Evaluation and validation of a PrintrLab-based LAMP assay to identify Trypanosoma cruzi in newborns in Bolivia: a proof-of-concept study.

BACKGROUND: Vertical transmission of Trypanosoma cruzi represents approximately 20% of new Chagas disease cases. Early detection and treatment for women of childbearing age and newborns is a public health priority, but the lack of a simple and reliable diagnostic test remains a major barrier. We aimed to evaluate the performance of a point-of-care loop-mediated isothermal amplification (LAMP) assay for the detection of T cruzi. METHODS: In this proof-of-concept study, we coupled a low-cost 3D printer repurposed for sample preparation and amplification (PrintrLab) to the Eiken T cruzi-LAMP prototype to detect vertically transmitted T cruzi, which we compared with standardised PCR and with the gold-standard algorithm (microscopy at birth and 2 months and serological study several months later). We screened pregnant women from two hospitals in the Bolivian Gran Chaco province, and those who were seropositive for T cruzi were offered the opportunity for their newborns to be enrolled in the study. Newborns were tested by microscopy, LAMP, and PCR at birth and 2 months, and by serology at 8 months. FINDINGS: Between April 23 and Nov 17, 2018, 986 mothers were screened, among whom 276 were seropositive for T cruzi (28·0% prevalence, 95% CI 25·6-31·2). In total, 224 infants born to 221 seropositive mothers completed 8 months of follow-up. Congenital transmission was detected in nine of the 224 newborns (4·0% prevalence, 1·9-7·5) by direct microscopy observation, and 14 more cases were diagnosed serologically (6·3%, 3·6-10·3), accounting for an overall vertical transmission rate of 10·3% (6·6-15·0; 23 of 224). All microscopy-positive newborns were positive by PrintrLab-LAMP and by PCR, while these techniques respectively detected four and five extra positive cases among the remaining 215 microscopy-negative newborns. INTERPRETATION: The PrintrLab-LAMP yielded a higher sensitivity than microscopy-based analysis. Considering the simpler use and expected lower cost of LAMP compared with PCR, our findings encourage its evaluation in a larger study over a wider geographical area. FUNDING: Inter-American Development Bank.

Empowering Potential of the My Assistive Technology Guide: Exploring Experiences and User Perspectives.

The use of assistive technology (AT) devices enhances older adults' function in daily activities. However, the lack of awareness of AT among potential AT users has been identified as a major barrier to its adoption. This study aimed to assess the quality of the Mi Guía de Asistencia Tecnológica (MGAT) web app, which provides information on AT, from the perspective of older Latinos with physical disabilities, and to explore their experience using the MGAT. We employed a convergent parallel mixed-method design involving 12 older Latinos living in Puerto Rico. In Phase I, the researchers trained the participants in the use of the MGAT. In Phase II, participants were encouraged to use it for 30 days. In Phase III, the participants completed the User Mobile Application Rating Scale and individual interviews, analyzed with descriptive statistics and a directed thematic content analysis. The quality of the MGAT was rated high in both the objective (mean = 3.99; SD = 0.7) and subjective (mean = 4.13; SD = 1.1) domains. Qualitative data revealed the MGAT was accessible, usable, desirable, credible, useful, and valuable to increasing older Latinos' AT knowledge, function, and autonomy. The MGAT has the potential to increase AT awareness and adoption among older adults.

Predictors of developing renal dysfunction following diagnosis of transthyretin cardiac amyloidosis.

BACKGROUND: In patients with transthyretin cardiac amyloidosis (ATTR-CA), renal dysfunction is a poor prognostic indicator. Limited data are available on variables that portend worsening renal function (wRF) among ATTR-CA patients. OBJECTIVES: This study assesses which characteristics place patients at higher risk for the development of wRF (defined as a drop of ≥10% in glomerular filtration rate [GFR]) within the first year following diagnosis of ATTR-CA. METHODS: We included patients with ATTR-CA (n = 134) evaluated between 2/2016 and 12/2022 and followed for up to 1 year at our amyloid clinic. Patients were stratified into two groups: a group with maintained renal function (mRF) and a group with wRF and compared using appropriate testing. Significant variables in the univariate analysis were included in the multivariable logistic regression model to determine characteristics associated with wRF. RESULTS: Within a follow-up period of 326 ± 118 days, the median GFR% change measured -6% [-18%, +8]. About 41.8% (n = 56) had wRF, while the remainder had mRF. In addition, in patients with no prior history of chronic kidney disease (CKD), 25.5% developed de novo CKD. On multivariable logistic regression, only New York Heart Association (NYHA) class ≥III (odds ratio [OR]: 3.9, 95% confidence interval [CI]: [1.6-9.3]), history of ischemic heart disease (IHD) (OR: 0.3, 95% CI: [0.1-0.7]), and not receiving SGLT-2i (OR: 0.1, 95% CI: [0.02-0.5]) were significant predictors of wRF. CONCLUSION: Our study demonstrated that the development of de novo renal dysfunction or wRF is common following the diagnosis of ATTR-CA. Additionally, we identified worse NYHA class and no prior history of IHD as significant predictors associated with developing wRF, while receiving SGLT-2i therapy appeared to be protective in this population.

Role for advanced heart failure therapies in the management of influenza B-associated fulminant myocarditis with recovery.

A woman presented to the emergency department for syncope after developing influenza-like symptoms. She tested positive for influenza B. The patient rapidly decompensated into cardiogenic shock over 2 days, requiring aggressive pharmacological therapy and temporary mechanical circulatory support. She made a full recovery. This case highlights the importance of early intervention, urgent transplant evaluation and guideline directed medical therapy in the treatment of fulminant myocarditis secondary to influenza B infection.

Leadless pacemaker in heart transplantation: a case report and literature review.

Our case demonstrates the safe and effective use of a leadless pacemaker in a heart transplant recipient. A man in his 60s with a history of heart transplantation with biatrial anastomosis 7 months prior presented to the emergency department after several syncopal episodes. Telemetry monitoring revealed a paroxysmal complete atrioventricular block. Given his immunocompromised state and prior dual chamber pacemaker extraction at the time of heart transplantation, the patient underwent successful implantation of a leadless pacemaker. Over the past 5 years since device implantation, the patient has not had any syncopal events nor has he had any device-related complications, such as infection.

Safety and Efficacy of Traditional Heart Failure Therapies in Patients With Cardiac Amyloidosis and Heart Failure.

Randomized controlled trials have demonstrated mortality benefits for several medication classes in patients with heart failure (HF), especially with reduced ejection fraction (EF). However, the benefit of these traditional HF therapies in patients with HF from cardiac amyloidosis is unclear. our study aimed to evaluate the safety and efficacy of traditional HF therapies in patients with cardiac amyloidosis and HF with reduced EF or HF with mid-range EF (HFmrEF). We conducted a single-center retrospective study. Patients were included if they were diagnosed with cardiac amyloidosis and HF with reduced EF or HF with mid-range EF between January 2012 and 2022. The primary outcomes of interest were medication use patterns (for ß blockers [BB], angiotensin-converting enzyme inhibitors [ACEI], angiotensin receptor blockers [ARBs], angiotensin receptor neprilysin inhibitors [ARNI], and mineralocorticoid receptor antagonists [MRAs]); potential medication side effects (symptomatic bradycardia, fatigue, hypotension, lightheadedness, and syncope); hospitalization; and death. The associations of BB, ACEI/ARB/ARNI, and MRA use with clinical outcomes were evaluated using Kaplan-Meier and Cox proportional hazards regression. A total of 82 patients met study criteria. At time of cardiac amyloidosis diagnosis, 63.4% were on a BB, 51.2% were on an ACEI/ARB/ARNI, and 43.9% were on an MRA. At last follow-up, 51.2% were on a BB, 35.4% were on an ACEI/ARB/ARNI, and 43.9% were on an MRA. There were no statistically significant differences in rates of potential medication side effects in patients on the medication class compared with those who were not. There was no association with hospitalization or mortality for baseline or follow-up BB, ACEI/ARB/ARNI, or MRA use. In conclusion, BBs, ACEI/ARB/ARNIs, and MRAs may be safely used in this population. However, their use does not appear to improve mortality or hospitalization.

Left ventricular assist device thrombosis in the setting of supratherapeutic international normalized ratio (INR) and bleeding.

A 71-year-old female with heart failure who underwent left ventricular assist device (LVAD) placement presented for evaluation of low hemoglobin and dark stools. She also had leg pain, numbness, and weakness for which she was taking ibuprofen. She was found to have a gastrointestinal bleed, INR of 4.3, and arterial thrombi in the left leg. She was stabilized, had her anticoagulation held, and underwent mechanical thrombectomy. On hospital day 6, LVAD interrogation revealed signs of thrombosis, while subsequent labs revealed a persistently supratherapeutic INR of 5.2. The patient had the LVAD removed and underwent further hematologic workup. Her platelets remained normal throughout the admission, indicating this was not acute disseminated intravascular coagulation (DIC), thrombotic thrombocytopenic purpura (TTP), or heparin induced thrombocytopenia (HIT). Echocardiography identified it as a primary thrombus. This case illustrates the importance of appropriate anticoagulation to balance the bleeding risk with the risk of thrombi, as well as the importance of maintaining high suspicion for LVAD thrombosis regardless of INR.

Enterocutaneous fistula formation after cardiac transplantation due to injury from LVAD driveline migration.

A man in his early 20s with heart failure with reduced ejection fraction secondary to non-compaction cardiomyopathy (Titin (TTN) gene mutation positive) was transitioned from left ventricular assist device (LVAD) mechanical support to heart transplantation. Transplantation was successful; however, LVAD explantation resulted in innumerable complications secondary to penetration of the driveline into the peritoneal cavity. He developed an enterocutaneous fistula which led to concurrent malnutrition, poor wound healing, systemic infection, and allograft rejection in a patient less than 1 month after heart transplantation on immunosuppression.

Driveline erosion of the colon as a late complication of LVAD implantation.

A 69-year-old man with ischemic cardiomyopathy underwent left ventricular assist device (LVAD) implantation as destination therapy. One month after LVAD placement, the patient reported abdominal pain with driveline site purulence. Serial wound and blood cultures were positive for various Gram-positive and Gram-negative organisms. Abdominal imaging revealed a possible intracolonic course of the driveline at the splenic flexure, but there were no imaging findings suggestive of bowel perforation. A colonoscopy did not identify a perforation. The patient was treated with antibiotics but continued to experience driveline infections over the next 9 months until frank stool started draining from the driveline exit site. Our case illustrates driveline erosion of the colon causing the insidious formation of an enterocutaneous fistula and highlights a rare late complication of LVAD therapy. Learning objective: Colonic erosion by the driveline can cause enterocutaneous fistula formation over a period of months. A change from typical infectious organisms for driveline infection should prompt investigation of a gastrointestinal source. In cases where computed tomography of the abdomen does not show perforation and there is concern for an intracolonic course of the driveline, colonoscopy or laparoscopy may be diagnostic.

Expanding heart transplantation in 2022 and beyond.

PURPOSE OF REVIEW: Despite advances in the technology of mechanical circulatory support, the need for heart transplantation continues to grow. The longevity of heart transplants continues to be superior to mechanical solutions, though the short-term differences are shrinking. In this review, we cover three timely developments and summarize the recent literature. RECENT FINDINGS: After stagnant rates of heart transplant activity for some years, recently, transplant volume has increased. The developments that have ignited interest have been the use of hepatitis C infected donors, which can now be safely transplanted with the advent of curative oral regimens, and the worldwide use of donors following withdrawal of life support as opposed to traditional brain death donors. In addition, the recent experience of human cardiac xenotransplantation has been very exciting, and though it is not of clinical utility yet, it holds the promise for a virtually unlimited supply of organs at some time in the future. SUMMARY: Much work remains to be done, but together, all three of these developments are exciting and important to be aware of in the future. Each will contribute to additional donors for human heart transplantation and hopefully will alleviate suffering and death on the waiting list.

Achalasia as an Unusual Cause of Acute Cellular Rejection of a Transplanted Heart.

A 68-year-old female with end-stage heart failure presented to the hospital for heart transplant. She was diagnosed with achalasia 14 months prior and treated with frequent botulinum toxin injections. She underwent orthotopic heart transplant on the day of admission and was extubated a few days later. She developed intractable nausea and vomiting. Her first endomyocardial biopsy revealed moderate, approaching severe rejection. She was treated with high-dose intravenous pulse steroids. Fluoroscopy at the time of follow-up biopsy showed undigested pills in her esophagus with narrowing at the distal end and thus failure to deliver immunosuppressive therapy. This case highlights achalasia as an etiology for acute rejection and its potential management.

Evolving Presentation of Cardiogenic Shock: A Review of the Medical Literature and Current Practices.

Cardiogenic shock (CS) remains a leading cause of morbidity and mortality among patients with cardiovascular disease. In the past, acute myocardial infarction was the leading cause of CS. However, in recent years, other etiologies, such as decompensated chronic heart failure, arrhythmia, valvular disease, and post-cardiotomy, each with distinct hemodynamic profiles, have risen in prevalence. The number of treatment options, particularly with regard to device-mediated therapy has also increased. In this review, we sought to survey the medical literature and provide an update on current practices.

Cefazolin plus ertapenem and heart transplantation as salvage therapy for refractory LVAD infection due to methicillin-susceptible Staphylococcus aureus: A case series.

The use of left ventricular assist devices (LVADs) is increasingly more common as the availability of donor organs in relation to failing hearts is outstandingly limited. Infections are the most common complications in LVAD recipients, particularly those caused by Staphylococcus spp. Refractory LVAD-related infections are not uncommon as achieving adequate source control is often not feasible before heart transplantation. Evidence suggest that cefazolin plus ertapenem is effective in refractory methicillin-susceptible Staphylococcus aureus (MSSA) bacteremia, but this approach has not been described in LVAD recipients. In this article, we report two cases of refractory MSSA bacteremia in LVAD recipients that were successfully treated with salvage therapy with cefazolin plus ertapenem and subsequent heart transplantation. This treatment strategy should be considered in patients with refractory LVAD-associated infection due to MSSA that are not responding to standard treatment.

Development and Evaluation of a Three-Dimensional Printer-Based DNA Extraction Method Coupled to Loop Mediated Isothermal Amplification for Point-of-Care Diagnosis of Congenital Chagas Disease in Endemic Regions.

Vertical transmission of Trypanosomacruzi is the cause of congenital Chagas disease, a re-emerging infectious disease that affects endemic and nonendemic regions alike. An early diagnosis is crucial because prompt treatment achieves a high cure rate, precluding evolution to symptomatic chronic Chagas disease. However, early diagnosis involves low-sensitive parasitologic assays, making necessary serologic confirmation after 9 months of life. With the aim of implementing early diagnostic strategies suitable for minimally equipped laboratories, a T. cruzi-loop-mediated isothermal amplification (LAMP) prototype was coupled with an automated DNA-extraction device repurposed from a three-dimensional printer (PrintrLab). The whole process takes <3 hours to yield a result, with an analytical sensitivity of 0.1 to 2 parasite equivalents per milliliter, depending on the T. cruzi strain. Twenty-five blood samples from neonates born to seropositive mothers were tested blindly. In comparison to quantitative real-time PCR, the PrintrLab-LAMP dual strategy showed high agreement, while both molecular-based methodologies yielded optimal sensitivity and specificity with respect to microscopy-based diagnosis of congenital Chagas disease. PrintrLab-LAMP detected all 10 congenitally transmitted T. cruzi infections, showing promise for point-of-care early diagnosis of congenital Chagas disease.

MoonProt 3.0: an update of the moonlighting proteins database.

MoonProt 3.0 (http://moonlightingproteins.org) is an updated open-access database storing expert-curated annotations for moonlighting proteins. Moonlighting proteins have two or more physiologically relevant distinct biochemical or biophysical functions performed by a single polypeptide chain. Here, we describe an expansion in the database since our previous report in the Database Issue of Nucleic Acids Research in 2018. For this release, the number of proteins annotated has been expanded to over 500 proteins and dozens of protein annotations have been updated with additional information, including more structures in the Protein Data Bank, compared with version 2.0. The new entries include more examples from humans, plants and archaea, more proteins involved in disease and proteins with different combinations of functions. More kinds of information about the proteins and the species in which they have multiple functions has been added, including CATH and SCOP classification of structure, known and predicted disorder, predicted transmembrane helices, type of organism, relationship of the protein to disease, and relationship of organism to cause of disease.

Advanced heart failure therapies in patients with stable HIV infection.

BACKGROUND: Human immunodeficiency virus (HIV) infection affects nearly 38 million people worldwide. Patients living with HIV (PLHIV) on modern highly active antiretroviral therapy face significant morbidity and mortality related to the progression of chronic diseases, which lead to an increase in the burden of end-stage organ disease and organ failure. PLHIV present a two fold increased risk of heart failure as compared with the general population, with a prevalence of clinical heart failure of 6.5 %. Orthotopic heart transplantation (OHT) is rarely performed in HIV-positive patients despite the fact that HIV-associated cardiomyopathy is a major long-term complication of HIV infection. MATERIAL AND METHODS: We present a case of PLHIV presenting with decompensated heart failure, requiring initial therapy with left ventricular assist device, followed by heart transplantation, accompanied by an update on current concepts, and experience in the field. DISCUSSION AND CONCLUSION: HIV-associated cardiomyopathy is a major long-term complication of HIV infection. LVAD support or OHT should also be encouraged among HIV-positive patients as current data indicates that AHFT is safe in carefully selected HIV-positive patients and outcomes are similar to those of HIV-negative patients.

Disparities in Survival with Bystander CPR following Cardiopulmonary Arrest Based on Neighborhood Characteristics.

The American Heart Association reports the annual incidence of out-of-hospital cardiopulmonary arrests (OHCA) is greater than 300,000 with a survival rate of 9.5%. Bystander cardiopulmonary resuscitation (CPR) saves one life for every 30, with a 10% decrease in survival associated with every minute of delay in CPR initiation. Bystander CPR and training vary widely by region. We conducted a retrospective study of 320 persons who suffered OHCA in South Florida over 25 months. Increased survival, overall and with bystander CPR, was seen with increasing income (p = 0.05), with a stronger disparity between low- and high-income neighborhoods (p = 0.01 and p = 0.03, resp.). Survival with bystander CPR was statistically greater in white- versus black-predominant neighborhoods (p = 0.04). Increased survival, overall and with bystander CPR, was seen with high- versus low-education neighborhoods (p = 0.03). Neighborhoods with more high school age persons displayed the lowest survival. We discovered a significant disparity in OHCA survival within neighborhoods of low-income, black-predominance, and low-education. Reduced survival was seen in neighborhoods with larger populations of high school students. This group is a potential target for training, and instruction can conceivably change survival outcomes in these neighborhoods, closing the gap, thus improving survival for all.

HIV-associated primary effusion lymphoma presenting as a paracardial mass.

Primary effusion lymphoma (PEL), a rare type of non-Hodgkin's lymphoma, is an AIDS-defining illness and always associated with human herpesvirus 8 (HHV-8). Classic presentations involve the pleural, pericardial or peritoneal cavities. Infrequently, extracavitary solid tumours develop. Treatment of PEL requires chemotherapy and highly active antiretroviral therapy (HAART). We report a case of a 46-year-old man, who presented with right-sided chest pain, dyspnoea and night sweats. Evaluation revealed decreased breath sounds and dullness to percussion on the right side of the chest. Imaging demonstrated a 6.1 cm×6.3 cm right paracardial mass and right-sided pleural effusion. Pleural fluid was HHV-8 positive. The patient was diagnosed with PEL with extracavitary involvement and treated with chemotherapy and concurrent HAART. This case is the first reported case of extracavitary paracardial involvement and adds new insight to the accepted treatment for PEL with extracavitary lesions.