Faculty Bibliography

Mesenteric malperfusion is a rare complication of aortic dissection associated with high mortality. Diagnosis requires a high degree of suspicion as treatment is time-sensitive, necessitating early revascularization to prevent bowel necrosis, sepsis, and multi-organ failure. Advances in endovascular techniques have improved outcomes and survival over traditional approaches. Management of type A aortic dissection with mesenteric malperfusion has shifted from central aortic repair first to a two-stage approach with revascularization and delayed aortic repair. Thoracic endovascular aortic repair has become the standard treatment for type B aortic dissection with mesenteric malperfusion. However, finding the balance between aortic repair and treating mesenteric malperfusion remains a challenge. This review highlights current strategies and promising research into new endovascular techniques and refining treatment pathways.

OBJECTIVES/OBJECTIVE:To evaluate mail-in semen collection services for cryopreservation, focusing on costs, transparency, and efficacy due to the advancements of direct access to fertility testing and treatment. METHODS:Using Google, we identified eight prominent companies offering mail-in sperm cryopreservation services. We analyzed their costs, storage practices, marketing strategies, and prescription requirements. For comparison, we examined academic institutions offering similar services, exploring differences in pricing, processes, and accessibility. RESULTS:The average upfront cost to process and freeze sperm was $730 (range $329 to $1575) with 10-year storage costs of $3117, on average (range $1450 to $5500), which may or may not be guaranteed to remain level. Not all services disclosed future costs such as transport, thawing, and disposal fees, with some firms being less transparent. Two firms offered client depositor storage on-site and the remainder outsourced to partner labs scattered around the country. One facility offered storage of tissue samples for men with azoospermia; none of the companies required men to have an order from their doctor to use the service. CONCLUSIONS:Mail-in cryopreservation services provide convenience but present challenges, including varying costs, transparency issues, and potential limitations in medical oversight. Integrating these services into traditional healthcare settings could optimize patient outcomes and satisfaction.

We carried out a single-cell (sc) multiomic analysis on a series of MYD88 mutated Waldenström macroglobulinemia (WM) cases and identified two distinct subtypes of disease, memory B-cell-like (MBC-like) and plasma cell-like (PC-like), based on their expression of key lineage defining genes. Biologically, the subtypes are characterized by their variable capacity to differentiate fully towards a plasma cell (PC) and exhibit unique transcriptomic, chromatin accessibility, and genomic profiles. The MBC-like subtype is unable to differentiate beyond the memory B-cell (MBC) stage, upregulates key MBC genes, and is characterized by upregulated BCR and AKT/mTOR signaling. In contrast, the PC-like subtype can partially differentiate towards a PC, upregulates key PC genes, has enhanced NF-kB signaling, and has an upregulated unfolded protein response. Pseudotime trajectory analysis of combined scRNA-sequencing and scATAC-sequencing supports the variable differentiation capacity of each subtype and implicate key transcription factors SPI1, SPIB, BCL11A, and XBP1 in these features. The existence and generalizability of the two disease subtypes were validated further using hierarchical clustering of bulk RNA-seq data from a secondary set of cases. The biological significance of the subtypes was further established using whole genome sequencing, where it was shown that CXCR4, NIK, and ARID1A mutations occur predominantly in the MBC-like subtype and 6q deletions in the PC-like subtype. We conclude that the variable differentiation blockade seen in WM manifests itself clinically as two disease subtypes with distinct epigenetic, mutational, transcriptional, and clinical features with potential implications for WM treatment strategies.

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.

OBJECTIVE:Surgery for mitral valve disease in patients with mitral annular calcification (MAC) remains challenging. There is no consensus on the ideal management strategy or patient selection, and perioperative and periprocedural morbidity and mortality rates remain high. The recent surge of patients presenting with MAC has been accompanied by increased interest in MAC surgery and interventions. This expert consensus document is meant to provide a simplified outline for managing MAC, including patient selection, imaging, and surgical and transcatheter therapeutic options, with a particular focus on conventional surgical techniques and hybrid approaches. METHODS:The American Association for Thoracic Surgery Clinical Practice Standards Committee assembled an international panel of cardiac surgeons and structural heart interventionalists with established expertise in the field of MAC. A comprehensive literature review was performed by the panel and a medical librarian. Clinical recommendations were developed utilizing a modified Delphi method. RESULTS:Expert consensus was reached on 33 recommendations, with class of recommendation and level of evidence, for each of 5 main topics: (1) preoperative evaluation for patients with MAC, patient selection, and indications for intervention; (2) standard surgical techniques in MAC; (3) hybrid procedures in MAC; (4) transcatheter MAC interventions; and (5) complications and bailout of MAC surgery and interventions. CONCLUSIONS:Despite the complexity and heterogenicity of patients presenting with MAC, consensus on several key recommendations was reached by this American Association for Thoracic Surgery expert panel. These recommendations provide guidance for cardiac surgeons and structural heart interventionists in treating most patients who present with MAC.

INTRODUCTION/BACKGROUND:on the amount of FFP needed to normalize the R-time. METHODS:(ΔPV) and ΔR-time within 24 h of administration of FFP. Responders were divided in high and low based on a decrease in R-time > 5 min after the administration of FFP. Data presented as mean ± SD and median with interquartile range were analyzed with parametric and non-parametric tests as applicable. RESULTS:before transfusions but it was affected by the amount FFP and the resulting ΔPV (483 ± 173 vs. 296 ± 99 and 17.0% ± 6.6% vs. 8.6% ± 3.0%; p < 0.05). CONCLUSIONS:is the key element required to estimate the volume of FFP needed to correct a prolonged R-time.

OBJECTIVE:To evaluate the Maryland All-Payer Model's impact on the rate of elective major joint replacement surgery. STUDY DESIGN/METHODS:A retrospective cohort study of patients in Maryland undergoing elective major joint replacement between 2011 and 2018 was performed using a 20% fee-for-service Medicare sample in a difference-in-difference framework with patients undergoing hip fracture repair serving as controls. METHODS:Among Maryland residents, there were 7147 Medicare fee-for-service patients undergoing elective major joint replacement and 1008 Medicare fee-for-service beneficiaries undergoing hip fracture repair. We used patient-level generalized linear models with a negative binomial family function and a log link function to estimate the association of the All-Payer Model with the rate of elective major joint replacement surgery. RESULTS:Under the All-Payer Model, the rate of elective major joint replacement surgery increased more than that of hip fracture repair (adjusted relative risk, 1.31; 95% CI, 1.15-1.51). Compared with hospitals without affiliates in adjacent states (Maryland-only hospitals), those with affiliates (Maryland hospitals with affiliates) saw rates of elective major joint replacement grow more slowly (adjusted relative risk, 0.87; 95% CI, 0.80-0.95) after the All-Payer Model. Furthermore, major joint replacement rates for Maryland residents at affiliated hospitals in adjacent states increased from 4.26 per 10,000 in the preintervention period to 5.23 per 10,000 in the postintervention period. CONCLUSIONS:Under the All-Payer Model, population-based rates of elective major joint replacement surgery increased more rapidly than did rates of hip fracture repair. Although rates of major joint replacement at Maryland hospitals with affiliates grew more slowly than for Maryland-only hospitals, rates among Maryland residents increased at the affiliates in adjacent states.

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).