DOCK2 is involved in the host genetics and biology of severe COVID-19.

Identifying the host genetic factors underlying severe COVID-19 is an emerging challenge1-5. Here we conducted a genome-wide association study (GWAS) involving 2,393 cases of COVID-19 in a cohort of Japanese individuals collected during the initial waves of the pandemic, with 3,289 unaffected controls. We identified a variant on chromosome 5 at 5q35 (rs60200309-A), close to the dedicator of cytokinesis 2 gene (DOCK2), which was associated with severe COVID-19 in patients less than 65 years of age. This risk allele was prevalent in East Asian individuals but rare in Europeans, highlighting the value of genome-wide association studies in non-European populations. RNA-sequencing analysis of 473 bulk peripheral blood samples identified decreased expression of DOCK2 associated with the risk allele in these younger patients. DOCK2 expression was suppressed in patients with severe cases of COVID-19. Single-cell RNA-sequencing analysis (n = 61 individuals) identified cell-type-specific downregulation of DOCK2 and a COVID-19-specific decreasing effect of the risk allele on DOCK2 expression in non-classical monocytes. Immunohistochemistry of lung specimens from patients with severe COVID-19 pneumonia showed suppressed DOCK2 expression. Moreover, inhibition of DOCK2 function with CPYPP increased the severity of pneumonia in a Syrian hamster model of SARS-CoV-2 infection, characterized by weight loss, lung oedema, enhanced viral loads, impaired macrophage recruitment and dysregulated type I interferon responses. We conclude that DOCK2 has an important role in the host immune response to SARS-CoV-2 infection and the development of severe COVID-19, and could be further explored as a potential biomarker and/or therapeutic target.

Relationship between coronary high-intensity plaques on T1-weighted imaging by cardiovascular magnetic resonance and vulnerable plaque features by near-infrared spectroscopy and intravascular ultrasound: a prospective cohort study.

BACKGROUND: This study aimed to compare the coronary plaque characterization by cardiovascular magnetic resonance (CMR) and near-infrared spectroscopy (NIRS)-intravascular ultrasound (IVUS) (NIRS-IVUS), and to determine whether pre-percutaneous coronary intervention (PCI) evaluation using CMR identifies high-intensity plaques (HIPs) at risk of peri-procedural myocardial infarction (pMI). Although there is little evidence in comparison with NIRS-IVUS findings, which have recently been shown to identify vulnerable plaques, we inferred that CMR-derived HIPs would be associated with vulnerable plaque features identified on NIRS-IVUS. METHODS: 52 patients with stable coronary artery disease who underwent CMR with non-contrast T1-weighted imaging and PCI using NIRS-IVUS were studied. HIP was defined as a signal intensity of the coronary plaque-to-myocardial signal intensity ratio (PMR) ≥ 1.4, which was measured from the data of CMR images. We evaluated whether HIPs were associated with the NIRS-derived maximum 4-mm lipid-core burden index (maxLCBI4mm) and plaque morphology on IVUS, and assessed the incidence and predictor of pMI defined by the current Universal Definition using high-sensitive cardiac troponin-T. RESULTS: Of 62 lesions, HIPs were observed in 30 lesions (48%). The HIP group had a significantly higher remodeling index, plaque burden, and proportion of echo-lucent plaque and maxLCBI4mm ≥ 400 (known as large lipid-rich plaque [LRP]) than the non-HIP group. The correlation between the maxLCBI4mm and PMR was significantly positive (r = 0.51). In multivariable logistic regression analysis for prediction of HIP, NIRS-derived large LRP (odds ratio [OR] = 5.41; 95% confidence intervals [CIs] 1.65-17.8, p = 0.005) and IVUS-derived echo-lucent plaque (OR = 5.12; 95% CIs 1.11-23.6, p = 0.036) were strong independent predictors. Furthermore, pMI occurred in 14 of 30 lesions (47%) with HIP, compared to only 5 of 32 lesions (16%) without HIP (p = 0.005). In multivariable logistic regression analysis for prediction of incidence of pMI, CMR-derived HIP (OR = 5.68; 95% CIs 1.53-21.1, p = 0.009) was a strong independent predictor, but not NIRS-derived large LRP and IVUS-derived echo-lucent plaque. CONCLUSIONS: There is an important relationship between CMR-derived HIP and NIRS-derived large LRP. We also confirmed that non-contrast T1-weighted CMR imaging is useful for characterization of vulnerable plaque features as well as for pre-PCI risk stratification. Trial registration The ethics committee of Juntendo Clinical Research and Trial Center approved this study on January 26, 2021 (Reference Number 20-313).

Clinical significance of 123I-BMIPP washout rate in patients with uncertain chronic heart failure.

BACKGROUND: Recently, triglyceride deposit cardiomyovasculopathy (TGCV) with defective intracellular lipolysis was found to be a disease that causes heart failure. As a diagnostic criterion for TGCV, an Iodaine-123-ß-methyl iodophenyl-pentadecanoic acid washout rate (BMIPP WOR) of < 10% is used, but its clinical significance in patients with heart failure remains to be clarified. METHODS: In 62 hospitalized patients with chronic heart failure, 123I-BMIPP myocardial single-photon emission computed tomography (SPECT) was performed predischarge state. The prevalence of TGCV was investigated. Subsequently, follow-up was conducted for ≥ 90 days (mean: 724.6 ± 392.7 days), and the association between the BMIPP WOR and cardiac events was examined, establishing all-cause mortality and admission due to heart failure as endpoints. RESULTS: Of the 62 patients, the WOR was < 10% in 41 (66.1%). Of these, 26 (41.9%) were diagnosed with definite TGCV. Furthermore, cardiac events were noted in 12 patients (19.4%). Analysis with Cox proportional hazards models showed that the BMIPP WOR < 4.5% was a significant event-predicting factor [HR 4.29, 95% CI: 1.20-16.87; p = 0.0245]. On a Kaplan-Meier curve, the WOR was 4.5%; there was a significant difference in the incidence of events (p = 0.0298). CONCLUSION: In the predischarge state of heart failure, 123I-BMIPP myocardial SPECT was performed. In approximately 40% of the patients, a diagnosis of TGCV was made. The results suggested that the BMIPP WOR is useful for predicting the prognosis of chronic heart failure patients regardless of TGCV.

Coronary flow disturbance assessed by vorticity as a cause of functionally significant stenosis.

OBJECTIVES: Vorticity calculated using computational fluid dynamics (CFD) could assess the flow disturbance generated by coronary stenosis. The purpose of this study was to investigate whether vorticity would be an underlying cause of functionally significant stenosis assessed by invasive fractional flow reserve (FFR). METHODS: This retrospective study included 113 patients who underwent coronary CT angiography showing intermediate stenosis and subsequent invasive FFR between December 2015 and March 2020. Vorticity at the stenosis site was calculated using a mesh-free CFD method. We also evaluated the minimum lumen area (MLA) and diameter stenosis (DS) of the lesion. Invasive FFR of ≤ 0.80 was considered functionally significant. Data were compared using Student's t-test and logistic regression analysis was performed. RESULTS: Of the evaluated 144 vessels, 53 vessels (37%) showed FFR ≤ 0.80. Vorticity of significant stenosis was significantly higher than non-significant stenosis (569 ± 78 vs. 328 ± 34 s-1, p < 0.001). A significant negative relationship was present between vorticity and invasive FFR (R2 = 0.31, p < 0.001). Multivariate logistic regression analysis including MLA and DS showed that vorticity (per 100 s-1, odds ratio: 1.36, 95% confidence interval: 1.21-1.57, p < 0.001) was a statistically significant factor to detect functional significance. The area under the receiver operating characteristic curve statistically significantly increased when vorticity was combined with DS and MLA (0.76 vs. 0.87, p = 0.001). CONCLUSIONS: Vorticity had a statistically significant negative relationship with invasive FFR independent of geometric stenosis. KEY POINTS: • Flow disturbance caused by coronary stenosis could be evaluated by calculating vorticity which is defined as the norm of the rotation of the velocity vector. • Vorticity was statistically significantly higher in stenosis with functional significance than stenosis without. • Vorticity has an additive value to detect functionally significant stenosis over geometrical stenosis.

Plaque characteristics on coronary CT angiography associated with the positive findings of fractional flow reserve and instantaneous wave-free ratio.

BACKGROUND: Fractional flow reserve (FFR) and instantaneous wave-free ratio (iFR) are useful in determining indications for revascularization of coronary artery disease (CAD). Although the discordance of FFR and iFR was noted in approximately 20%, this cause has not been well established. We investigated patient background and features on coronary CT angiography (CCTA) showing not only FFR- and iFR-positive findings but also discordance between FFR ≤ 0.8 and iFR ≤ 0.89. METHODS: Subjects were consecutively treated in 83 cases with 105 vessels in which stenosis of 30-90% was detected at one vessel of at least 2 mm or more in the major epicardial vessels and FFR and iFR was performed within subsequent 90 days, among suspected CAD which underwent CCTA. The factors affecting not only FFR- and iFR-positive findings, respectively, but also discordance between FFR and iFR was evaluated using logistic regression analysis on per-patient and per-vessel basis. RESULTS: FFR- and iFR-positive findings were observed in 42 vessels (40.0%) and 34 vessels (32.3%), respectively. Discordance between FFR ≤ 0.8 and iFR ≤ 0.89 was observed in 22 vessels (21.0%) of 21 patients. In multivariate logistic analysis, LAD (OR 3.55; 95%CI 1.20-11.71; p = 0.0217) and lumen volume/myocardial weight (L/M) ratio (OR 0.93; 0.86-0.99, p = 0.0290) were significant predictors for FFR-positive findings. For iFR-positive findings, LAD (OR 3.86; 95%CI 1.12-13.31; p = 0.0236) was only significant predictor. In FFR ≤ 0.8 and iFR > 0.89 group (15 vessels, 14.3%), positive remodeling (PR) (OR 5.03, 95%CI 1.23-20.48, p = 0.0205) was significant predictor. In FFR > 0.8 and iFR ≤ 0.89 group (7 vessels, 6.7%), there were no significant predictors. CONCLUSION: On CCTA characteristics, a relevant predictor for FFR-positive findings included low L/M ratio. PR was significant predictor in FFR-positive, iFR-negative patients among those with discordance between the FFR and iFR.

Low coenzyme Q10 levels in patients with acute cardiovascular disease are associated with long-term mortality.

Coenzyme Q10 (CoQ10) plays a potential role in the prevention and treatment of cardiovascular disease through improved cellular bioenergetics. Critical illness in the intensive care unit has been reported to be associated with decreased circulating CoQ10 levels, and we previously demonstrated the association of low CoQ10 levels with in-hospital mortality. However, the association of CoQ10 with the acute phase of cardiovascular disease and long-term mortality remains unclear. We enrolled 242 consecutive patients with cardiovascular disease admitted to the coronary care unit of Juntendo University Hospital to investigate the association between long-term mortality and serum CoQ10 levels. During a mean follow-up of 3.2 years, 58 patients died. The mean serum CoQ10 levels were significantly lower in the non-survivors than in the survivors (0.48 ± 0.27 vs. 0.58 ± 0.38 mg/L; p = 0.035). Compared with the patients with above-median CoQ10 levels (0.46 mg/L), the cumulative incidence of all-cause mortality was significantly higher in those with lower CoQ10 levels (p = 0.025). Multivariate Cox regression analysis further demonstrated that lower CoQ10 levels were associated with poor prognosis. Low serum CoQ10 levels during the acute phase of cardiovascular diseases were associated with long-term mortality in patients, suggesting the utility of low serum CoQ10 levels as a predictor and potential therapeutic target.

COVID-19-induced acute renal tubular injury associated with elevation of serum inflammatory cytokine.

BACKGROUND: Severe acute respiratory syndrome Coronavirus 2 has rapidly spread worldwide, with acute kidney injury (AKI) as one of the manifestations with unknown causal mechanisms. We aimed to investigate tubular injury by assessing tubular markers and their association with the severity of Coronavirus disease 2019 (COVID-19). METHODS: We examined the associations between laboratory markers and urinary levels of N-acetyl-ß-D-glucosaminidase (uNAG), ß2-microglobulin (u ß2MG), α1-microglobulin (u α1MG), and liver-type fatty acid binding protein (L-FABP). We studied 18 COVID-19 patients without previous chronic kidney disease and analyzed the relationship between the urinary biomarkers and inflammatory markers in patients with severe (n = 7) or non-severe (n = 11) COVID-19, defined by requirements of supplemental oxygen. RESULTS: Fourteen patients (78%) showed abnormal urinalysis findings and two (11%) developed AKI. Patients with severe COVID-19 had significantly higher levels of proteinuria, uNAG, uß2MG, uα 1MG, and L-FABP than those with non-severe disease. Serum levels of interleukin-6 (IL-6) were significantly higher on admission in all severe COVID-19 cases and correlated with the levels of L-FABP, uß2MG, uα1MG, uNAG, and proteinuria. Moreover, the changes in serum IL-6 (ΔIL-6) levels from baseline to 7 days after admission significantly correlated with ΔL-FABP and Δuß2MG. CONCLUSIONS: Levels of tubular injury markers, especially L-FABP and uß2MG, were significantly associated with IL-6 levels even in patients with no evident AKI. This suggests that L-FABP and uß2MG could be useful as early detective biomarkers for COVID-19 associated renal injury.

[Immune thrombocytopenia preceded by asymptomatic COVID-19 infection].

Immune thrombocytopenia (ITP) may occur following a viral infection. We report the case of a 30-year-old woman with thrombocytopenia who was subsequently diagnosed with ITP. Although she was asymptomatic, chest computed tomography (CT) showed ground-glass opacities in the lower lung regions. The patient had a positive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) real-time polymerase chain reaction (RT-PCR) test. She responded well to 400 mg/kg of intravenous immunoglobulin therapy. Coronavirus disease of 2019 or COVID-19 should be considered as a cause of ITP during the pandemic, and chest CT scans and RT-PCR tests should be performed in patients suspected of ITP.

Adjustment of CT-fractional flow reserve based on fluid-structure interaction underestimation to minimize 1-year cardiac events.

The purpose of the study was to evaluate the optimal cut-off value of CT-Fractional Flow Reserve (CT-FFR) using fluid-structure interaction and how to adjust the CT-FFR's underestimation from a standpoint of minimize 1-year cardiac events. Subjects were 38 cases with 44 vessels in which stenosis of 30-90% was detected using one-rotation scanning by 320-row coronary CT angiography (CCTA) and invasive FFR (i-FFR) was performed within subsequent 90 days. CT-FFR was calculated using on-site from the multiple cardiac phases. A hypothetical 1-year cardiac event incidence was estimated using previous evidences when revascularization was decided based on CT-FFR. We assessed the optimal cut-off value of CT-FFR and how to correct the CT-FFR to minimize hypothetical cardiac events under four different disease prevalence (20%, 25%, 30%, 35%, and 40%). A total of 16 vessels had i-FFR ≤ 0.8. On per-patient basis, the sensitivity, specificity, positive predict value, negative predict value, and diagnostic accuracy of CT-FFR â‰¦ 0.8 vs CCTA > 50% to detect functional stenosis defined as invasive FFR â‰¦ 0.80 were 93.3% vs 73.3%, 73.9% vs 26.1%, 70.0% vs 39.3%, 94.4% vs 60.0%, and 81.6% vs 44.7%, respectively. For minimize 1-year cardiac events, the optimal cut-off value for more than 30% of disease prevalence was 0.80. However, the optimal cut-off value for 20, 25, and 30% was 0.54 in any cases. After the adjustment of CT-FFR using a formula of 0.3X + 0.634 for CT-FFR < 0.7 to counteract its underestimation, the % reduction of the events for 20, 25, 30, 35, and 40% at a 0.80 cut-off were 19.0%, 15.6%, 12.6%, 10.0%, and 7.7% respectively. It was reasonable to support that the optimal cut-off value was 0.80 in disease prevalence of more than 30% for minimize 1-year cardiac events. However, underestimation should be adjusted to reduce cardiac events, especially when disease prevalence is low.

Chest X-Ray Revealed a Slowly Progressive Giant Right Coronary Artery Aneurysm in an Asymptomatic Patient.

A giant right coronary artery aneurysm (60 × 70 mm in size) was incidentally found by chest X-ray as an abnormal right atrial enlargement, and it needed surgical resection. Although the majority of giant coronary artery aneurysms present with symptoms of coronary ischemia, this case presented without any specific symptom. This study indicates that when chest X-ray shows abnormal atrial enlargement, a differential diagnosis of giant coronary artery aneurysm may need to be considered.

Clinical significance of transluminal attenuation gradient in 320-row area detector coronary CT angiography.

The clinical significance of the transluminal attenuation gradient (TAG) has not been established. We evaluated the incremental diagnostic value of TAG by 320-row area detector computed tomography (320-ADCT). Subjects were 65 patients who underwent one-rotation scanning by 320-ADCT and invasive coronary angiography (ICA) within 3 months. TAG values were obtained for the major epicardial vessels 2 mm or more each in RCA, LAD and LCX using automatic analysis software. Moreover, TAG values that excluded calcified lesions in calculation of the regression line were also evaluated (excluded-TAG). In LAD, 21 intermediate lesions underwent functional flow reserve (FFR), and the incremental diagnostic value for functional stenosis was evaluated. The TAG values in the normal vessels were - 8.3 ± 5.0 (HU/cm) for the RCA (n = 32), - 23.3 ± 4.3 for the LAD (n = 9) and - 20.6 ± 10.0 for the LCX (n = 32). The RCA value was significantly higher (p < 0.001). The TAG values with stenosis degrees of ≤ 25%, 26-75%, ≥ 76% on ICA were - 8.3 ± 5.0 (n = 32) vs - 10.3 ± 7.2 (n = 25) vs - 10.0 ± 5.4 (n = 4) in the RCA, - 23.3 ± 4.3 (n = 9) vs - 21.0 ± 11.5 (n = 35) vs - 23.5 ± 15.3 (n = 10) in the LAD and - 21.1 ± 15.1 (n = 32) vs - 21.1 ± 15.1 (n = 16) vs - 17.7 ± 15.7 (n = 6) in the LCX, with no significant difference among the three groups. The excluded-TAG values also showed no significant difference. The area under the curve in the diagnosis of FFR < 0.8 in 21 LAD cases was 0.542 for CT only, 0.694 for CT + TAG, and 0.694 for CT + excluded-TAG. In single time-phase scanning by 320-ADCT, TAG does not offer an incremental diagnostic value.

Low circulating coenzyme Q10 during acute phase is associated with inflammation, malnutrition, and in-hospital mortality in patients admitted to the coronary care unit.

Coenzyme Q10 (CoQ10) has a potential role in the prevention and treatment of heart failure through improved cellular bioenergetics. In addition, it has antioxidant, free radical scavenging, and vasodilatory effects that may be beneficial. Although critical illness in intensive care unit is associated with decreased circulating CoQ10 levels, the clinical significance of CoQ10 levels during acute phase in the patients of cardiovascular disease remains unclear. We enrolled 257 consecutive cardiovascular patients admitted to the coronary care unit (CCU). Serum CoQ10 levels were measured after an overnight fast within 24 h of admission. We examined the comparison of serum CoQ10 levels between survivors and in-hospital mortalities in patients with cardiovascular disease. Serum CoQ10 levels during the acute phase in patients admitted to the CCU had similar independent of the diagnosis. CoQ10 levels were significantly lower in patients with in-hospital mortalities than in survivors (0.43 ± 0.19 vs. 0.55 ± 0.35 mg/L, P = 0.04). In patients admitted to the CCU, CoQ10 levels were negatively associated with age and C-reactive protein levels, and positively associated with body mass index, total cholesterol, and high-density lipoprotein cholesterol levels. Low CoQ10 levels correlated with low diastolic blood pressure. Multivariate logistic regression analysis demonstrated that low CoQ10 levels were an independent predictor of in-hospital mortality. Low serum CoQ10 levels during acute phase are significantly associated with cardiovascular risk and in-hospital mortality in patients admitted to the CCU.

Myocardial triglyceride content in patients with left ventricular hypertrophy: comparison between hypertensive heart disease and hypertrophic cardiomyopathy.

Proton magnetic resonance spectroscopy (1H-MRS) enables the assessment of myocardial triglyceride (TG) content, which is reported to be associated with cardiac dysfunction and morphology accompanied by metabolic disorder and cardiac hemodynamic status. The clinical usefulness of myocardial TG content measurements in patients with left ventricular hypertrophy (LVH) has not been fully investigated. We examined whether myocardial TG content assessed by 1H-MRS was useful for diagnosis in patients with LVH. To quantify myocardial TG content, we conducted 1H-MRS in 35 subjects with LVH. Left ventricular function was measured by cardiac magnetic resonance imaging. Patients were assigned to a hypertensive heart disease (HHD, n = 10) or hypertrophic cardiomyopathy (HCM, n = 25) group based on the histology and/or late gadolinium enhancement pattern. The myocardial TG content was significantly higher in the HHD group than in the HCM group (2.14 ± 1.29 vs. 1.09 ± 0.72 %, P < 0.001). Myocardial TG content were significantly and negatively correlated with LV mass (r = -0.41, P < 0.04) and stroke volume (r = -0.64, P < 0.05) in the HCM group and HHD group, respectively. In a multivariate analysis, LV mass volume and diagnosis of HCM or HHD were independent factors of the myocardial TG content. The results suggest that myocardial metabolism may differ between HCM and HHD patients and that measurement of myocardial TG content by 1H-MRS may be useful for evaluating the myocardial metabolic features of LVH.

Low and exacerbated levels of 1,5-anhydroglucitol are associated with cardiovascular events in patients after first-time elective percutaneous coronary intervention.

BACKGROUND: Postprandial hyperglycemia plays an important role in the pathogenesis of coronary artery disease and cardiovascular events. Serum 1,5-anhydroglucitol (1,5-AG) levels are known to be a clinical marker of postprandial hyperglycemia. However, the impact of 1,5-AG level on cardiovascular events has not been fully investigated. METHODS: We enrolled 240 consecutive patients who had undergone first-time elective percutaneous coronary intervention (PCI) with follow-up angiography within 1 year. We excluded patients with a history of acute coronary syndrome, advanced chronic kidney disease (estimated glomerular filtration rate <30 mL/min/1.73 m2), or uncontrolled diabetes mellitus (HbA1c ≥7.0 %). Fasting blood glucose (FBS), HbA1c, and 1,5-AG levels were measured prior to PCI and at the time of follow-up angiography. Clinical events, including target lesion revascularization, target vessel revascularization, and revascularization of new lesions, were evaluated. RESULTS: Subjects were divided into two groups according to clinical outcomes: the Event (+) group (n = 40) and the Event (-) group (n = 200). No significant differences were observed, except for the number of diseased vessels and the prevalence of statin use, in baseline clinical characteristics between the two groups. Serum levels of 1,5-AG at follow-up were significantly lower in the Event (+) group than in the Event (-) group (P = 0.02). A significant reduction in 1,5-AG level from baseline to follow-up was observed in the Event (+) group compared with the Event (-) group (P = 0.04). The association between 1,5-AG levels at follow-up and clinical events remained significant after adjustment for independent variables, including FBS and HbA1c levels (P = 0.04). CONCLUSIONS: Low and exacerbated levels of 1,5-AG were associated with cardiovascular events in the present study, indicating that postprandial hyperglycemia is an important risk factor for adverse clinical events even in patients with HbA1c < 7.0 %, following first-time elective PCI.

Clinical benefits of bortezomib-containing regimens for newly diagnosed AL amyloidosis with severe cardiac impairment.

Cardiac amyloid light-chain amyloidosis (AL amyloidosis) is a rare disease with a very poor prognosis, associated with plasma cell dyscrasias such as monoclonal gammopathy of undetermined significance and multiple myeloma. Though bortezomib-containing regimens have achieved high hematologic response rates, there are still few reports describing the outcomes of Japanese patients. Six patients with severe cardiac AL amyloidosis were treated with bortezomib-containing regimens. Involved free light chain (iFLC) decreased immediately in most of these cases. However, the condition of heart failure and N-terminal pro-B-type natriuretic peptide (NT-proBNP) worsened in the early phase of this treatment and then improved several months later. At 29 months, the median duration of follow-up (2-47months), all patients remain alive except one who died of sudden cardiac arrest. Bortezomib-containing regimens are considered to be among the effective treatments for severe cardiac AL amyloidosis.

Case report: Ensitrelvir for treatment of persistent COVID-19 in lymphoma patients: a report of two cases.

Persistent COVID-19 is a well recognized issue of concern in patients with hematological malignancies. Such patients are not only at risk of mortality due to the infection itself, but are also at risk of suboptimal malignancy-related outcomes because of delays and terminations of chemotherapy. We report two lymphoma patients with heavily pretreated persistent COVID-19 in which ensitrelvir brought about radical changes in the clinical course leading to rapid remissions. Patient 1 was on ibrutinib treatment for mantle cell lymphoma when he developed COVID-19 pneumonia which was severe and ongoing for 2 months despite therapy with molnupiravir, multiple courses of remdesivir, one course of sotrovimab, tocilizumab, and steroids. Patient 2 was administered R-CHOP therapy for diffuse large B-cell lymphoma when he developed COVID-19 which was ongoing for a month despite treatment with multiple courses of remdesivir and one course of sotrovimab. A 5-day administration of ensitrelvir promptly resolved the persistent COVID-19 accommodated by negative conversions of RT-qPCR tests in both patients within days. Ensitrelvir is a novel COVID-19 therapeutic that accelerates viral clearance through inhibition of the main protease of SARS-CoV-2, 3-chymotrypsin-like protease, which is vital for viral replication. Ensitrelvir is a promising treatment approach for immunocompromised lymphoma patients suffering from persisting and severe COVID-19.

Identification of risk factors for the onset of delirium associated with COVID-19 by mining nursing records.

COVID-19 has a range of complications, from no symptoms to severe pneumonia. It can also affect multiple organs including the nervous system. COVID-19 affects the brain, leading to neurological symptoms such as delirium. Delirium, a sudden change in consciousness, can increase the risk of death and prolong the hospital stay. However, research on delirium prediction in patients with COVID-19 is insufficient. This study aimed to identify new risk factors that could predict the onset of delirium in patients with COVID-19 using machine learning (ML) applied to nursing records. This retrospective cohort study used natural language processing and ML to develop a model for classifying the nursing records of patients with delirium. We extracted the features of each word from the model and grouped similar words. To evaluate the usefulness of word groups in predicting the occurrence of delirium in patients with COVID-19, we analyzed the temporal changes in the frequency of occurrence of these word groups before and after the onset of delirium. Moreover, the sensitivity, specificity, and odds ratios were calculated. We identified (1) elimination-related behaviors and conditions and (2) abnormal patient behavior and conditions as risk factors for delirium. Group 1 had the highest sensitivity (0.603), whereas group 2 had the highest specificity and odds ratio (0.938 and 6.903, respectively). These results suggest that these parameters may be useful in predicting delirium in these patients. The risk factors for COVID-19-associated delirium identified in this study were more specific but less sensitive than the ICDSC (Intensive Care Delirium Screening Checklist) and CAM-ICU (Confusion Assessment Method for the Intensive Care Unit). However, they are superior to the ICDSC and CAM-ICU because they can predict delirium without medical staff and at no cost.

Additional prognostic impact of plaque characterization with on-site CT-derived fractional flow reserve in coronary CT angiography.

BACKGROUND: On-site computed tomography-derived fractional flow reserve (CT-FFR) is a feasible method for examining lesion-specific ischemia, and plaque analysis of coronary CT angiography (CCTA) is useful for predicting future cardiac events. However, their utility and association on a per-vessel level remain unclear. METHODS: We analyzed vessels showing 50-90 % stenosis on CCTA where planned revascularization was not performed after CCTA within 90 days. Relevant features, including CT-FFR and the plaque burden [necrotic core to the total plaque volume (% necrotic core), and non-calcified plaque (NCP) to vessel volume (% NCP)] using a novel algorithm for analyzing plaque to predict vessel-oriented composite outcomes (VOCO), including cardiac death, non-fatal myocardial infarction, and unplanned vessel-related revascularization, were assessed. RESULTS: In 256 patients (68.7 ±â€¯9.4 years; 73.8 % male) with 354 vessels (10.5 % CT-FFR ≤ 0.80), VOCO occurred in 24 vessels (6.8 %) during a median follow-up of 3.6 years. Multivariable Cox analysis revealed CT-FFR ≤ 0.80 had the pronounced impact on VOCO, and moreover, higher % necrotic core and % NCP were independently associated with VOCO [adjusted hazard ratio 3.43 (95 % confidence interval 1.42-8.29) and 4.05 (1.19-13.71), respectively], especially for vessels with CT-FFR > 0.80. CONCLUSIONS: In vessels without planned revascularization, per-vessel CT-FFR ≤ 0.80 was the notable predictor of future cardiac events. Additionally, necrotic core volume and NCP were identified as independent predictors along with CT-FFR.

Validation of telemedicine-based self-assessment of vital signs for patients with COVID-19: A pilot study.

INTRODUCTION: In the ongoing COVID-19 pandemic, the development of a system that would prevent the infection of healthcare providers is in urgent demand. We sought to investigate the feasibility and validity of a telemedicine-based system in which healthcare providers remotely check the vital signs measured by patients with COVID-19. METHODS: Patients hospitalized with confirmed or suspected COVID-19 measured and uploaded their vital signs to secure cloud storage. Additionally, the respiratory rates were monitored using a mat-type sensor placed under the bed. We assessed the time until the values became available on the Cloud and the agreements between the patient-measured vital signs and simultaneous healthcare provider measurements. RESULTS: Between 26 May-23 September 2020, 3835 vital signs were measured and uploaded to the cloud storage by the patients (n=16, median 72 years old, 31% women). All patients successfully learned how to use these devices with a 10-minute lecture. The median time until the measurements were available on the cloud system was only 0.35 min, and 95.2% of the vital signs were available within 5 min of the measurement. The agreement between the patients' and healthcare providers' measurements was excellent for all parameters. Interclass coefficient correlations were as follows: systolic (0.92, p<0.001), diastolic blood pressure (0.86, p<0.001), heart rate (0.89, p<0.001), peripheral oxygen saturation (0.92, p<0.001), body temperature (0.83, p<0.001), and respiratory rates (0.90, p<0.001). CONCLUSIONS: Telemedicine-based self-assessment of vital signs in patients with COVID-19 was feasible and reliable. The system will be a useful alternative to traditional vital sign measurements by healthcare providers during the COVID-19 pandemic.

Artificial intelligence-based point-of-care lung ultrasound for screening COVID-19 pneumoniae: Comparison with CT scans.

BACKGROUND: Although lung ultrasound has been reported to be a portable, cost-effective, and accurate method to detect pneumonia, it has not been widely used because of the difficulty in its interpretation. Here, we aimed to investigate the effectiveness of a novel artificial intelligence-based automated pneumonia detection method using point-of-care lung ultrasound (AI-POCUS) for the coronavirus disease 2019 (COVID-19). METHODS: We enrolled consecutive patients admitted with COVID-19 who underwent computed tomography (CT) in August and September 2021. A 12-zone AI-POCUS was performed by a novice observer using a pocket-size device within 24 h of the CT scan. Fifteen control subjects were also scanned. Additionally, the accuracy of the simplified 8-zone scan excluding the dorsal chest, was assessed. More than three B-lines detected in one lung zone were considered zone-level positive, and the presence of positive AI-POCUS in any lung zone was considered patient-level positive. The sample size calculation was not performed given the retrospective all-comer nature of the study. RESULTS: A total of 577 lung zones from 56 subjects (59.4 ± 14.8 years, 23% female) were evaluated using AI-POCUS. The mean number of days from disease onset was 9, and 14% of patients were under mechanical ventilation. The CT-validated pneumonia was seen in 71.4% of patients at total 577 lung zones (53.3%). The 12-zone AI-POCUS for detecting CT-validated pneumonia in the patient-level showed the accuracy of 94.5% (85.1%- 98.1%), sensitivity of 92.3% (79.7%- 97.3%), specificity of 100% (80.6%- 100%), positive predictive value of 95.0% (89.6% - 97.7%), and Kappa of 0.33 (0.27-0.40). When simplified with 8-zone scan, the accuracy, sensitivity, and sensitivity were 83.9% (72.2%- 91.3%), 77.5% (62.5%- 87.7%), and 100% (80.6%- 100%), respectively. The zone-level accuracy, sensitivity, and specificity of AI-POCUS were 65.3% (61.4%- 69.1%), 37.2% (32.0%- 42.7%), and 97.8% (95.2%- 99.0%), respectively. INTERPRETATION: AI-POCUS using the novel pocket-size ultrasound system showed excellent agreement with CT-validated COVID-19 pneumonia, even when used by a novice observer.