High-risk screening for Fabry disease in hemodialysis patients in Chiba Prefecture, Japan.

BACKGROUND: High-risk screening for Fabry disease in dialysis patients is an effective means for reducing the number of undiagnosed cases. However, such screening has not been conducted in Chiba Prefecture, Japan. Herein, we aimed to estimate the prevalence of Fabry disease among patients undergoing hemodialysis in Chiba Prefecture by high-risk screening using α-galactosidase A (αGal A) activity measurement, and examine the hemodialysis effect on αGal A activity. METHODS: Patients who underwent maintenance hemodialysis at 25 facilities in Chiba Prefecture were recruited. The αGal A activity was measured using the dried blood spot (DBS) test as the first screening. If the enzyme activity was lower than the cut-off, the second screening was performed with the same method before and after dialysis. RESULTS: Overall, 2924 patients (2036 men and 888 women) were included from which 94 cases (45 men and 48 women) showed decreased αGAL activity in the first screening and 3 (two men and one women) in the second screening. Genetic testing was performed in 3 patients, and the c.1078G > A mutation in GLA gene was detected in one male patient (0.03%). There has been a statistically significant decrease in αGal A activity of DBS at post-dialysis compared to that at pre-dialysis (20.5 ± 10.4 pmol/h/disk and 22.7 ± 11.5 pmol/h/disk, p < 0.0001). CONCLUSION: The prevalence of Fabry disease among patients undergoing hemodialysis in Chiba Prefecture was estimated as 0.03%. This is the first time that dialysis has been shown to affect the αGal A activity.

Relationship between changes in symptoms and antibody titers after a single vaccination in patients with Long COVID.

Coronavirus disease 2019 (COVID-19) is spreading worldwide; there is a need to address its sequelae known as Long COVID. This study evaluated postvaccination changes in symptoms and antibody titers in patients with Long COVID. Patients visiting the outpatient department specializing in Long COVID at our hospital were enrolled. Changes in symptoms were evaluated before and 14-21 days after first vaccination. Antibody titers were measured using ARCHITECT SARS-CoV-2 IgG II Quant at the same time. This study included 42 patients (median age: 45 years; 17 [40.5%] men). Median pre- and postvaccination antibody titers were 456 and 28,963 AU/ml, respectively. Postvaccination symptoms (fatigue, joint pain, and taste and olfactory abnormalities) were relieved, worsened, and unchanged in 7 (16.7%), 9 (21.4%), and 26 (61.9%) patients, respectively. Ratios of pre- and postvaccination antibody titers were 53, 40, and 174 in the unchanged, relief, and worsened groups, respectively. The worsened group had the significantly highest antibody titer ratio (p = 0.02). The higher increased rate of the antibody titer in the worsened group than in the nonworsened group suggests an excessive immune response to vaccination associated with worsening of sequelae. Although patients with Long COVID should be vaccinated, additional concerns should be addressed.

Investigation of the incidence of immunisation stress-related response following COVID-19 vaccination in healthcare workers.

INTRODUCTION: Safe vaccination worldwide is critical to end the coronavirus disease 2019 (COVID-19) pandemic. We aimed to evaluate adverse reactions to vaccination using a web-based questionnaire and examine the risk factors for the occurrence of immunisation stress-related response (ISRR). METHODS: We conducted a questionnaire survey using Google Form® among the employees of St. Marianna University Hospital who had received the COVID-19 vaccine between April 2021 and May 2021, 1 week after the first and second vaccinations. We developed and used a questionnaire to identify individuals with ISRR according to the World Health Organization diagnostic criteria. A generalised linear mixed model was constructed with ISRR onset as the dependent variable, subjects as the random factor, and each parameter as a fixed factor. A multivariate model was constructed using the forced imputation method with factors that were significant in the univariate analysis. RESULTS: We enrolled 2,073 and 1,856 respondents in the first and second questionnaire surveys, respectively. Fifty-five and 33 ISRR cases were identified in the first and second vaccinations, respectively. In the univariate analysis, strong pre-vaccination anxiety (odds ratio [OR], 2.3; 95% confidence interval [CI], 1.30-4.12, p = 0·004) and history of allergy (OR, 1.6; 95% CI, 1.14-2.24, p = 0·007) were significant risk factors. Multivariate analysis also showed that strong pre-vaccination anxiety (OR, 2.1; 95% CI, 1.15-3.80, p = 0.016) and history of allergy (OR, 1.5; 95% CI, 1.09-2.15, p = 0.014) were significant risk factors. CONCLUSIONS: Confirmation of allergy prior to vaccination and subsequent action are essential for addressing ISRR.

A novel approach to the selection of an appropriate pacing position for optimal cardiac resynchronization therapy using CT coronary venography and myocardial perfusion imaging: FIVE STaR method (fusion image using CT coronary venography and perfusion SPECT applied for cardiac resynchronization therapy).

BACKGROUND: Nearly one-third of patients with advanced heart failure (HF) do not benefit from cardiac resynchronization therapy (CRT). We developed a novel approach for optimizing CRT via a simultaneous assessment of the myocardial viability and an appropriate lead position using a fusion technique with CT coronary venography and myocardial perfusion imaging. METHODS AND RESULTS: The myocardial viability and coronary venous anatomy were evaluated by resting Tc-99m-tetrofosmin myocardial perfusion imaging (MPI) and contrast CT venography, respectively. Using fusion images reconstructed by MPI and CT coronary venography, the pacing site and lead length were determined for appropriate CRT device implantations in 4 HF patients. The efficacy of this method was estimated by the symptomatic and echocardiographic functional parameters. In all patients, fusion images using MPI and CT coronary venograms were successfully reconstructed without any misregistration and contributed to an effective CRT. Before the surgery, this method enabled the operators to precisely identify the optimal indwelling site, which exhibited myocardial viability and had a lead length necessary for an appropriate device implantation. CONCLUSIONS: The fusion image technique using myocardial perfusion imaging and CT coronary venography is clinically feasible and promising for CRT optimization and enhancing the patient safety in patients with advanced HF.

Determining the factors affecting serum presepsin level and its diagnostic utility: A cross-sectional study.

INTRODUCTION: This study aimed to identify factors affecting presepsin levels and to determine their diagnostic utility. METHODS: This cross-sectional study was conducted at an outpatient clinic and emergency department at an acute care hospital in Japan between January 2015 and December 2017. We enrolled 1,840 consecutive outpatients with at least one measurement of serum presepsin, who were suspected of having bacterial infection. The outcome variables were bacterial infection, lower respiratory tract infection, urinary tract infection, cholangitis, and other infections diagnoses, based on the chart review. We collected blood analysis data on the patients' presepsin levels. RESULTS: There was a significant association between presepsin level and the diagnosis of bacterial infection even when adjusted for age, sex, renal function, and biliary enzyme levels. An increase of 1 unit in the log of presepsin values resulted in a relative risk ratio of 1.71 (1.09-2.66), 2.1 (1.58-2.79), 2.93 (2.05-4.19), 4.7(2.90-7.61), and 2.41(1.70-3.43), for bacterial infection, lower respiratory tract infection, urinary tract infection, cholangitis, and other infections, respectively. CONCLUSIONS: Presepsin showed a statistically significant increase in the diagnosis of bacterial infections (lower respiratory tract infections, urinary tract infections, cholangitis, and non-severe patients) in a community hospital setting. However, in patients with renal dysfunction, presepsin levels should be interpreted with caution.

Cardiac Resynchronization Therapy for Improving Non-Uniform Thickening of Left Ventricular Wall: Assessment by Quantitative Gated Myocardial Perfusion SPECT.

Cardiac resynchronization therapy (CRT) improves cardiac dyssynchrony in heart failure patients with a wide QRS electrocardiogram (ECG). Assessment of left ventricular (LV) dyssynchrony using echocardiography or other imaging modalities is important to predict CRT effectiveness. In this study, we retrospectively evaluated cardiac nuclear imaging of ECG-gated myocardial perfusion single-photon emission computed tomography (SPECT) with 99mTc-sestamibi for CRT candidate (n = 120) with severe heart failure and wide QRS (> 120 msec) in ECG. To analyze LV non-uniformity, we used the quantitative gated SPECT (QGS) software to calculate changes in regional LV wall thickness during a cardiac cycle (i.e., wall thickening scores). Cardiac events (heart failure, ventricular arrhythmias and cardiac death) after CRT during 38 ± 22 (SD) months were also evaluated. In 97 of 120 patients who underwent QGS before and 6 months after CRT, CRT homogenized non-uniform wall thickening between septal and lateral of the LV especially in CRT responders. This observation was indicated as increase in the lateral deflection (XWT) of wall thickening scores before CRT and its decrease after CRT. In 120 patients with QGS before CRT, the larger XWT before CRT (≥ 16.5) predicted better prognoses after CRT. This finding was similarly observed even in patients with narrower baseline QRS (≤ 140 msec; n = 41 of 120), who usually have less benefits from CRT. In conclusion, CRT improved non-uniformity of wall thickening between the LV septal and lateral regions evaluated using QGS, which is predictive of better prognosis in the chronic phase after CRT.

Successful epicardial ablation for ventricular tachycardia originating from the true apex of apical aneurysm associated with hypertrophic cardiomyopathy.

Hypertrophic cardiomyopathy (HCM) with apical aneurysm (AA) is rare, but has been reported to be associated with refractory ventricular tachycardias (VTs). Majority of such cases had a central isthmus of the reentry circuit on the border zone of AA. In this report, we describe a rare case of the successful epicardial ablation for a refractory VT originating from a true apex of the aneurysm in a HCM patient. Mid-diastolic potential during sustained VT was recorded at the isolated epicardial myocardium surround by the gross unexcitable scar in AA, and radiofrequency current application rendered VT non-inducible.

Analysis of the Correlation between the Myocardial Expression of DPP-4 and the Clinical Parameters of Patients with Heart Failure.

Dipeptidyl peptidase-4 (DPP-4) inhibitors are widely used as antidiabetic drugs. We recently reported that DPP-4 inhibition has beneficial effects on heart failure (HF) mice model. Furthermore, we confirmed that myocardial DPP-4 activity was significantly increased in HF mice compared with non-HF mice. The aim of this study was to investigate the level of myocardial CD26 (DPP-4) expression and its association to clinical parameters in HF patients.Endomyocardial biopsy (EMB) specimens (n = 33) were obtained from HF patients who were admitted to Chiba University Hospital from June 2006 to July 2012. EMB specimens were fixed in formaldehyde and stained with Masson's trichrome staining or with anti-CD26 antibody. Patients were divided into the high CD26 density (CD26-H) or low CD26 density groups (CD26-L). DPP-4 density was compared with blood brain natriuretic peptide (BNP) level and echocardiographic parameters at one year after EMB. Although there were no significant differences in echocardiographic parameters between the CD26-H group and CD26-L group, blood BNP levels were higher in the CD26-H group than in the CD26-L group at one year after EMB. Multivariate regression analysis showed that CD26 density was also an independent determinant of blood BNP levels at one year after EMB.The level of myocardial CD26 expression might be a predictive marker of prognosis in patients with HF.

The effects of dipeptidyl peptidase-4 on cardiac fibrosis in pressure overload-induced heart failure.

Dipeptidyl peptidase-4 (DPP-4) inhibitors are hypoglycemic agents. DPP-4 inhibitor has cardioprotective effects after transverse aortic constriction (TAC), but role of DPP-4 on cardiac fibrosis after TAC is not well known. Our aim was to determine the effects of DPP-4 on cardiac fibrosis in murine TAC model. Wild-type mice and DPP-4 knockout mice were subjected to TAC. Wild-type mice were then treated with vehicle or DPP-4 inhibitor. DPP-4 activities in serum and heart tissue were significantly increased at 2 weeks after TAC, but they were significantly decreased by DPP-4 inhibitor treatment. The inhibition of DPP-4 did not affect left ventricular hypertrophy, but improved cardiac function and decreased myocardial and perivascular fibrosis after TAC. The inhibition of DPP-4 decreased the collagen type III/I ratio in myocardium. These results suggest that DPP-4 inhibition ameliorates the progression of heart failure after TAC by changing the quality and quantity of cardiac fibrosis.

DPP-4 inhibition protects human umbilical vein endothelial cells from hypoxia-induced vascular barrier impairment.

Dipeptidyl peptidase-4 (DPP-4) inhibitors are relatively new class of anti-diabetic drugs. Some protective effects of DPP-4 on cardiovascular disease have been described independently from glucose-lowering effect. However, the detailed mechanisms by which DPP-4 inhibitors exert on endothelial cells remain elusive. The purpose of this research was to determine the effects of DPP-4 inhibitor on endothelial barrier function. Human umbilical vein endothelial cells (HUVECs) were cultured and exposed to hypoxia in the presence or absence of Diprotin A, a DPP-4 inhibitor. Immunocytochemistry of vascular endothelial (VE-) cadherin showed that jagged VE-cadherin staining pattern induced by hypoxia was restored by treatment with Diprotin A. The increased level of cleaved ß-catenin in response to hypoxia was significantly attenuated by Diprotin A, suggesting that DPP-4 inhibition protects endothelial adherens junctions from hypoxia. Subsequently, we found that Diprotin A inhibited hypoxia-induced translocation of NF-κB from cytoplasm to nucleus through decreasing TNF-α expression level. Furthermore, the tube formation assay showed that Diprotin A significantly restored hypoxia-induced decrease in number of tubes by HUVECs. These results suggest that DPP-4 inhibitior protects HUVECs from hypoxia-induced barrier impairment.

The effects of DPP-4 inhibitor on hypoxia-induced apoptosis in human umbilical vein endothelial cells.

Dipeptidyl peptidase-4 (DPP-4) inhibitors are a new class of oral hypoglycemic agents for patients with type 2 diabetes mellitus and have potential antiatherosclerotic properties. Meanwhile, it is unclear how DPP-4 inhibitors have protective effects on atherosclerosis. Our aim was to determine the effects and its mechanisms of DPP-4 inhibitors on cultured endothelial cells. Human umbilical vein endothelial cells (HUVECs) were cultured in hypoxic condition. To evaluate the protective effects of DPP-4 inhibitor on HUVECs, DPP-4 inhibitor was added in the cell culture medium and the cell viability was assessed by TUNEL assay. And we examined the intracellular signaling pathways in relation to the effects of DPP-4 inhibitor. DPP-4 inhibition had beneficial effects by inhibiting the apoptosis under hypoxic conditions in HUVECs. The antiapoptotic effects of DPP-4 inhibitor were abolished by the pretreatment with a CXCR4 antagonist or a Stat3 inhibitor. DPP-4 inhibition has beneficial effects on HUVECs by inhibiting the apoptosis under hypoxic conditions. SDF-1α/CXCR4/Stat3 pathways might be involved in the mechanisms of the cytoprotective effects of DPP-4 inhibitor. These results suggested that DPP-4 inhibitor has a potential for protecting vessels.

DPP-4 inhibition has beneficial effects on the heart after myocardial infarction.

AIMS: Dipeptidyl peptidase-4 (DPP-4) inhibitors are reported to have protective effects on various cells but it is unclear how DPP-4 inhibitors have cardioprotective effects. Our aim was to study the mechanisms of cardioprotective effects by DPP-4 inhibition. METHODS AND RESULTS: C57BL/6 mice and DPP-4 knockout (DPP-4KO) mice were subjected to left coronary artery ligation to produce acute myocardial infarction (MI). C57BL/6 mice were then treated with vehicle or DPP-4 inhibitor. Left ventricular function, infarct size, the number of vessels, and myocardial ischemia were assessed at 5days after MI. The treatment with DPP-4 inhibitor significantly improved cardiac function and decreased the infarct size. DPP-4 inhibitor increased the ratio of endothelial cell numbers to a cardiomyocyte. The extent of myocardial ischemia and the number of TUNEL-positive cells in the border area were significantly decreased by DPP-4 inhibitor. Stromal cell-derived factor-1α (SDF-1α) level in myocardium was significantly increased by DPP-4 inhibitor. Those cardioprotective effects after MI were also recognized in DPP-4KO mice. DPP-4 protein was expressed on rat neonatal cardiomyocytes and DPP-4 inhibitor significantly reduced hypoxia-induced apoptosis in the cardiomyocytes. However, this effect was abolished by the pretreatment with a CXCR4 antagonist or a signal transducer and activator of transcription 3 (STAT3) inhibitor. The beneficial effects of DPP-4 inhibitor on heart failure after MI were abolished by cardiomyocyte-specific deletion of STAT3. CONCLUSIONS: DPP-4 inhibition may have direct protective effects on the post-MI heart by inducing an antiapoptotic effect and inhibiting a decrease in vessel number through the SDF-1α/CXCR4-mediated STAT3 signaling pathway.

Deletion of CD28 Co-stimulatory Signals Exacerbates Left Ventricular Remodeling and Increases Cardiac Rupture After Myocardial Infarction.

BACKGROUND: Inflammatory responses, especially by CD4(+)T cells activated by dendritic cells, are known to be important in the pathophysiology of cardiac repair after myocardial infarction (MI). Although co-stimulatory signals through B7 (CD80/86) and CD28 are necessary for CD4(+)T cell activation and survival, the roles of these signals in cardiac repair after MI are still unclear. METHODS AND RESULTS: C57BL/6 (Control) mice and CD28 knockout (CD28KO) mice were subjected to left coronary artery permanent ligation. The ratio of death by cardiac rupture within 5 days after MI was significantly higher in CD28KO mice compared with Control mice. Although there were no significant differences in the infarct size between the 2 groups, left ventricular end-diastolic and end-systolic diameters were significantly increased, and fractional shortening was significantly decreased in CD28KO mice compared with Control mice. Electron microscopic observation revealed that the extent of extracellular collagen fiber was significantly decreased in CD28KO mice compared with Control mice. The number of α-smooth muscle actin-positive myofibroblasts was significantly decreased, and matrix metalloproteinase-9 activity and the mRNA expression of interleukin-1ß were significantly increased in CD28KO mice compared with Control mice. CONCLUSIONS: Deletion of CD28 co-stimulatory signals exacerbates left ventricular remodeling and increases cardiac rupture after MI through prolongation of the inflammatory period and reduction of collagen fiber in the infarct scars. (Circ J 2016; 80: 1971-1979).

Liposome Membrane as a Platform for the L-Pro-Catalyzed Michael Addition of trans-ß-Nitrostyrene and Acetone.

Herein, we show that the L-proline (L-Pro)-catalyzed Michael addition of trans-ß-nitrostyrene and acetone can proceed in "water" using liposome membranes and that the membrane fluidity and polarity are major controlling factors for this reaction. The highest conversion and rate constant of the reaction within the liposomes was achieved with the 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC)/1,2-dipalmitoyl-3-trimethylammoniumpropane (DPTAP) system. The catalytic activity of L-Pro in the liposome suspension was found to be comparable to that in a DMSO system. The reaction rate constant was found to be controlled by both the phase state of the liposome membrane and the surface charge on the membrane. Greater enantioselectivity was achieved in the presence of the liposomes than in DMSO solution, with corresponding enantiomeric excess values of 97.6% for the DOPC/DPTAP liposome system and 10% in DMSO. The hydrophobic region of the liposome membrane, which is a relatively stable self-organizing system, can serve as an effective "platform" for molecular recognition and selective conversion in aqueous media.

Factors predicting the cause and prognosis of central line-associated bloodstream infections.

The increased use of indwelling catheters has led to an increased number of deaths due to central line-associated bloodstream infection (CLABSI). Improving CLABSI outcomes requires the identification of clinical characteristics affecting drug selection and factors associated with poor prognosis. The medical records of inpatients admitted to St. Marianna University School of Medicine between April 1, 2010 and March 31, 2013 were evaluated for the results of catheter tip cultures. The clinical characteristics of these cases and the characteristics of the pathogens involved were investigated to identify prognostic factors. Of the 1629 catheter cultures investigated, 183 were CLABSIs. Among them, 105 were caused by gram-positive bacteria, 43 by gram-negative bacteria, and 35 by fungi. Gram-negative CLABSIs were more common in cases with prior colonization by gram-negative bacteria and post-surgical cases. Fungal CLASBIs were more common in the cases with prior colonization by fungi, high-calorie infusion enforcement, broad-spectrum antibiotic treatment, and post-surgical cases. Death was significantly more likely in cases with findings of inflammation at the catheter insertion site and in those with abnormal body temperature, tachycardia, or abnormal white blood cell count. Thus, when treating CLABSI in post-surgical cases and in cases with prior colonization by gram-negative bacteria, therapy should include anti-pseudomonal agents. Considering the factors predicting poor prognostic identified in this study, clinicians must check the vital signs and catheter insertion site in patients with indwelling catheters.

[A case of Streptococcus gallolyticus subsp. gallolyticus infective endocarditis with colon adenoma].

An 80-year-old Japanese man had a fall presented with a 3-week history of right lumbago exacerbated by body movement as well as a 1-week history of anomalous behavior and appetite loss. He visited our hospital complaining of difficulty in standing up. He had a history of mitral prolapse due to an unknown rupture of the chordae tendineae 3 years earlier, which resulted in moderate mitral valve regurgitation and atrial fibrillation. Upon visiting the hospital, he had petechial hemorrhage and jaundice of the conjunctiva, a systolic murmur (Levine II/VI) at the apex and 4th interspace of the left sternal border, and a positive right straight leg raising test result. Moderate bilirubinemia and disseminated intravascular coagulation which were considered to have been produced secondarily were observed. Infective endocarditis was suspected, and 3 sets of blood culture were extracted. The patient was admitted on the same day. Blood cultures were positive for Streptococcus gallolyticus subsp. gallolyticus (6/6) on the following day. Transesophagela echocardiography was carried out on the same day, and vegetation with a diameter of 4mm was observed in the anterior mitral leaflet; the patient was subsequently diagnosed as having infective endocarditis. Colonic endoscopy was performed after hospitalization. Twelve colonic adenomata were found, and endoscopic mucosal resection was performed on one polyp. The bacterium found in the culture was classified as Streptococcus bovis type I, which causes infective endocarditis and bacteremia. Furthermore, this bacteria is a relatively rare causative organism of infective endocarditis. Tolerance to macrolide and tetracycline are reported in the literature. Moreover, the cell wall of this bacterium may have low pathogenicity as well as cause chronic inflammation in the large intestine mucous membrane, colonic polyps, and colorectal cancer. Several colonic adenomata and a partial shift to a malignant pathology were observed in this case. When this bacterium is detected, searching for a pathological change in the large intestine is believed to be indispensable.

Treatment of long COVID complicated by postural orthostatic tachycardia syndrome-Case series research.

Background: Coronavirus disease 2019 (COVID-19) sequelae, also known as long COVID, can present with various symptoms. Among these symptoms, autonomic dysregulation, particularly postural orthostatic tachycardia syndrome (POTS), should be evaluated. However, previous studies on the treatment of POTS complicated by COVID-19 are lacking. Therefore, this study aimed to investigate the treatment course of long COVID complicated by POTS. Methods: The medical records of patients who complained of fatigue and met the criteria for POTS diagnosis were reviewed. We evaluated the treatment days, methods and changes in fatigue score, changes in heart rate on the Schellong test, and social situation at the first and last visits. Results: Thirty-two patients with long COVID complicated by POTS were followed up (16 males; median age: 28 years). The follow-up period was 159 days, and the interval between COVID-19 onset and initial hospital attendance was 97 days. Some patients responded to ß-blocker therapy. Many patients had psychiatric symptoms that required psychiatric intervention and selective serotonin reuptake inhibitor prescription. Changes in heart rate, performance status, and employment/education status improved from the first to the last visit. These outcomes were believed to be because of the effects of various treatment interventions and spontaneous improvements. Conclusions: Our study suggests that the condition of 94% of patients with POTS complicated by long COVID will improve within 159 days. Therefore, POTS evaluation should be considered when patients with long COVID complain of fatigue, and attention should be paid to psychological symptoms and the social context.

A novel double GLA gene mutation of W24R and N419D in a patient with cardiac Fabry disease.

Fabry disease (FD) is an X-linked lysosomal storage disorder caused by insufficient activity of α-galactosidase A (α-Gal A) encoded by GLA. The enzymatic defect causes the progressive accumulation of sphingolipids in various tissues and body fluids, causing systemic disorders. We report a rare familial case of inherited cardiac FD associated with a novel double mutation in the GLA gene: W24R and N419D. A young man with severe obesity was admitted for heart failure (HF) with the diagnosis of dilated cardiomyopathy. Left ventricular hypertrophy was suspected during HF treatment after discharge, and in association with his mother's family history of cardiac diseases and sudden death, the etiology of the hypertrophy was re-examined. Very low α-Gal A activity confirmed the diagnosis of FD. Gene mutation analysis of GLA demonstrated a double mutation: W24R and N419D. Proband analysis revealed the same double mutation in his mother. Although she had no signs or symptoms of FD, we detected mild accumulation of globotriaosylsphingosine. The good laboratory practice-validated assay using HEK293 cells showed that the double mutation was amenable to migalastat, a pharmacological chaperone stabilizing α-Gal A. This case highlights a novel double gene mutation in GLA (W24R and N419D) identified in a family with FD. Although clinical significance of each mutation remains unknown, its combination might work synergistically to attain or augment pathogenicity.

The relationship between having a usual source of primary care and COVID-19 parental vaccine hesitancy: A nationwide survey among Japanese mothers.

Background: Studies have shown that a usual source of care increases the receipt of child preventive care; however, the relationship between having a usual source of primary care and COVID-19 parental vaccine hesitancy has not been fully investigated. The aims of this study were to elucidate the characteristics of mothers with a primary care physician, and to explore the relationship between having a usual source of primary care and COVID-19 parental vaccine hesitancy among mothers in Japan. Method: This cross-sectional survey-based study included 4516 mothers. Using a chi-square test, the characteristics of mothers with and without a primary care physician were compared. Poisson regression was applied to evaluate the relationship between having a usual source of primary care and parental COVID-19 vaccine hesitancy. Results: Mothers with a usual source of primary care had higher education, lower mental distress, had younger children, and were less hesitant toward the child's COVID-19 vaccination. Vaccine hesitancy was observed in 39.8% of mothers with a usual source of primary care and 45.5% of those without. Poisson regression analysis showed that mothers with a primary care physician were less vaccine-hesitant (IRR = 0.90, 95% CI = 0.84-0.96) after adjusting for potential confounders. Conclusion: This study suggested that having a usual source of primary care may contribute to lower parental COVID-19 vaccine hesitancy. However, the high vaccine hesitancy rate, even among mothers with a usual source of primary care, warrants healthcare providers to be equipped to help parents make informed decisions about vaccination through the continuity of care.

Deprescribing as an Opportunity to Facilitate Patient-Centered Care: A Qualitative Study of General Practitioners and Pharmacists in Japan.

Deprescribing has recently been applied to address polypharmacy, particularly among older adults. However, the characteristics of deprescribing that are likely to improve health outcomes have not been well studied. This study explored the experiences and perspectives of general practitioners and pharmacists with regard to deprescribing in older adults with multimorbidity. A qualitative study was conducted involving eight semi-structured focus group interviews with 35 physicians and pharmacists from hospitals, clinics, and community pharmacies. Thematic analysis was applied to identify themes using the theory of planned behavior as a guide. The results illustrated a metacognitive process, as well as influencing factors, through which healthcare providers commit to shared decision making for deprescribing. Healthcare providers acted on the basis of their attitudes and beliefs on deprescribing, the influence of subjective norms, and perceived behavioral control for deprescribing. These processes are influenced by factors such as drug class, prescribers, patients, deprescribing experience, and environment/education. Healthcare providers' attitudes, beliefs, and behavioral control (along with deprescribing strategies) evolve in a dynamic interplay with experience, environment, and education. Our results can serve as a foundation for the development of effective patient-centered deprescribing to improve the safety of pharmaceutical care for older adults.