Demographic and Clinical Factors Associated with Bacterial or Nonbacterial Etiologies of Acute Undifferentiated Febrile Illness: Findings from a 3-Year Observational Study in Thailand, 2017-2020.

Acute undifferentiated febrile illness (AUFI) is often undiagnosed in Thailand, resulting in delayed or ineffective treatment. We compared the demographic, exposure history, and clinical characteristics of AUFI patients with laboratory evidence of bacterial and nonbacterial pathogens. Patients aged 2-80 years presenting to 12 hospitals in Nakhon Phanom and Tak provinces were enrolled from April 2017 through May 2020. Interviews were conducted and blood, urine, and sputum were collected for culture as well as rapid diagnostic and molecular testing. A total of 1,263 patients tested positive for one or more bacterial, viral, or parasitic pathogens and were included in the analysis. Multivariable logistic regression was performed to compare factors associated with bacterial infections versus nonbacterial infections. Bacterial infections were more commonly identified in participants from Nakhon Phanom than Tak. Bacterial infections were independently associated with several factors including age ≥50 years (adjusted odds ratio [95% CI]): (4.18 [2.85-6.14]), contact with farm animals (1.82 [1.29-2.57]), antibiotic use within 72 hours of hospital presentation (2.37 [1.50-3.74]), jaundice (2.31 [1.15-4.63]), existing comorbidities (2.77 [1.93-3.96]), contact with febrile individuals (0.42 [0.31-0.57]), muscle pain (0.44 [0.31-0.64]), and rash (0.45 [0.29-0.70]). Bacterial infections were also associated with longer hospitalization (2.75 [2.08-3.64]) and lower odds of recovery at the time of discharge (0.14 [0.07-0.31]). Consideration of patient characteristics and signs/symptoms may help to inform targeted laboratory testing for suspected infectious etiologies. Understanding factors associated with bacterial and non-bacterial causes of AUFI may aid diagnosis and judicious use of antibiotics in resource-limited settings.

Characteristics, risk factors, and outcomes related to Zika virus infection during pregnancy in Northeastern Thailand: A prospective pregnancy cohort study, 2018-2020.

BACKGROUND: In response to the 2015-2016 Zika virus (ZIKV) outbreak and the causal relationship established between maternal ZIKV infection and adverse infant outcomes, we conducted a cohort study to estimate the incidence of ZIKV infection in pregnancy and assess its impacts in women and infants. METHODOLOGY/PRINCIPAL FINDINGS: From May 2018-January 2020, we prospectively followed pregnant women recruited from 134 participating hospitals in two non-adjacent provinces in northeastern Thailand. We collected demographic, clinical, and epidemiologic data and blood and urine at routine antenatal care visits until delivery. ZIKV infections were confirmed by real-time reverse transcriptase polymerase chain reaction (rRT-PCR). Specimens with confirmed ZIKV underwent whole genome sequencing. Among 3,312 women enrolled, 12 (0.36%) had ZIKV infections, of which two (17%) were detected at enrollment. Ten (83%, 3 in 2nd and 7 in 3rd trimester) ZIKV infections were detected during study follow-up, resulting in an infection rate of 0.15 per 1,000 person-weeks (95% CI: 0.07-0.28). The majority (11/12, 91.7%) of infections occurred in one province. Persistent ZIKV viremia (42 days) was found in only one woman. Six women with confirmed ZIKV infections were asymptomatic until delivery. Sequencing of 8 ZIKV isolates revealed all were of Asian lineage. All 12 ZIKV infected women gave birth to live, full-term infants; the only observed adverse birth outcome was low birth weight in one (8%) infant. Pregnancies in 3,300 ZIKV-rRT-PCR-negative women were complicated by 101 (3%) fetal deaths, of which 67 (66%) had miscarriages and 34 (34%) had stillbirths. There were no differences between adverse fetal or birth outcomes of live infants born to ZIKV-rRT-PCR-positive mothers compared to live infants born to ZIKV-rRT-PCR-negative mothers. CONCLUSIONS/SIGNIFICANCE: Confirmed ZIKV infections occurred infrequently in this large pregnancy cohort and observed adverse maternal and birth outcomes did not differ between mothers with and without confirmed infections.

3D Imaging Reveals Complex Microvascular Remodeling in the Right Ventricle in Pulmonary Hypertension.

BACKGROUND: Pathogenic concepts of right ventricular (RV) failure in pulmonary arterial hypertension focus on a critical loss of microvasculature. However, the methods underpinning prior studies did not take into account the 3-dimensional (3D) aspects of cardiac tissue, making accurate quantification difficult. We applied deep-tissue imaging to the pressure-overloaded RV to uncover the 3D properties of the microvascular network and determine whether deficient microvascular adaptation contributes to RV failure. METHODS: Heart sections measuring 250-µm-thick were obtained from mice after pulmonary artery banding (PAB) or debanding PAB surgery and properties of the RV microvascular network were assessed using 3D imaging and quantification. Human heart tissues harvested at the time of transplantation from pulmonary arterial hypertension cases were compared with tissues from control cases with normal RV function. RESULTS: Longitudinal 3D assessment of PAB mouse hearts uncovered complex microvascular remodeling characterized by tortuous, shorter, thicker, highly branched vessels, and overall preserved microvascular density. This remodeling process was reversible in debanding PAB mice in which the RV function recovers over time. The remodeled microvasculature tightly wrapped around the hypertrophied cardiomyocytes to maintain a stable contact surface to cardiomyocytes as an adaptation to RV pressure overload, even in end-stage RV failure. However, microvasculature-cardiomyocyte contact was impaired in areas with interstitial fibrosis where cardiomyocytes displayed signs of hypoxia. Similar to PAB animals, microvascular density in the RV was preserved in patients with end-stage pulmonary arterial hypertension, and microvascular architectural changes appeared to vary by etiology, with patients with pulmonary veno-occlusive disease displaying a lack of microvascular complexity with uniformly short segments. CONCLUSIONS: 3D deep tissue imaging of the failing RV in PAB mice, pulmonary hypertension rats, and patients with pulmonary arterial hypertension reveals complex microvascular changes to preserve the microvascular density and maintain a stable microvascular-cardiomyocyte contact. Our studies provide a novel framework to understand microvascular adaptation in the pressure-overloaded RV that focuses on cell-cell interaction and goes beyond the concept of capillary rarefaction.

Mortality and morbidity after combined heart and liver transplantation in the failing Fontan: An updated dual center retrospective study.

INTRODUCTION: As the adult Fontan population with Fontan associated liver disease continues to increase, more patients are being referred for transplantation, including combined heart and liver transplantation. METHODS: We report updated mortality and morbidity outcomes after combined heart and liver transplant in a retrospective cohort series of 40 patients (age 14 to 49 years) with Fontan circulation across two centers from 2006-2022. RESULTS: The 30-day, 1-year, 5-year and 10-year survival rate was 90%, 80%, 73% and 73% respectively. Sixty percent of patients met a composite comorbidity of needing either post-transplant mechanical circulatory support, renal replacement therapy or tracheostomy. Cardiopulmonary bypass time > 283 min (4.7 h) and meeting the composite comorbidity were associated with mortality by Kaplan Meier analysis. CONCLUSION: Further study to mitigate early mortality and the above comorbidities as well as the high risk of bleeding and vasoplegia in this patient population is warranted.

Beating Heart Transplant Procedures Using Organs From Donors With Circulatory Death.

Importance: The use of ex vivo normothermic organ perfusion has enabled the use of deceased after circulatory death (DCD) donors for heart transplants. However, compared with conventional brain death donation, DCD heart transplantation performed with ex vivo organ perfusion involves an additional period of warm and cold ischemia, exposing the allograft to multiple bouts of ischemia reperfusion injury and may contribute to the high rates of extracorporeal membrane oxygenation usage after DCD heart transplantation. Objective: To assess whether the beating heart method of DCD heart transplantation is safe and whether it has an acceptable rate of extracorporeal membrane oxygenation use postoperatively. Design, Setting, and Participants: This case series includes 10 patients with end-stage heart failure undergoing DCD heart transplantation at a single academic medical center from October 1, 2022, to August 3, 2023. Data were analyzed from October 2022 to August 2023. Interventions: Using a beating heart method of implantation of the donor allograft. Main Outcomes and Measures: The main outcome was primary graft dysfunction necessitating postoperative initiation of mechanical circulatory support. Survival and initiation of mechanical circulatory support were secondary outcomes. Results: In this case series, 10 consecutive patients underwent DCD heart transplantation via the beating heart method. Ten of 10 recipients were male (100%), the mean (SD) age was 51.2 (13.8) years, and 7 (70%) had idiopathic dilated cardiomyopathy. Ten patients (100%) survived, and 0 patients had initiation of extracorporeal membrane oxygenation postoperatively. No other mechanical circulatory support, including intra-aortic balloon pump, was initiated postoperatively. Graft survival was 100% (10 of 10 patients), and, at the time of publication, no patients have been listed for retransplantation. Conclusions and Relevance: In this study of 10 patients undergoing heart transplantation, the beating heart implantation method for DCD heart transplantation was safe and may mitigate ischemia reperfusion injury, which may lead to lower rates of primary graft dysfunction necessitating extracorporeal membrane oxygenation. These results are relevant to institutions using DCD donors for heart transplantation.

Underdiagnosis in clinical documentation of community-acquired sepsis among children admitted to hospitals in two rural provinces: Thailand, October-December 2017.

Paediatric sepsis prevalence data from low-income and middle-income countries are lacking. In a cross-sectional study, we assessed clinician recognition and documentation of non-neonatal community-acquired paediatric sepsis in two rural border provinces in Thailand among children admitted between October and December 2017. Of the 152 children meeting sepsis criteria (26.9 paediatric sepsis patients per 1000 admissions), 15 (9.9%) had a clinician-documented admission diagnosis of sepsis or septic shock and 18 (11.8%) had a discharge diagnosis with International Classification of Diseases-10 codes related to sepsis. Clinician underdocumentation may cause challenges in global paediatric sepsis surveillance.

Prevalence of Urogenital Mycoplasma genitalium Infection at 2 US Army Medical Facilities.

BACKGROUND: Sexually transmitted infections (STIs) have a high incidence in the US Armed Forces and can adversely impact service members' ability to perform their duties. Better knowledge of Mycoplasma genitalium (MG) epidemiology in the military is needed to understand the potential impact of this emerging pathogen on force readiness. METHODS: We conducted cross-sectional analyses of data from US Army service members and other Military Health System beneficiaries participating in a trial of an STI/HIV behavioral intervention at Fort Liberty, NC, and Joint Base Lewis-McChord, WA. At enrollment, participants completed questionnaires and provided biological specimens for nucleic acid amplification testing for MG, Chlamydia trachomatis (CT), and Neisseria gonorrhoeae (NG). We used principal component analysis and robust Poisson regression to examine associations between participant characteristics and prevalent urogenital MG. RESULTS: Among 432 participants enrolled between November 2020 and February 2023, 43 had MG (prevalence, 10.0%), of whom 13 had coinfection with another bacterial STI (all 13 were positive for CT, with 1 also positive for NG). The prevalence of MG was significantly higher among female (13.5%) versus male (7.6%; P = 0.048) participants and non-Hispanic Black (14.9%) versus non-Hispanic White participants (6.6%; P = 0.045). Single relationship status and increased number of recent sexual partners were correlated, and their component was associated with higher MG prevalence (adjusted prevalence ratio, 2.11; 95% confidence interval, 1.29-3.48). CONCLUSIONS: The high prevalence of urogenital MG among Military Health System beneficiaries highlights the importance of understanding the potential clinical sequelae of MG and conducting additional epidemiologic research in military settings.

Beating Heart Transplantation: How to Do It.

Heart transplantation utilizing deceased after circulatory death (DCD) donors has expanded the donor pool through the use of ex vivo normothermic perfusion. Compared with brain death donation, the conventional method of performing DCD heart transplantation includes an additional period of warm and cold ischemia. We have developed a beating heart implantation technique that obliviates the need for a second cardioplegic arrest and the associated reperfusion injury. We hypothesize this reproducible method may improve short-term and long-term outcomes to mirror results seen in brain death donors and provide details on how to perform beating heart transplantation.

Blood transfusion in aortic root surgery impairs midterm survival.

Objective: To evaluate the effect of perioperative allogeneic packed red blood cell (RBC) transfusion during aortic root replacement. Method: We reviewed patients undergoing aortic root replacement at our institution between March 2014 and April 2020. In total, 760 patients underwent aortic root replacement, of whom 442 (58%) received a perioperative RBC transfusion. Propensity score matching was used to account for baseline and operative differences resulting in 159 matched pairs. All-cause mortality was assessed with Kaplan-Meier curves. Data were obtained from our institutional Society of Thoracic Surgeons database and chart review. Results: After propensity score matching, the RBC-transfused and -nontransfused groups were similar for all preoperative characteristics. Cardiopulmonary bypass time, crossclamp time, and lowest operative temperature were similar between the transfused and nontransfused groups (standardized mean difference <0.05). RBC transfusion was associated with more frequent postoperative ventilation greater than 24 hours (36/159 [23%] vs 19/159 [12%]; P = .01), postoperative hemodialysis (9/159 [5.7%] vs 0/159 [0%]; P = .003), reoperation for mediastinal hemorrhage (9/159 [5.7%] vs 0/159 [0%]; P = .003), and longer intensive care unit and hospital length of stay (3 vs 2 days and 8 vs 6 days respectively; P < .001). Thirty-day operative mortality after propensity score matching was similar between the cohorts (1.9%; 3/159 vs 0%; P = .2), and 5-year survival was reduced in the RBC transfusion cohort (90.2% [95% confidence interval, 84.1%-96.7%] vs 97.1% [95% confidence interval, 92.3%-100%] P = .035). Conclusions: Aortic root replacement frequently requires RBC transfusion during and after the operation, but even after matching for observed preoperative and operative characteristics, RBC transfusion is associated with more frequent postoperative complications and reduced midterm survival.

Outcomes after concomitant arch replacement at the time of aortic root surgery.

Background: Contemporary series of aortic arch replacement at the time of aortic root surgery are limited in number of patients and mostly address hemiarch replacement. We describe outcomes after aortic root and concomitant arch replacement, including total arch replacement. Methods: This single-institution retrospective review studied 1196 consecutive patients from May 2004 to September 2020 who underwent first-time aortic root replacement. Patients undergoing surgery for endocarditis were excluded (n = 68, 5.7%). Patients undergoing concomitant root and arch replacement were propensity matched with patients undergoing isolated root surgery based on indication, clinical and operative characteristics, demographics, medical history including connective tissue disorders, and urgency. Multivariable Cox proportional hazards and logistic regression modeling were used to assess the primary outcome of all-cause mortality and the secondary outcomes of prolonged ventilator use, postoperative blood transfusion, and debilitating stroke, adjusted for patient and operative characteristics. Results: Among the 1128 patients who underwent aortic root intervention during the study period, 471 (41.8%) underwent concomitant aortic arch replacement. Most underwent hemiarch replacement (n = 411, 87.4%); 59 patients (12.6%) underwent total arch replacement (with elephant trunk: n = 23, 4.9%; without elephant trunk: n = 36, 7.7%). The mean follow-up time was 4.6 years postprocedure. Operative mortality was 2.2%, and total mortality over the entire study period was 9.2%. Propensity matching generated 348 matches (295 concomitant hemiarch, 53 concomitant total arch). Concomitant hemiarch (hazard ratio, 1.00; 95% confidence interval, 0.54-1.86, P = .99) and total arch replacement (hazard ratio, 1.60, 95% confidence interval, 0.72-3.57, P = .24) were not significantly associated with increased mortality. Rates of stroke were not significantly different among each group: isolated root (n = 11/348, 3.7%), root + hemiarch (n = 17/295, 5.8%), and root + total arch (n = 3/53, 5.7%) replacement (P = .50), nor was the adjusted risk of stroke. Both concomitant arch interventions were associated with prolonged ventilator use and use of postoperative blood transfusions. Conclusions: Hemiarch and total arch replacement are safe to perform at the time of aortic root intervention, with no significant differences in survival or stroke rates, but increased ventilator and blood product use.

Percutaneous Bailout Technique for Trapping an Embolized Valve During Valve-in-Valve TAVR.

A complex 15-year treatment history of a 75-year-old man with New York Heart Association class III symptoms is presented via images and video. His treatment history was noteworthy of bicuspid aortic valve (AV) and a ventricular septal defect (VSD), for which he had an AV replacement and VSD closure in 2005. In 2015, he underwent redo AV replacement and root reconstruction. Echocardiography demonstrated severe bioprosthetic AV stenosis and moderate AV regurgitation. Valve-in-valve transcatheter aortic valve replacement with a Sentinel cerebral protection device was recommended. Pre-operative computed tomography scan showed dilated aortic root and descending aorta with evidence of pseudocoarcta- tion. This case highlights the need for multidisciplinary team approach and the in-depth knowledge of various devices and techniques available.

Outcomes of Reoperative Aortic Root Replacement After Previous Acute Type A Dissection Repair.

Limited aortic root repair for acute type A dissection is associated with greater risk of proximal reoperations compared to full aortic root replacement. Surgical outcomes for patients undergoing reoperative root replacement after previous dissection repair are unknown. This study seeks to determine outcomes for these patients to further inform the debate surrounding optimal upfront management of the aortic root in acute dissection. Retrospective record review of all patients who underwent full aortic root replacement after a previous type A dissection repair operation at a tertiary academic referral center from 2004-2020 was performed. Among 57 cases of reoperative root replacement after type A repair, 35 cases included concomitant aortic arch replacements, and 21 cases involved coronary reconstruction (unilateral or bilateral modified Cabrol grafts). There were 3 acute postoperative strokes and 4 operative mortalities (composite 30-day and in-hospital deaths, 7.0%). Mid-term outcomes were equivalent for patients who required arch replacement compared to isolated proximal repairs (81.8% vs 80.6% estimated 5-year survival, median follow-up 5.53 years. Reoperative root replacement after index type A dissection repairs, including those with concomitant aortic arch replacement and/or coronary reconstruction is achievable with acceptable outcomes at an experienced aortic center.

Analysis of the revised heart allocation policy and the influence of increased mechanical circulatory support on survival.

OBJECTIVES: In 2018, the new United Network for Organ Sharing heart allocation policy took effect. This study evaluated waitlist mortality, mechanical circulatory support utilization, and its influence on posttransplant survival. METHODS: Two 12-month cohorts matched for time of year before and after the policy change were defined by inclusion criteria of first-time transplant recipients aged 18 years or older who were listed and underwent transplant during the same era. Student t test and Wilcoxon rank-sum test were used for mean and median differences, respectively. Categorical variables were compared using χ2 or Fisher exact test. Kaplan-Meier curves were used to characterize survival, including time-to-event analysis with the log-rank test. Fine-Gray modeling was used to characterize waitlist mortality. Cox proportional-hazard models were used for multivariate analysis. RESULTS: Waitlist mortality in the new era is significantly improved based on a competing-risks model (Gray test P = .0064). Unadjusted 180-day posttransplant mortality increased from 5.8% during the old era to 8.0% during the new (P = .0134). However, time-to-event analysis showed similar 180-day survival in both eras. After risk adjustment, the hazard ratio for posttransplant 180-day mortality during the new era was 1.18 (95% CI, 0.85-1.64; P = .333). The posttransplant 180-day mortality of the extracorporeal membrane oxygenation bridge-to-transplant subgroup improved from 28.6% in the old era to 8.4% in the new era (P = .0103; log-rank P = .0021). Patients with an intra-aortic balloon pump at the time of transplant had similar 180-day posttransplant mortality between eras (5.4% vs 7.0%; P = .4831). CONCLUSIONS: The United Network for Organ Sharing policy change is associated with reduced waitlist mortality and similar risk adjusted posttransplant 180-day mortality. The new era is also associated with improved 180-day survival in patients undergoing bridge to transplant with extracorporeal membrane oxygenation.

Surgical management of severe mitral annular calcification.

BACKGROUND: Surgical management of severe mitral annular calcification (MAC) presents a challenging problem for even the most experienced surgeons. Preoperative planning is the most effective strategy to mitigate risk in these scenarios. MAC alone should not disqualify a patient from consideration for mitral valve repair, although the presence of concurrent greater than moderate stenosis warrants consideration of mitral valve replacement. METHODS: While repair and replacement techniques for mitral regurgitation in the setting of MAC overlap with those used to repair a non-calcified mitral apparatus, there are unique considerations to the surgical conduct of these procedures. Specifically, this article describes techniques that may be employed when the severity of MAC precludes typical repair or replacement strategies. RESULTS: Between 2014 and 2021, 77 patients were operated on by a single surgeon for mitral valve disease complicated by severe MAC. Using the systematic approach described herein, 1-year mortality was 7.8% and overall mortality over a follow-up period extending 1 to 8 years was 9.1%. CONCLUSIONS: Despite the inherent challenges of mitral valve repair or replacement in the setting of severe MAC, a systematic approach beginning with preoperative planning, modification of annular suture placement, and techniques to mitigate severe complications have, in our experience, resulting in a reliable methodology for managing severe MAC with excellent outcomes.