SARS-CoV-2 infection-induced immune thrombocytopenia: a systematic review of current reports.

Immune thrombocytopenia (ITP) is an autoimmune disorder characterized by a low platelet count with increased risk of bleeding, and viral infection may trigger ITP. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection-induced ITP has been increasingly reported. We systemically reviewed the previously reported cases of SARS-CoV-2 infection-induced ITP and identified a total of 105 patients from 68 studies. The median age was 61 years, and 14 patients (12%) were < 18 years old (pediatric cases). In adult cases, a total of 53% patients were classified as moderate to severe SARS-CoV-2 infection. The median platelet count at diagnosis and nadir were 6,000/µL and 4,000/µL, respectively. When comparing platelet levels between non-severe SARS-CoV-2 infection and moderate to severe SARS-CoV-2 infection, the median values of platelet levels at diagnosis were not significantly different between the groups (4,000/µL in non-severe SARS-CoV-2 infection and 9,000/µL in moderate to severe SARS-CoV-2 infection, p-value = 0.22). Median nadir platelet levels were also not significantly different between groups (4,000/µL in non-severe SARS-CoV-2 infection and 8,000/µL in moderate to severe SARS-CoV-2 infection, p-value = 0.27). More than half of the cases (53 patients) were treated with combination therapy including steroid, intravenous immunoglobulin, and eltrombopag. Major bleeding and intracranial hemorrhage occurred in ten (11%) and six (6.6%) cases, respectively. The overall mortality rate was 7%. In pediatric cases, none of the patients experienced major bleeding and lethal outcomes.

Pulse wave signal-driven machine learning for identifying left ventricular enlargement in heart failure patients.

BACKGROUND: Left ventricular enlargement (LVE) is a common manifestation of cardiac remodeling that is closely associated with cardiac dysfunction, heart failure (HF), and arrhythmias. This study aimed to propose a machine learning (ML)-based strategy to identify LVE in HF patients by means of pulse wave signals. METHOD: We constructed two high-quality pulse wave datasets comprising a non-LVE group and an LVE group based on the 264 HF patients. Fourier series calculations were employed to determine if significant frequency differences existed between the two datasets, thereby ensuring their validity. Then, the ML-based identification was undertaken by means of classification and regression models: a weighted random forest model was employed for binary classification of the datasets, and a densely connected convolutional network was utilized to directly estimate the left ventricular diastolic diameter index (LVDdI) through regression. Finally, the accuracy of the two models was validated by comparing their results with clinical measurements, using accuracy and the area under the receiver operating characteristic curve (AUC-ROC) to assess their capability for identifying LVE patients. RESULTS: The classification model exhibited superior performance with an accuracy of 0.91 and an AUC-ROC of 0.93. The regression model achieved an accuracy of 0.88 and an AUC-ROC of 0.89, indicating that both models can quickly and accurately identify LVE in HF patients. CONCLUSION: The proposed ML methods are verified to achieve effective classification and regression with good performance for identifying LVE in HF patients based on pulse wave signals. This study thus demonstrates the feasibility and potential of the ML-based strategy for clinical practice while offering an effective and robust tool for diagnosing and intervening ventricular remodeling.

Pulse wave-based evaluation of the blood-supply capability of patients with heart failure via machine learning.

Pulse wave, as a message carrier in the cardiovascular system (CVS), enables inferring CVS conditions while diagnosing cardiovascular diseases (CVDs). Heart failure (HF) is a major CVD, typically requiring expensive and time-consuming treatments for health monitoring and disease deterioration; it would be an effective and patient-friendly tool to facilitate rapid and precise non-invasive evaluation of the heart's blood-supply capability by means of powerful feature-abstraction capability of machine learning (ML) based on pulse wave, which remains untouched yet. Here we present an ML-based methodology, which is verified to accurately evaluate the blood-supply capability of patients with HF based on clinical data of 237 patients, enabling fast prediction of five representative cardiovascular function parameters comprising left ventricular ejection fraction (LVEF), left ventricular end-diastolic diameter (LVDd), left ventricular end-systolic diameter (LVDs), left atrial dimension (LAD), and peripheral oxygen saturation (SpO2). Two ML networks were employed and optimized based on high-quality pulse wave datasets, and they were validated consistently through statistical analysis based on the summary independent-samples t-test (p > 0.05), the Bland-Altman analysis with clinical measurements, and the error-function analysis. It is proven that evaluation of the SpO2, LAD, and LVDd performance can be achieved with the maximum error < 15%. While our findings thus demonstrate the potential of pulse wave-based, non-invasive evaluation of the blood-supply capability of patients with HF, they also set the stage for further refinements in health monitoring and deterioration prevention applications.

Hemodynamic parameters at rest predicting exercise capacity in patients supported with left ventricular assist device.

Left ventricular assist devices improve prognosis and quality of life, but exercise capacity remains limited in most patients after device implantation. Left ventricular assist device optimization through right heart catheterization reduces device-related complications. However, hemodynamic parameters associated with exercise capacity under optimized conditions. The aim of this study was to elucidate the predictors of exercise capacity from hemodynamic parameters at rest after left ventricular assist device optimization. We retrospectively reviewed 24 patients who underwent a ramp test with right heart catheterization, echocardiography and cardiopulmonary exercise testing more than 6 months after left ventricular assist device implantation. Pump speed was optimized to a lower setting that achieved right atrial pressure < 12 mmHg, pulmonary capillary wedge pressure < 18 mmHg, and cardiac index > 2.2 L/min/m2, then exercise capacity was assessed by cardiopulmonary exercise testing. After left ventricular assist device optimization, the mean right atrial pressure, pulmonary capillary wedge pressure, cardiac index, and peak oxygen consumption were 7 ± 5 mmHg, 10 ± 7 mmHg, 2.7 ± 0.5 L/min/m2, and 13.2 ± 3.0 mL/min/kg, respectively. Pulse pressure, stroke volume, right atrial pressure, mean pulmonary artery pressure, and pulmonary capillary wedge pressure were significantly associated with peak oxygen consumption. Multivariate linear regression analysis of factors predicting peak oxygen consumption revealed that pulse pressure, right atrial pressure, and aortic insufficiency remained independent predictors (ß = 0.401, p = 0.007; ß = - 0.558, p < 0.001; ß = - 0.369, p = 0.010, respectively). Our findings suggests that cardiac reserve, volume status, right ventricular function, and aortic insufficiency predict exercise capacity in patients with a left ventricular assist device.

The Effects of Endoplasmic Reticulum Stress via Intratracheal Instillation of Water-Soluble Acrylic Acid Polymer on the Lungs of Rats.

Polyacrylic acid (PAA), an organic chemical, has been used as an intermediate in the manufacture of pharmaceuticals and cosmetics. It has been suggested recently that PAA has a high pulmonary inflammatory and fibrotic potential. Although endoplasmic reticulum stress is induced by various external and intracellular stimuli, there have been no reports examining the relationship between PAA-induced lung injury and endoplasmic reticulum stress. F344 rats were intratracheally instilled with dispersed PAA (molecular weight: 269,000) at low (0.5 mg/mL) and high (2.5 mg/mL) doses, and they were sacrificed at 3 days, 1 week, 1 month, 3 months and 6 months after exposure. PAA caused extensive inflammation and fibrotic changes in the lungs' histopathology over a month following instillation. Compared to the control group, the mRNA levels of endoplasmic reticulum stress markers Bip and Chop in BALF were significantly increased in the exposure group. In fluorescent immunostaining, both Bip and Chop exhibited co-localization with macrophages. Intratracheal instillation of PAA induced neutrophil inflammation and fibrosis in the rat lung, suggesting that PAA with molecular weight 269,000 may lead to pulmonary disorder. Furthermore, the presence of endoplasmic reticulum stress in macrophages was suggested to be involved in PAA-induced lung injury.

Fulminant Myocarditis with SARS-CoV-2 Infection: A Narrative Review from the Case Studies.

One of the severe complications of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is myocarditis. However, the characteristics of fulminant myocarditis with SARS-CoV-2 infection are still unclear. We systematically reviewed the previously reported cases of fulminant myocarditis associated with SARS-CoV-2 infection from January 2020 to December 2022, identifying 108 cases. Of those, 67 were male and 41 female. The average age was 34.8 years; 30 patients (27.8%) were ≤20 years old, whereas 10 (9.3%) were ≥60. Major comorbidities included hypertension, obesity, diabetes mellitus, asthma, heart disease, gynecologic disease, hyperlipidemia, and connective tissue disorders. Regarding left ventricular ejection fraction (LVEF) at admission, 93% of the patients with fulminant myocarditis were classified as having heart failure with reduced ejection fraction (LVEF ≤ 40%). Most of the cases were administered catecholamines (97.8%), and mechanical circulatory support (MCS) was required in 67 cases (62.0%). The type of MCS was extracorporeal membrane oxygenation (n = 56, 83.6%), percutaneous ventricular assist device (Impella®) (n = 19, 28.4%), intra-aortic balloon pumping (n = 12, 12.9%), or right ventricular assist device (n = 2, 3.0%); combination of these devices occurred in 20 cases (29.9%). The average duration of MCS was 7.7 ± 3.8 days. Of the 76 surviving patients whose cardiac function was available for follow-up, 65 (85.5%) recovered normally. The overall mortality rate was 22.4%, and the recovery rate was 77.6% (alive: 83 patients, dead: 24 patients; outcome not described: 1 patient).

Twisting and Protonation of Retinal Chromophore Regulate Channel Gating of Channelrhodopsin C1C2.

Channelrhodopsins (ChRs) are light-gated ion channels and central optogenetic tools that can control neuronal activity with high temporal resolution at the single-cell level. Although their application in optogenetics has rapidly progressed, it is unsolved how their channels open and close. ChRs transport ions through a series of interlocking elementary processes that occur over a broad time scale of subpicoseconds to seconds. During these processes, the retinal chromophore functions as a channel regulatory domain and transfers the optical input as local structural changes to the channel operating domain, the helices, leading to channel gating. Thus, the core question on channel gating dynamics is how the retinal chromophore structure changes throughout the photocycle and what rate-limits the kinetics. Here, we investigated the structural changes in the retinal chromophore of canonical ChR, C1C2, in all photointermediates using time-resolved resonance Raman spectroscopy. Moreover, to reveal the rate-limiting factors of the photocycle and channel gating, we measured the kinetic isotope effect of all photoreaction processes using laser flash photolysis and laser patch clamp, respectively. Spectroscopic and electrophysiological results provided the following understanding of the channel gating: the retinal chromophore highly twists upon the retinal Schiff base (RSB) deprotonation, causing the surrounding helices to move and open the channel. The ion-conducting pathway includes the RSB, where inflowing water mediates the proton to the deprotonated RSB. The twisting of the retinal chromophore relaxes upon the RSB reprotonation, which closes the channel. The RSB reprotonation rate-limits the channel closing.

Stent-Graft Placement for Radiation-Induced Abdominal Aortic Stenosis after Renal Autotransplantation.

Renovascular hypertension (RVH) is a common cause of secondary hypertension. However, there have been no reports on RVH due to radiation-induced abdominal aorta stenosis after renal autotransplantation. A 27-year-old woman with a history of neuroblastoma treated by radiation therapy and RVH treated with renal autotransplantation presented with hypertension and dyspnea. At age 19, she had experienced hypertensive heart failure due to RVH from radiation-induced left renal artery stenosis and had undergone renal autotransplantation involving the extraction of her left kidney. Her systolic blood pressure (BP) was well-controlled but had increased progressively. She was diagnosed with hypertensive heart failure and admitted to hospital. Although her dyspnea soon subsided after treatment, her BP remained high. Renal artery ultrasound revealed no obvious stenosis. The ankle brachial pressure index (ABI) showed a significant bilateral decrease to 0.71/0.71 (right/left) from 0.94/0.95 eight years before. Magnetic resonance angiography and aortic angiography revealed severe stenosis in the abdominal aorta, and the systolic pressure gradient of intra-aortic blood flow, distal and proximal to a stenotic lesion, was 58 mmHg. These arterial stenoses in the irradiated area were highly suggestive of radiation-induced vasculopathy. She finally underwent an endovascular VIABAHN VBX balloon-expandable stent-graft placement for this radiation-induced abdominal aorta stenosis, which resolved the pressure gradient. After the procedure, her ABI improved to 0.91/0.88 and her BP was well-controlled. This is the first case of successful stent-graft placement for RVH after renal autotransplantation due to radiation-induced abdominal aorta stenosis as a consequence of neuroblastoma.

Inflammogenic effect of polyacrylic acid in rat lung following intratracheal instillation.

BACKGROUND: Some organic chemicals are known to cause allergic disorders such as bronchial asthma and hypersensitivity pneumonitis, and it has been considered that they do not cause irreversible pulmonary fibrosis. It has recently been reported, however, that cross-linked acrylic acid-based polymer, an organic chemical, might cause serious interstitial lung diseases, including pulmonary fibrosis. We investigated whether or not intratracheal instillation exposure to cross-linked polyacrylic acid (CL-PAA) can cause lung disorder in rats. METHODS: Male F344 rats were intratracheally instilled with dispersed CL-PAA at low (0.2 mg/rat) and high (1.0 mg/rat) doses, and were sacrificed at 3 days, 1 week, 1 month, 3 months and 6 months after exposure to examine inflammatory and fibrotic responses and related gene expressions in the lungs. Rat lungs exposed to crystalline silica, asbestos (chrysotile), and NiO and CeO2 nanoparticles were used as comparators. RESULTS: Persistent increases in total cell count, neutrophil count and neutrophil percentage, and in the concentration of the cytokine-induced neutrophil chemoattractant (CINC)-1, CINC-2 and C-X-C motif chemokine 5 (CXCL5), which correlated with lung tissue gene expression, were observed in bronchoalveolar lavage fluid (BALF) from 3 days until at least 1 month following CL-PAA intratracheal instillation. Persistent increases in heme oxygenase-1 (HO-1) in the lung tissue were also observed from 3 days to 6 months after exposure. Histopathological findings of the lungs demonstrated that extensive inflammation at 3 days was greater than that in exposure to silica, NiO nanoparticles and CeO2 nanoparticles, and equal to or greater than that in asbestos (chrysotile) exposure, and the inflammation continued until 1 month. Fibrotic changes also progressed after 1 month postexposure. CONCLUSION: Our results suggested that CL-PAA potentially causes strong neutrophil inflammation in the rat and human lung.

Performance of the Jarvik 2000 left ventricular assist device on mid-term hemodynamics and exercise capacity.

The hemodynamic and exercise capacity performance of the Jarvik 2000 left ventricular assist device (LVAD), which is generally used in patients with small body size and relatively preserved cardiac function, is not well understood. We retrospectively examined 18 patients implanted with the Jarvik 2000 LVAD. Pump rotation speed was optimized by the hemodynamic ramp test one year after implantation based on the criteria of mean pulmonary capillary wedge pressure (PCWP) < 18 mmHg, mean right atrial pressure (RAP) < 12 mmHg, and cardiac index (CI) > 2.2 L/min/m2 as well as echocardiographic parameters. Exercise capacity was assessed by cardiopulmonary exercise test in an optimized setting. To investigate the impacts of larger body surface area (BSA) and extremely impaired pre-implantation cardiac function on hemodynamics and exercise capacity, two correlation analyses based on BSA and original CI were performed. At a pump speed of 9500 ± 707 rpm, the mean pulmonary artery pressure, PCWP, RAP, and CI were 17 ± 5 mmHg, 9 ± 5 mmHg, 6 ± 4 mmHg, and 2.82 ± 0.54 L/min/m2, respectively. Only one patient failed to achieve the hemodynamic criteria. The peak VO2 and VE/VCO2 slope were 12.9 ± 3.1 mL/min/kg and 37.7 ± 15.0, respectively. There was an inverse correlation between original CI and heart rate (r = -0.60, p = 0.01), and a weak correlation between BSA and PCWP (r = 0.43, p = 0.08). Based on this study, the overall performance of the Jarvik 2000 device was acceptable, and the patients' body size and original cardiac function had minimum effect on the performance of this device.

Effect of Different Molecular Weights of Polyacrylic Acid on Rat Lung Following Intratracheal Instillation.

BACKGROUND: We conducted intratracheal instillations of different molecular weights of polyacrylic acid (PAA) into rats in order to examine what kinds of physicochemical characteristics of acrylic acid-based polymer affect responses in the lung. METHODS: F344 rats were intratracheally exposed to a high molecular weight (HMW) of 598 thousand g/mol or a low molecular weight (LMW) of 30.9 thousand g/mol PAA at low and high doses. Rats were sacrificed at 3 days, 1 week, 1 month, 3 months and 6 months post exposure. RESULTS: HMW PAA caused persistent increases in neutrophil influx, cytokine-induced neutrophil chemoattractants (CINC) in the bronchoalveolar lavage fluid (BALF), and heme oxygenase-1 (HO-1) in the lung tissue from 3 days to 3 months and 6 months following instillation. On the other hand, LMW PAA caused only transient increases in neutrophil influx, CINC in BALF, and HO-1 in the lung tissue from 3 days to up to 1 week or 1 month following instillation. Histopathological findings of the lungs demonstrated that the extensive inflammation and fibrotic changes caused by the HMW PAA was greater than that in exposure to the LMW PAA during the observation period. CONCLUSION: HMW PAA induced persistence of lung disorder, suggesting that molecular weight is a physicochemical characteristic of PAA-induced lung disorder.

Crosslinked Structure of Polyacrylic Acid Affects Pulmonary Fibrogenicity in Rats.

We conducted intratracheal instillations of polyacrylic acid (PAA) with crosslinking and non-crosslinking into rats in order to examine what kinds of physicochemical characteristics of acrylic-acid-based polymers affect responses in the lung. F344 rats were intratracheally exposed to similar molecular weights of crosslinked PAA (CL-PAA) (degree of crosslinking: ~0.1%) and non-crosslinked PAA (Non-CL-PAA) at low and high doses. Rats were sacrificed at 3 days, 1 week, 1 month, 3 months, and 6 months post-exposure. Both PAAs caused increases in neutrophil influx, cytokine-induced neutrophil chemoattractants (CINC) in the bronchoalveolar lavage fluid (BALF), and heme oxygenase-1 (HO-1) in the lung tissue from 3 days to 6 months following instillation. The release of lactate dehydrogenase (LDH) activity in the BALF was higher in the CL-PAA-exposed groups. Histopathological findings of the lungs demonstrated that the extensive fibrotic changes caused by CL-PAA were also greater than those in exposure to the Non-CL- PAA during the observation period. CL-PAA has more fibrogenicity of the lung, suggesting that crosslinking may be one of the physicochemical characteristic factors of PAA-induced lung disorder.

Staphylococcus aureus Bacteremia With Disseminated Multiple Foci and Pyomyositis in an Immunocompetent Patient: A Case Report.

Pyomyositis is an uncommon primary infection of skeletal muscle resulting in muscle inflammation followed by pus formation. Pyomyositis is typically caused by Staphylococcus aureus (S. aureus), and most cases are associated with skin penetration and/or immunosuppressive conditions in tropical or even temperate climates. We report a previously healthy, immunocompetent 44-year-old man who presented with fever and right lower back pain. He had received an analgesic injection for his back pain 12 days prior to this visit. His clinical course was further complicated by the coexistence of multiple muscular abscesses, renal infarction, and septic arthritis of the right shoulder. He underwent computed tomography-guided drainage of the abscess. The abscess and blood cultures were positive for methicillin-susceptible S. aureus. The patient responded well to prolonged treatment with cefazolin and cephalexin and was discharged 12 weeks after initial admission.

Infective endocarditis caused by Lactococcus garvieae: A case report and review of the literature.

Lactococcus garvieae is a Gram-positive coccus that can be easily misidentified as Enterococcus spp. or streptococci. Infection with L. garvieae is associated with the consumption of raw fish and unpasteurized dairy products. Although rare, it can cause infective endocarditis (IE). Herein, we report a case in which aortic valve replacement (AVR) was required for IE caused by L. garvieae. A 79-year-old Japanese man with a history of hypertension, myocardial infarction, gastroesophageal reflux disease (GERD), and abdominal aortic aneurysm presented with loss of appetite, myalgia, and difficulty in moving. Physical examination revealed a diastolic murmur, an Osler's node on the right first toe, dental caries, and a palpable spleen, suggesting IE. Transthoracic echocardiography revealed a large, mobile vegetation on the aortic valve, which was associated with severe aortic regurgitation. Blood cultures revealed L. garvieae. The patient received antibiotic therapy, underwent AVR, and recovered without major complications. To date, 30 cases of L. garvieae-associated IE have been reported. We reviewed and summarized all cases of L. garvieae-associated IE including our case.

Peripartum cardiomyopathy in patients with psychiatric disorders successfully treated with bromocriptine: Two case reports.

Peripartum cardiomyopathy (PPCM) is a rare disorder in which left ventricular systolic dysfunction and heart failure symptoms occur during the peripartum period. Inhibition of prolactin secretion by bromocriptine mediates beneficial effects on cardiac function in PPCM. Mental disorders are also associated with the onset of PPCM. Psychiatric medications for mental disorders would affect serotonin production and tryptophan and dopamine metabolism, and they are associated with PPCM. Conversely, bromocriptine affects psychiatric symptoms; therefore, the treatment of PPCM complicated by mental disorders using bromocriptine may be difficult. Herein, we report cases of two patients with PPCM and mental disorders successfully treated with bromocriptine therapy. The first case involved a 33-year-old woman with a history of atypical depression and anxiety disorder, who developed PPCM with a left ventricular ejection fraction (LVEF) of 19 %. The second case was that of a 42-year-old woman with a history of bipolar and panic disorders who developed PPCM with an LVEF of 18 %. Both patients were administered bromocriptine; however, psychiatric symptoms did not worsen and cardiac function improved. We also review the literature on the relationship between PPCM and mental disorders. Learning objective: Mental disorders and psychiatric medications may be associated with the onset of peripartum cardiomyopathy (PPCM). Although bromocriptine has beneficial effects on PPCM, it has also been reported to increase the risk of worsening psychiatric symptoms; therefore, the efficacy and safety of bromocriptine in PPCM patients with mental disorders is controversial. Our cases showed that bromocriptine can be used safely without worsening psychiatric symptoms in PPCM with mental disorders.