Abnormalities of Hippocampal Subfield and Amygdalar Nuclei Volumes and Clinical Correlates in Behavioral Variant Frontotemporal Dementia with Obsessive-Compulsive Behavior-A Pilot Study.

(1) Background: The hippocampus (HP) and amygdala are essential structures in obsessive-compulsive behavior (OCB); however, the specific role of the HP in patients with behavioral variant frontotemporal dementia (bvFTD) and OCB remains unclear. (2) Objective: We investigated the alterations of hippocampal and amygdalar volumes in patients with bvFTD and OCB and assessed the correlations of clinical severity with hippocampal subfield and amygdalar nuclei volumes in bvFTD patients with OCB. (3) Materials and methods: Eight bvFTD patients with OCB were recruited and compared with eight age- and sex-matched healthy controls (HCs). Hippocampal subfield and amygdalar nuclei volumes were analyzed automatically using a 3T magnetic resonance image and FreeSurfer v7.1.1. All participants completed the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS), Neuropsychiatric Inventory (NPI), and Frontal Behavioral Inventory (FBI). (4) Results: We observed remarkable reductions in bilateral total hippocampal volumes. Compared with the HCs, reductions in the left hippocampal subfield volume over the cornu ammonis (CA)1 body, CA2/3 body, CA4 body, granule cell layer, and molecular layer of the dentate gyrus (GC-ML-DG) body, molecular layer of the HP body, and hippocampal tail were more obvious in patients with bvFTD and OCB. Right subfield volumes over the CA1 body and molecular layer of the HP body were more significantly reduced in bvFTD patients with OCB than in those in HCs. We observed no significant difference in amygdalar nuclei volume between the groups. Among patients with bvFTD and OCB, Y-BOCS score was negatively correlated with left CA2/3 body volume (τb = -0.729, p < 0.001); total NPI score was negatively correlated with left GC-ML-DG body (τb = -0.648, p = 0.001) and total bilateral hippocampal volumes (left, τb = -0.629, p = 0.002; right, τb = -0.455, p = 0.023); and FBI score was negatively correlated with the left molecular layer of the HP body (τb = -0.668, p = 0.001), CA4 body (τb = -0.610, p = 0.002), and hippocampal tail volumes (τb = -0.552, p < 0.006). Mediation analysis confirmed these subfield volumes as direct biomarkers for clinical severity, independent of medial and lateral orbitofrontal volumes. (5) Conclusions: Alterations in hippocampal subfield volumes appear to be crucial in the pathophysiology of OCB development in patients with bvFTD.

Diagnosis and Management of Fabry Disease in High-Risk Renal Disease Patients in Taiwan: A Single Center Study.

BACKGROUND: Fabry disease (FD) is an X-linked inborn error of lysosomal storage disorder, a deficiency in lysosomal hydrolase α-galactosidase A activity due to pathogenic variants in the GLA gene. Accumulation of globotriaosylceramide in multiple organs contributes to end-stage kidney disease, heart failure, and cerebrovascular accidents. METHODS: We began the FD screening program by involving male patients older than 20 years of age who were on chronic dialysis, had a post-kidney transplantation, and were part of the Pre-End Stage Renal Disease Program in our hospital. α-galactosidase A activity was detected through an initial dried blood spots screen assay, followed by levels of lyso-globotriaosylceramide and sequencing of the GLA gene when screening patients with suspected FD to confirm their diagnosis. RESULTS: A total of 1812 patients had been FD screened, with the prevalence of FD being approximately 0.16 % (3/1812) up until June 2022. Interestingly, we confirmed a family cluster (2 sons and their mother) of having the c.936+919G>A mutation (designated GLA IVS4) with hypertrophic cardiomyopathy in Taiwan and another with the mutation c.644A>G (p.Asn215Ser), a more common later-onset variant reported in people of European or North American descent. Two patients were confirmed with cardiomyopathy through a cardiac biopsy, with their cardiac function later reversed after enzyme replacement therapy. CONCLUSIONS: The FD screening test detects chronic kidney disease due to an unknown etiology and prevents other organ complications. Early detection of FD is crucial for reversing target organ damage with enzyme replacement therapy.

Adverse Effects of Denosumab in Kidney Transplant Recipients: A 20-Year Retrospective Single-Center Observation Study in Central Taiwan.

BACKGROUND: Bone loss can be noted in kidney transplantation recipients (KTRs) and can be related to fracture events. Denosumab, a potent monoclonal antibody to RANK ligand, increases lumbar bone mineral density. However, safety data for denosumab remain limited regarding transplant recipients. Hypocalcemia and increased genital tract infections have been mentioned as adverse effects in KTRs after being prescribed denosumab. METHODS: We retrospectively analyzed the electronic medical records of KTRs during the recent 20 years who had been prescribed antiresorptive therapy and were >18 years old. Medical records and their clinical data were reviewed and analyzed. We compared the frequency of adverse effects between denosumab with other antiresorptive therapies. RESULTS: A total of 70 KTRs were enrolled, with 46 patients being given denosumab and the first injection being noted on October 31, 2014. No significant differences were seen in mortality rate, opportunistic infection, pneumonia, or genitourinary tract infection. One diagnosis of osteonecrosis of the jaw was noted in the denosumab group (2.2%). A higher incidence of hypocalcemia (<8.4 mg/dL) was noted in the denosumab group (34.8%), and a higher but nonsignificant difference in the incidence of severe hypocalcemia was also noted in the group. CONCLUSIONS: Denosumab may be considered as safe as other antiresorptive therapies for KTRs. However, more hypocalcemia events have been noted, so medical personnel may need to be cautious when prescribing its use.

Risk of Parkinson's disease following gout: a population-based retrospective cohort study in Taiwan.

BACKGROUND: The progressive neurodegenerative disorder Parkinson disease (PD) is well-established as the second most common neurodegenerative disease. Associations between the sequential risk of PD and gout have been addressed in other studies, but findings have been inconclusive. Accordingly, we executed the present study with the purpose of assessing PD risk in patients with gout. METHODS: From Taiwan's National Health Insurance Research Database, we identified the data of patients newly diagnosed as having gout between January 1, 2000 and December 1, 2000. A cohort of patients without gout, matched for sex and age, was constructed for comparison. Hazard ratios (HRs) and the incidence rate of subsequent PD were calculated for both cohorts and separately for male and female groups. The gout and comparison cohorts consisted of 7900 patients each. RESULTS: The HR for PD was not significantly higher in the gout cohort compared with the control cohort (HR 1.01, 95% confidence interval [CI], 0.93-1.31, P = .268), even after adjustment for age, urbanization, monthly income, sex, and comorbidities. We did not observe gender differences in the gout-PD association (male: HR 1.01, 95% CI, 0.88-1.36, P = .400; female: HR 1.11, 95% CI, 0.84-1.46, P = .466). CONCLUSIONS: Our study identified that there was no protective effect of gout for the risk of PD in the Taiwanese population.

Nationwide epidemiology and prognosis of dialysis-requiring acute kidney injury (NEP-AKI-D) study: Design and methods.

AIM: Acute kidney injury (AKI) carries an increasing incidence rate worldwide and increases the risk of developing end-stage renal disease (ESRD) as well as the medical expenses during the post-AKI course. The Taiwan Consortium for Acute Kidney Injury and Renal Diseases (CAKs) has thus launched a nationwide epidemiology and prognosis of dialysis-requiring acute kidney injury (NEP-AKI-D) study, which prospectively enrols critically ill patients with AKI. Through thoroughly evaluating the risk and prognostic factors of AKI, we hope to lower the incidence of AKI and ESRD from the perspective of AKI-ESRD interaction. METHODS: The CAKs includes 30 hospitals which distribute widely through the four geographical regions (north, middle, south, and east) of Taiwan, and have a 1:1 ratio of medical centres to regional hospitals in each region. The NEP-AKI-D study enrols intensive care unit-based AKI patients who receive dialysis in the four seasonal sampled months (October 2014, along with January, April, and July 2015) in the included hospitals. The collected data include demographic information, pertaining laboratory results, dialysis settings and patient outcomes. The data are uploaded in a centre website and will be audited by on-site principal investigators, computer logic gates, and the CAKs staffs. The outcomes of interest are in-hospital mortality, dialysis-dependency and readmission rate within 90 days after discharge. CONCLUSION: The NEP-AKI-D study enrols a large number of representative AKI patients throughout Taiwan. The results of the current study are expected to provide more insight into the risk and prognostic factors of AKI and further attenuated further chronic kidney disease transition.

Risk of psychiatric disorders following gastroesophageal reflux disease: a nationwide population-based cohort study.

BACKGROUND: Recent studies have shown that the peripheral inflammation may cause the up-regulation of central nervous system inflammation and therefore possibly plays a vital role in the pathophysiology of subsequent psychiatric disorders. OBJECTIVE: We explored the relationship between gastroesophageal reflux disease (GERD) and the subsequent development of psychiatric disorders including schizophrenia as well as bipolar, depressive, anxiety, and sleep disorders. METHODS: We investigated patients who were diagnosed with GERD according to the data in the Taiwan National Health Insurance Research Database. A comparison cohort comprised patients without GERD who were matched according to age and sex. The incidence rate and the hazard ratios (HRs) of subsequent new-onset psychiatric disorders were calculated for both cohorts, based on the diagnoses of psychiatrists. RESULTS: The GERD cohort consisted of 3813 patients, and the comparison cohort comprised 15,252 matched control patients without GERD. The risks of depressive disorder (HR=3.37, 95% confidence interval [CI]=2.49-4.57), anxiety disorder (HR=2.99, 95% CI=2.12-4.22), and sleep disorder (HR=2.69, 95% CI=1.83-3.94), were higher in the GERD cohort than in the comparison cohort. In addition, the incidence of newly diagnosed depressive, anxiety, and sleep disorders remained significantly increased in all of the stratified follow-up durations (0-1, ≥1year). CONCLUSIONS: GERD may increase the risks of subsequent depressive, anxiety, and sleep disorders. These psychiatric disorders have a negative effect on people's quality of life. Clinicians should pay a particular attention to psychiatric comorbidities in GERD patients.

Risk of developing depressive disorders following rheumatoid arthritis: a nationwide population-based study.

BACKGROUND & AIMS: To evaluate the risk of depressive disorders among rheumatoid arthritis (RA) by using the Taiwan National Health Insurance Research Database (NHIRD). METHODS: We conducted a retrospective study of a matched cohort of 18 285 participants (3 657 RA patients and 14 628 control patients) who were selected from the NHIRD. Patients were observed for a maximum of 10 years to determine the rates of newly diagnosed depressive disorders, and Cox regression was used to identify the risk factors associated with depressive disorders in RA patients. RESULTS: During the 10-year follow-up period, 205 (11.2 per 1000 person-years) RA patients and 384 (5.1 per 1000 person-years) control patients were diagnosed with depressive disorders. In RA patients, most depressive disorders (n = 163, 80%) developed with five years of being diagnosed with RA. The incidence risk ratio of depressive disorders between RA patients and control patients was 2.20 (95% confidence interval [CI], 1.84-2.61, P<.001). After adjusting for age, sex, and comorbidities, RA patients were 2.06 times more likely to develop depressive disorders (95% CI, 1.73-2.44, P<.001) compared with the control patients. Hyperthyroidism (HR = 1.67) was an independent risk factor for depressive disorders in patients with RA. CONCLUSIONS: The likelihood of developing depressive disorders is greater among RA patients than among patients without RA. Symptoms of depression should be sought in patients with RA.