Causal relationship between gut microbiota and diabetic nephropathy: A bidirectional mendelian randomization study.

In this study, we summarized the key findings and potential implications of association studies investigating the relationship between gut microbiota composition and risks for Diabetic nephropathy (DN). We used Mendelian randomization (MR) analysis to explore the relationship between gut microbiota and DN using two different publicly available DN databases. The results were also summarized using five mainstream MR analysis methods. We controlled for various possible biases in the results. The results showed that specific bacterial genera were associated with increased or decreased risk of DN. These associations can be attributed to a variety of factors, including metabolites produced by certain bacteria. Most of our findings are consistent with the existing research findings, but there are still some differences with the existing results. In addition, we also pointed out that some microbiota that may be associated with DN but remain unnoticed can bring new research directions. Our work made use of MR, a reliable technique for examining causal correlations using genetic data investigating potential processes, carrying out longitudinal studies, looking into intervention options, and using a multi-omics approach may be future research avenues. Further, our findings also point to a few unexplored possible study paths for DN in the future. These initiatives may improve our reconciliation of the internal relationships between the gut microbiota and DN and pave the way for more precise prevention and treatment methods. However, it is also critical to recognize any potential restrictions, such as those caused by sample size, population variety, and analytical techniques.

Neuropsychiatric Symptoms Predict Faster Cognitive Decline in Dementia Collaborative Care Than Antipsychotic Use.

Background: To compare short-term cognitive outcomes among groups with and without neuropsychiatric symptoms (NPSs) or antipsychotic prescription and to determine which disease status or treatment modality is associated with relatively faster cognitive decline. Methods: We retrospectively analyzed a prospective cohort of patients diagnosed with dementia and mild cognitive impairment. All participants were evaluated using the Cognitive Abilities Screening Instrument (CASI) during their initial clinical assessments and at the annual follow-up. The dependent variable was annual delta CASI. Multivariate linear regression analysis was used to assess the degree of association between NPS, antipsychotic use, and cognitive decline after adjusting for confounding factors. Neuropsychiatric symptoms were examined individually to determine their predictive value for cognitive decline. Results: A total of 407 (N = 407) patients were included in the study. NPSs, rather than antipsychotic use, led to faster cognitive decline. A higher baseline NPI total score predicted a significantly faster decline in CASI scores (1-year delta CASI = -0.22, 95% CI = -0.38~ -0.05, p = 0.010). Specific items (delusions, agitation, depression, anxiety, euphoria, and apathy) in the NPS significantly increased cognitive decline. Conclusion: Certain neuropsychiatric symptoms, rather than antipsychotic use, lead to faster cognitive decline in a dementia collaborative care model. Checking for and providing appropriate interventions for NPS in people with dementia and their caregivers are highlighted.

The Effectiveness of the Case Manager-Centered Collaborative Care Model with Computer-Assisted Assessment on Quality Indicators for the Care of Dementia.

INTRODUCTION: This study aimed to investigate the influence of case management and its corresponding computer-assisted assessment system on the quality improvement of dementia care. METHODS: This observational study enrolled 2029 patients and their caregivers at Changhua Christian Hospital in Taiwan. Physicians who made the diagnosis of dementia would introduce the patient and caregiver dyad to the case manager-centered collaborative care team after obtaining agreement. The achievement rates of 11 quality indicators (QIs) comprising timely diagnostic evaluations, regular screens of cognition and neuropsychiatric symptoms, caregiver support, and proper medication prescriptions were counted. Different timeframes (≤4 months, 4 months-1 year, 1-2 years, 2-3 years, or ≥3 years) from diagnosis of dementia to collaborative care intervention were compared. RESULTS: A significantly higher attainment rate was achieved for patients with earlier entry into the collaborative team model, including QIs about timely diagnosis and regular screening, and caregiver support. The QIs regarding dementia medication prescriptions and documentation of the risk of antipsychotics remained similar regardless of the time of entry into the model. The completion rates of QIs also improved after the information system was launched. CONCLUSIONS: Physician-case manager co-management in the setting of a collaborative care model with a computer-assisted assessment system helps improve QI achievement for dementia care.

Prevalent landscape of tumor genomic alterations of luminal B1 breast cancers using a comprehensive genomic profiling assay in Taiwan.

BACKGROUND: The human epidermal growth factor receptor 2 (HER2) negative luminal B1 subtype of breast cancer has been reported with a poorer outcome than luminal A in recent studies. This study aimed to investigate the molecular alterations and identify potential therapeutic targets by analyzing the genetic profiling from a cohort of luminal B1 breast cancer in Taiwan. METHODS: We enrolled patients with luminal B1 breast cancer in our study. They were classified as patients who received curative surgery and adjuvant or neoadjuvant chemotherapy as the low-risk group, and who had advanced or metastatic disease or early relapse during the follow-up time as the high-risk group. Using targeted sequencing, we evaluated genomic alterations, interpreting variants with the ESMO Scale of clinical actionability of molecular targets (ESCAT). RESULTS: A total of 305 luminal B1 breast cancer patients underwent targeted sequencing analyses. The high-risk patients reported more actionable genes and called variants than the low-risk group (P < 0.05). PIK3CA (42%), FGFR1 (25%), and BRCA1/2 (10.5%) were the most prevalent ESCAT actionable alterations in luminal B1 breast cancer. There was no difference in the prevalence of actionable mutations between these two groups, except for ERBB2 oncogenic mutations, which were more prevalent among the high-risk than the low-risk group (P < 0.05). Alterations in PTEN, ERBB2, and BRCA1/2 were associated with disease relapse events in luminal B1 breast cancer. CONCLUSIONS: PIK3CA, FGFR1, and BRCA1/2 were the most prevalent actionable alterations among Taiwanese luminal B1 breast cancer. Moreover, PTEN and BRCA1/2 was significantly associated with disease relapse.

Prevalence of BRCA1, BRCA2, and PALB2 genomic alterations among 924 Taiwanese breast cancer assays with tumor-only targeted sequencing: extended data analysis from the VGH-TAYLOR study.

BACKGROUND: The homologous recombination (HR) repair pathway for DNA damage, particularly the BRCA1 and BRCA2 genes, has become a target for cancer therapy, with poly ADP-ribose polymerase (PARP) inhibitors showing significant outcomes in treating germline BRCA1/2 (gBRCA1/2) mutated breast cancer. Recent studies suggest that some patients with somatic BRCA1/2 (sBRCA1/2) mutation or mutations in HR-related genes other than BRCA1/2 may benefit from PARP inhibitors as well, particularly those with PALB2 mutations. The current analysis aims to evaluate the prevalence of genetic alterations specific to BRCA1, BRCA2, and PALB2 in a large cohort of Taiwanese breast cancer patients through tumor-targeted sequencing. METHODS: A total of 924 consecutive assays from 879 Taiwanese breast cancer patients underwent tumor-targeted sequencing (Thermo Fisher Oncomine Comprehensive Assay v3). We evaluated BRCA1, BRCA2, and PALB2 mutational profiles, with variants annotated and curated by the ClinVAR, the Oncomine™ Knowledgebase Reporter, and the OncoKB™. We also conducted reflex germline testing using either whole exome sequencing (WES) or whole genome sequencing (WGS), which is ongoing. RESULTS: Among the 879 patients analyzed (924 assays), 130 had positive mutations in BRCA1 (3.1%), BRCA2 (8.6%), and PALB2 (5.2%), with a total of 14.8% having genetic alterations. Co-occurrence was noted between BRCA1/BRCA2, BRCA1/PALB2, and BRCA2/PALB2 mutations. In BRCA1-mutated samples, only p.K654fs was observed in three patients, while other variants were observed no more than twice. For BRCA2, p.N372H was the most common (26 patients), followed by p.S2186fs, p.V2466A, and p.X159_splice (5 times each). For PALB2, p.I887fs was the most common mutation (30 patients). This study identified 176 amino acid changes; 60.2% (106) were not documented in either ClinVAR or the Oncomine™ Knowledgebase Reporter. Using the OncoKB™ for annotation, 171 (97.2%) were found to have clinical implications. For the result of reflex germline testing, three variants (BRCA1 c.1969_1970del, BRCA1 c.3629_3630del, BRCA2 c.8755-1G > C) were annotated as Pathogenic/Likely pathogenic (P/LP) variants by ClinVar and as likely loss-of-function or likely oncogenic by OncoKB; while one variant (PALB2 c.448C > T) was not found in ClinVar but was annotated as likely loss-of-function or likely oncogenic by OncoKB. CONCLUSION: Our study depicted the mutational patterns of BRCA1, BRCA2, and PALB2 in Taiwanese breast cancer patients through tumor-only sequencing. This highlights the growing importance of BRCA1/2 and PALB2 alterations in breast cancer susceptibility risk and the treatment of index patients. We also emphasized the need to meticulously annotate variants in cancer-driver genes as well as actionable mutations across multiple databases.

Concordance of Targeted Sequencing from Circulating Tumor DNA and Paired Tumor Tissue for Early Breast Cancer.

In this study, we evaluated the concordance of targeted sequencing between paired ctDNA and matched tumor samples from early breast cancers treated with curative intention. Molecular profiling was performed using the Oncomine Comprehensive Assay v3 and the Oncomine Breast cfDNA Assay v2. The liquid biopsy detection rate was 39% (all-stage breast cancers, n = 612). Among 246 early-stage patients assayed for both ctDNA and matched tumor, the cfDNA assay detected 73 (29.6%) and the comprehensive assay detected 201 (81.7%) breast cancers with at least one alteration (χ2 test, p = 0.001). In total, 67 (25.6%) cases tested positive on both platforms, while the cfDNA and comprehensive assays detected an additional 10 (4%) and 138 (56%) cases, respectively. The most prevalent mutant genes were TP53 (68.3%) and KRAS (53.5%), while the PIK3CA (39.4%), AKT1 (45.9%), and ERBB2 (17.1%) mutations constituted biomarkers for FDA-approved therapeutics. Our study showed that tumor tissue should be the source of actionable mutation detection for early breast cancers, considering that the concordance rate between tumor and liquid biopsy was only one-quarter.

Correlation of an immune-related 8-gene panel with pathologic response to neoadjuvant chemotherapy in patients with primary breast cancers.

Neoadjuvant chemotherapy (NACT)-induced pathologic complete response (pCR) is associated with a favorable prognosis for breast cancer. Prior research links tumor-infiltrating lymphocytes with breast cancer chemotherapy response, suggesting the tumor-immune microenvironment's role. The aim of this study was to evaluate the immune-related genes that exhibit associations with the response to NACT. In this study, we analyzed a total of 37 patients (aged 27-67) who received NACT as the first-line treatment for primary breast cancer, followed by surgery. This group consisted of nine patients (24.3 %) with estrogen receptor (ER)-positive/HER2-negative status, ten patients (27.0 %) with ER-positive/HER2-positive status, five patients (13.5 %) with ER-negative/HER2-positive status, and thirteen patients (35.1 %) with triple-negative breast cancer (TNBC). Among these patients, twelve (32.4 %) achieved a pCR, with eight (66.6 %) having HER2-positive tumors, and the remaining four having TNBC. To identify immune-related genes linked with pCR in subjects with breast cancer prior to NACT, we collected fresh tissues for next-generation sequencing. Patients with pCR had higher expressions of eight genes, KLRK1, IGJ, CD69, CD40LG, MS4A1, CD1C, KLRB1, and CA4, compared to non-pCR patients. The 8-gene signature was associated with good prognosis and linked to better relapse-free survival in patients receiving chemotherapy. The expression of these genes was involved in better drug response, displaying a positive correlation with the infiltration of immune cells. In conclusion, we have identified eight immune-related genes that are associated with a favorable prognosis and positive responses to drugs. This 8-gene signature could potentially provide prognostic insights for breast cancer patients undergoing NACT.

Prevalence of PIK3CA mutations in Taiwanese patients with breast cancer: a retrospective next-generation sequencing database analysis.

Background: Breast cancer is the most common cancer type that affects women. In hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) advanced breast cancer (ABC), phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) is the most frequently mutated gene associated with poor prognosis. This study evaluated the frequency of PIK3CA mutations in the Taiwanese breast cancer population. Methodology: This is a retrospective study; patient data were collected for 2 years from a next-generation sequencing database linked to electronic health records (EHRs). The primary endpoint was the regional prevalence of PIK3CA mutation. The secondary endpoints were to decipher the mutation types across breast cancer subtype, menopausal status, and time to treatment failure after everolimus (an mTOR inhibitor) or cyclin-dependent kinase 4/6 (CDK4/6) inhibitor treatment. Results: PIK3CA mutations were identified in 278 of 728 patients (38%). PIK3CA mutations were reported in 43% of patients with HR-/HER2+ subtype and 42% of patients with HR+/HER2- postmenopausal status. A lower prevalence of PIK3CA mutations was observed in triple-negative (27%) and HR+/HER2- premenopausal patients (29%). The most common mutation was at exon 20 (H1047R mutation, 41.6%), followed by exon 9 (E545K mutation, 18.9% and E542K mutation, 10.3%). Among patients treated with CDK4/6 inhibitors, the median time to treatment failure was 12 months (95% CI: 7-21 months) in the PIK3CA mutation cohort and 16 months (95% CI: 11-23 months) in the PIK3CA wild-type cohort, whereas patients receiving an mTOR inhibitor reported a median time to treatment failure of 20.5 months (95% CI: 8-33 months) in the PIK3CA mutation cohort and 6 months (95% CI: 2-9 months) in the PIK3CA wild-type cohort. Conclusion: A high frequency of PIK3CA mutations was detected in Taiwanese patients with breast cancer, which was consistent with previous studies. Early detection of PIK3CA mutations might influence therapeutic decisions, leading to better treatment outcomes.

Molecular Engineering to Boost the Photo-Oxidase Activity of Molecular Rotors in Colorimetric Sensing of Temperatures.

Some organic dyes and photosensitizers with strong visible absorption can behave as photo-responsive oxidase mimics. However, the relationship between the photo-oxidase activity and molecular structure remains unclear to date. In this work, a new type of photosensitizer with the characteristics of molecular rotors, namely DPPy, served as the molecular scaffold for further investigation. To adjust the photocatalytic oxidation ability, DAPy and CBPy were designed and synthesized based on the enhancement and diminishment of the intramolecular charge transfer (ICT) process, respectively. Kinetic studies revealed that DAPy and CBPy both exhibited highly efficient photo-activated oxidase-like activity with 3,3',5,5'-tetramethylbenzidine (TMB) as the substrate, which were in good accordance with their molecular engineering to promote either type I or type II reactive oxygen species (ROS) generation. Impressively a colorimetric method based on the visible light induced oxidase-like activity of molecular rotors was developed to determine the environmental temperature for the first time. Both DAPy and CBPy showed distinct sensitivities toward temperature as compared with several molecular rotors based on the typical fluorimetric detection. This work provides a new strategy for the application of molecular rotors to overcome the non-emissive challenge in temperature sensing.

Clinical characteristics and treatment outcomes of invasive ductal and lobular carcinoma: analyses of 54,832 taiwan cancer registry index cases.

PURPOSE: Invasive lobular cancer (ILC) is the second most common histology type of breast cancer followed by invasive ductal carcinoma (IDC). This study aimed to investigate the characteristic, treatment strategies, and clinical outcomes of ILC based on a national population-based cancer registry. METHODS: This study recruited 2671 ILC and 52,215 IDC patients diagnosed between 2011 and 2017 using the Taiwan Cancer Registry (TCR). Correlations between ILC and IDC subgroups were assessed using 1:4 propensity score matching and compared using the χ2 test. Disease free survival(DFS) and overall survival(OS) were estimated using the Kaplan-Meier method with the log-rank test. The risk of disease relapse and mortality were assessed using Cox proportional hazards model. RESULTS: ILC patients had larger tumor sizes, more positive axillary lymph node involvement, lower tumor grade, and higher cancer stage than IDC patients. After matching, ILC patients had a significantly higher rate of receiving mastectomy (58.93% and 53.85%) and positive surgical margin regardless of surgery type. ILC exhibited a significantly higher rate of distant metastasis than IDC(3.67% and 2.93%), but no difference in local recurrence rate, DFS or OS between the two groups. Higher cancer stage, higher grade, and mastectomy were risk factors for disease relapse and cancer-specific mortality. The hormone receptor-positive and HER2 over-expression subtypes were found to be associated with a reduced risk of disease relapse, while only PR positivity was associated with a decreased risk of mortality. (all P-values < 0.05). CONCLUSION: ILC patients had a higher mastectomy rate, higher surgical margin rate and distant metastasis rate than IDC patients. There is no significant difference in DFS or OS between ILC and IDC patients. Mastectomy was associated with poor outcomes regardless of ILC or IDC.

The association of trastuzumab with atrial fibrillation and heart failure in breast cancer patients in routine clinical practice: a population-based propensity score matching and competing risk model analysis.

PURPOSE: Trastuzumab, a potent anti-human epidermal growth factor receptor 2 (HER2) monoclonal antibody, is conditionally reimbursed by the Taiwan National Health Insurance (NHI) for HER2-positive breast cancer (BC). Trastuzumab-induced cardiotoxicity studies have well characterized heart failure (HF) but fewer addressed arrhythmia, particularly the association of potential life threatening atrial fibrillation (Af) is poorly characterized. We aimed to study the trastuzumab-related risk of Af and HF using the claimed data of Taiwan NHI. METHODS: A nationwide retrospective cohort of patients with BC from the Taiwan NHI reimbursement database from January 2007 to December 2016 was analyzed. Propensity score matching and competing risk model analysis were used for adjusting confounding concurrent medication or comorbidities and competing events. The HF study was used to validate the method used. RESULTS: For Af, 12,472 trastuzumab users were matched with 12,472 non-trastuzumab users. For HF, 12,241 trastuzumab users and 12,241 non-users were enrolled. We found that trastuzumab users had significantly worse HF-free survival but not Af-free survival than non-trastuzumab users. In the competing risk analysis, the use of trastuzumab did not increase the risk of Af (hazard ratio [HR] 0.76, P = 0.0006) but was associated with HF (HR 1.19, P = 0.0052). The risk trends among stratifications by comorbidities and concurrent medication remained in similar directions for both Af and HF. CONCLUSION: Trastuzumab in real-world practice was associated with an increased risk of HF, but was not associated with an increased risk of Af in BC patients. Trastuzumab-induced arrhythmogenic effects may be masked by concurrent heart-protecting measures, more prominent roles of comorbidities or concurrent medications under real-world settings. Further studies are required.

Applying Apriori algorithm to explore long-term care services usage status-Variables based on the combination of patients with dementia and their caregivers.

Purpose: The aim of this study was to identify the combination of patients with dementia and their caregivers' characteristics associated with long-term care (LTC) services usage. Patients and methods: A cross-sectional study was conducted with 475 patients with mild, moderate, and severe dementia at Changhua Christian Hospital, Taiwan. Eleven types of variables from patients with dementia, nine types of variables from patients' caregivers, and 15 types of LTC services were used for this study. The Apriori algorithm was employed to identify the attributes from the patients and their caregivers who used a particular LTC service from a comprehensive viewpoint. Results: A total of 75 rules were generated by the Apriori algorithm with support of 2%, confidence of 80%, and lift >1. Among these rules, 25 rules belonged to home personal care services which were summarized further into four general rules for home personal care services. On the other hand, 50 rules belonged to assistive devices that were summarized further into 21 general rules based on their similarities. Patient's walking ability, patient's emotional liability, unemployed or retired caregivers, caregivers' feelings with either helplessness or hopelessness, and caregivers who cared for patients with dementia solely were found to be the critical variables to use home personal care services. In contrast, patient's walking ability, age, and severity as well as caregivers' age, mood, marital status, caregiving burden, and the patient being cared for mainly by a foreign care helper were found to be the critical variables to use assistive devices. Conclusion: This study showed preliminary results on the LTC service usage from patients with dementia and their caregivers residing in the community. Understanding the patient-caregiver dyad's profile leads the service providers, policymakers, and the referral team to tailor service provisions better to meet the needs and identify the potential target groups. The findings in this study serve as references to reduce caregivers' burden as well as to improve the quality of care for patients with dementia.

Computed Tomography-Guided Endoscopic Surgery in Lumbar Disc Herniation With High-grade Migration: A Retrospective, Comparative Study.

BACKGROUND: Symptomatic herniated intervertebral discs are debilitating. However, surgical management poses a significant challenge for endoscopic spine surgeons, especially in high-grade migrated lesions. OBJECTIVES: This study aimed to  assess the surgical and clinical outcomes after applying a computed tomography navigated percutaneous endoscopic lumbar discectomy. STUDY DESIGN: The data of patients with high-grade lumbar disc migration who underwent percutaneous endoscopic lumbar discectomy at our spine center were retrospectively collected and analyzed from November 2017 to May 2019. The patients were divided into 2 groups based on different workflows, with group O who underwent percutaneous endoscopic lumbar discectomy with computed-tomography navigation (O-arm), and group C who underwent conventional fluoroscopic guidance (C-arm). SETTING: Twenty-one (n = 21) patients were enrolled with data fully documented. There were 9 patients in group O (n = 9) and 12 patients in group C (n = 12). METHODS: An intraoperative 3-dimensional image was obtained using the O-arm device (O-arm®, Medtronic, Inc., Louisville, CO, United States) after patient positioning in group O, and enable multiplanar visualization during exploring the entry point, trajectory, orientation, and finally discectomy. In group C, conventional imaging scanner intensifier (C-arm) was used during the procedure. RESULTS: The operative time (99.4 ± 40.7 vs 86.9 ± 47.9 minutes, P = .129), blood loss (11.1 ± 15.7 vs 6.7 ± 8.2 mL, P = .602), and hospital stay (2.9 ± 0.3 vs 2.8 ± 0.6 days, P = .552) were similar between the 2 groups. However, group O showed more reduction in the pain and faster functional recovery immediately after the surgery (Visual Analog Score [VAS]: -9 vs -6.7, P =.277; Oswestry Disability Index [ODI]: -53.2% vs -29.1%, P = 0.006) and during the one-year follow-up (VAS: -8.1 vs -7.3, P =.604; ODI: -56.7% vs -40.1%, P = .053) compared with group C. LIMITATIONS: The retrospective nature of the study design, the small population size, and the shorter period of follow-up required further study. CONCLUSIONS: Computed tomography-navigated percutaneous endoscopic surgery is safe and effective for lumbar disc herniation with high-grade migration, and enhance early functional recovery even compared with conventional fluoroscopic guidance.

Percutaneous Endoscopic Surgery Alone to Treat Severe Infectious Spondylodiscitis in the Thoracolumbar Spine: A Reparative Mechanism of Spontaneous Spinal Arthrodesis.

BACKGROUND: Infective spondylodiscitis has been treated solely with antibiotics based on the pathogen identified. Surgical intervention was used in cases of unidentified pathogens, failed antibiotic treatment, neurological deficit, or instability. The standard surgical procedure was debridement and interbody fusion with a bone graft through the anterior approach, followed by posterior instrumentation. Recently, percutaneous endoscopic surgery has been proven to be safe and effective for treating infectious spondylodiscitis. The results of endoscopy surgery treatment alone for infectious spondylodiscitis with severe bony destruction were analyzed in this study. OBJECTIVE: To describe the clinical and radiological outcomes in patients with infectious spondylodiscitis and severe bony destruction, who were treated with minimally invasive endoscopic surgery alone. STUDY DESIGN: Retrospective observational study (Institutional Review Board: CMUH 105-REC2-101). SETTING: An inpatient surgery center. METHODS: The study included 24 patients with infectious spondylodiscitis and severe bony destruction treated with endoscopy surgery. The patients were treated according to the endoscopic surgical protocol and were followed up for at least 5 years. A retrospective chart review was conducted to evaluate the locations, symptoms and signs, comorbidity, pain scale, and functional outcome. Laboratory data, such as erythrocyte sedimentation rate and C-reactive protein level, and clinical outcomes, including the pain scale, visual analogue scale, and functional score of Oswestry disability index, were recorded. All patients underwent a preoperative magnetic resonance imaging (MRI) scan and were carefully reviewed and classified based on the severity, including endplate erosion, bone edema (low T1, high T2), loss of vertebral height, paravertebral inflammation, paravertebral abscess, and epidural abscess. All patients underwent a plain film follow-up at 3, 6, 9, 12, and 18 months after surgery and computed tomography at 12 months postoperatively. RESULTS: The comorbidities of patients were categorized according to the Charlson Comorbidity Index. The results revealed 10 lesions on the thoracic or upper lumbar spine (between T10 and L3) and 14 on the lower lumbar spine (between L3 and S1). Bone destruction as a result of severe infection and loss of disc height was observed in most cases. During the final follow-up, no significant changes were observed in the sagittal alignment, and a kyphotic angle change of less than 10° was observed in 20 cases. Syndesmophyte formation along the anterior longitudinal ligament (ALL), paravertebral syndesmophyte formation, intervertebral bony fusion, and bony ankylosis of the facet joints in the form of osteophyte formation and fusion were noted. No posterior instrumentation surgery was performed for instability in our case series. LIMITATIONS: This was a retrospective observational clinical case series with small sample size. CONCLUSIONS: A trend of spontaneous spinal arthrodesis, including syndesmophyte formation along the ALL, paravertebral ligaments, direct intervertebral bone growth, and bony ankylosis of the facet joint were observed after a minimally invasive endoscopy treatment for infectious spondylodiscitis. The stability of the 3 columns resulted in segmental stability, which prevented the progression of the kyphotic deformity. Percutaneous endoscopic surgery is safe and effective for treating infectious spondylodiscitis even in patients with severe bony destruction.

Prediction of Institutionalization for Patients With Dementia in Taiwan According to Condition at Entry to Dementia Collaborative Care.

This study aimed to examine the institutionalization rate in patients with dementia in Taiwan, identify the predictors of institutionalization, and conduct a mediation analysis of caregiver burden between neuropsychiatric symptoms and institutionalization. We analyzed data from a retrospective cohort registered in dementia collaborative care (N = 518). The analyses applied univariate and multivariate Cox proportional hazard regression with Firth's penalized likelihood to assess the relationship between each predictor at entry and institutionalization for survival analysis. Thirty (5.8%) patients were censored due to institutionalization after a median follow-up of one-and-a-half years. Neuropsychiatric symptoms, loss of walking ability, and living alone predicted institutionalization. Caregiver burden may partially mediate the effects of neuropsychiatric symptoms and institutionalization. High caregiver burden due to presence of neuropsychiatric symptoms may partially contribute to institutionalization among people living with dementia in Taiwan. However, proper management of neuropsychiatric symptoms and caregiver empowerment may ameliorate institutionalization risk.

Prevalence of Tumor Genomic Alterations in Homologous Recombination Repair Genes Among Taiwanese Breast Cancers.

PURPOSE: Deleterious germline BRCA1/2 mutations are among the most highly pathogenic variants in hereditary breast and ovarian cancer syndrome. Recently, genes implicated in homologous recombination repair (HRR) pathways have been investigated extensively. Defective HRR genes may indicate potential clinical benefits from PARP (poly ADP ribose polymerase) inhibitors beyond BRCA1/2 mutations. METHODS: We evaluated the prevalence of BRCA1/2 mutations as well as alterations in HRR genes with targeted sequencing. A total of 648 consecutive breast cancer samples were assayed, and HRR genes were evaluated for prevalence in breast cancer tissues. RESULTS: Among 648 breast cancers, there were 17 truncating and 2 missense mutations in BRCA1 and 45 truncating and 1 missense mutation in BRCA2, impacting 3% and 5% of the study population (collectively altered in 6%) with cooccurrence of BRCA1/2 in 7 breast cancers. On the other hand, HRR genes were altered in 122 (19%) breast cancers, while TBB (Talazoparib Beyond BRCA) trial-interrogated genes (excluding BRCA1/2) were mutated in 107 (17%) patients. Beyond BRCA1/2, the most prevalent HRR mutant genes came from ARID1A (7%), PALB2 (7%), and PTEN (6%). Collectively, 164 (25%) of the 648 Taiwanese breast cancer samples harbored at least one mutation among HRR genes. CONCLUSIONS: The prevalence of BRCA1/2 mutations was far below one tenth, while the prevalence of HRR mutations was much higher and approached one-fourth among Taiwanese breast cancers. Further opportunities to take advantage of defective HRR genes for breast cancer treatment should be sought for the realization of precision medicine.

Clinical outcomes and metastatic behavior between de novo versus recurrent HER2-positive metastatic breast cancer: A 17-year single-institution cohort study at Taipei Veterans General Hospital.

BACKGROUND: To assess the clinical outcomes and metastatic behavior between de novo versus recurrent human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer (MBC) based on a single-institution database in Taiwan. METHODS: We retrospectively identified patients diagnosed between January 2000 and December 2017 with de novo stage IV or recurrent HER2-positive MBC. Several variables were recorded in patients with recurrent disease: age at diagnosis, metastatic site, hormone receptor (HR) status, HER2 status, and disease-free interval (DFI). Treatments and metastatic patterns were compared between de novo stage IV and recurrent MBC cohorts. Post-metastasis survival (PMS) was estimated using the Kaplan-Meier method with log-rank tests. Hazard ratios and 95% CIs were estimated using Cox regression analysis. RESULTS: In total, 1360 patients were diagnosed with breast cancer with HER2 overexpression. At baseline, de novo stage IV patients were older than recurrent MBC patients (median age 58 vs 53). The majority of the de novo stage IV patients were diagnosed after 2010, while most of the recurrent MBC patients were diagnosed during 2000-2009. An increased number of de novo stage IV patients underwent targeted therapy than recurrent MBC patients was also noted. PMS in patients with de novo stage IV and recurrent MBC was 79.2 months and 61.8 months, respectively, which indicated significant better survival in de novo stage IV than those with recurrent MBC disease. Longer survival was also noted in de novo stage IV and recurrent MBC with DFI >24 months than in those with recurrent MBC with DFI <24 months and in patients receiving HER2-targeted therapy after MBC diagnosis than in those not receiving the therapy. However, median PMS showed no significant difference between patients with the luminal B2 (HR-positive, HER2-negative) and HER2-enriched (HR-negative, HER2-positive) subtypes. After adjustment in multivariate analysis, a low risk of BC-specific death was observed in patients aged >50 years, those receiving HER2-targeted therapy for MBC, and those with oligometastasis, while patients with first metastases to the liver or brain showed a higher risk of BC-specific death than those without metastases. CONCLUSION: De novo and recurrent MBC have distinct characteristic, metastatic patterns and outcomes in Asian HER2-positive breast cancer patients. The age distribution and survivals between HR+/- status were different to non-Asian group. These differences should be further investigated in the future considering ethnic factor.

Acute Hepatitis Due to Agomelatine Use in Elderly Women with Depression: Case Series.

Although agomelatine may be associated with an increased risk of hepatotoxicity, the incidence rate of acute hepatitis seemed divergent between clinical trials and daily practice. Whether aging or gender is a risk factor in developing hepatotoxicity due to agomelatine is not clear. We present 3 older female cases with acute hepatitis occurring due to highly probable idiosyncratic drug-induced liver injury caused by agomelatine. From these cases, regular surveillance on liver function in the older women taking antidepressants would be of benefits.

VGH-TAYLOR: Comprehensive precision medicine study protocol on the heterogeneity of Taiwanese breast cancer patients.

Heterogeneity in breast cancer leads to diverse morphological features and different clinical outcomes. There are inherent differences in breast cancer between the populations in Asia and in western countries. The use of immune-based treatment in breast cancer is currently in the developmental stage. The VGH-TAYLOR study is designed to understand the genetic profiling of different subtypes of breast cancer in Taiwan and define the molecular risk factors for breast cancer recurrence. The T-cell receptor repertoire and the potential effects of immunotherapy in breast cancer subjects is evaluated. The favorable biomarkers for early detection of tumor recurrence, diagnosis and prognosis may provide clues for the selection of individualized treatment regimens and improvement in breast cancer therapy.

Lay abstract We describe the rationale and design for the VGH-TAYLOR study, which includes Taiwanese patients with breast cancer and with a wide spectrum of clinical scenarios covering different breast cancer subtypes and clinical settings, such as the neoadjuvant, adjuvant and metastatic settings. The gene expression profile and genetic mutations of breast cancer subjects with the primary and recurrent tumors are compared. We also explore whether immune-related gene expression and diversity have any impact on response to treatment and survival. This study aims to discover biomarkers of detection of cancer relapse, diagnosis and prognosis that may enable personalized medicine and improvement in breast cancer treatment. Clinical trial registration: NCT04626440 (ClinicalTrials.gov).