Faculty Bibliography

BACKGROUND:The prognostic impact of cohesin mutations in patients with acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS) is controversial. METHODS:In patients with AML and MDS who underwent next-generation sequencing at the authors' center during 2017-2023, the authors assessed the landscape of cohesin mutations and the impact of co-occurring mutations on overall survival (OS) and compared outcomes between patients with cohesin mutations and those with wild-type (WT) cohesin genes. RESULTS:The study included 83 patients, 36 with cohesin mutations (STAG2, n = 28; SMC1A, n = 7; SMC3, n = 3; co-expression of cohesin mutations, n = 2) and 47 with WT cohesin genes. Of the 36 patients with cohesin mutations, 17 (47%) had AML (six de novo and 11 secondary), and 19 (53%) had MDS. Patients who had STAG2 mutations had better median OS than patients who had only SMC1A and SMC3 mutations (26 vs. 10 months; p = .043). SRSF2 mutation was the most frequent co-occurring mutation (n = 12; 33%) and was associated with worse median OS than WT SRSF2 (13 vs. 43 months; p = .016). Seven patients (19%) with cohesin mutations underwent hematopoietic transplantation; their median OS was 70 months. Compared with the WT cohesin group, patients who had cohesin mutations were more likely to have adverse-risk AML (82% vs. 53%). The median OS was similar among patients with adverse-risk AML in the cohesin-mutation and WT cohesin groups (10 vs. 14 months, respectively; p = .9). CONCLUSIONS:The current study provides insight into the prognostic impact of cohesin mutations and co-occurring mutations in patients with myeloid malignancies.

BACKGROUND:Disruption of ambulatory healthcare in New York City (NYC) during the COVID-19 pandemic was common, but the impact on the cardiometabolic health of vulnerable patient groups is unknown. Therefore, we estimated the effect of total care disruption (TCD) on blood pressure (BP) control among older NYC residents with hypertension and at least one other chronic condition, and examined whether neighborhood poverty moderated this impact. METHODS:From the INSIGHT Clinical Research Network, we identified NYC residents ≥50 years of age with hypertension and at least one other chronic condition. TCD was defined as no ambulatory or telehealth visit during the pandemic. We contrasted the change in prevalence of controlled BP (BP <140/90) before and after the pandemic among those with and without TCD via an inverse probability weighted (IPW) difference-in-difference regression model. RESULTS:Among 212,673 eligible individuals, mean age was 69.5 years (SD: 10.2 years) and 15.1% experienced TCD. BP control declined from 52.4% to 45.9% among those with TCD and from 53.6% to 48.9% among those without TCD. After IPW adjustment, a larger decline in BP control was noted among those with TCD (adjusted difference-in-difference = 1.13 percentage points (95% CI 0.32-1.94, p-value=0.0058)). There was no consistent difference in the relationship between TCD and post-pandemic BP control across neighborhood poverty levels. CONCLUSION/CONCLUSIONS:COVID-19-related TCD was associated with a modest decline in BP control among older adults with hypertension in NYC; this was not moderated by neighborhood poverty level.

Idursulfase is the first-line and only available enzyme replacement therapy (ERT) for Mucopolysaccharidosis type II (MPS II), or Hunter Syndrome. Deficiency in the lysosomal enzyme iduronate-2-sulfatase leads to progressive skeletal deformities, neurologic deterioration, airway obstruction, and cardiomyopathy. In severe cases, these deformities can lead to death during teenage years (Stapleton et al. 2017). Continuous treatment with ERT is essential to prevent irreversible changes. However, 16 out of 108 (15%) patients had hypersensitivity reactions to idursulfase during clinical trials. Hypersensitivity reactions have also been reported several years into treatment (Elaprase 2018). Therefore, it is critical to evaluate for hypersensitivity reactions and desensitize patients to idursulfase. We report a fourteen-year-old male who was evaluated using a nonirritating skin test concentration and underwent a novel desensitization protocol for Lysosomal Storage Disease ERT.

Hyperattenuating contents detected in the gastrointestinal (GI) tract on CT scans are commonly seen and are almost always due to the purposeful ingestion of an oral contrast agent, usually barium- or iodine-based, used for evaluating the GI tract. Occasionally, other ingested material such as antacids or other medications, foreign objects, and medical devices can also be hyperattenuating. While these are usually correctly identified, these materials can potentially be misdiagnosed as a pathologic condition. Lokelma (sodium zirconium cyclosilicate (SZC)) is an increasingly used agent to treat hyperkalemia and has a hyperattenuating appearance on CT due to the presence of zirconium. However, this is not well known to the radiologic community. Here, we describe a case where SZC was seen in the GI tract on CT and misinterpreted as an acute GI bleed. A 72-year-old woman underwent single (portal venous) phase intravenous contrast-enhanced abdominal and pelvic CT after presenting to the ED with a lower GI bleed. The CT showed intraluminal hyperattenuation within the cecum, which was diagnosed prospectively as an active GI bleed. A CT angiogram of the abdomen and pelvis performed the following day for follow-up showed the hyperattenuating contents to be present on the non-IV contrast-enhanced series of the study, thereby proving that it was not due to active bleeding. Further investigation of the patient's medical record showed that the patient was being treated with SZC for hyperkalemia, accounting for the hyperattenuating cecal contents. Awareness of the hyperattenuating appearance of SZC on CT by radiologists and clinical staff can help avoid confusion and misdiagnosis.

This observational cohort study examined the association between Alzheimer's disease and related dementias (ADRD) and hospital and skilled nursing facility (SNF) utilization among community-dwelling older adults aged 65 and older. Using four waves of longitudinal survey data from the 2016-2022 Health and Retirement Study conducted by the University of Michigan and multivariate, individual-level regressions, we found that the cognitive impairment but no dementia (CIND) and ADRD groups exhibited similar patterns in hospitalizations, hospital visits, and total hospital days compared to the normal cognition group. However, CIND was significantly associated with increased odds of SNF stays (odds ratio [OR], 1.22) and a higher number of SNF visits (incidence rate ratio [IRR], 1.45) than the normal cognition group. Higher odds of any SNF stay (OR, 1.26) and number of SNF visits (IRR, 1.45) were also observed for ADRD compared to normal cognition. These findings suggest that CIND or ADRD was not associated with hospital use but was significantly associated with increased SNF use.

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.

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.

Caffeine is administered to preterm infants in neonatal intensive care units for prevention and treatment of apnea of prematurity. Although caffeine's primary effect is to impact the respiratory drive of preterm infants, caffeine also has anti-inflammatory properties. This study investigated the role of caffeine on the inflammatory gene expression in THP-1 pre-monocytes exposed to lipopolysaccharide (LPS) in vitro, mimicking a clinical pro-inflammatory scenario. The effects of different physiologic dosages of caffeine administration post-LPS (treatment with caffeine) and pre-LPS (prophylaxis with caffeine) on pro-inflammatory gene expressions (TNF-α, NF-κB, IL-8, PPARγ) of the THP-1 cells were investigated. The post-LPS group showed a dose-dependent decrease in TNF-α at a caffeine concentration of 100 μM and NF-κB gene expression at 50 and 100 μM, with the implication that this is an optimal anti-inflammatory caffeine concentration range. Clinically, this would correspond to a serum caffeine level between 10 and 20 μg/mL, respectively. For the pre-LPS group, TNF-α and NF-κB gene expression decreased at all studied caffeine concentrations. These findings point to caffeine's potential therapeutic capacity in regulating monocyte inflammatory responses to gram-negative infections in addition to regulating neuron response in the brainstem for preterm infants.