Tafenoquine versus Primaquine to Prevent Relapse of Plasmodium vivax Malaria.

BACKGROUND: Tafenoquine, a single-dose therapy for Plasmodium vivax malaria, has been associated with relapse prevention through the clearance of P. vivax parasitemia and hypnozoites, termed "radical cure." METHODS: We performed a phase 3, prospective, double-blind, double-dummy, randomized, controlled trial to compare tafenoquine with primaquine in terms of safety and efficacy. The trial was conducted at seven hospitals or clinics in Peru, Brazil, Colombia, Vietnam, and Thailand and involved patients with normal glucose-6-phosphate dehydrogenase (G6PD) enzyme activity and female patients with moderate G6PD enzyme deficiency; all patients had confirmed P. vivax parasitemia. The patients were randomly assigned, in a 2:1 ratio, to receive a single 300-mg dose of tafenoquine or 15 mg of primaquine once daily for 14 days (administered under supervision); all patients received a 3-day course of chloroquine and were followed for 180 days. The primary safety outcome was a protocol-defined decrease in the hemoglobin level (>3.0 g per deciliter or ≥30% from baseline or to a level of <6.0 g per deciliter). Freedom from recurrence of P. vivax parasitemia at 6 months was the primary efficacy outcome in a planned patient-level meta-analysis of the current trial and another phase 3 trial of tafenoquine and primaquine (per-protocol populations), and an odds ratio for recurrence of 1.45 (tafenoquine vs. primaquine) was used as a noninferiority margin. RESULTS: A protocol-defined decrease in the hemoglobin level occurred in 4 of 166 patients (2.4%; 95% confidence interval [CI], 0.9 to 6.0) in the tafenoquine group and in 1 of 85 patients (1.2%; 95% CI, 0.2 to 6.4) in the primaquine group, for a between-group difference of 1.2 percentage points (95% CI, -4.2 to 5.0). In the patient-level meta-analysis, the percentage of patients who were free from recurrence at 6 months was 67.0% (95% CI, 61.0 to 72.3) among the 426 patients in the tafenoquine group and 72.8% (95% CI, 65.6 to 78.8) among the 214 patients in the primaquine group. The efficacy of tafenoquine was not shown to be noninferior to that of primaquine (odds ratio for recurrence, 1.81; 95% CI, 0.82 to 3.96). CONCLUSIONS: Among patients with normal G6PD enzyme activity, the decline in hemoglobin level with tafenoquine did not differ significantly from that with primaquine. Tafenoquine showed efficacy for the radical cure of P. vivax malaria, although tafenoquine was not shown to be noninferior to primaquine. (Funded by GlaxoSmithKline and Medicines for Malaria Venture; GATHER ClinicalTrials.gov number, NCT02216123 .).

Single-Dose Tafenoquine to Prevent Relapse of Plasmodium vivax Malaria.

BACKGROUND: Treatment of Plasmodium vivax malaria requires the clearing of asexual parasites, but relapse can be prevented only if dormant hypnozoites are cleared from the liver (a treatment termed "radical cure"). Tafenoquine is a single-dose 8-aminoquinoline that has recently been registered for the radical cure of P. vivax. METHODS: This multicenter, double-blind, double-dummy, parallel group, randomized, placebo-controlled trial was conducted in Ethiopia, Peru, Brazil, Cambodia, Thailand, and the Philippines. We enrolled 522 patients with microscopically confirmed P. vivax infection (>100 to <100,000 parasites per microliter) and normal glucose-6-phosphate dehydrogenase (G6PD) activity (with normal activity defined as ≥70% of the median value determined at each trial site among 36 healthy male volunteers who were otherwise not involved in the trial). All patients received a 3-day course of chloroquine (total dose of 1500 mg). In addition, patients were assigned to receive a single 300-mg dose of tafenoquine on day 1 or 2 (260 patients), placebo (133 patients), or a 15-mg dose of primaquine once daily for 14 days (129 patients). The primary outcome was the Kaplan-Meier estimated percentage of patients who were free from recurrence at 6 months, defined as P. vivax clearance without recurrent parasitemia. RESULTS: In the intention-to-treat population, the percentage of patients who were free from recurrence at 6 months was 62.4% in the tafenoquine group (95% confidence interval [CI], 54.9 to 69.0), 27.7% in the placebo group (95% CI, 19.6 to 36.6), and 69.6% in the primaquine group (95% CI, 60.2 to 77.1). The hazard ratio for the risk of recurrence was 0.30 (95% CI, 0.22 to 0.40) with tafenoquine as compared with placebo (P<0.001) and 0.26 (95% CI, 0.18 to 0.39) with primaquine as compared with placebo (P<0.001). Tafenoquine was associated with asymptomatic declines in hemoglobin levels, which resolved without intervention. CONCLUSIONS: Single-dose tafenoquine resulted in a significantly lower risk of P. vivax recurrence than placebo in patients with phenotypically normal G6PD activity. (Funded by GlaxoSmithKline and Medicines for Malaria Venture; DETECTIVE ClinicalTrials.gov number, NCT01376167 .).

Kidney function and daily emtricitabine/tenofovir disoproxil fumarate pre-exposure prophylaxis against HIV: results from the real-life multicentric demonstrative project PrEP Brazil.

BACKGROUND: Pre-Exposure Prophylaxis (PrEP) has demonstrated efficacy in the reduction of sexually transmitted HIV infections. The prolonged use of tenofovir disoproxil fumarate (TDF) and emtricitabine (FTC) co-formulation (TDF/FTC), however, may result in augmented risk of renal toxicity. We aimed to evaluate changes in the estimated Glomerular Filtration Rate (eGFR) in a real-world population setting of participants enrolled in PrEP Brazil, a 48-week prospective, open-label, demonstration study to assess the feasibility of daily oral TDF/FTC used by men who have sex with men and transgender women at high-risk of HIV infection, all over 18 years old. METHODS: Kidney function was assessed by serial measurement of serum creatinine and eGFR with the Modification of Diet in Renal Disease Study (MDRD) formula on weeks 4, 12, 24, 36 and 48. Adherence to PrEP was assessed by dosing TDF concentration in dried blood spots at weeks 4 and 48, measured by liquid chromatography-mass spectrometry or mass spectrometry. RESULTS: Of 392 participants completing the 48-week follow-up protocol with TDF blood detectable levels and eGFR measures, 43.1% were young adults, of Caucasian ethnic background (57.9%), with BMI below 30 kg/m2, without arterial hypertension. At screening, median eGFR was 93.0 mL/min/1.73 m2. At week 4 follow-up, 90 (23% of the study population) participants presented reductions in eGFR greater than 10 mL/min/1.73 m2 as compared to baseline eGFR, some as large as 59 mL/min/1.73 m2, but with no clinical outcomes (adverse events and renal adverse events) severe enough to demand TDF/FTC discontinuation. A negative relationship was observed between TDF blood levels and eGFR at weeks 4 (r = - 0.005; p < 0.01) and 48 (r = - 0.006; p < 0.01). CONCLUSIONS: These results suggest that the renal function profile in individuals on TDF/FTC may be assessed on week 4 and then only annually, allowing a more flexible medical follow-up in primary care centers.

Methylprednisolone as Adjunctive Therapy for Patients Hospitalized With Coronavirus Disease 2019 (COVID-19; Metcovid): A Randomized, Double-blind, Phase IIb, Placebo-controlled Trial.

BACKGROUND: Steroid use for coronavirus disease 2019 (COVID-19) is based on the possible role of these drugs in mitigating the inflammatory response, mainly in the lungs, triggered by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This study aimed to evaluate the efficacy of methylprednisolone (MP) among hospitalized patients with suspected COVID-19. METHODS: A parallel, double-blind, placebo-controlled, randomized, Phase IIb clinical trial was performed with hospitalized patients aged ≥18 years with clinical, epidemiological, and/or radiological suspected COVID-19 at a tertiary care facility in Manaus, Brazil. Patients were randomly allocated (1:1 ratio) to receive either intravenous MP (0.5 mg/kg) or placebo (saline solution) twice daily for 5 days. A modified intention-to-treat (mITT) analysis was conducted. The primary outcome was 28-day mortality. RESULTS: From 18 April to 16 June 2020, 647 patients were screened, 416 were randomized, and 393 were analyzed as mITT, with 194 individuals assigned to MP and 199 to placebo. SARS-CoV-2 infection was confirmed by reverse transcriptase polymerase chain reaction in 81.3%. The mortality rates at Day 28 were not different between groups. A subgroup analysis showed that patients over 60 years old in the MP group had a lower mortality rate at Day 28. Patients in the MP arm tended to need more insulin therapy, and no difference was seen in virus clearance in respiratory secretion until Day 7. CONCLUSIONS: The findings of this study suggest that a short course of MP in hospitalized patients with COVID-19 did not reduce mortality in the overall population. CLINICAL TRIALS REGISTRATION: NCT04343729.

Transplant trends in Mexico during the COVID-19 pandemic: Disparities within healthcare sectors.

Healthcare systems worldwide were challenged during the COVID-19 pandemic. In Mexico, the public hospitals that perform most transplants were adapted to provide care for COVID-19 patients. Using a nationwide database, we describe the first report of the impact of COVID-19 and related transplantation healthcare policies in a middle-income country by comparing statistics before and during the pandemic (pre-COVID: March 2019-February 2020 vs. COVID era: March 2020-February 2021) and by type of institution (public vs. private). The global reduction in transplantation was higher in public institutions compared with private institutions, 89% versus 62%, respectively, p < .001. When analyzing by organ, kidney transplantation decreased by 89% at public versus 57% at private, p < .001; cornea by 88% at public versus 64% at private, p < .001; liver by 88% at public versus 35% at private, p < .001; and heart by 88% in public versus 67% at private institutions, p = .4. The COVID-19 pandemic along with the implemented health policies were associated with a decrease in donations, waiting list additions, and a decrease in transplantation, particularly at public institutions, which care for the most vulnerable.

Covid-19 Automated Diagnosis and Risk Assessment through Metabolomics and Machine Learning.

COVID-19 is still placing a heavy health and financial burden worldwide. Impairment in patient screening and risk management plays a fundamental role on how governments and authorities are directing resources, planning reopening, as well as sanitary countermeasures, especially in regions where poverty is a major component in the equation. An efficient diagnostic method must be highly accurate, while having a cost-effective profile. We combined a machine learning-based algorithm with mass spectrometry to create an expeditious platform that discriminate COVID-19 in plasma samples within minutes, while also providing tools for risk assessment, to assist healthcare professionals in patient management and decision-making. A cross-sectional study enrolled 815 patients (442 COVID-19, 350 controls and 23 COVID-19 suspicious) from three Brazilian epicenters from April to July 2020. We were able to elect and identify 19 molecules related to the disease's pathophysiology and several discriminating features to patient's health-related outcomes. The method applied for COVID-19 diagnosis showed specificity >96% and sensitivity >83%, and specificity >80% and sensitivity >85% during risk assessment, both from blinded data. Our method introduced a new approach for COVID-19 screening, providing the indirect detection of infection through metabolites and contextualizing the findings with the disease's pathophysiology. The pairwise analysis of biomarkers brought robustness to the model developed using machine learning algorithms, transforming this screening approach in a tool with great potential for real-world application.

Should we care about Plasmodium vivax and HIV co-infection? A systematic review and a cases series from the Brazilian Amazon.

BACKGROUND: Malaria and HIV are two important public health issues. However, evidence on HIV-Plasmodium vivax co-infection (HIV/PvCo) is scarce, with most of the available information related to Plasmodium falciparum on the African continent. It is unclear whether HIV can change the clinical course of vivax malaria and increase the risk of complications. In this study, a systematic review of HIV/PvCo studies was performed, and recent cases from the Brazilian Amazon were included. METHODS: Medical records from a tertiary care centre in the Western Brazilian Amazon (2009-2018) were reviewed to identify HIV/PvCo hospitalized patients. Demographic, clinical and laboratory characteristics and outcomes are reported. Also, a systematic review of published studies on HIV/PvCo was conducted. Metadata, number of HIV/PvCo cases, demographic, clinical, and outcome data were extracted. RESULTS: A total of 1,048 vivax malaria patients were hospitalized in the 10-year period; 21 (2.0%) were HIV/PvCo cases, of which 9 (42.9%) had AIDS-defining illnesses. This was the first malaria episode in 11 (52.4%) patients. Seven (33.3%) patients were unaware of their HIV status and were diagnosed on hospitalization. Severe malaria was diagnosed in 5 (23.8%) patients. One patient died. The systematic review search provided 17 articles (12 cross-sectional or longitudinal studies and 5 case report studies). A higher prevalence of studies involved cases in African and Asian countries (35.3 and 29.4%, respectively), and the prevalence of reported co-infections ranged from 0.1 to 60%. CONCLUSION: Reports of HIV/PvCo are scarce in the literature, with only a few studies describing clinical and laboratory outcomes. Systematic screening for both co-infections is not routinely performed, and therefore the real prevalence of HIV/PvCo is unknown. This study showed a low prevalence of HIV/PvCo despite the high prevalence of malaria and HIV locally. Even though relatively small, this is the largest case series to describe HIV/PvCo.

Performance of a sensitive haemozoin-based malaria diagnostic test validated for vivax malaria diagnosis in Brazilian Amazon.

BACKGROUND: Vivax malaria diagnosis remains a challenge in malaria elimination, with current point of care rapid diagnostic tests (RDT) missing many clinically significant infections because of usually lower peripheral parasitaemia. Haemozoin-detecting assays have been suggested as an alternative to immunoassay platforms but to date have not reached successful field deployment. Haemozoin is a paramagnetic crystal by-product of haemoglobin digestion by malaria parasites and is present in the food vacuole of malaria parasite-infected erythrocytes. This study aimed to compare the diagnostic capability of a new haemozoin-detecting platform, the Gazelle™ device with optical microscopy, RDT and PCR in a vivax malaria-endemic region. METHODS: A comparative, double-blind study evaluating symptomatic malaria patients seeking medical care was conducted at an infectious diseases reference hospital in the western Brazilian Amazon. Optical microscopy, PCR, RDT, and Gazelle™ were used to analyse blood samples. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and Kappa values were calculated. RESULTS: Out of 300 patients, 24 test results were excluded from the final analysis due to protocol violation (6) and inconclusive and/or irretrievable results (18). Gazelle™ sensitivity was 96.1 % (91.3-98.3) and 72.1 % (65.0-78.3) when compared to optical microscopy and PCR, respectively whereas it was 83.9 % and 62.8 % for RDTs. The platform presented specificity of 100 % (97.4-100), and 99.0 % (94.8-99.9) when compared to optical microscopy, and PCR, respectively, which  was the same for RDTs. Its correct classification rate was 98.2 % when compared to optical microscopy and 82.3 % for PCR; the test's accuracy when compared to optical microscopy was 98.1 % (96.4-99.7), when compared to RDT was 95.2 % (93.0-97.5), and when compared to PCR was 85.6 % (82.1-89.1). Kappa (95 % CI) values for Gazelle™ were 96.4 (93.2-99.5), 88.2 (82.6-93.8) and 65.3 (57.0-73.6) for optical microscopy, RDT and PCR, respectively. CONCLUSIONS: The Gazelle™ device was shown to have faster, easier, good sensitivity, specificity, and accuracy when compared to microscopy and was superior to RDT, demonstrating to be an alternative for vivax malaria screening particularly in areas where malaria is concomitant with other febrile infections (including dengue fever, zika, chikungunya, Chagas, yellow fever, babesiosis).

Neurological Manifestations Associated with Parvovirus B19 Infection in Immunocompetent Children: Case Series and Systematic Review.

An increasing number of reports have described human parvovirus B19 infection in association with a variety of neurological manifestations, especially in children. This study assessed the clinical and laboratory outcomes found in a case series of immunocompetent children who tested positive for parvovirus B19 by qualitative polymerase chain reaction assays of cerebrospinal fluid, in a tertiary referral center in the western Brazilian Amazon. We screened 178 children with clinically diagnosed central nervous system infections (meningoencephalitis). Of these, five (2.8%) were positive for parvovirus B19. A literature review also presented herein identified a further 50 cases of parvovirus B19 with neurological manifestations. Thus, even if the classic signs of parvovirus B19 infection are absent, such as the well-known rash, children with signs of neurological infection should also be evaluated for parvovirus B19 infection.

Bariatric Surgery in End-Stage Heart Failure: Feasibility in Successful Attainment of a Target Body Mass Index.

INTRODUCTION: Orthotopic heart transplantation (OHT) is contraindicated in morbidly obese patients with end-stage heart failure (HF), for whom cardiac allograft is the only means for long-term survival. Bariatric surgery may allow them to achieve target body mass index (BMI) for OHT METHODS: From 4/2014 to 12/2018, 26 morbidly obese HF patients who did not meet BMI eligibility criteria for OHT underwent laparoscopic bariatric surgery. Outcomes of interest were median difference in BMI, number of patients achieving target BMI for OHT, and 30-day mortality. RESULTS: Median age was 49 (IQR 14) years, and 13 (50%) were women. HF was mainly systolic (15 patients, 58%). The median LVEF was 27% (IQR 37%). At the time of bariatric surgery, 12 (46%) patients had mechanical circulatory support: 2 (8%) concomitant left ventricular assist device (LVAD) placements, 8 (31%) LVAD already-in-place, and 2 (8%) intra-aortic balloon pumps. There was no 30-day mortality, but one mortality on postoperative day 48. Over a median follow-up of 6 months (range 0-36 months, IQR 17), there was a significant reduction in BMI (p<0.0001). The median postoperative BMI was 36.7 (IQR 8.7), compared to preoperative median BMI of 42.7 (IQR 9.4). Target BMI of < 35 was achieved in 11 (42%) patients. Three patients (12%) have undergone OHT. CONCLUSION: Bariatric surgery in end-stage HF is feasible and results in a high number of patients achieving target BMI, increasing their probability of undergoing OHT. The presence of a LVAD should not preclude these patients from undergoing a bariatric intervention.

Bothrops atrox Snakebite: How a Bad Decision May Lead to a Chronic Disability: A Case Report.

Snakebites are a neglected and underestimated global health hazard. In the Brazilian Amazon, Bothrops snakebites are the most prevalent and may lead to severe complications. Here we describe a severe case of Bothrops atrox snakebite that, owing to delayed medical assistance, presented with renal and respiratory failure, compartment syndrome, and tissue necrosis. After several fasciotomy surgeries, the patient survived; however, he showed significant functional disability. Prompt management of snake envenomation would aid in the early diagnosis of local and systemic complications and, consequently, would result in a better functional outcome with improved quality of life.

Clinical Spectrum of Primaquine-induced Hemolysis in Glucose-6-Phosphate Dehydrogenase Deficiency: A 9-Year Hospitalization-based Study From the Brazilian Amazon.

Despite glucose-6-phosphate dehydrogenase (G6PD) deficiency prevalence of 5% in the Amazon, primaquine is administered without G6PD screening. This is an important cause of hospitalization among Plasmodium vivax-infected individuals, leading to life-threatening anemia and acute renal failure across endemic areas. In Manaus, the frequency of primaquine-induced hemolysis was 85.2 cases per 100 000 primaquine users.

Dilemma in the Brazilian Tropical Medicine: 'Is speed more important than direction?'

With the recent changes in the epidemiology of infectious diseases in Brazil, research funding has been changing in a manner that does not properly consider biodiversity and poverty-related diseases. The burden of disease and the affected neglected populations need to be part of the equation in developeding countries with limited funding.

Polymorphisms in TLRs influence circulating cytokines production in Plasmodium vivax malaria: TLR polymorphisms influence cytokine productions in malaria-vivax.

The efficiency of the immune system has been shaped throughout the evolutionary process allowing adaptations. In a Plasmodium vivax infection, the host attempts to develop an innate immune response to keep in check the parasite that is associated with inflammatory and regulatory processes. Production of pro-inflammatory and regulatory cytokines simultaneously appears to be a balancing mechanism for the host to prevent the onset of severe disease. Changes in the dynamics of circulating cytokines production can influence the pathogenesis, severity of the disease and episodes of recurrent Plasmodium vivax malaria (Pv-malaria). A cross-sectional study was conducted in endemic areas for Pv-malaria in the Amazonas State, Brazil. Several SNPs in TLR genes were genotyped by PCR-RFLP in 137 patients infected with P. vivax. Circulating cytokines IL-6, TNF, IL-2, IL-10, IFN-γ and IL-4 were measured by CBA. Influence of the studied SNPs on circulating cytokines was investigated by applying the Kruskal-Wallis test followed by Dunns' multiple comparison post-test. A Spearman correlation test also was performed to elaborate circulating cytokine networks and to demonstrate the level of interaction between each molecule. Individuals with genotypes A/G (TLR4 A299G), C/C (TLR6 S249P) and T/T (TLR9 -1486C/T) appear to produce less/gain IL-6, IFN-γ, IL-10, IL-2 and IL-4 compared to patients with wild-type and heterozygous genotypes. In addition, these genotypes seem to influence the interaction network between the molecules studied, causing a lower interaction, absence or even negative interaction between the cytokines. Data presented in this study suggests the influence of polymorphisms TLR4 (A299G), TLR6 (S249P) and TLR9 (-1486C/T) on the production of circulating cytokines during Pv-malaria.

Impact of flow, gradient, and left ventricular function on outcomes after transcatheter aortic valve replacement.

OBJECTIVES: To assess the impact of low flow with and without preserved left ventricular ejection fraction (LVEF) on outcomes after transcatheter aortic valve replacement (TAVR). BACKGROUND: Prior studies have shown that patients with low flow, AVG, and LVEF have worse outcomes after TAVR. It is unclear whether low AVG and LVEF remain prognostic after adjusting for flow, and how the outcomes of patients with low flow with and without preserved LVEF compare after TAVR. The goal of this study was to provide insight into these open questions. METHODS: Data from 340 TAVR patients at Brigham and Women's Hospital from 2011 through 2015 were analyzed. Low flow was defined as stroke volume index (SVI) ≤35 mL/m2 , low AVG as mean gradient < 40 mmHg, and reduced LVEF as < 50%. RESULTS: Low flow was present in 96 (28.2%) patients, 48 (50.0%) of whom also had reduced LVEF. At 1 year, low flow was associated with increased mortality (21.9 vs 7.4%; P = 0.0002) and heart failure (HF) (20.8 vs 5.3%; P = 0.0113). Among patients with low flow, those with preserved LVEF had increased mortality (HR 5.17, 95% CI 2.73-9.80; P < 0.001) and HF (HR 7.69, 95% CI 3.86-15.31; P < 0.001). After adjusting for clinical factors, patients with low flow had increased mortality (HR 6.51, 95% CI 2.98-14.22; P < 0.001) and HF (HR 5.52, 95% CI 2.34-12.98; P < 0.001), while neither low AVG nor low LVEF were associated with increases in mortality or HF. CONCLUSIONS: In patients undergoing TAVR, low flow was an independent predictor of 1-year mortality and HF, and a stronger predictor than either low AVG or LVEF. Patients with low flow and preserved EF had increased mortality and HF at 1-year, while those with low flow and reduced EF had outcomes similar to patients with normal flow.

Sudden spleen rupture in a Plasmodium vivax-infected patient undergoing malaria treatment.

BACKGROUND: Splenomegaly is one of the most common features of malaria. However, spontaneous splenic rupture, although unusual, represents a severe complication often leading to death. It is mostly seen in acute infection and primary attack, and it is most commonly associated with Plasmodium vivax. Here, a case of spontaneous splenic rupture diagnosed with a portable ultrasound apparatus shortly after starting treatment and with recurrent parasitaemia after splenectomy, is reported. CASE DESCRIPTION: In November 2015, a 45-year-old Brazilian man presented to the hospital in Manaus with fever, headache and myalgia. He was diagnosed with P. vivax malaria and, after a normal G6PD test, he started treatment with chloroquine and primaquine and was discharged. Two days later, he went back to the hospital with abdominal pain, dyspnea, dry cough, pallor, oliguria and fever. Using a portable ultrasound, he was diagnosed of rupture of the spleen, which was removed by emergency surgery. After this episode, he suffered two more malaria episodes with high parasitaemia at approximately 2-month intervals. DNA from different portions of the spleen was extracted and a qualitative PCR was performed to detect P. vivax. CONCLUSIONS: The splenic rupture suffered by this patient occurred 2 days after starting the treatment. Having a portable ultrasound apparatus may have saved the patient's life, as it revealed a haemorrhage needing an urgent surgery. Parasites were detected by PCR in the extracted spleen. This patient suffered two more vivax malaria diagnosed episodes in spite of receiving and completing treatment with chloroquine and primaquine for each clinical attack. Splenic rupture during acute malaria is uncommon, but it is likely underdiagnosed and underreported, because the lack of means and equipment hinders diagnostic confirmation, especially in endemic areas.

Clinical Significance of Greater Implantation Height with SAPIEN 3 Transcatheter Heart Valve.

BACKGROUND: A lower rate of permanent pacemaker (PPM) has been linked to a target aortic implantation height (AIH) >0.70, following transcatheter aortic valve replacement (TAVR) with the SAPIEN 3 valve. Based on clinical experience, it was hypothesized that a higher AIH (≥0.85) would lower the rate of PPM implantation. METHODS: A total of 127 patients (66 females, 61 males; mean age 82 ± 8 years) underwent TAVR with the SAPIEN 3 valve between May 2015 and July 2016. AIH was defined as the proportion of the valve frame above the aortic annulus in the post-deployment aortogram. A target AIH (≥0.70) was achieved in 113 patients (89%). Cases were stratified into a High Implantation (HI) group (AIH ≥0.85; 33 patients) or a Standard Implantation (SI) group (AIH <0.85; 94 patients). RESULTS: The mean Society of Thoracic Surgeons Predicted Risk of Mortality (STS-PROM) score of all patients was 6.4 ± 3.5%. Preoperative right bundle branch block (RBBB) was prevalent in 13% of SI patients, and in 18% of HI patients (p = 0.56). There were no significant differences in operative mortality (3.2% versus 0%), median length of stay (2 days versus 3 days) and incidence of moderate-to-severe paravalvular leak (3.2% versus 0%; all p >0.410) between SI and HI patients, respectively. Likewise, the incidence of new PPM did not differ between the two groups (12% in HI versus 13% in SI; p ≥0.99). The mean AIH was similar for patients with PPM implantation (0.80 ± 0.08) compared to those without (0.78 ± 0.06; p = 0.520). Preoperative RBBB was significantly associated with PPM implantation (odds ratio (OR) 10.1; p = 0.002), and patients who underwent PPM implantation had a higher operative mortality (12.5% versus 1%; p = 0.040). CONCLUSIONS: Among TAVR patients who received the SAPIEN 3 heart valve, a higher AIH (≥0.85) was not associated with a lower rate of PPM implantation or increased operative mortality. Prior RBBB was the only independent risk factor for new PPM implantation. Long-term follow up is crucial in determining the clinical significance of PPM implantation.

Surgical pulmonary embolectomy and catheter-directed thrombolysis for treatment of submassive pulmonary embolism.

BACKGROUND: Acute pulmonary embolism (PE) with preserved hemodynamics but right ventricular dysfunction, classified as submassive PE, carries a high risk of mortality. We report the results for patients who did not qualify for medical therapy and required treatment of submassive PE with surgical pulmonary embolectomy and catheter-directed thrombolysis (CDT). METHODS: Between October 1999 and May 2015, 133 submassive PE patients underwent treatment with pulmonary embolectomy (71) and CDT (62). A multidisciplinary PE response team helped to determine the most appropriate treatment strategy on a case-by-case basis. The EkoSonic ultrasound-facilitated thrombolysis system (EKOS) was used for CDT, which was introduced in 2010. RESULTS: The mean age of submassive PE patients was 57.3 years, which included 36.8% females. PE risk factors included previous deep venous thrombosis (46.6%), immobility (36.1%), recent surgery (30.8%), and cancer (22.6%), P < 0.05. The most common indication for advanced treatment was right ventricular strain (42.9%), P = 0.03. The frequency of surgical pulmonary embolectomy remained stable even after incorporating the EKOS procedure into our treatment algorithm, with statistically similar operative mortality. Bleeding was observed in six CDT patients and one pulmonary embolectomy patient (P < 0.05). Follow-up echocardiography was available for 61% of the overall cohort, of whom 76.5% had no residual moderate or severe right ventricular dysfunction. CONCLUSIONS: Pulmonary embolectomy and CDT are important contemporary advanced treatment options for selected high-risk patients with submassive PE, who do not qualify for medical therapy.

Metabolome-wide association study of peripheral parasitemia in Plasmodium vivax malaria.

BACKGROUND: Plasmodium vivax is one of the leading causes of malaria worldwide. Infections with this parasite cause diverse clinical manifestations, and recent studies revealed that infections with P. vivax can result in severe and fatal disease. Despite these facts, biological traits of the host response and parasite metabolism during P. vivax malaria are still largely underexplored. Parasitemia is clearly related to progression and severity of malaria caused by P. falciparum, however the effects of parasitemia during infections with P. vivax are not well understood. RESULTS: We conducted an exploratory study using a high-resolution metabolomics platform that uncovered significant associations between parasitemia levels and plasma metabolites from 150 patients with P. vivax malaria. Most plasma metabolites were inversely associated with higher levels of parasitemia. Top predicted metabolites are implicated into pathways of heme and lipid metabolism, which include biliverdin, bilirubin, palmitoylcarnitine, stearoylcarnitine, phosphocholine, glycerophosphocholine, oleic acid and omega-carboxy-trinor-leukotriene B4. CONCLUSIONS: The abundance of several plasma metabolites varies according to the levels of parasitemia in patients with P. vivax malaria. Moreover, our data suggest that the host response and/or parasite survival might be affected by metabolites involved in the degradation of heme and metabolism of several lipids. Importantly, these data highlight metabolic pathways that may serve as targets for the development of new antimalarial compounds.

Alternative transmission routes in the malaria elimination era: an overview of transfusion-transmitted malaria in the Americas.

BACKGROUND: Transfusion-transmitted (TT) malaria is an alternative infection route that has gained little attention from authorities, despite representing a life-threatening condition. There has been no systematic review of this health problem in American countries. The aim of this study was to describe the clinical and epidemiological characteristics of TT malaria in the Americas and identify factors associated with lethality based on the studies published in the literature. METHODS: Potentially relevant papers in all languages were retrieved from MEDLINE and LILACS. Additional articles were obtained from reviews and original papers. Publications on screening of candidate blood donors and on surveillance of TT malaria cases were included. Odds ratios with respective 95% confidence intervals (95% CI) were calculated. Epidemiological characteristics of blood donors of TT malaria cases, including a pooled positivity of different tests for malaria diagnosis, were retrieved. RESULTS: A total of 63 publications regarding TT malaria from seven countries were included, from 1971 to 2016. A total of 422 cases of TT malaria were recorded. Most TT malaria cases were in females (62.0%) and 39.5% were in the ≥61 years-old age group. About half of all cases were from Mexico (50.7%), 40.3% from the United States of America (USA) and 6.6% from Brazil. Gyneco-obstetrical conditions (67.3%), surgical procedures (20.6%) and complications from neoplasias (6.1%) were the most common indications of transfusion. Packed red blood cells (RBCs) (50.7%) and whole blood (43.3%) were the blood products mostly associated with TT malaria. Cases were mostly caused by Plasmodium malariae (58.4%), followed by Plasmodium vivax (20.7%) and Plasmodium falciparum (17.9%). A total of 66.6% of cases were diagnosed by microscopy. Incubation period of 2-3 weeks was the most commonly observed (28.6%). Lethality was seen in 5.3% of cases and was associated with living in non-endemic countries, P. falciparum infection and concomitant neoplastic diseases. CONCLUSION: There is an important research and knowledge gap regarding the TT malaria burden in Latin American countries where malaria remains endemic. No screening method that is practical, affordable and suitably sensitive is available at blood banks in Latin American countries, where infections with low parasitaemia contribute greatly to transmission. Lethality from TT malaria was not negligible. TT malaria needs to be acknowledged and addressed in areas moving toward elimination.