Insights into microorganisms, associated factors, and the oral microbiome in infective endocarditis patients.

Introduction: Infective Endocarditis (IE) is a rare, life-threatening infection of the endocardium with multisystem effects. Culprit microorganisms derived from different niches circulate through the bloodstream and attach to the endocardium, particularly the heart valves. This study aimed to investigate culprit microorganisms among a cross-sectional cohort of IE patients, their associated factors, and to explore the potential relationship to the oral microbiome. Methods: In this observational study, we undertook a cross-sectional analysis of 392 medical records from patients diagnosed with IE. The primary outcome of this study was to analyse the association between the IE culprit microorganisms and the underlying anatomical types of IE (native valve (NVE), prosthetic valve (PVE), or cardiac device-related (CDE)). Secondary outcomes encompassed a comparative analysis of additional factors, including: the treatment approaches for IE, and the categorisation of blood cultures, extending to both genus and species levels. Additionally, we cross-referenced and compared the species-level identification of IE bacteraemia outcome measures with data from the expanded Human Oral Microbiome Database (eHOMD). Results: A culprit microorganism was identified in 299 (76.28%) case participants. Staphylococcal infections were the most common (p < 0.001), responsible for 130 (33.16%) hospitalisations. There were 277 (70.66%) cases of NVE, 104 (26.53%) cases of PVE, and 11 (2.81%) cases of CDE. The majority of PVE occurred on prosthetic aortic valves (78/104, 75%), of which 72 (93.5%) were surgical aortic valve replacements (SAVR), 6 (7.8%) were transcatheter aortic valve implants, and one transcatheter pulmonary valve implant. Overall, underlying anatomy (p = 0.042) as well as the treatment approaches for IE (p < 0.001) were significantly associated with IE culprit microorganisms. Cross-reference between IE bacteraemia outcomes with the eHOMD was observed in 267/392 (68.11%) cases. Conclusions: This study demonstrated that IE patients with a history of stroke, smoking, intravenous drug use, or dialysis were more likely to be infected with Staphylococcus aureus. CDE case participants and patients who had previous SAVR were most associated with Staphylococcus epidermidis. IE patients aged 78+ were more likely to develop enterococci IE than other age groups. Oral microorganisms indicated by the eHOMD are significantly observed in the IE population. Further research, through enhanced dental and medical collaboration, is required to correlate the presence of oral microbiota as causative factor for IE.

Pronounced QT Prolongation During General Anesthesia in a Child with Left Ventricular Noncompaction Cardiomyopathy: A Case Report.

We report the case of an 8-year-old boy with left ventricular noncompaction cardiomyopathy (LVNC) and QT prolongation who experienced further prolongation of the QTc during general anesthesia for extraction of a maxillary mesiodens. Pronounced prolongation of the QTc was observed after induction of general anesthesia with thiamylal and during emergence. No notable fluctuations in blood pressure, heart rate, and estimated continuous cardiac output were observed. We considered it likely that the QT prolongation was triggered by thiamylal and increased sympathetic nervous system activity. During general anesthesia for children with LVNC and QT prolongation, it is necessary to monitor intraoperative hemodynamic fluctuations and prepare for the possible occurrence of arrhythmias.

Total Intravenous Anesthesia Using Remimazolam and Continuous Cardiac Output Monitoring for Dental Anesthesia in a Patient With Takayasu's Arteritis: A Case Report.

Takayasu's arteritis is a persistent chronic progressive inflammation of the large- and medium-caliber arteries. Controlling cardiovascular variability during anesthesia and overcoming difficulties of cardiovascular monitoring due to the impaired vessels are important in patients with Takayasu's arteritis. Remimazolam is a novel short-acting benzodiazepine with mild effects on hemodynamics. We report the case of a patient with Takayasu's arteritis who underwent oral surgery under general anesthesia. This report highlights the use of remimazolam and remifentanil to reduce hemodynamic perturbations using estimated continuous cardiac output monitoring.

Hybrid cardiac rehabilitation - The state of the science and the way forward.

Cardiac rehabilitation (CR) improves exercise capacity and health-related quality of life (HRQoL) in a broad range of patients, including those with coronary artery disease, heart failure (HF), after heart valve surgery, and after heart transplantation. Unfortunately, in traditional center-based CR programs participation and adherence are low. A hybrid model of CR, combining center-based and home-based CR services, has been proposed and is currently being studied as a potential way to help bridge the participation gap, while maintaining the beneficial patient outcomes from CR. However, the ideal composition of a hybrid CR program has not been universally agreed upon. In the present review, we define hybrid CR as any combination of supervised center-based and monitored home-based exercise, where at least two of the core components of CR are addressed. Using this definition, we searched for studies comparing hybrid CR with: (1) traditional center-based CR among CAD patients, (2) usual care among CAD patients, and (3) usual care among HF patients. We found nine studies which fit both our definition and comparison groups. The structure of the hybrid CR programs differed for each study, but typically began with a center-based component lasting 2-11 weeks and transitioned to a home-based component lasting 10-22 weeks, with 3-5 exercise sessions per week composed of either walking (usually with a treadmill) or cycling for 25-35 min at 60-75% maximal heart rate. Patients recorded data from home exercise sessions, via either a digital heart rate monitor or accelerometer, into logbooks which were reviewed by a therapist at specified intervals (often via telephone). Counseling on risk factor management was predominantly provided during the center-based component. In these studies, hybrid CR led to similar short-term outcomes compared to traditional CR in patients with coronary artery disease (CAD), as well as increased adherence and reduced delivery costs. Compared with usual care, in patients with CAD, hybrid CR reduced cardiovascular events, and improved lipid profiles, exercise capacity, and HRQoL. In patients with HF, compared with usual care, hybrid CR improved physical function, exercise capacity, and HRQoL. Ongoing studies may clarify the combination of center-based and home-based CR which produces superior outcomes, and may also better define the role that technology should play in CR interventions.

Incidence of Cancer Treatment Induced Arrhythmia Associated with Immune Checkpoint Inhibitors.

BACKGROUND: Cancer treatmentinduced arrhythmia (CTIA) is a well-recognized form of cardiotoxicity associated with chemotherapy. Immune checkpoint inhibitors (ICI) have been associated with important forms of cardiotoxicity, including myocarditis. However, the incidence of CTIA associated with ICI has not been well characterized. METHODS: We reviewed all patients treated with ICIs at our institution from Jan. 2010 to Oct. 2015. CTIA was defined as a new diagnosis of clinically relevant arrhythmia within 6 months after ICI initiation. RESULTS: During the study period, 268 patients were treated with immune checkpoint inhibitors, of whom 190 received monotherapy with ipilimumab (n=114), nivolumab (n=52) or pembrolizumab (n=24) and 78 received combination therapy: ipilimumab & nivolumab (n=37), ipilimumab & pembrolizumab (n=39) and nivolumab & pembrolizumab (n=2). Four patients (1.5%) developed CTIA. Of these, 3 patients developed a new diagnosis of atrial fibrillation (AF), one of whom required cardioversion. In 2 cases of new-onset AF, significant provoking factors were present in addition to ICI therapy including thyrotoxicosis in one and metabolic disarray in another. Six patients (2.2%) with a pre-existing diagnosis of paroxysmal AF experienced episodes within 6 months of initiating ICI therapy. None of the arrhythmic events were associated with known or suspected myocarditis. CONCLUSIONS: The incidence of arrhythmic complications associated with immune checkpoint inhibitors appears to be very low (~1.5%). Patients with a pre-existing diagnosis of AF may be at-risk of recurrence during ICI treatment and should be monitored accordingly. These suggest that from an arrhythmia perspective, ICIs appear to be very safe and well-tolerated.

Protein Stability Buffers the Cost of Translation Attenuation following eIF2α Phosphorylation.

Phosphorylation of the translation initiation factor eIF2α is a rapid and vital response to many forms of stress, including protein-misfolding stress in the endoplasmic reticulum (ER stress). It is believed to cause a general reduction in protein synthesis while enabling translation of few transcripts. Such a reduction of protein synthesis comes with the threat of depleting essential proteins, a risk thought to be mitigated by its transient nature. Here, we find that translation attenuation is not uniform, with cytosolic and mitochondrial ribosomal subunits being prominently downregulated. Translation attenuation of these targets persists after translation recovery. Surprisingly, this occurs without a measurable decrease in ribosomal proteins. Explaining this conundrum, translation attenuation preferentially targets long-lived proteins, a finding not only demonstrated by ribosomal proteins but also observed at a global level. This shows that protein stability buffers the cost of translational attenuation, establishing an evolutionary principle of cellular robustness.

Coagulopathy reversal in intracerebral haemorrhage.

As intracerebral hemorrahge becomes more frequent as a result of an aging population with greater comorbidities, rapid identification and reversal of precipitators becomes increasingly paramount. The aformentioned population will ever more likely be on some form of anticoagulant therapy. Understanding the mechanisms of these agents and means by which to reverse them early on is critical in managing the acute intracerebral hemorrhage.

Diffuse alveolar haemorrhage associated with subsequent development of ANCA positivity and emphysema in three young adults.

BACKGROUND: Diffuse alveolar haemorrhage (DAH) is characterized by the diffuse accumulation of red blood cells within the alveoli, presence of ground glass opacities and/or consolidation on computed tomography (CT). Aside from identifiable non-immune causes, DAH is classically subdivided into idiopathic (idiopathic pulmonary haemosiderosis, IPH) and autoimmune DAH. Here we describe three cases presenting with recurrent pulmonary haemorrhage, initially classified as IPH, who, several years after first presentation, develop anti myeloperoxidase antibodies (MPO) positivity, emphysema on CT and, in one case, renal involvement. CASE PRESENTATION: Patient 1 was diagnosed with IPH aged 14. Her disease remained poorly controlled despite immunosuppression, although ANCA remained negative over the years. Nineteen years from initial presentation, she developed MPO-ANCA positive antibodies and mild renal impairment. She was treated with Rituximab with good response. From first presentation, the chest CT was consistently characterized by diffuse ground-glass opacities and interlobular septal thickening. Ten years later, cystic opacities consistent with emphysema, with a striking peribronchovascular distribution, developed. Patient 2 was diagnosed with IPH aged 32. He was treated with corticosteroids and methotrexate, with fluctuating response. At 11 years from initial presentation, MPO-ANCA positivity was identified, and emphysema with a peribronchovascular distribution was observed on CT, with subsequent significant increase in extent. Patient 3 was diagnosed with IPH at the age of seven, and had recurrent episodes of haemoptysis of varying degree of severity, treated with intermittent courses of corticosteroids until age 11, when he was intubated due to severe DAH. Eight years after the diagnosis emphysematous changes were noted on CT and MPO-ANCA positivity developed for the first time 11 years after initial diagnosis. CONCLUSIONS: We believe these three cases highlight: 1) the possibility of development of ANCA positivity several years down the line from first DAH presentation 2) the possibility that DAH may lead to cystic/emphysematous changes with peribronchovascular distribution on CT. Moreover, the need for ongoing immunosuppressive treatment and the development of emphysema, emphasize a possible role played by autoimmune phenomena, even when DAH is initially diagnosed as "idiopathic". Further studies are required to better understand the relationship between DAH, ANCA positivity and development of emphysema.

Validation of the Khorana score in acute myeloid leukemia patients: a single-institution experience.

BACKGROUND: Although patients with acute myeloid leukemia (AML) were shown to have an increased risk of thrombosis, no thrombosis risk assessment scoring system has been developed for AML patients. The Khorana Risk Score (KRS), which has been widely used for thrombosis risk assessment in the clinical setting, was developed on the basis of solid tumor data and has not been validated among AML patients. This study aims to validate the use of the KRS as a thrombosis risk-scoring system among patients with AML. METHODS: Using data from H. Lee Moffitt Cancer Center and Research Institution's Total Cancer Care Research Study, we retrospectively identified patients who were histologically confirmed with AML from 2000 to 2018. Clinical and laboratory variables at the time of AML diagnosis were characterized and analyzed. The thrombotic event rate was estimated with the Kaplan-Meier method and compared using the log-rank test. RESULTS: A total of 867 AML patients were included in the analysis. The median age at AML diagnosis was 75 years (range, 51-96), and the majority were male (65%, n = 565). A total of 22% (n = 191), 51% (n = 445), 24% (n = 207), and 3% (n = 24) of patients had a KRS of 0, 1, 2, and 3, respectively. A total of 42 thrombotic events (3% [n = 6/191] with a KRS of 1; 5% [n = 23/445] with a KRS of 2; 6.3% [n = 13/207] with a KRS of 3) were observed, with a median follow-up of 3 months (range, 0.1-307). There was no statistical difference in the risk of thrombosis between these groups (P = .1949). CONCLUSIONS: Although there was an increased risk of thrombosis associated with a higher KRS among AML patients with a KRS of 1 to 3, the difference was not statistically significant. Furthermore, only a few patients were found to have a KRS > 3, and this was largely due to pancytopenia, which is commonly associated with AML. These results indicate the need for a better thrombotic risk-scoring system for AML patients.

Influence of the marvelous™ three-way stopcock on the natural frequency and damping coefficient in blood pressure transducer kits.

Two types of Planecta™ ports are commonly used as sampling ports in blood pressure transducer kits: a flat-type port (FTP) and a port with a three-way stopcock (PTS). Recently, a new type of three-way stopcock (Marvelous™) has been released as a Planecta™ counterpart, but its effects on the frequency characteristics and reliability of blood pressure monitoring have not been investigated. We assessed the influence of the Marvelous™ stopcock on the frequency characteristics of the pressure transducer kit. The basic pressure transducer kit, DT4812J, was modified by replacing one or two of the original three-way stopcocks with Marvelous™ stopcocks. The frequency characteristics (i.e., natural frequency and damping coefficient) of each kit were determined using wave parameter analysis software, and subsequently evaluated on a Gardner chart. Replacement of the original blood pressure transducer kit stopcocks with Marvelous™ stopcocks decreased the natural frequency (48.3 Hz) to 46.3 Hz or 44.8 Hz, respectively; the damping coefficient was not significantly changed. Plotting the data on a Gardner chart revealed that the changes fell within the adequate dynamic response region, indicating they were within the allowable range. Insertion of Marvelous™ stopcocks slightly affects the natural frequency of the pressure transducer kit, similar to inserting a PTS. The results indicate that the Marvelous™ stopcock is useful for accurate monitoring of arterial blood pressure, and may be recommended when insertion of two or more closed-loop blood sampling systems is necessary.