of developing preeclampsia when both conditions occur together and may benefit from close monitoring and early interventions for these modifiable risk factors.

Macrophages are essential immune cells that play crucial roles in inflammation and tissue homeostasis, and are important regulators of metabolic processes, such as the metabolism of glucose, lipids, and amino acids. The regulation of macrophage metabolism by circadian clock genes has been emphasized in many studies. Changes in metabolic profiles occurring after the perturbation of macrophage circadian cycles may underlie the etiology of several diseases. Specifically, chronic inflammatory disorders, such as atherosclerosis, diabetes, cardiovascular diseases, and liver dysfunction, are associated with poor macrophage metabolism. Developing treatment approaches that target metabolic and immunological ailments requires an understanding of the complex relationships among clock genes, disease etiology, and macrophage metabolism. This review explores the molecular mechanisms through which clock genes regulate lipid, amino acid, and glucose metabolism in macrophages, and discusses their potential roles in the development and progression of metabolic disorders. The findings underscore the importance of maintaining circadian homeostasis in macrophage function as a promising avenue for therapeutic intervention in diseases involving metabolic dysregulation, given its key roles in inflammation and tissue homeostasis. Moreover, reviewing the therapeutic implications of circadian rhythm in macrophages can help minimize the side effects of treatment. Novel strategies may be beneficial in treating immune-related diseases cause by shifted and blunted circadian rhythms via light exposure, jet lag, seasonal changes, and shift work or disruption to the internal clock (such as stress or disease).

BACKGROUND:The PARTNER 3 (Safety and Effectiveness of the SAPIEN 3 Transcatheter Heart Valve in Low Risk Patients with Aortic Stenosis) trial compared SAPIEN 3 transcatheter aortic valve replacement (TAVR) to surgery in low-risk patients with symptomatic, severe aortic stenosis. Echocardiographic outcomes at 5 years are unknown. OBJECTIVES/OBJECTIVE:This study sought to compare 5-year echocardiographic results of TAVR and surgery in the PARTNER 3 trial. METHODS:Echocardiograms for 1,000 randomized patients were obtained at baseline, 30 days, 1 year, and annually through 5 years and were analyzed by a core lab consortium. The composite primary endpoint of death, stroke, or rehospitalization was adjudicated by a clinical events committee. RESULTS:At 5 years, ≥ mild aortic regurgitation was higher following TAVR vs surgery (24.5% vs 6.3%; P < 0.001), with low ≥ moderate aortic regurgitation in both groups. TAVR patients had higher mean transaortic gradient (12.8 ± 6.5 vs 11.7 ± 5.6 mm Hg; P < 0.001), stroke volume index (44.6 ± 9.7 vs 41.1 ± 9.2; P < 0.0001), and aortic valve area (1.87 ± 0.46 vs 1.82 ± 0.46; P = 0.895). Fewer TAVR patients had low-flow stroke volume index (P < 0.001) and left ventricular hemodynamic burden (valvulo-arterial impedance; P < 0.01). Tricuspid annular plane systolic excursion was also higher with TAVR (P < 0.001), as was right ventricular-to-pulmonary artery coupling (P < 0.0001). In the combined cohorts, 30-day moderate to severe prosthesis-patient mismatch, mild to severe aortic regurgitation, or low stroke volume index were not predictive of clinical outcomes; only low right ventricular-to-pulmonary artery coupling and high valvulo-arterial impedance at 30 days were associated with increased risk of the 5-year composite primary endpoint. CONCLUSIONS:In low-risk patients with severe aortic stenosis, TAVR, compared to surgery, was associated with similar, stable valve hemodynamics at 5 years with less frequent low-flow state, lower valvulo-arterial impedance, and better right ventricular function. (PARTNER 3 Trial: Safety and Effectiveness of the SAPIEN 3 Transcatheter Heart Valve in Low Risk Patients with Aortic Stenosis [P3]; NCT02675114).

BACKGROUND:Postoperative pain control in cardiac surgery is often managed with opioid medications. Insufficient analgesia can result in complications including splinting, pneumonia, and delay of appropriate rehabilitation. Given the risks and adverse effects of opioids including sedation, respiratory depression, delirium, and decreased gastrointestinal motility, hyperalgesia and potential for addiction, strategies for opioid reduction are likely to improve outcomes, therefore multimodal opioid sparing pain regimens are preferred. Recently, there is increased evidence that low dose Ketamine, an N-methyl-D-Aspartate (NMDA) receptor antagonist, is safe and effective for analgesia in postoperative patients and may be appropriate to this setting. METHODS:This is a single center, retrospective, observational, cohort study over a one year period involving postoperative adult cardiac surgery comparing those who received a single dose of postoperative ketamine, 0.3 mg/kg over 30 min, with those who did not receive any ketamine. Other analgesic protocols were similar between groups and did not include additional ketamine. A total of 120 patient charts were reviewed, of which 96 met inclusion criteria, 32 in the ketamine group and 64 in the standard care group. Charts were reviewed for opioid and other pain medication requirements during the postoperative period and on discharge, and for secondary outcomes: hospital length of stay, ICU length of stay, in-hospital and 30-day mortality, 30-day readmission, and rates of delirium, emergence reactions, and need for escalated respiratory support. RESULTS:The group who received postoperative ketamine required 28.8 morphine milligram equivalents (MME) less postoperative opioid (90.1 mg vs 118.9 mg, p = 0.167), and was prescribed an average of 15.8 MME less on discharge (p < 0.001). Intraoperatively, both groups received 1000 mg acetaminophen, 2 mg intravenous morphine and 100 mcg fentanyl, 26 MME, by protocol. No ketamine was administered intraoperatively or preoperatively. The groups differed in respect to operation type and controlling for this parameter failed to achieve significance in needs during admission (p = 0.215), but remained significant on discharge (p = 0.02). The non-ketamine group received more ketorolac (15.5 vs 10.1, p = 0.06). The ketamine group required less acetaminophen but more gabapentin. There was no difference in hospital or ICU length of stay. There was no delirium or mortality in either group. Respiratory depression occurred in 15 patients who all subsequently received ketamine. No patient developed respiratory depression after ketamine. CONCLUSIONS:Ketamine may be a reasonable choice for postoperative cardiac surgery analgesia and may reduce the need for opioids on discharge, and possibly during admission.

BackgroundThrombosis is the second leading cause of death in cancer patients and treatment for thrombosis and prevention for secondary prophylaxis is anticoagulation. Low-molecular-weight heparin (LMWH) is more effective than vitamin K antagonists for the treatment of cancer-associated thromboembolism (CAT). Direct oral anticoagulants (DOACs) are non-inferior to dalteparin in treating CAT with similar major bleeding risks. Major guidelines recommend DOACs for CAT; however, data comparing individual DOACs to enoxaparin is lacking. The purpose of this study is to evaluate the efficacy and safety of DOACs compared to LMWH for CAT.MethodsA multi-site retrospective review was conducted in adult cancer patients with a CAT history who received either a DOAC (apixaban or rivaroxaban) or LMWH (enoxaparin). Primary efficacy and safety endpoints were recurrent thromboembolism and major bleeding occurrences. Secondary endpoints included time to subsequent CAT occurrence, time to first bleed event post initial CAT, and incidence of clinically relevant non-major and minor bleeding.ResultsA total of 102 patients were included in the study. There was no significant difference among the groups with respect to time to subsequent CAT (p = 0.5625). However, patients who received apixaban and rivaroxaban had a 2.39 times and 3.26 times higher risk of subsequent CAT respectively compared to those who received enoxaparin. Major bleeding rates were also not statistically significant (p = 0.465), despite enoxaparin having the highest rate at 8.8% and no rivaroxaban patients experiencing major bleeding.ConclusionNo differences were observed between rivaroxaban, apixaban, and enoxaparin in rates of recurrent venous thromboembolism (VTE) and bleeding.

INTRODUCTION/BACKGROUND:Wound care is an essential discipline in plastic surgery, especially as the prevalence of chronic wounds, such as pressure injuries, is increasing. The escalating volume of patient data and the numerous variables influencing wound outcomes are making traditional manual chart reviews in wound care and research increasingly complex and burdensome. The emergence of Natural Language Processing (NLP) software based on large language models (LLMs) such as ChatGPT presents an opportunity to automate the data extraction process. This study harnesses the capabilities of ChatGPT, hosted by our medical center's secure, private Azure OpenAI service, to automatically extract and process variables from patient charts following sacral wound visits. We assess ChatGPT's potential to revolutionize chart review through improved data retrieval accuracy and efficiency. METHODS:We evaluated the use of the medical center's internal ChatGPT in chart review. ChatGPT and a Python script were integrated into the existing chart review process for patients with sacral wounds from 2 hospital cohorts to extract and format variables related to wound care. Metrics include time taken for review, accuracy of extracted information, and assessment of ChatGPT-generated insights. RESULTS:ChatGPT reduced the average time per chart review from 7.56 minutes with the manual method to 1.03 minutes using ChatGPT. Furthermore, it achieved a 0.957 overall accuracy rate compared to manual chart review, ranging from 0.747 to 0.986 across extracted data elements. ChatGPT was also able to synthesize accurate narrative descriptions of patient wounds. CONCLUSIONS:We highlight ChatGPT's potential to enhance speed and precision of chart review in the context of both clinical care and wound care research, offering valuable implications for integration of artificial intelligence in healthcare workflows.