Citations

Abstract Introduction Non-cardiovascular end-organ dysfunction is an important determinant of outcomes in cardiac intensive care unit (CICU) patients. We examined the association between in-hospital mortality with the severity and extent of admission liver function test (LFT) abnormalities in a heterogeneous CICU population. Purpose We hypothesized that a greater severity or extent of LFT abnormalities would be associated with higher in-hospital mortality. Methods We included consecutive unique adult CICU patients with available data for one or more of the admission LFT values of interest. Admission laboratory values were defined as those closest to CICU admission. We used the NIH Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 to categorize the severity of each LFT abnormality from Grade 0 (normal) to Grade 4 (life-threatening). We defined the extent of LFT abnormality as the number of individual LFTs meeting criteria for CTCAE Grade 1 or greater. The primary outcome of interest was all-cause in-hospital mortality. Odds ratio (OR) and 95% confidence interval (CI) values for in-hospital mortality were estimated using logistic regression, before and after multivariable adjustment. Results Of 12,428 unique CICU patients, 5,144 were excluded due to a lack of available data for any admission LFT values. The remaining 7,284 patients comprised the final study population. Among patients with available data for each individual LFT, abnormal values were present in: AST, 2,743/5,733 (47.8%); ALT 1,576/5,512 (28.6%); ALK 611/3,684 (16.6%); and TB 898/5,155 (17.4%). A total of 864 (11.9%) patients died during hospitalization. In-hospital mortality was higher for patients with one or more LFTs meeting criteria for CTCAE Grade 1 or greater (17.9% vs. 6.4%, adjusted OR 1.54 [1.27-1.86], p <0.001). A stepwise increase in in-hospital mortality was observed with increasing CTCAE grade, both overall (adjusted OR 1.25 per each higher CTCAE grade [1.16-1.34], p <0.001); (Figure 1A), and for each individual LFT (Figure 1B). Conclusion Cardiohepatic syndrome is an important predictor of prognosis in CICU patients, as the extent and severity of LFT abnormalities are strongly associated with in-hospital mortality. This is the first large-scale study to examine the association between the magnitude of hepatic biomarker derangement with in-hospital mortality in unselected CICU patients. Patients with markedly elevated LFT values exhibited the highest risk of in-hospital mortality. This analysis advocates for the inclusion of commonly obtained LFTs in future risk-prediction tools for enhanced prognostication.

Abstract Background The overall survival of patients with advanced thyroid cancers that have progressed following targeted therapies is limited, indicating a strong need for salvage treatments. Methods We retrospectively analyzed patients with refractory advanced thyroid cancer treated with pemetrexed‐carboplatin (PC) at Mayo Clinic since 2019. Results Eleven patients, three with anaplastic thyroid cancer (ATC), seven with differentiated or poorly differentiated thyroid cancer (DTC), and one with oncocytic carcinoma of the thyroid, were treated with novel salvage PC. Patients with DTC ( n = 7) had durable responses with a median progression‐free survival of 29 months. One responder included a patient with ATC whose disease progressed following pembrolizumab/axitinib, lenvatinib, and dabrafenib/trametinib. On this fourth line treatment, the patient remains on therapy to date, over 12 months after initial response. Conclusions This case series reinforces prior published phase I clinical trial data and shows that pemetrexed can have potent efficacy in the treatment of the most advanced thyroid cancers.

Abstract Background/Introduction Patients with ATTR-CM can have lower circulating TTR levels, which is associated with worsening of cardiac function and increased risk of cardiovascular mortality.[1] Acoramidis has been shown to reduce cardiovascular mortality and hospitalization, while increasing circulating TTR levels, in the ATTRibute-CM phase 3 study.[2] Purpose I. Evaluate serum TTR levels in participants (pts) receiving acoramidis vs those who received tafamidis in the placebo group in ATTRibute-CM at Month 30. II. Evaluate serum TTR levels in pts who transitioned from placebo+tafamidis to acoramidis in the open-label long term extension (OLE) study. Methods ATTRibute-CM study: Eligible pts with ATTR-CM were randomized in a 2:1 ratio to receive acoramidis or placebo for 30 months. Pts in both groups had the option of initiating open-label, commercially available tafamidis after 12 months in the study. Upon completion of Month 30, pts were invited to participate in the OLE study. In OLE, pts who had previously received acoramidis continued acoramidis, and those who had previously received placebo+tafamidis were switched to acoramidis-only treatment. All pts in the OLE study received acoramidis only. Change in serum TTR levels in ATTRibute-CM and OLE at data cutoff (Oct 9, 2023) are summarised using descriptive statistics. Results In the phase 3 study, efficacy analyses were performed in 611 pts, of which 61 of 409 (14.9%) and 46 of 202 (22.8%) received tafamidis in acoramidis and placebo groups, respectively. The median time until tafamidis initiation was 17.8 and 16.1 months, respectively; median exposure duration was 11.6 and 10.5 months, for acoramidis and placebo groups, respectively.[3] Change from baseline (CFB) in serum TTR levels remained unchanged at Month 30 in the placebo-only group (mean [SD] = –0.4 [4.92] mg/dL). Characteristics of pts analysed are described in Fig. 1. A total of 380/611 pts (62.2%) entered the OLE study (229 pts continued acoramidis only, and 23 switched from placebo+tafamidis to acoramidis). At the time of data cutoff, 214 pts who had received acoramidis only completed Month 6 in OLE versus 18 who switched from placebo+tafamidis to acoramidis. At Month 30 in ATTRibute-CM, CFB in serum TTR levels were higher for patients who received acoramidis only than those receiving placebo+tafamidis (Fig 2A). Serum TTR levels increased further in pts who switched from placebo+tafamidis to acoramidis in OLE (Fig. 2B). The OLE study is ongoing, and this analysis includes pts who completed the Month 6 visit at time of data-cut. Conclusion(s) CFB in serum TTR levels were higher in pts receiving acoramidis only than those receiving placebo+tafamidis at Month 30 in the double-blind study. A further significant increase in serum TTR levels was observed in those who received placebo+tafamidis and switched to acoramidis in OLE.

Abstract Background Acute decompensated heart failure (HF) refractory to medical management deteriorates quickly to cardiogenic shock, ultimately requiring mechanical circulatory support (MCS). These devices aim to provide circulatory support as a bridge to advanced therapies. We report patient outcomes with the latest minimally invasive temporary MCS device: Impella 5.5 with SmartAssist. Methods All patients who underwent Impella 5.5 implantation between January 2020 and December 2023 were analyzed. Duration of Impella support and peri-implant parameters were collected from electronic medical records. ANOVA was performed and utilized a p-value of <0.05 as significant for statistical analysis. Results During our review period, a total of 99 patients were supported with Impella 5.5 in the setting of cardiogenic shock. 92 were bridged to heart transplant (BTT), of which 17 also received combined kidney transplantation. Two underwent durable VAD implantation (BTVAD), and 3 had native heart recovery (BTR) and explant. Two patients died, yielding a survival rate of 98%. For BTT group, the median age was 60 years (52-65) at implant and a median BMI of 27 kg/m² (24-31) with a mean support duration of 29 days (SD ±24). Baseline GFR was 49 mL/min/1.73m² (35-65). In the BTVAD group, the median BMI was 43 kg/m² (39-46) with an average duration of support of 22 days (SD ±8) with a GFR of 55 mL/min/1.73m² (38-73). The BTR group had a median BMI of 29 kg/m² (27-30) with an average duration of support of 15 days (SD ±7) and a lower baseline GFR of 36 mL/min/1.73m² (26 – 37) compared to BTT or BTVAD. The two patients that died were supported for an average of 42 days (SD ±9.2) and expired due to non-candidacy in the setting of newly detected prostate cancer in one patient and multi-organ failure in another. All BTVAD and BTT patients did not have a stroke or major vascular complications before terminal therapy. Conclusion Our center highlights the role of early Impella 5.5 placement in the stabilization of patients in cardiogenic shock, thereby providing both patients and providers time for decision-making while optimizing end-organ perfusion beyond the accepted duration of 14 days.Impella Data - Entire CohortImpella Data - Stratified by Outcome

ABSTRACTBackgroundBecause premorbid BMI strongly predicts the amount of weight loss in anorexia nervosa (AN)/atypical AN, we hypothesize that weight loss triggers both disorders by inducing the endocrine adaptation to starvation.MethodWe propose research to capture the onset of AN/atypical AN following intentional, otherwise behaviorally motivated, or unintentional weight loss in relationship to premorbid weight.ResultsWe propose retrospective and prospective studies to examine the temporal development of symptoms in AN/atypical AN. Given a greater frequency of weight loss behaviors in individuals with high BMIs, patients with intentionally driven weight loss should demonstrate a higher mean weight loss and greater premorbid weight and shape concerns. Practice guidelines necessitate weight gain for AN recovery, yet how weight gain induces improvements is unspecified and warrants systematic elucidation. Finally, we highlight implications for the current conceptualization of genetic and environmental contributors of AN/atypical AN in twin and molecular genetic studies.ConclusionWe propose separating the starvation‐induced mechanisms relevant for AN/atypical AN development from the reasons/mechanisms inherent to weight loss.

A male patient in his 70s with a history of tobacco use, organising pneumonia and rheumatoid arthritis that had been treated for several years with rituximab currently being treated with tocilizumab, presented with progressively worsening shortness of breath, increasing oxygen requirements and weakness. He had a history of COVID-19 infection 6 months prior to presentation. Initial COVID-19 PCR testing at presentation was negative. Bronchoalveolar lavage was positive for COVID-19 but negative for spike antibodies. It was thought that he did not clear his prior COVID-19 infection due to his immunocompromised state while taking rituximab. On recommendation of infectious disease, he was treated with a prolonged course of nirmatrelvir/ritonavir, remdesivir and corticosteroids with significant symptom improvement.

AbstractBackgroundCrystal‐storing histiocytosis (CSH) is a rare form of histiocytosis with intralysosomal accumulations of immunoglobulins or paraproteins that aggregate as crystals. Central nervous system (CNS) involvement of CSH is uncommon but should be considered in cases of persistent parenchymal enhancement on neuroimaging.MethodsWe describe one local case of CNS CSH and 10 additional cases identified by literature review.ResultsAmong 11 CSH patients, lesions involved either the dura (2/11) or brain parenchyma (9/11). Two cases had leptomeningeal enhancement. One case had spinal cord involvement. Two cases were associated with marginal zone lymphoma; one case was associated with an immunoglobulin A‐plasma cell dyscrasia. Eight of 11 cases had outcome data available: 7/8 cases had clinical and/or radiological improvement and 1/8 had radiological stability.ConclusionsCentral nervous system involvement of CSH is rare. Potential cases should be comprehensively evaluated for lymphoma or myeloma with positron emission tomography/computed tomography (CT) of the body or alternatively, CT of the chest, abdomen, pelvis and nuclear bone scan, bone marrow biopsy, serum protein electrophoresis, and cerebrospinal fluid protein electrophoresis. Treatment is targeted toward the underlying malignancy.

Background Acute ischemic stroke arising from medium vessel occlusions (MeVO) poses substantial challenges in treatment and management. This study aims to elucidate the outcomes and factors contributing to achieving excellent recanalization (modified Thrombolysis in Cerebral Infarction [mTICI] 2c–3) versus successful recanalization (mTICI 2b) in patients with MeVO stroke undergoing mechanical thrombectomy (MT). Methods We conducted a multinational study analyzing data from the MAD‐MT (Multicenter Analysis of Distal Medium Vessel Occlusions: Effect of Mechanical Thrombectomy) registry, encompassing 37 centers across North America, Asia, and Europe, collected between September 2017 and July 2023. The study included acute ischemic stroke patients with MeVO treated with MT, with or without intravenous thrombolysis, who achieved mTICI 2b–3 post‐MT. Results Among 1463 patients with successful recanalization (mTICI 2b–3), 523 achieved mTICI 2b recanalization, and 940 achieved mTICI 2c–3. Distal occlusions exhibited higher odds of excellent recanalization compared with proximal MeVO vessel occlusions (odds ratio, 1.58; 95% CI, 1.17–2.15; P = 0.003). Cardioembolic stroke pathogenesis was associated with a higher likelihood of excellent recanalization (1.67; 95% CI, 1.07–2.59; P = 0.018). Patients achieving mTICI 2c–3 recanalization demonstrated lower initial National Institutes of Health Stroke Scale scores, significant improvements in postprocedural National Institutes of Health Stroke Scale shift, and a higher percentage of favorable 90‐day outcomes compared with those with mTICI 2b. However, no significant difference in 90‐day mortality rates was observed. Conclusion This study underscores that among patients with MeVO stroke with successful recanalization (mTICI 2b–3) there is higher likelihood of achieving excellent recanalization (mTICI 2c–3) in distal occlusions and cardioembolic pathogenesis. mTICI 2c–3 scores post‐MT correlate with improved clinical outcomes compared with mTICI 2b, affirming the superiority of excellent recanalization over successful recanalization in patients with MeVO stroke. Further prospective studies and randomized controlled trials are warranted for validation.

Abstract Objectives This study aimed to evaluate critical care provider perspectives about diagnostic practices for rare and atypical infections and the potential for using artificial intelligence (AI) as a decision support system (DSS). Methods We conducted an anonymous web-based survey among critical care providers at Mayo Clinic Rochester between November 25, 2023, and January 15, 2024, to evaluate their experience with rare and atypical infection diagnostic processes and AI-based DSSs. We also assessed the perceived usefulness of AI-based DSSs, their potential impact on improving diagnostic practices for rare and atypical infections, and the perceived risks and benefits of their use. Results A total of 47/143 providers completed the survey. Thirty-eight out of 47 agreed that there was a delay in diagnosing rare and atypical infections. Among those who agreed, limited assessment of specific patient factors and failure to consider them were the most frequently cited important contributing factors (33/38). Thirty-eight out of 47 reported familiarity with the AI-based DSS applications available to critical care providers. Less than half (18/38) thought AI-based DSSs often provided valuable insights into patient care, but almost three-quarters (34/47) thought AI-based DDSs often provided valuable insight when specifically asked about their ability to improve the diagnosis of rare and atypical infections. All respondents rated reliability as important in enhancing the perceived utility of AI-based DSSs (47/47) and almost all rated interpretability and integration into the workflow as important (45/47). The primary concern about implementing an AI-based DSS in this context was alert fatigue (44/47). Conclusion Most critical care providers perceive that there are delays in diagnosing rare infections, indicating inadequate assessment and consideration of the diagnosis as the major contributors. Reliability, interpretability, workflow integration, and alert fatigue emerged as key factors impacting the usability of AI-based DSS. These findings will inform the development and implementation of an AI-based diagnostic algorithm to aid in identifying rare and atypical infections.