Citations

ABSTRACT Medically important pathogenic fungi invade vertebrate tissue and are considered primary when part of their nature life cycle is associated with an animal host and are usually able to infect immunocompetent hosts. Opportunistic fungal pathogens complete their life cycle in environmental habitats or occur as commensals within or on the vertebrate body, but under certain conditions can thrive upon infecting humans. The extent of host damage in opportunistic infections largely depends on the portal and modality of entry as well as on the host’s immune and metabolic status. Diseases caused by primary pathogens and common opportunists, causing the top approximately 80% of fungal diseases [D. W. Denning, Lancet Infect Dis, 24:e428–e438, 2024, https://doi.org/10.1016/S1473-3099(23)00692-8 ], tend to follow a predictive pattern, while those by occasional opportunists are more variable. For this reason, it is recommended that diseases caused by primary pathogens and the common opportunists are named after the etiologic agent, for example, histoplasmosis and aspergillosis, while this should not be done for occasional opportunists that should be named as [causative fungus] [clinical syndrome], for example, Alternaria alternata cutaneous infection. The addition of a descriptor that identifies the location or clinical type of infection is required, as the general name alone may cover widely different clinical syndromes, for example, “rhinocerebral mucormycosis.” A list of major recommended human and animal disease entities (nomenclature) is provided in alignment with their causative agents. Fungal disease names may encompass several genera of etiologic agents, consequently being less susceptible to taxonomic changes of the causative species, for example, mucormycosis covers numerous mucormycetous molds.

Context.— Cardiac and pulmonary allograft recipients represent a unique population, frequently interacting with support groups and exhibiting intense curiosity about their pathology. Like other solid organ transplant patients, they have enduring and frequent interaction with the laboratory for routine allograft surveillance. Objective.— To address patient requests to understand what happens to their explanted organ and to better understand their disease while simultaneously improving awareness of pathologists’ roles in their continuing care. Design.— At routine follow-up appointments, transplant nurse coordinators offer each allograft recipient the opportunity to interact with a pathologist in our “ On My Path ” program. Organ viewing occurs in a private setting, in a specialized room. Relevant pathology is discussed, and questions are answered, with documentation in the medical record. The patient is subsequently gifted a 3-dimensional model of their explanted organ. Transplant coordinators were surveyed for their feedback on the experience. Results.— One hundred fifty-eight interactions have been documented (2017–2022) at our institution, including patients who underwent cardiac transplant (96, 61%), single or bilateral lung transplant (54, 34%), or combination lung and heart transplant (8, 5%). Transplant coordinators reported an increase in patient understanding of their disease and emotional closure related to the disease through the On My Path program. Conclusions.— Pathologists providing direct patient care is a feasible model that addresses currently unmet desires of the transplant population to better understand their pathology. Providing a 3-dimensional model helps to empower patients and drives satisfaction. These interactions also improve awareness about pathology as a discipline and its importance in the continued care of transplant recipients.

Abstract Background The left ventricular (LV) force, also known as elastance, serves as a load-independent indicator of contractility and can be noninvasively assessed through echocardiography. In hypertrophic cardiomyopathy (HCM), the heightened presence of the active state of myosin heads results in an increased LV force. Purpose To assess the prognostic value of increased LV elastance at rest in patients with HCM. Methods We enrolled 1420 HCM patients (age 50±16 years, 907 males, 64%) with ejection fraction (EF) ≥50%, referred for rest transthoracic echocardiography (TTE) in 10 quality-controlled labs from 7 countries. TTE assessment included peak left ventricular outflow tract gradient (LVOTG), EF, and LV force (systolic blood pressure + LVOTG/LV end-systolic volume assessed with 2-D, mmHg/mL). All patients were followed up. All-cause death was the outcome measure. Results At a median follow-up of 83 months, 150 deaths occurred (Group 1). At study entry, Group 1 patients had the same ESC-Sudden cardiac death score compared to survivors (Group 2). In Group 1 compared to Group 2, TTE showed higher values of MR severity, E/e’ , left atrial volume index, estimated systolic pulmonary artery pressure, and force (see table). At multivariable Cox analysis, only age (HR =1.08, 95% CI=1.03-1.14, p=0.001) and force > median value of 5.3 mmHg/mL (HR = 2.14, 95% CI 1.53-2.99, p=0.020) were independent predictors of mortality. Ten-year survival was 95% in the pooled first (<3.8 mmHg/mL) and second (3.8-5.2 mmHg/mL) quartiles vs 80% in the pooled third (5.3-7.8 mmHg/mL) and fourth quartiles (>7.8 mmHg/mL), see figure. Conclusion HCM patients with higher values of resting LV elastance show a worse survival, highlighting the dark prognostic side of an excess of force in these patients. Table Legends E/e’, early mitral inflow to early mitral annulus motion ratio, EF, left ventricular ejection fraction, LAVI, left atrial volume index; LVOTG, left ventricular outflow tract peak gradient, MR, mitral regurgitation; MWT, maximal wall thickness, NYHA, New York Heart Association classification, RWT, relative wall thickness; SCD risk, risk score for sudden cardiac death in hypertrophic cardiomyopathy, SPAP, systolic pulmonary arterial pressure.Table.Clinical and TTE findingsFigure.Survival in the force quartiles

Background Transcranial Doppler (TCD) is a non-invasive, bedside tool that allows for real-time monitoring of the patient’s hemodynamic status following mechanical thrombectomy (MT). This systematic review and meta-analysis aims to evaluate the predictive value of TCD parameters following successful MT (Thrombolysis in Cerebral Infarction 2b–3). Methods In July 2024, we searched PubMed, Embase, and Scopus, to identify observational studies in which TCD parameters were measured within 48 hours of MT. Using random-effects models, we compared four TCD parameters (mean flow velocity (MFV), MFV index, pulsatility index (PI), and peak systolic velocity (PSV) among groups with vs without hemorrhagic transformation (HT) and favorable vs poor functional recovery (modified Rankin Scale 0–2 vs 3–6). Results Eleven studies comprising 1432 patients (59% male; mean age range: 63–73 years) were included. The MFV and MFV index were higher in patients with HT (Hedges' g=0.42 and 0.54, P=0.015 and 0.005, respectively). Patients with MFV index ≥1.3 showed a higher risk of all HT (RR 1.97; 95% confidence interval (CI) 1.28 to 3.03, P=0.002), symptomatic HT (RR 4.68; 95% CI 1.49 to 14.65, P=0.008), and poor functional status at 90 days (RR 1.65; 95% CI 1.27 to 2.14, P=0.029), respectively. There was no difference in mean PSV (P=0.1) and PI (P=0.3) among groups with and without HT. Conclusion This study underscores the prognostic value of the MFV index in predicting HT, symptomatic HT, and poor functional recovery after successful MT in the anterior circulation. Large-scale, multi-center studies are necessary to confirm these findings and to validate the MFV index as a reliable predictor for improving post-thrombectomy care.

AbstractBackgroundThe clinical relevance of cardiac troponin (cTn) elevation in takotsubo syndrome (TTS) remains uncertain. The present study sought to investigate the role of cardiac troponin (cTn) elevations in mortality prediction of patients with Takotsubo syndrome (TTS).MethodsPatients enrolled in the International Takotsubo (InterTAK) Registry from January 2011 to February 2020 with available data on peak cTn levels were included in the analysis. Peak cTn levels during the index hospitalization were used to define clinically relevant myocardial injury. The threshold at which clinically relevant myocardial injury drives mortality at 1 year was identified using restricted cubic spline analysis.ResultsOut of 2′938 patients, 222 (7.6%) patients died during 1‐year follow‐up. A more than 28.8‐fold increase of cTn above the upper reference limit was identified as threshold for clinically relevant myocardial injury. The presence of clinically relevant myocardial injury was significantly associated with an increased risk of mortality at 5 years (adjusted HR 1.58, 95% CI 1.18–2.12, p =.002). Clinically relevant myocardial injury was related to an increased 5‐year mortality risk in patients with apical TTS (adjusted HR 1.57, 95% CI 1.21–2.03, p =.001), in presence of physical stressors (adjusted HR 1.60, 95% CI 1.22–2.11, p =.001), and in absence of emotional stressors (adjusted HR 1.49, 95% CI, 1.17–1.89, p =.001).ConclusionThis study for the first time determined a troponin threshold for the identification of TTS patients at excess risk of mortality. These findings advance risk stratification in TTS and assist in identifying patients in need for close monitoring and follow‐up.

AbstractBackgroundCervical artery dissection (CAD) is a common cause of ischemic stroke in young adults. Local blood clot formation and distal emboli are the key mechanisms for the development of stroke in patients with CAD. Microemboli distal to the dissection point can be detected as high‐intensity transient signals (HITS) using transcranial Doppler (TCD). Despite this unique capability, TCD is used inconsistently in the management of CAD. In this international survey, we aim to explore the frequency and potential barriers to TCD use in CAD.MethodThis study was an international electronic survey, based on the Antithrombotic Treatment for Stroke Prevention in Cervical Artery Dissection (STOP‐CAD) study, aiming at evaluating the use of TCD in diagnosing and managing CAD patients. A comprehensive questionnaire was developed to gather insights into the current practices, perceptions, and potential barriers to the effective use of TCD in participating centers. The collected data was then analyzed.ResultsFifty‐eight medical centers with advanced stroke care capabilities from Europe and United States participated in this study. Half (29 out of 58) of the sites routinely perform TCD on CAD patients, particularly in the presence of carotid or vertebral artery stenosis, complete carotid occlusion, and early neurologic deterioration. The primary reason for participating institutions not performing TCD was because its results would not change their practice. The protocol for TCD monitoring and managing HITS‐positive CAD patients varied among centers but transitioning from antiplatelet to anticoagulant was the most common practice in this patient population.ConclusionHalf of the stroke centers in our survey routinely perform TCD monitoring for CAD patients. The detection of HITS in CAD patients is a warning sign for providers, which may prompt a change in secondary stroke prevention management. However, a standard protocol for performing TCD in CAD and treatment recommendations for HITS‐positive CAD are not currently available, which warrants further research.

Abstract Background Professional medical societies recommend that carrier screening for 113 different genetic disorders be offered during pregnancy or preconception to all individuals, regardless of ancestry, in order to provide more equitable opportunities for patients to ascertain their reproductive risks. In our clinical laboratory experience, however, the vast majority of healthcare providers continue to order carrier screening for only cystic fibrosis (CF), which is disproportionately common in white individuals of Northern European descent. Our highest volume CF screening test is performed on >10,500 diverse patients per year and utilizes a targeted genotyping array that detects >500 variants in CFTR and >1200 variants in >150 other pertinent genes. Here we report the inequities in diagnostic yield among our first 8,000 patients for whom only limited testing was ordered and examine the barriers to widespread adoption of more inclusive carrier screening. Methods Three carrier screening options (CF, CF+spinal muscular atrophy [SMA], CF+SMA+fragile X syndrome [FXS]+hemoglobinopathies) were ordered clinically and performed on DNA extracted from 8,000 whole blood samples from unique individuals utilizing a custom SNP array (Thermo Fisher GeneTitanTM platform) designed to detect >1700 pathogenic variants in 218 different genes. Data was retrospectively reviewed to determine overall detection rates for carriers of all recommended conditions vs. only the condition(s) included in the originally ordered service. Finally, reproductive health providers at nine different ordering sites across the U.S. were interviewed regarding their current carrier screening practices. Results Patients were referred for testing by 119 different clinical facilities. 98.1% (7847/8000) had CF-only testing ordered, 1.2% (99/8000) had CF+SMA testing ordered, and 0.68% (54/8000) had testing for CF+SMA+FXS+hemoglobinopathies ordered. 7.1% (568/8000) of patients had reportable variants in CFTR. Had CF+SMA testing been ordered on all 8,000 patients, however, the diagnostic yield would have been 8.9%. Of the patients who had CF-only or CF+SMA testing ordered, 11.9% (943/7946) were found to be carriers of hemoglobinopathies. Finally, had all 8000 patients had testing for all currently recommended targets on the panel, the diagnostic yield would have increased to 55% (4396/8000). Ordering providers at 9/50 different contacted sites agreed to interview requests. 100% (9/9) of respondents indicated that their patients experience significant disparities in access to carrier screening, and that the primary cause of these inequities was insufficient insurance reimbursement. 67% (6/9) of respondents indicated that >50% of their patient population identified as non-white and would have “very strongly” benefitted from “testing for other disorders beyond CF.” Conclusions Despite clinical practice guidelines urging for more population-neutral carrier screening, major gaps exist between what is recommended versus ultimately ordered. This significantly limits the clinical utility of testing, especially in patients from underrepresented backgrounds. Improved insurance coverage for more inclusive carrier screening is needed to help reduce such disparities.

Telemedicine for stroke (Telestroke) has been a key component to efficient, widespread acute stroke care for many years. The expansion of reimbursement through the Furthering Access to Stroke Telemedicine Act and rapid deployment of telemedicine resources during the COVID-19 public health emergency have further expanded remote care, with practitioners of varying educational backgrounds, and experience providing acute stroke care via telemedicine (Telestroke). Some Telestroke practitioners have not had fellowship-level vascular neurology training and many are without training specific to virtual modalities. While many vascular neurology fellowship programs incorporate Telestroke training into the curriculum, components of this curriculum are not consistent, extent of involvement is variable, and not all fellows receive hands-on training in remote care. Furthermore, the extent of training and evaluation of Telestroke in American Board of Psychiatry and Neurology training requirements and Accreditation Council for Graduate Medical Education assessments for vascular neurology fellowship are not standardized. We suggest that Telestroke be formally incorporated into vascular neurology fellowship curricula and provide considerations for key components of this training and metrics for evaluation.