Rediscovery of the implication of albuminuria in heart failure: emerging classic index for cardiorenal interaction.

The development of new drugs and device therapies has led to remarkable advancements in heart failure (HF) treatment in the past couple of decades. However, it becomes increasingly evident that guideline-directed medical therapy cannot be one-size-fits-all across a wide range of ejection fractions (EFs) and various aetiologies. Therefore, classifications solely relying on EF and natriuretic peptide make optimization of treatment challenging, and there is a growing exploration of new indicators that enable efficient risk stratification of HF patients. Particularly when considering HF as a multi-organ interaction syndrome, the cardiorenal interaction plays a central role in its pathophysiology, and albuminuria has gained great prominence as its biomarker, independent from glomerular filtration rate. Albuminuria has been shown to exhibit a linear correlation with cardiovascular disease and HF prognosis in multiple epidemiological studies, ranging from normal (<30 mg/g) to high levels (>300 mg/g). However, on the other hand, it is only recently that the details of the pathological mechanisms that give rise to albuminuria have begun to be elucidated, including the efficient compaction/tightening of the glomerular basement membrane by podocytes and mesangial cells. Interestingly, renal disease, diabetes, and HF damage these components associated with albuminuria, and experimental models have demonstrated that recently developed HF drugs reduce albuminuria by ameliorating these pathological phenotypes. In this review, facing the rapid expansion of horizons in HF treatment, we aim to clarify the current understanding of the pathophysiology of albuminuria and explore the comprehensive understanding of albuminuria by examining the clinically established evidence to date, the pathophysiological mechanisms leading to its occurrence, and the outcomes of clinical studies utilizing various drug classes committed to specific pathological mechanisms to put albuminuria as a novel axis to depict the pathophysiology of HF.

Trends in Nationally Notifiable Infectious Diseases in Humans and Animals during COVID-19 Pandemic, South Korea.

We investigated trends in notifiable infectious diseases in both humans and animals during the COVID-19 pandemic in South Korea and compared those data against expected trends had nonpharmaceutical interventions (NPIs) not been implemented. We found that human respiratory infectious diseases other than COVID-19 decreased by an average of 54.7% after NPIs were introduced. On the basis of that trend, we estimated that annual medical expenses associated with respiratory infections other than COVID-19 also decreased by 3.8% in 2020 and 18.9% in 2021. However, human gastrointestinal infectious diseases and livestock diseases exhibited similar or even higher incidence rates after NPIs were instituted. Our investigation revealed that the preventive effect of NPIs varied among diseases and that NPIs might have had limited effectiveness in reducing the spread of certain types of infectious diseases. These findings suggest the need for future, novel public health interventions to compensate for such limitations.

Exploring preventive factors against insufficient antibody positivity rate for foot-and-mouth disease in pig farms in South Korea: a preliminary ecological study.

BACKGROUND: Foot-and-mouth disease (FMD) is a highly contagious viral disease in livestock that has tremendous economic impact nationally. After multiple FMD outbreaks, the South Korean government implemented a vaccination policy for efficient disease control. However, during active surveillance by quarantine authorities, pig farms have reported an insufficient antibody positivity rate to FMD. OBJECTIVE: In this study, the spatial and temporal trends of insufficiency among pig farms were analyzed, and the effect of the number of government veterinary officers was explored as a potential preventive factor. METHODS: Various data were acquired, including national-level surveillance data for antibody insufficiency from the Korea Animal Health Integrated System, the number of veterinary officers, and the number of local pig farms. Temporal and geographical descriptive analyses were conducted to overview spatial and temporal trends. Additionally, logistic regression models were employed to investigate the association between the number of officers per pig farm with antibody insufficiency. Spatial cluster analysis was conducted to detect spatial clusters. RESULTS: The results showed that the incidence of insufficiency tended to decrease in recent years (odds ratio [OR], 0.803; 95% confidence interval [95% CIs], 0.721-0.893), and regions with a higher density of governmental veterinary officers (OR, 0.942; 95% CIs, 0.918-0.965) were associated with a lower incidence. CONCLUSIONS: This study implies that previously conducted national interventions would be effective, and the quality of government-provided veterinary care could play an important role in addressing the insufficient positivity rate of antibodies.

A single-blind randomised study comparing the efficacy of fluconazole and itraconazole for the treatment of Malassezia dermatitis in client-owned dogs.

BACKGROUND: No reports have compared the clinical therapeutic efficacy of fluconazole and itraconazole in canine Malassezia dermatitis. OBJECTIVES: The study aimed to compare the clinical therapeutic efficacy of fluconazole and itraconazole and to evaluate the adverse effects of fluconazole in canine Malassezia dermatitis. ANIMALS: Sixty-one client-owned dogs with Malassezia dermatitis. MATERIALS AND METHODS: The enrolled animals were randomly divided into groups receiving 5 mg/kg fluconazole (5FZ), 10 mg/kg fluconazole (10FZ) or 5 mg/kg itraconazole (5IZ). The drugs were orally administered once daily for 28 days. Cytological examination, clinical index score (CIS), pruritus Visual Analog Scale (PVAS) evaluation and blood analysis (for 5FZ only) were performed on Day (D)0, D14 and D28. RESULTS: On D14, significant reductions in mean yeast count (MYC), CIS and PVAS were observed in the 5FZ (n = 20, p < 0.01), 10FZ (n = 17, p < 0.01) and 5IZ (n = 16, p < 0.05) groups. In all three groups, a significant reduction (p < 0.001) in MYC, CIS and PVAS expression was observed on D28. There was no significant difference in the percentage reduction of MYC, CIS and PVAS among the groups. Moreover, there was a significant difference (p < 0.05) in each group between D14 and D28, except for the percentage reduction in MYC in the 10FZ and 5IZ groups. No adverse effects of fluconazole were observed in the 5FZ or 10FZ groups. CONCLUSIONS AND CLINICAL RELEVANCE: This study indicates that 5FZ and 10FZ are as effective as itraconazole in canine Malassezia dermatitis.

Associations of meteorological factors and dynamics of scrub typhus incidence in South Korea: A nationwide time-series study.

Scrub typhus, also known as Tsutsugamushi disease, is a climate-sensitive vector-borne disease that poses a growing public health threat. However, studies on the association between scrub typhus epidemics and meteorological factors in South Korea need to be complemented. Therefore, we aimed to analyze the association among ambient temperature, precipitation, and the incidence of scrub typhus in South Korea. First, we obtained data on the weekly number of scrub typhus cases and concurrent meteorological variables at the city-county level (Si-Gun) in South Korea between 2001 and 2019. Subsequently, a two-stage meta-regression analysis was conducted. In the first stage, we conducted time-series regression analyses using a distributed lag nonlinear model (DLNM) to investigate the association between temperature, precipitation, and scrub typhus incidence at each location. In the second stage, we employed a multivariate meta-regression model to combine the association estimates from all municipalities, considering regional indicators, such as mite species distribution, Normalized Difference Vegetation Index (NDVI), and urban-rural classification. Weekly mean temperature and weekly total precipitation exhibited a reversed U-shaped nonlinear association with the incidence of scrub typhus. The overall cumulative association with scrub typhus incidence peaked at 18.7 C° (with RRs of 9.73, 95% CI: 5.54-17.10) of ambient temperature (reference 9.7 C°) and 162.0 mm (with RRs of 1.87, 95% CI: 1.02-3.83) of precipitation (reference 2.8 mm), respectively. These findings suggest that meteorological factors contribute to scrub typhus epidemics by interacting with vectors, reservoir hosts, and human behaviors. This information serves as a reference for future public health policies and epidemiological research aimed at controlling scrub typhus infections.

Ecological drivers for poultry farms predisposed to highly pathogenic avian influenza virus infection during the initial phase of the six outbreaks between 2010-2021: a nationwide study in South Korea.

Background: Highly pathogenic avian influenza (HPAI) has caused substantial economic losses worldwide. An understanding of the environmental drivers that contribute to spillover transmission from wild birds to poultry farms is important for predicting areas at risk of introduction and developing risk-based surveillance strategies. We conducted an epidemiological study using data from six HPAI outbreak events in South Korea. Materials and methods: An aggregate-level study design was implemented using third-level administrative units in South Korea. Only regions with high natural reservoir suitability were included. The incidence of HPAI at chicken and duck farms during the initial phase (30 and 45 days after the first case) of each outbreak event was used as the outcome variable, assuming that cross-species transmission from wild birds was the dominant exposure leading to infection. Candidate environmental drivers were meteorological factors, including temperature, precipitation, humidity, and altitude, as well as the proportion of protected area, farm density, deforestation level, and predator species richness. Logistic regression models were implemented; conditional autoregression models were used in cases of spatial autocorrelation of residuals. Results: Lower temperature, higher farm density, and lower predator species richness were significantly associated with a higher risk of HPAI infection on chicken farms. Lower temperature, higher proportion of protected area, and lower predator species richness were significantly associated with a higher risk of HPAI infection on duck farms. Conclusion: The predicted dominant transmission routes on chicken and duck farms were horizontal and spillover, respectively. These results reveal a potential protective effect of predator species richness against HPAI outbreaks. Further studies are required to confirm a causal relationship.

Fifty Years of the National Rabies Control Program in Brazil under the One Health Perspective.

In 1973, the National Rabies Program was created in Brazil through an agreement between the Ministry of Health and Agriculture. Since its beginning, it developed integrated action through access to free post-exposure prophylaxis (PEP) for people at risk, dog vaccination campaigns, a joint surveillance system, and awareness. This study aims to describe human rabies in Brazil under the One Health perspective in recent decades, including achievements in the control of dog-mediated cases and challenges in human cases transmitted by wild animals. This paper also explores possible drivers of human rabies in the Northeast Region with half of the cases. The first part of this study was descriptive, presenting data and examples by periods. Statistical analysis was performed in the last period (2010-2022) to explore possible drivers. Dog-mediated human cases decreased from 147 to 0, and dog cases decreased from 4500 to 7. A major challenge is now human cases transmitted by wild animals (bats, non-human primates, and wild canids). Most current human cases occur in municipalities with a tropical and subtropical moist broadleaf forest biome and a Gini index higher than 0.5. In the multivariable analysis, an association with temperature was estimated (OR = 1.739; CI95% = 1.181-2.744), and primary healthcare coverage (OR = 0.947; CI95% = 0.915-0.987) was identified as a protector. It is possible to significantly reduce the number of dog-mediated human rabies cases through the efforts presented. However, Brazil has wildlife variants of the rabies virus circulating. The association of human cases with higher temperatures in the Northeast is a concern with climate change. To reduce human cases transmitted by wild animals, it is important to continue distributing free PEP, especially in remote at-risk areas in the Amazon Region, and to increase awareness.

Analysis of the effectiveness of non-pharmaceutical interventions on influenza during the Coronavirus disease 2019 pandemic by time-series forecasting.

BACKGROUND: Coronavirus disease 2019 (COVID-19) was first identified in South Korea during the 2019-2020 seasonal influenza epidemic. The social distancing measures, as effective non-pharmaceutical interventions (NPIs), adopted to mitigate the spread of COVID-19 might have influenced influenza activity. We evaluated IFV(influenza virus) activity during the COVID-19 pandemic and the effect of NPI intensity on influenza transmission. METHODS: IFV activity and epidemic duration during COVID-19 pandemic were predicted under a counterfactual scenario with no NPIs against COVID-19. The Seasonal Autoregressive Integrated Moving Average Model was used to quantify the effects of NPIs on the transmission of influenza virus. Influenza-like illness/1000 outpatients and IFV positivity rate from the 2011-2012 to 2021-2022 seasons were used in this study. RESULTS: Comparison of the 2020-2021 and 2021-2022 seasonal influenza activities with those in 2013-2019 showed that COVID-19 outbreaks and associated NPIs such as face mask use, school closures, and travel restrictions reduced the influenza incidence by 91%. Without NPIs against COVID-19, the rates of influenza-like illness and IFV positivity would have been high during the influenza epidemic season, as in previous seasons. NPI intensity decreased the transmission of influenza; the magnitude of the reduction increased as the intensity of social-distancing measures increased (weak social distancing; step-by-step daily recovery: 58.10%, strong social distancing; special quarantine measures: 95.12%). CONCLUSIONS: Our results suggest that NPIs and personal hygiene can be used to suppress influenza transmission. NPIs against COVID-19 may be useful strategies for the prevention and control of influenza epidemics.

Potential applicability of the importation risk index for predicting the risk of rarely imported infectious diseases.

BACKGROUND: There have been many prediction studies for imported infectious diseases, employing air-travel volume or the importation risk (IR) index, which is the product of travel-volume and disease burden in the source countries, as major predictors. However, there is a lack of studies validating the predictability of the variables especially for infectious diseases that have rarely been reported. In this study, we analyzed the prediction performance of the IR index and air-travel volume to predict disease importation. METHODS: Rabies and African trypanosomiasis were used as target diseases. The list of rabies and African trypanosomiasis importation events, annual air-travel volume between two specific countries, and incidence of rabies and African trypanosomiasis in the source countries were obtained from various databases. RESULTS: Logistic regression analysis showed that IR index was significantly associated with rabies importation risk (p value < 0.001), but the association with African trypanosomiasis was not significant (p value = 0.923). The univariable logistic regression models showed reasonable prediction performance for rabies (area under curve for Receiver operating characteristic [AUC] = 0.734) but poor performance for African trypanosomiasis (AUC = 0.641). CONCLUSIONS: Our study found that the IR index cannot be generally applicable for predicting rare importation events. However, it showed the potential utility of the IR index by suggesting acceptable performance in rabies models. Further studies are recommended to explore the generalizability of the IR index's applicability and to propose disease-specific prediction models.

Ambient PM2.5 exposures could increase risk of tuberculosis recurrence.

BACKGROUND: The effect of ambient PM2.5 on the incidence of tuberculosis (TB) has been investigated in epidemiological studies. However, they did not separately study new and relapsed TB infection and focused on relatively short-term effects of PM2.5. In this regard, we examined the associations of long-term PM2.5 exposures with both new and relapsed TB incidences in South Korea, where the disease burden of TB is greatest among high-income countries. METHODS: An area-level ecological study of 250 districts was conducted from 2015 to 2019. Age- and sex-standardized TB incidence ratios for each district and year were used as outcome variables, and their associations with PM2.5 concentrations for one to five-year average were examined. Negative binomial regression models incorporating spatiotemporal autocorrelation were employed using integrated nested Laplace approximations. Stratified analyses were conducted by type of TB (total, new, and relapsed cases). RESULTS: Districts with higher PM2.5 concentrations tended to have significantly higher TB recurrence rate. The relative risks per 10 µg/m3 PM2.5 increase were 1.218 (95% credible interval 1.051-1.411), 1.260 (1.039-1.527) and 1.473 (1.015-2.137) using the two, three and five-year average PM2.5 exposures, respectively. CONCLUSIONS: The results imply that interventions for reducing air pollution might help prevent TB recurrence.

Association of Deforestation With Severe Fever With Thrombocytopenia Syndrome.

BACKGROUND: Severe fever with thrombocytopenia syndrome (SFTS) virus was first isolated in China in 2009 and has since spread to several Asian countries. SFTS is closely related to environmental factors that accelerate vector growth. We evaluated the associations of SFTS and deforestation with environmental variables. METHODS: For this observational study, we generated multiple Poisson models using national SFTS outbreak data (2013-2018) and official environmental data for Korea. We included established risk factors as variables. Deforestation was used as the main variable. All variables were analyzed according to their spatial characteristics using the R-INLA package. RESULTS: SFTS cases increased over time and peaked in 2017, at 272, followed by a decrease in 2018. Disease mapping showed a high incidence of SFTS nationwide, with particular risks in Gangwon and Gyeonggi Provinces in the north, and Jeju in the south of South Korea. Deforestation was significantly associated with a higher risk of SFTS in the final model (relative risk, 1.751 [95% confidence interval, 1.125-2.743]). CONCLUSIONS: SFTS outbreaks are associated with deforestation. Therefore, deforestation in Gyeonggi, Gangwon, and Jeju provinces of South Korea needs to be considered in vector-control strategies and active surveillance of SFTS occurrence.

Phylodynamic analysis revealed that human mobility and vaccination were correlated to the local spread of SARS-CoV-2 in Republic of Korea.

Following the global emergence of the SARS-CoV-2 Alpha variant of concern (VOC) in 2020, the Delta variant triggered another wave in 2021. The AY.69 lineage, a Delta VOC, was particularly prevalent in Republic of Korea (South Korea) from May 2021 to January 2022, despite the synchronized implementation of vaccination programmes and non-pharmaceutical interventions (NPIs) such as social distancing. In this study, we used phylogeographic analysis combined with a generalized linear model (GLM) to examine the impact of human movement and vaccination on viral transmission. Our findings indicated that transmission primarily originated in South Korea's metropolitan areas, and a positive correlation was observed between total human mobility (tracked by GPS on mobile phones and estimated through credit card consumption) and viral spread. The phylodynamic analysis further revealed that non-vaccinated individuals were the primary transmitters of the virus during the study period, even though vaccination programmes had commenced three months prior to the AY.69 outbreak. Our study emphasizes the need to focus on controlling SARS-CoV-2 transmission in metropolitan regions and among unvaccinated populations. Furthermore, the positive correlation between mobility data and viral dissemination could contribute to the development of more accurate predictive models for local spread of pandemics.

Outbreak of severe diarrhea due to zoonotic Cryptosporidium parvum and C. xiaoi in goat kids in Chungcheongbuk-do, Korea.

Severe diarrhea was reported in goat kids in Chungcheongbuk-do, Korea, from 2021 to 2023, and Cryptosporidium infection was suspected. To confirm the cause of this outbreak, fecal samples were collected from goat farms where diarrhea had been reported and analyzed for Cryptosporidium infection using a molecular assay. A total of 65 fecal samples, including 37 from goats with diarrhea and 28 from goats without diarrhea, were collected from six goat farms. Forty-eight of the goats were kids (<2 months) and 17 were adults (>1 year). Cryptosporidium was identified in 53.8% (35/65) of total samples. Overall, 86.5% (32/37) of the diarrheic fecal samples tested positive; however, Cryptosporidium was not detected in any fecal sample from non-diarrheic adult goats. Therefore, cryptosporidiosis was significantly associated with diarrhea in goat kids, and adult goats were not responsible for transmission of Cryptosporidium to them. Phylogenetic analysis and molecular characterization revealed two Cryptosporidium species, namely, C. parvum (n = 28) and C. xiaoi (n = 7). In the C. parvum-positive samples, gp60 gene analysis revealed three zoonotic subtypes-IIaA18G3R1, IIdA15G1, and IIdA16G1. To the best of our knowledge, this study is the first to identify C. parvum IIaA18G3R1 and IIdA16G1 in goats, as well as the first to identify C. xiaoi in goats in Korea. These results suggest that goat kids play an important role as reservoir hosts for different Cryptosporidium species and that continuous monitoring with biosecurity measures is necessary to control cryptosporidiosis outbreaks.

Mean pulmonary artery pressure estimated by echocardiogram rapidly exceeds 20 mmHg from the normal range in patients with connective tissue disease.

Earlier intervention for pulmonary hypertension (PH) has been reported to improve the prognosis of patients with connective tissue disease (CTD). However, it is not fully elucidated how rapidly PH develops in patients showing normal mean pulmonary arterial pressure (mPAP) at the index investigation. We evaluated 191 CTD patients with normal mPAP retrospectively. The mPAP was estimated by the formerly defined method employing echocardiography (mPAPecho). We investigated predictive factors that predict increasing mPAPecho at follow-up transthoracic echocardiography (TTE) using uni- and multi variable analysis. The mean age was 61.5 years old, and 160 patients were female. The percentage of patients in whom mPAPecho exceeded 20 mmHg at follow-up TTE was 38%. Multivariable analysis revealed that acceleration time/ejection time (AcT/ET) measured at the right ventricular outflow tract at initial TTE was independently associated with the consequent increase of mPAPecho at the follow-up TTE. When using 0.43 of best cutoff value in AcT/ET calculated by receiver operating characteristic analysis, the change in mPAPecho in patients with low AcT/ET was significantly higher than in those with high AcT/ET (3.05 mmHg in patients with AcT/ET < 0.43 and 1.00 mmHg in patients with AcT/ET ≥ 0.43, p < 0.001). Thirty-eight percent of CTD patients who show the normal estimated mPAP by TTE develop gradual elevation of mPAP to the level to consider early intervention within 2 years. AcT/ET at initial TTE can predict increasing mPAP at follow-up TTE.

Plasma renin activity variation following admission predicts patient outcome in acute decompensated heart failure with reduced and mildly reduced ejection fraction.

Plasma renin activity (PRA) level at admission is reported to be a prognostic predictor of acute decompensated heart failure (ADHF) patients. Although PRA is affected during hospitalization by several factors including fluid volume and drug titration, whether the changes in PRA levels during hospitalization (ΔPRA) are associated with prognosis of ADHF patients are largely unknown. PURPOSE: Investigate the predictive impact of ΔPRA on the prognosis of ADHF patients with reduced ejection fraction (HFrEF) and mildly reduced ejection fraction (HFmrEF). METHODS: Retrospectively analyzed consecutive 116 HFrEF and HFmrEF patients admitted for ADHF. PRA measurements were acquired at admission and at discharge. The primary outcome was a composite of cardiovascular death and HF re-hospitalization. RESULTS: Out of 116 patients, 85 had PRA measurements both at admission and at discharge. Compared to admission, PRA level was significantly higher at discharge (0.8 (IQR 0.3-2.2) to 2.8 (IQR 1.0-7.2), p < 0.001). Tertiary groups ranked by PRA level on admission showed trend of poor prognosis in order of high, mid, and low PRA level (p = 0.07). On the contrary, PRA level at discharge significantly differentiated the prognosis and was poor in order of high, low, and mid (p = 0.026). Next, when the participants were divided into tertiary groups ranked by ΔPRA, prognosis worsened in the order of "minimal", "decreasing", and the "increasing" tier. Cubic splines analysis also indicate a similar tendency. CONCLUSIONS: In ADHF patients with HFrEF and HFmrEF, patients with minimal ΔPRA showed the better prognosis over the those with either increasing or decreasing.

Clinical utility of reticulocyte hemoglobin equivalent in patients with heart failure.

Anemia and iron deficiency (ID) are common in patients with heart failure (HF) and intravenous (IV) administration of iron to patients hospitalized for decompensated HF with ID improves outcome. The diagnosis of ID in routine practice is based on serum ferritin and transferrin saturation (TSAT) but both have limitations; alternatives should be considered. Reticulocyte hemoglobin equivalent (Ret-He) reflects iron content in reticulocytes but its clinical utility in patients with HF remains uncertain. We prospectively enrolled 142 patients hospitalized for decompensated HF. Sixty five percent had ID as defined in current international guidelines. Ret-He was directly correlated with serum iron and ferritin concentrations and with TSAT. There was a poor relationship between quartile of Ret-He and HF hospitalization or death but increases or decreases in Ret-He between admission and discharge were associated with a worse outcome. The clinical utility of Ret-He for identifying ID and predicting response to IV iron and prognosis for patients with HF requires further investigation.

Severe acute heart failure during or following cytokine release syndrome after CAR T-cell therapy.

Although cardiac dysfunction after chimeric antigen receptor (CAR) T-cell therapy has been increasingly reported, the underlying dynamics and pathogenesis are not well documented. Herein, we describe the clinical presentation and treatment for two patients who developed severe acute heart failure after CAR T-cell therapy. Both cases shared several common characteristics, including the bone marrow involvement at the time of CAR T-cell therapy and early onset of cytokine release syndrome (CRS) with fever developing on the day of CAR T-cell infusion. Patients with early onset and/or severe CRS should be carefully monitored for the possibility of heart failure.