Association between roxadustat use and suppression of thyroid function: a systematic review and meta-analysis.

BACKGROUND: Based on several case reports and observational studies, there is a growing concern regarding the potential association between roxadustat, a hypoxia-inducible factor prolyl-hydroxylase inhibitor, and suppression of thyroid function. In this systematic review and meta-analysis (PROSPERO: CRD42023471516), we aimed to evaluate the relationship between roxadustat use and suppression of thyroid function. METHODS: We conducted a comprehensive search of MEDLINE via PubMed, ClinicalTrials.gov, and the Cochrane Central Register of Controlled Trials databases using the search term "roxadustat" to identify all relevant studies. The study population comprised adults with renal anemia who participated in a randomized controlled trial or observational study, with roxadustat as the intervention and a placebo or erythropoiesis-stimulating agent (ESA) as the comparator. The primary outcome was suppression of thyroid function and the secondary outcome was hypothyroidism. A meta-analysis was conducted using the DerSimonian-Laird random effects model based on the size of the intention-to-treat population, and the odds ratio (OR) and 95% confidence interval (CI) were calculated. Two reviewers independently screened the articles, extracted data, and assessed studies using the ROBINS-I tool. RESULTS: Of the six studies eligible for inclusion, a meta-analysis was performed using data from two observational studies comparing roxadustat and ESA. The meta-analysis showed that the incidence of suppression of thyroid function was significantly higher with roxadustat use than with ESA use (OR: 6.45; 95% CI: 3.39-12.27; I2 = 12%). Compared with ESA, roxadustat seemed to potentially increase the risk for suppression of thyroid function in patients with renal anemia. CONCLUSIONS: Our findings highlighted the importance of monitoring thyroid function in patients treated with roxadustat. The results of this review may enhance the safety of using roxadustat to treat renal anemia through advance recognition of the risk for suppression of thyroid function.

Lithium-Modified TiO2 Surface by Anodization for Enhanced Protein Adsorption and Cell Adhesion.

Promoting osseointegration is an essential step in improving implant success rates. Lithium has gradually gained popularity for promoting alkaline phosphatase activity and osteogenic gene expression in osteoblasts. The incorporation of lithium into a titanium surface has been reported to change its surface charge, thereby enhancing its biocompatibility. In this study, we applied anodization as a novel approach to immobilizing Li on a titanium surface and evaluated the changes in its surface characteristics. The objective of this study was to determine the effect of Li treatment of titanium on typical proteins, such as albumin, laminin, and fibronectin, in terms of their adsorption level as well as on the attachment of osteoblast cells. Titanium disks were acid-etched by 66 wt % H2SO4 at 120 °C for 90 s and set as the control group. The etched samples were placed in contact with an anode, while a platinum bar served as the counter electrode. Both electrodes were mounted on a custom electrochemical cell filled with 1 M LiCl. The samples were anodized at constant voltages of 1, 3, and 9 V. Scanning electron microscopy (SEM) and confocal laser scanning microscopy (CLSM) results showed no significant differences in the topography. However, the ζ potentials of the 3 V group were higher than those of the control group at a physiological pH of 7.4. Interestingly, the adsorption level of the extracellular matrix protein was mostly enhanced on the 3 V-anodized surface. The number of attached cells on the Li-anodized surfaces increased. The localization of vinculin at the tips of the stretching cytoplasmic projections was observed more frequently in the osteoblasts on the 3 V-anodized surface. Although the optimal concentration or voltage for Li application should be investigated further, this study suggests that anodization could be an effective method to immobilize lithium ions on a titanium surface and that modifying the surface charge characteristics enables a direct protein-to-material interaction with enhanced biological adhesion.

Chiral Van Der Waals Superlattices for Enhanced Spin-Selective Transport and Spin-Dependent Electrocatalytic Performance.

The emergence of the chiral-induced spin-selectivity (CISS) effect offers a new avenue for chiral organic molecules to autonomously manipulate spin configurations, thereby opening up possibilities in spintronics and spin-dependent electrochemical applications. Despite extensive exploration of various chiral systems as spin filters, one often encounters challenges in achieving simultaneously high conductivity and high spin polarization (SP). In this study, a promising chiral van der Waals superlattice, specifically the chiral TiS2 crystal, is synthesized via electrochemical intercalation of chiral molecules into a metallic TiS2 single crystal. Multiple tunneling processes within the highly ordered chiral layered structure of chiral TiS2 superlattices result in an exceptionally high SP exceeding 90%. This remarkable observation of significantly high SP within the linear transport regime is unprecedented. Furthermore, the chiral TiS2 electrode exhibits enhanced catalytic activity for oxygen evolution reaction (OER) due to its remarkable spin-selectivity for triplet oxygen evolution. The OER performance of chiral TiS2 superlattice crystals presented here exhibits superior characteristics to previously reported chiral MoS2 catalysts, with an approximately tenfold increase in current density. The combination of metallic conductivity and high SP sets the stage for the development of a new generation of CISS materials, enabling a wide range of electron spin-based applications.

Severe disseminated infection by hypermucoviscous Klebsiella pneumoniae successfully treated by intensive therapy with continuous hemodiafiltration using AN69ST: A case report and review of the literature.

Klebsiella pneumoniae (Kpn) is one of the most common gram-negative bacilli causing lung, urinary tract, and biliary tract infections. However, as a distinct entity from classic Kpn, hypervirulent Kpn causing liver abscess, endophthalmitis, and lung abscess with poor prognoses has been reported mainly in East and Southeast Asia since the mid-1980s. Although the definition of hypervirulent Kpn is unclear, the hypermucoviscosity of Kpn is considered an important feature of hypervirulence. We present a case of emphysematous pyelonephritis accompanied by septic shock and acute kidney injury caused by hypermucoviscous Kpn infection that was successfully treated by intensive treatment. A 70-year-old woman with type 2 diabetes mellitus was diagnosed with emphysematous pyelonephritis, and string test-positive Kpn was detected in blood and urine cultures and percutaneous catheter drainage fluid from the renal pelvis. The patient was treated with intensive therapies including antibiotics, ventilator management, and continuous hemodiafiltration (CHDF) using AN69ST, which can absorb cytokines. During the course of treatment, the infection was complicated by pyogenic spondylitis, which was cured by antimicrobial therapy, and the patient was transferred to another hospital for rehabilitation on day 119 after admission. Hypermucoviscous Kpn infection often has a severe course, and it is important to initiate multidisciplinary treatment at an early stage, including rifampicin, which is expected to inhibit the viscosity of hypermucoviscous Kpn. In the current case, immediate CHDF using AN69ST was also considered a life-saving treatment because it improved both volume overload and neutrophil-activated hypercytokinemia.

Exploration of the optimal GS-441524 trough concentration for treating COVID-19.

OBJECTIVES: Remdesivir (RDV) is the cornerstone for treating coronavirus disease 2019 (COVID-19). The active metabolite of RDV, GS-441524 (a nucleoside analogue), has high interindividual variability in plasma concentrations; however, its concentration-response relationship is still unclear. This study investigated the target GS-441524 trough concentration for symptom improvement in COVID-19 pneumonia. METHODS: This single-center, retrospective, observational study included Japanese patients (age ≥15 years) with COVID-19 pneumonia who were administered RDV for ≥3 days from May 2020 to August 2021. To determine the cut-off value of GS-441524 trough concentration on Day 3, achievement of the National Institute of Allergy and Infectious Disease Ordinal Scale (NIAID-OS) ≤3 after RDV administration was evaluated using the cumulative incidence function (CIF) with the Gray test and time-dependent receiver operating characteristic (ROC) analysis. Multivariate logistic regression analysis was performed to determine factors influencing GS-441524 target trough concentrations. RESULTS: The analysis comprised 59 patients. The CIF revealed that GS-441524 trough concentration ≥70 ng/mL was associated with the achievement of NIAID-OS ≤3 (P = 0.047), which was significant based on the time-dependent ROC analysis. Factors influencing GS-441524 trough concentration ≥70 ng/mL included a decrease in estimated glomerular filtration rate (eGFR) [adjusted odds ratio (aOR) = 0.96, 95% confidence interval (CI) 0.92-0.99; P = 0.027] and BMI ≥25 kg/m2 (aOR = 0.26, 95% CI 0.07-0.86; P = 0.031). CONCLUSION: GS-441524 trough concentration ≥70 ng/mL is a predictor of efficacy in COVID-19 pneumonia. The presence of lower eGFR or BMI ≥25 kg/m2 was associated with achieving GS-441524 trough concentration ≥70 ng/mL.

Repetitive postoperative extubation failure due to dynamic inspiratory airway collapse concomitant with subglottic stenosis in a patient who previously underwent tracheostomy.

BACKGROUND: This report describes a case of dynamic inspiratory airway collapse concomitant with subglottic stenosis in a patient who previously underwent tracheostomy that led to repeated post-operative extubation failure. CASE PRESENTATION: A 43-year-old woman who had undergone tracheostomy 25 years previously was admitted to our intensive-care unit (ICU) after coronary artery bypass graft surgery. On postoperative day (POD) 0, she was extubated, but stridor was observed. We suspected upper airway obstruction and she was therefore reintubated. Before reintubation, urgent laryngotracheoscopy revealed dynamic inspiratory airway collapse and obstruction concomitant with subglottic stenosis. Preoperative computed tomography showed mild subglottic stenosis. Although intravenous corticosteroids were administered to prevent tracheal mucosal edema and a cuff leak test was confirmed to be negative, she developed extubation failure on POD6. On POD12, we performed tracheostomy to reduce mechanical irritation from the endotracheal tube. Mechanical ventilation was withdrawn and she discharged from the ICU. On POD33, her tracheostomy tube was removed and she remained clinically asymptomatic. CONCLUSIONS: We should be aware of the history of tracheostomy, especially at high tracheostomy sites, even in the absence of respiratory symptoms as risk factors for dynamic inspiratory airway collapse concomitant with subglottic stenosis contributing to repeated respiratory failure after extubation. J. Med. Invest. 70 : 301-305, February, 2023.

Clinical characteristics and factors related to infection with SCCmec type II and IV Methicillin-resistant Staphylococcus aureus in a Japanese secondary care facility: a single-center retrospective study.

OBJECTIVES: Differences in virulence genes, including psm-mec, which is a phenol-soluble modulin-mec (PSM-mec) encoding gene, of predominant staphylococcal cassette chromosome mec (SCCmec) types II and IV Methicillin-resistant Staphylococcus aureus (MRSA) may contribute to the virulence and clinical features of MRSA in Japan. We aimed to clarify the clinical characteristics and risk factors of infection among SCCmec types II and IV MRSA isolates from a Japanese secondary acute care hospital. METHODS: We analysed 58 SCCmec type II and 83 SCCmec type IV MRSA isolates collected from blood, central venous catheter tips, deep or superficial tissues, and sputum. RESULTS: SCCmec type II MRSA risk factors for progression to infection were seb, enterotoxin gene cluster, psm-mec mutation, and vancomycin minimum inhibitory concentrations (MIC) of 1 or 2 mg/L as virulence factors (adjusted odds ratio [aOR] = 11.8; 95% confidence interval [CI]: 2.49-77.7; P = 0.004); solid tumour was a host factor (aOR = 25.9; 95% CI: 3.66-300; P = 0.003). SCCmec type IV MRSA risk factors were sea, cna, and vancomycin MIC of 1 or 2 mg/L as virulence factors (aOR = 3.14; 95% CI: 1.06-10.6; P = 0.049) and intravascular indwelling catheter as host factors (aOR = 3.78; 95% CI: 1.03-14.5; P = 0.045). Compared with SCCmec type II, SCCmec type IV MRSA resulted in more frequent bloodstream infections and higher Sequential Organ Failure Assessment scores. CONCLUSION: We found that factors related to virulence genes and bacteriological and host characteristics are associated with SCCmec types II and IV MRSA infection and severity. These risk factors may be useful criteria for designing infection control programs.

The quality and quantity of sleep on dexmedetomidine during high-flow nasal cannula oxygen therapy in critically ill patients.

Purpose : High-flow nasal cannula oxygen therapy (HFNC) is a new type of non-invasive respiratory support for acute respiratory failure patients. However, patients receiving HFNC often develop sleep disturbances. We therefore examined whether dexmedetomidine could preserve the sleep characteristics in patients who underwent HFNC. Patients and Methods : This was a pilot, randomized controlled study. We assigned critically ill patients treated with HFNC to receive dexmedetomidine (0.2 to 0.7 µg / kg / h, DEX group) or not (non-DEX group) at night (9:00 p.m. to 6:00 a.m.). Polysomnograms were monitored during the study period. The primary outcomes were total sleep time (TST), sleep efficiency and duration of stage 2 non-rapid eye movement (stage N2) sleep. Results : Of the 28 patients who underwent randomization, 24 were included in the final analysis (12 patients per group). Dexmedetomidine increased the TST (369 min vs. 119 min, p = 0.024) and sleep efficiency (68% vs. 22%, P = 0.024). The duration of stage N2 was increased in the DEX group compared with the non-DEX group, but this finding did not reach statistical significance. The incidences of respiratory depression and hemodynamic instability were similar between the two groups. Conclusions : In critically ill patients who underwent HFNC, dexmedetomidine may optimize the sleep quantity without any adverse events. J. Med. Invest. 69 : 266-272, August, 2022.

Y-specific amh allele, amhy, is the master sex-determining gene in Japanese flounder Paralichthys olivaceus.

Japanese flounder (Paralichthys olivaceus) is an important marine fish species of both fisheries and aquaculture in Northeast Asia. The commercial interest for all-female progenies due to several sex-related traits has prompted basic research on the mechanisms of sex determination in this species. By conducting a linkage analysis of the sex-determining locus, we initially identified 12 microsatellite markers linked to sex in 11 scaffolds, whose localization was restricted to a specific region of linkage group 9. Sequence analysis of this region identified 181 genes based on the UniProt database annotations. Among them, the amh gene was considered a potential candidate for sex determination because this gene is known to have taken over the role of sex determination in many teleosts. An in-depth sequence analysis of both the coding and non-coding regions of amh in XX and XY individuals detected nine SNPs linked with maleness. However, because these substitutions were synonymous, the upstream and downstream regions of amh were also investigated and a male-specific variant with deletions in the promoter region was detected. This truncated Y-specific amh variant was named amhy, and the amh shared by both sexes was named amhx. The association analysis using both females and males of the genotypic sex inferred by the presence/absence of amhy found complete association with phenotypic sex and genotype. Gene expression analysis in larvae derived from a single-pair progeny by quantitative real-time PCR detected amhy transcripts in the larval trunks between 20 and 100 days after hatching only in XY larvae. Localization of amhy by in situ hybridization was detected in presumptive Sertoli cells of XY gonads. Expression of amhx was almost undetectable in both XX and XY genotypes. Loss of Amh function by CRISPR-Cas9 induced male-to-female sex reversal, indicating that this gene was necessary for the masculinization of XY individuals. In conclusion, the complete linkage of amhy with males, its early expression in XY gonads before testicular differentiation, and the induction of sex reversal by loss-of-function mutation support the view that amhy is the sex-determining gene in this species.

Relationships between double cycling and inspiratory effort with diaphragm thickness during the early phase of mechanical ventilation: A prospective observational study.

BACKGROUND: Increased and decreased diaphragm thickness during mechanical ventilation is associated with poor outcomes. Some types of patient-ventilator asynchrony theoretically cause myotrauma of the diaphragm. However, the effects of double cycling on structural changes in the diaphragm have not been previously evaluated. Hence, this study aimed to investigate the relationship between double cycling during the early phase of mechanical ventilation and changes in diaphragm thickness, and the involvement of inspiratory effort in the occurrence of double cycling. METHODS: We evaluated adult patients receiving invasive mechanical ventilation for more than 48 h. The end-expiratory diaphragm thickness (Tdiee) was assessed via ultrasonography on days 1, 2, 3, 5 and 7 after the initiation of mechanical ventilation. Then, the maximum rate of change from day 1 (ΔTdiee%) was evaluated. Concurrently, we recorded esophageal pressure and airway pressure on days 1, 2 and 3 for 1 h during spontaneous breathing. Then, the waveforms were retrospectively analyzed to calculate the incidence of double cycling (double cycling index) and inspiratory esophageal pressure swing (ΔPes). Finally, the correlation between double cycling index as well as ΔPes and ΔTdiee% was investigated using linear regression models. RESULTS: In total, 19 patients with a median age of 69 (interquartile range: 65-78) years were enrolled in this study, and all received pressure assist-control ventilation. The Tdiee increased by more than 10% from baseline in nine patients, decreased by more than 10% in nine and remained unchanged in one. The double cycling indexes on days 1, 2 and 3 were 2.2%, 1.3% and 4.5%, respectively. There was a linear correlation between the double cycling index on day 3 and ΔTdiee% (R2 = 0.446, p = 0.002). The double cycling index was correlated with the ΔPes on days 2 (R2 = 0.319, p = 0.004) and 3 (R2 = 0.635, p < 0.001). CONCLUSIONS: Double cycling on the third day of mechanical ventilation was associated with strong inspiratory efforts and, possibly, changes in diaphragm thickness.

Down-regulation of the expression of cyclooxygenase-2 and prostaglandin E2 by interleukin-4 is mediated via a reduction in the expression of prostanoid EP4 receptors in HCA-7 human colon cancer cells.

Chronic inflammatory bowel disease (IBD), which is characterized by prolonged inflammation of the gastrointestinal tract is associated with an increased risk of colorectal cancer. Recent studies revealed that the pathology of IBD is caused by hyperactivated immune responses mediated by differentiated CD4+ naïve helper T cells, such as Th1 and Th17 cells, but not Th2 cells. The human E-type prostanoid 4 (EP4) receptor and its pathways have also been implicated in and/or associated with the early developmental stages of colorectal cancer along with increases in the levels of prostaglandin E2 (PGE2) and cyclooxygenase-2 (COX-2), the hallmarks of colorectal carcinogenesis. In the present study, using an in silico analysis and pharmacological experiments, we demonstrated that interleukin (IL)-4, a signature cytokine of Th2 cells, down-regulated the expression of COX-2 and PGE2 in the human colon cancer cell line, HCA-7. This result may be attributed to a reduction in the expression of prostanoid EP4 receptors through the induction of hypoxia inducible factor-1α via the interleukin-4 receptor-stimulated activation of signal transducer and activator of transcription 6. However, another major Th2 cytokine IL-13 had no effect on the expression of COX-2 or prostanoid EP4 receptors in HCA-7 cells. Therefore, instead of the hyperactivation of Th1/Th17 cells, the deactivation/down-regulation of Th2 cells followed by a decrease in the production of IL-4 in IBD may play a role in the cancerous transformation of cells, at least in prostanoid EP4 receptor-overactivated tumorigenesis.

Measurement of SARS-CoV-2 Antibody Titers Improves the Prediction Accuracy of COVID-19 Maximum Severity by Machine Learning in Non-Vaccinated Patients.

Numerous studies have suggested that the titers of antibodies against SARS-CoV-2 are associated with the COVID-19 severity, however, the types of antibodies associated with the disease maximum severity and the timing at which the associations are best observed, especially within one week after symptom onset, remain controversial. We attempted to elucidate the antibody responses against SARS-CoV-2 that are associated with the maximum severity of COVID-19 in the early phase of the disease, and to investigate whether antibody testing might contribute to prediction of the disease maximum severity in COVID-19 patients. We classified the patients into four groups according to the disease maximum severity (severity group 1 (did not require oxygen supplementation), severity group 2a (required oxygen supplementation at low flow rates), severity group 2b (required oxygen supplementation at relatively high flow rates), and severity group 3 (required mechanical ventilatory support)), and serially measured the titers of IgM, IgG, and IgA against the nucleocapsid protein, spike protein, and receptor-binding domain of SARS-CoV-2 until day 12 after symptom onset. The titers of all the measured antibody responses were higher in severity group 2b and 3, especially severity group 2b, as early as at one week after symptom onset. Addition of data obtained from antibody testing improved the ability of analysis models constructed using a machine learning technique to distinguish severity group 2b and 3 from severity group 1 and 2a. These models constructed with non-vaccinated COVID-19 patients could not be applied to the cases of breakthrough infections. These results suggest that antibody testing might help physicians identify non-vaccinated COVID-19 patients who are likely to require admission to an intensive care unit.

Interpretations of SARS-CoV-2 IgM and IgG antibody titers in the seroepidemiological study of asymptomatic healthy volunteers.

INTRODUCTION: The usefulness of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibody tests in asymptomatic individuals has not been well validated, although they have satisfied sensitivity and specificity in symptomatic patients. In this study, we investigated the significance of IgM and IgG antibody titers against SARS-CoV-2 in the serum of asymptomatic healthy subjects. METHODS: From June 2020, we recruited 10,039 participants to the project named the University of Tokyo COVID-19 Antibody Titer Survey (UT-CATS), and measured iFlash-SARS-CoV-2 IgM and IgG (YHLO IgM and IgG) titers in the collected serum. For the samples with increased IgM or IgG titers, we performed additional measurements using Elecsys Anti-SARS-CoV-2 Ig (Roche total Ig) and Architect SARS-CoV-2 IgG (Abbott IgG) and investigated the reactivity to N, S1, and receptor binding domain (RBD) proteins. RESULTS: After setting the cutoff value at 5 AU/mL, 61 (0.61%) were positive for YHLO IgM and 104 (1.04%) for YHLO IgG. Few samples with elevated YHLO IgM showed reactivity to S1 or RBD proteins, and IgG titers did not increase during the follow-up in any samples. The samples with elevated YHLO IgG consisted of two groups: one reacted to S1 or RBD proteins and the other did not, which was reflected in the results of Roche total Ig. CONCLUSIONS: In SARS-CoV-2 seroepidemiological studies of asymptomatic participants, sufficient attention should be given to the interpretation of the results of YHLO IgM and IgG, and the combined use of YHLO IgG and Roche total Ig might be more reliable.

Response kinetics of different classes of antibodies to SARS-CoV2 infection in the Japanese population: The IgA and IgG titers increased earlier than the IgM titers.

To better understand the immune responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in individuals with COVID-19, it is important to investigate the kinetics of the antibody responses and their associations with the clinical course in different populations, since there seem to be considerable differences between Western and Asian populations in the clinical features and spread of COVID-19. In this study, we serially measured the serum titers of IgM, IgG and IgA antibodies generated against the nucleocapsid protein (NCP), S1 subunit of the spike protein (S1), and receptor-binding domain in the S1 subunit (RBD) of SARS-CoV-2 in Japanese individuals with COVID-19. Among the IgM, IgG, and IgA antibodies, IgA antibodies against all of the aforementioned viral proteins were the first to appear after the infection, and IgG and/or IgA seroconversion often preceded IgM seroconversion. In regard to the timeline of the antibody responses to the different viral proteins (NCP, S1 and RBD), IgA against NCP appeared than IgA against S1 or RBD, while IgM and IgG against S1 appeared earlier than IgM/IgG against NCP or RBD. The IgG responses to all three viral proteins and responses of all three antibody classes to S1 and RBD were sustained for longer durations than the IgA/IgM responses to all three viral proteins and responses of all three antibody classes to NCP, respectively. The seroconversion of IgA against NCP occurred later and less frequently in patients with mild COVID-19. These results suggest possible differences in the antibody responses to SARS-CoV-2 antigens between the Japanese and Western populations.

Association of the Serum Levels of the Nucleocapsid Antigen of SARS-CoV-2 With the Diagnosis, Disease Severity, and Antibody Titers in Patients With COVID-19: A Retrospective Cross-Sectional Study.

Background: Several types of laboratory tests for COVID-19 have been established to date; however, the clinical significance of the serum SARS-CoV-2 nucleocapsid (N) antigen levels remains to be fully elucidated. In the present study, we attempted to elucidate the usefulness and clinical significance of the serum N antigen levels. Methods: We measured the serum N antigen levels in 391 serum samples collected from symptomatic patients with a confirmed diagnosis of COVID-19 and 96 serum samples collected from patients with non-COVID-19, using a fully automated chemiluminescence immunoassay analyzer. Results: Receiver operating characteristic analysis identified the optimal cutoff value of the serum N antigen level (cutoff index, based on Youden's index) as 0.255, which yielded a sensitivity and specificity for the diagnosis of COVID-19 of 91.0 and 81.3%, respectively. The serum N antigen levels were significantly higher in the patient groups with moderate and severe COVID-19 than with mild disease. Moreover, a significant negative correlation was observed between the serum N antigen levels and the SARS-CoV-2 IgG antibody titers, especially in patients with severe COVID-19. Conclusion: Serum N antigen testing might be useful both for the diagnosis of COVID-19 and for obtaining a better understanding of the clinical features of the disease.

ECG Localization Method Based on Volume Conductor Model and Kalman Filtering.

The 12-lead electrocardiogram was invented more than 100 years ago and is still used as an essential tool in the early detection of heart disease. By estimating the time-varying source of the electrical activity from the potential changes, several types of heart disease can be noninvasively identified. However, most previous studies are based on signal processing, and thus an approach that includes physics modeling would be helpful for source localization problems. This study proposes a localization method for cardiac sources by combining an electrical analysis with a volume conductor model of the human body as a forward problem and a sparse reconstruction method as an inverse problem. Our formulation estimates not only the current source location but also the current direction. For a 12-lead electrocardiogram system, a sensitivity analysis of the localization to cardiac volume, tilted angle, and model inhomogeneity was evaluated. Finally, the estimated source location is corrected by Kalman filter, considering the estimated electrocardiogram source as time-sequence data. For a high signal-to-noise ratio (greater than 20 dB), the dominant error sources were the model inhomogeneity, which is mainly attributable to the high conductivity of the blood in the heart. The average localization error of the electric dipole sources in the heart was 12.6 mm, which is comparable to that in previous studies, where a less detailed anatomical structure was considered. A time-series source localization with Kalman filtering indicated that source mislocalization could be compensated, suggesting the effectiveness of the source estimation using the current direction and location simultaneously. For the electrocardiogram R-wave, the mean distance error was reduced to less than 7.3 mm using the proposed method. Considering the physical properties of the human body with Kalman filtering enables highly accurate estimation of the cardiac electric signal source location and direction. This proposal is also applicable to electrode configuration, such as ECG sensing systems.