Comparing Low- or Standard-Dose Alteplase in Endovascular Thrombectomy: Insights From a Nationwide Registry.

BACKGROUND: Timely intravenous thrombolysis and endovascular thrombectomy are the standard reperfusion treatments for large vessel occlusion stroke. Currently, it is unknown whether a low-dose thrombolytic agent (0.6 mg/kg alteplase) can offer similar efficacy to the standard dose (0.9 mg/kg alteplase). METHODS: We enrolled consecutive patients in the multicenter Taiwan Registry of Endovascular Thrombectomy for Acute Ischemic Stroke who had received combined thrombolysis (within 4.5 hours of onset) and thrombectomy treatment from January 2019 to April 2023. The choice of low- or standard-dose alteplase was based on the physician's discretion. The outcomes included successful reperfusion (modified Thrombolysis in Cerebral Infarction score, 2b-3), symptomatic intracerebral hemorrhage, 90-day modified Rankin Scale score, and 90-day mortality. The outcomes between the 2 groups were compared using multivariable logistic regression and inverse probability of treatment weighting-adjusted analysis. RESULTS: Among the 2242 patients in the Taiwan Registry of Endovascular Thrombectomy for Acute Ischemic Stroke, 734 (33%) received intravenous alteplase. Patients in the low-dose group (n=360) were older, had more women, more atrial fibrillation, and longer onset-to-needle time compared with the standard-dose group (n=374). In comparison to low-dose alteplase, standard-dose alteplase was associated with a lower rate of successful reperfusion (81% versus 87%; adjusted odds ratio, 0.63 [95% CI, 0.40-0.98]), a numerically higher incidence of symptomatic intracerebral hemorrhage (6.7% versus 3.9%; adjusted odds ratio, 1.81 [95% CI, 0.88-3.69]), but better 90-day modified Rankin Scale score (functional independence [modified Rankin Scale score, 0-2], 47% versus 31%; adjusted odds ratio, 1.91 [95% CI, 1.28-2.86]), and a numerically lower mortality rate (9% versus 15%; adjusted odds ratio, 0.73 [95% CI, 0.43-1.25]) after adjusting for covariates. Similar results were observed in the inverse probability of treatment weighting-adjusted models. The results were consistent across predefined subgroups and age strata. CONCLUSIONS: Despite the lower rate of successful reperfusion and higher risk of symptomatic intracerebral hemorrhage with standard-dose alteplase, standard-dose alteplase was associated with a better functional outcome in patients receiving combined thrombolysis and thrombectomy.

Parkin drives pS65-Ub turnover independently of canonical autophagy in Drosophila.

Parkinson's disease-related proteins, PINK1 and Parkin, act in a common pathway to maintain mitochondrial quality control. While the PINK1-Parkin pathway can promote autophagic mitochondrial turnover (mitophagy) following mitochondrial toxification in cell culture, alternative quality control pathways are suggested. To analyse the mechanisms by which the PINK1-Parkin pathway operates in vivo, we developed methods to detect Ser65-phosphorylated ubiquitin (pS65-Ub) in Drosophila. Exposure to the oxidant paraquat led to robust, Pink1-dependent pS65-Ub production, while pS65-Ub accumulates in unstimulated parkin-null flies, consistent with blocked degradation. Additionally, we show that pS65-Ub specifically accumulates on disrupted mitochondria in vivo. Depletion of the core autophagy proteins Atg1, Atg5 and Atg8a did not cause pS65-Ub accumulation to the same extent as loss of parkin, and overexpression of parkin promoted turnover of both basal and paraquat-induced pS65-Ub in an Atg5-null background. Thus, we have established that pS65-Ub immunodetection can be used to analyse Pink1-Parkin function in vivo as an alternative to reporter constructs. Moreover, our findings suggest that the Pink1-Parkin pathway can promote mitochondrial turnover independently of canonical autophagy in vivo.

Prompt antimicrobial therapy and source control on survival and defervescence of adults with bacteraemia in the emergency department: the faster, the better.

BACKGROUND: Bacteraemia is a critical condition that generally leads to substantial morbidity and mortality. It is unclear whether delayed antimicrobial therapy (and/or source control) has a prognostic or defervescence effect on patients with source-control-required (ScR) or unrequired (ScU) bacteraemia. METHODS: The multicenter cohort included treatment-naïve adults with bacteraemia in the emergency department. Clinical information was retrospectively obtained and etiologic pathogens were prospectively restored to accurately determine the time-to-appropriate antibiotic (TtAa). The association between TtAa or time-to-source control (TtSc, for ScR bacteraemia) and 30-day crude mortality or delayed defervescence were respectively studied by adjusting independent determinants of mortality or delayed defervescence, recognised by a logistic regression model. RESULTS: Of the total 5477 patients, each hour of TtAa delay was associated with an average increase of 0.2% (adjusted odds ratio [AOR], 1.002; P < 0.001) and 0.3% (AOR 1.003; P < 0.001) in mortality rates for patients having ScU (3953 patients) and ScR (1524) bacteraemia, respectively. Notably, these AORs were augmented to 0.4% and 0.5% for critically ill individuals. For patients experiencing ScR bacteraemia, each hour of TtSc delay was significantly associated with an average increase of 0.31% and 0.33% in mortality rates for overall and critically ill individuals, respectively. For febrile patients, each additional hour of TtAa was significantly associated with an average 0.2% and 0.3% increase in the proportion of delayed defervescence for ScU (3085 patients) and ScR (1266) bacteraemia, respectively, and 0.5% and 0.9% for critically ill individuals. For 1266 febrile patients with ScR bacteraemia, each hour of TtSc delay respectively was significantly associated with an average increase of 0.3% and 0.4% in mortality rates for the overall population and those with critical illness. CONCLUSIONS: Regardless of the need for source control in cases of bacteraemia, there seems to be a significant association between the prompt administration of appropriate antimicrobials and both a favourable prognosis and rapid defervescence, particularly among critically ill patients. For ScR bacteraemia, delayed source control has been identified as a determinant of unfavourable prognosis and delayed defervescence. Moreover, this association with patient survival and the speed of defervescence appears to be augmented among critically ill patients.

Suture Contamination During Arthroscopic Rotator Cuff Repair Is Associated With Significantly Higher Retear Rates in Magnetic Resonance Imaging: A Matched-Pair Analysis.

PURPOSE: To evaluate the correlation between suture contamination and rotator cuff tendon retear after arthroscopic rotator cuff repair. METHODS: Patients undergoing primary arthroscopic rotator cuff repair from April 1, 2020, to September 30, 2022, were enrolled. Those younger than 18 years, with a history of shoulder surgeries or shoulder infection episodes, or who declined participation were excluded. A 5-cm section of the first-cut suture, originating from the anchor eyelet ends, in each rotator cuff repair surgery was subjected to bacteria culture and polymerase chain reaction analysis. Patients with positive culture findings were matched 1:1 to those with negative culture reports based on age, sex, tear size as well as involved tendons, preoperative fatty infiltration grade (Goutallier grade), and preoperative muscle atrophy grade (Warner score). Postoperative rotator cuff tendon retear assessments were conducted at the 6-month mark using the Sugaya classification via magnetic resonance imaging. The Wilcoxon signed-rank test was used for matched-pair comparisons between the groups. RESULTS: A total of 141 patients (60 men and 81 women) with a mean age of 61.0 ± 8 years were finally enrolled. Twenty-six patients (18 men and 8 women) had a positive culture, while 115 patients (42 men and 73 women) had a negative culture. After the propensity score matching process, 24 culture-negative patients (16 men and 8 women) were selected as the culture-negative group. Age, fatty infiltration grade, and muscle atrophy grade were not significantly different between matched groups. The retear grade in the culture-positive group was significantly higher than that in the culture-negative group (P = .020) under the matched-pair comparison. Cutibacterium acnes was the most prevalent bacterial species responsible for suture contamination. CONCLUSIONS: The matched-pair analysis revealed that the presence of bacterial contamination on sutures was associated with a higher risk of retear on magnetic resonance imaging following arthroscopic rotator cuff repair. LEVEL OF EVIDENCE: Level III, retrospective cohort study.

Dual antiplatelet therapy is associated with favorable outcome in acute minor stroke with an onset-to-door time beyond 24 h.

BACKGROUND/PURPOSE: In patients with noncardioembolic acute minor ischemic stroke (AMIS), dual antiplatelet therapy (DAPT) with aspirin plus clopidogrel within 24 h after stroke onset was more effective than aspirin alone. This study investigated the efficacy and safety of DAPT in AMIS patients with an onset-to-door time (OTDT) of more than 24 h. METHODS: This was a retrospective analysis of a prospective stroke registry from 2015 to 2021. Patients with AMIS and an OTDT within seven days were classified into the Early (≤24 h) and Late groups (>24 h) according to the time of antiplatelet administration after stroke onset. RESULTS: In total, 691 patients were identified. Of these, 446 (64.5%) and 245 (35.5%) patients were classified into the Early and Late groups, respectively. The rates of recurrent infarction and symptomatic intracranial hemorrhage at 90 days were similar between the single antiplatelet therapy (SAPT) and DAPT subgroups in both the Early and Late groups. More patients in the DAPT subgroup had a favorable outcome (modified Rankin scale of 0-1) at 90 days in both Early (84.2% versus 75.0%, p = 0.016) and Late (88.2% versus 76.9%, p = 0.040) groups. DAPT was independently associated with a favorable outcome in both the Early (odds ratio, 1.95; 95% CI, 1.15-3.32; p = 0.013) and Late (odds ratio, 2.72; 95% CI, 1.14-6.48; p = 0.024) groups. CONCLUSION: In patients with AMIS and an OTDT of more than 24 h, DAPT was associated with a favorable outcome at 90 days.

2024 TSOC/TSPS Joint Consensus: Strategies for Advanced Vascular Wound Management in Arterial and Venous Diseases.

The Taiwan Society of Cardiology (TSOC) and Taiwan Society of Plastic Surgery (TSPS) have collaborated to develop a joint consensus for the management of patients with advanced vascular wounds. The taskforce comprises experts including preventive cardiologists, interventionists, and cardiovascular and plastic surgeons. The consensus focuses on addressing the challenges in diagnosing, treating, and managing complex wounds; incorporates the perfusion evaluation and the advanced vascular wound care team; and highlights the importance of cross-disciplinary teamwork. The aim of this joint consensus is to manage patients with advanced vascular wounds and encourage the adoption of these guidelines by healthcare professionals to improve patient care and outcomes. The guidelines encompass a range of topics, including the definition of advanced vascular wounds, increased awareness, team structure, epidemiology, clinical presentation, medical treatment, endovascular intervention, vascular surgery, infection control, advanced wound management, and evaluation of treatment results. It also outlines a detailed protocol for assessing patients with lower leg wounds, provides guidance on consultation and referral processes, and offers recommendations for various wound care devices, dressings, and products. The 2024 TSOC/TSPS consensus for the management of patients with advanced vascular wounds serves as a catalyst for international collaboration, promoting knowledge exchange and facilitating advancements in the field of advanced vascular wound management. By providing a comprehensive and evidence-based approach, this consensus aims to contribute to improved patient care and outcomes globally.

Pre-existing humoral immunity and CD4+ T cell response correlate with cross-reactivity against SARS-CoV-2 Omicron subvariants after heterologous prime-boost vaccination.

BACKGROUND: Information regarding the heterologous prime-boost COVID vaccination has been fully elucidated. The study aimed to evaluate both humoral, cellular immunity and cross-reactivity against variants after heterologous vaccination. METHODS: We recruited healthcare workers previously primed with Oxford/AstraZeneca ChAdOx1-S vaccines and boosted with Moderna mRNA-1273 vaccine boost to evaluate the immunological response. Assay used: anti-spike RBD antibody, surrogate virus neutralizing antibody and interferon-γ release assay. RESULTS: All participants exhibited higher humoral and cellular immune response after the booster regardless of prior antibody level, but those with higher antibody level demonstrated stronger booster response, especially against omicron BA.1 and BA.2 variants. The pre-booster IFN-γ release by CD4+ T cells correlates with post-booster neutralizing antibody against BA.1 and BA.2 variant after adjustment with age and gender. CONCLUSIONS: A heterologous mRNA boost is highly immunogenic. The pre-existing neutralizing antibody level and CD4+ T cells response correlates with post-booster neutralization reactivity against the Omicron variant.

Extended skin cleaning on the shoulder with chlorhexidine reduces the cutaneous bacterial load but fails to decrease suture contamination in patients undergoing arthroscopy rotator cuff repair.

BACKGROUND: It remains unclear whether preoperative skin cleaning of the chin, neck, and chest with chlorhexidine soap can reduce suture contamination by Cutibacterium acnes in patients undergoing arthroscopic rotator cuff repair. METHODS: This study included patients who underwent primary arthroscopic rotator cuff repair. Exclusion criteria included age <18 years, previous shoulder surgery, history of shoulder infection, and allergy to chlorhexidine. Patients were randomized into 3 groups. Patients in the control group cleaned their skin with soap and water, as usual. Patients in the shoulder group cleaned their shoulders with chlorhexidine soap 3 days before surgery, whereas patients in the extended shoulder group additionally cleaned their chest, back, neck, and face with chlorhexidine soap. On the day of surgery, skin swab samples were obtained from the shoulder after surgical draping. After rotator cuff repair, sutures were cut from the anchor ends. Both traditional culture methods and polymerase chain reaction (PCR) were used. RESULTS: Ninety patients were enrolled (32 in the control group, 29 in the shoulder group, and 29 in the extended shoulder group) in the present study. The culture-positive rate from the posterior shoulder skin samples in the extended shoulder group (17.2%) was significantly lower than that in the control (40.6%) and shoulder (48.3%) groups (P = .036), whereas the culture-positive rates were not different among the 3 groups in other skin samples as well as the suture samples. The detection rates of C acnes in suture samples were 12.5%, 13.8%, and 17.2% in the control, shoulder, and extended shoulder groups, respectively (P = .603). CONCLUSION: Extensive skin cleaning of the shoulder region with chlorhexidine helps reduce the shoulder cutaneous bacterial load, but the detection of C acnes suture contamination in patients undergoing arthroscopic rotator cuff repair remained untouched regardless of the use of chlorhexidine soap in skin cleaning on the preoperative days.

Outcomes and Hemodynamic Performances of Transcatheter Aortic Valve Replacement with Two Generations of Self-Expanding Transcatheter Aortic Valves.

Background: The superiority of the new-generation self-expanding Evolut R compared with the first-generation CoreValve with regards to outcomes after transcatheter aortic valve replacement (TAVR) is unclear. The aim of this study was to investigate the hemodynamic and clinical performance of Evolut R compared with its direct predecessor, CoreValve, in a Taiwanese population. Methods: This study included all consecutive patients who underwent TAVR with either CoreValve or Evolut R between March 2013 and December 2020. Thirty-day Valve Academic Research Consortium-2 (VARC-2)-defined outcomes and hemodynamic performances were investigated. Results: There were no significant differences in baseline demographic characteristics between the patients receiving CoreValve (n = 117) or Evolut R (n = 117). Aortic valve-in-valve procedures for failed surgical bioprosthesis and procedures under conscious sedation were performed significantly more often with Evolut R. Pre-dilatation was performed significantly more often and contrast media volume was significantly higher with CoreValve. Stroke (0% vs. 4.3%, p = 0.024) and the need for emergent conversion to open surgery (0% vs. 5.1%, p = 0.012) were significantly lower in Evolut R than in CoreValve recipients. Evolut R significantly reduced 30-day composite safety endpoint (4.3% vs. 15.4%, p = 0.004). Conclusions: Advancements in transcatheter valve technologies have resulted in improved outcomes for patients undergoing TAVR with self-expanding valves. With the new-generation Evolut R, device success was high and the 30-day composite safety endpoint was significantly reduced after TAVR compared with CoreValve.

Aortic remodeling of the provisional extension to induce complete attachment technique in DeBakey type IIIb aortic dissection.

BACKGROUND/PURPOSE: Data about volumetric remodeling of the provisional extension to induce complete attachment (PETTICOAT) technique on DeBakey type IIIb aortic dissection in acute and subacute phases were scarce. The proper timing to perform this technique to promote false lumen reduction was also unknown. METHODS: Patients with DeBakey type IIIb aortic dissection who underwent the PETTICOAT technique between December 2005 and March 2017 were reviewed and divided into acute (treatment occurred ≦14 days after symptom onset) and subacute (15-90 days) groups. Remodeling parameters of the true and false lumens were analyzed. Receiver operating characteristic curve was used to deduce the timing of this technique. RESULTS: In the 2-year follow-up, the acute group (N = 20) demonstrated significant true lumen expansion and false lumen regression in the thoracic, abdominal, and total aorta. However, the subacute group (N = 20) only showed significant shrinkage in the false lumen of the thoracic and total aorta. Using PETTICOAT technique within 36 days after the aortic event may result in better total false lumen reduction. CONCLUSION: For DeBakey type IIIb aortic dissection, more prominent true lumen expansion and false lumen reduction were noted when using the PETTICOAT technique in the acute phase. When performed within 36 days after symptoms onset, the PETTICOAT technique may potentiate better total false lumen regression.

Acute delirium as an initial manifestation of COVID-19 patients with acute ischemic stroke: Report on two cases.

Psychiatric and neurological complications of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection are common. Psychiatric symptoms are so common that they are easily misinterpreted as an affective disorder induced by SARSCoV-2 infection. However, psychiatric symptoms, such as acute delirium, though rarely seen, can be the initial manifestations of acute ischemic stroke (AIS). These psychiatric symptoms may confuse the diagnosis of acute stroke, which needs correct and timely management. We report two hospitalized cases with SARS-CoV-2 infection and elevated serum D-dimer levels having acute delirium as the initial manifestation of AIS. The diagnostic processes were challenging and time-consuming, so reperfusion therapy could not be given in the therapeutic time window. The diagnoses of AIS were finally made by brain magnetic resonance imaging which showed diffusion restriction at the right middle cerebral artery territory in both cases. Features of psychiatric complications and stroke in coronavirus disease 2019 (COVID-19) patients are reviewed. For the hospitalized COVID-19 patients with elevated levels of serum Ddimer and acute delirium, acute stroke with neuropsychiatric manifestations should beconsidered.

Mobilization of Hematopoietic Stem and Progenitor Cells during Dengue Virus Infection.

Hematopoietic stem and progenitor cells (HSPCs) mobilization is the movement of HSPCs from the bone marrow to the peripheral blood or tissue induced by stress. HSPC mobilization is a well-known response to protect the host during infection through urgent differentiation of HSPCs to immune cells. Dengue virus (DENV) infection is known to cause stress in infected humans and the mobilizing capacity of HSPCs during DENV infection in affected patients has not been fully investigated. Here, we investigated whether DENV infection can induce HSPC mobilization and if the mobilized HSPCs are permissive to DENV infection. White blood cells (WBCs) were collected from dengue patients (DENV+) and healthy donors and analyzed by flow cytometry and plaque assay. Elevated HSPCs levels were found in the WBCs of the DENV+ group when compared to the healthy group. Mobilization of HSPCs and homing markers (skin and gut) expression decreased as the patients proceeded from dengue without symptoms (DWoWS) to severe dengue (SD). Mobilizing HSPCs were not only permissive to DENV infection, but infectious DENV could be recovered after coculture. Our results highlight the need for further investigation into HSPC mobilization or alterations of hematopoiesis during viral infections such as DENV in order to develop appropriate countermeasures.

Technical Characteristics and Feasibility of Coronary Angiography and Percutaneous Coronary Interventions Performed after Transcatheter Aortic Valve Replacement with Self-Expanding Valves.

BACKGROUND: Coronary angiography (CA) or percutaneous coronary intervention (PCI) after transcatheter aortic valve replacement (TAVR) may become technically challenging after implantation of the self-expanding Medtronic CoreValve (MCV) device, which extends above the coronary ostia. The aim of this study was to investigate the incidence and feasibility of CA or PCI and the outcomes of PCI after TAVR with the MCV device. METHODS: From July 2014 to April 2020, among 209 patients treated with TAVR with a MCV device, 14 (7%) underwent CA or PCI after the procedure at a mean duration of 28 ± 15 months at our institution. RESULTS: The mean age of the patients was 83 ± 6 years. Thirteen (93%) patients underwent CA due to angina symptoms with a positive noninvasive test, and 1 underwent CA for acute coronary syndrome. Most of the CA and PCI procedures were performed through a radial approach: 11 patients (79%) via the right radial artery, 1 (7%) the left radial artery, and 2 (14%) through the right femoral artery. CA of the left and right coronary arteries was successfully achieved in 13 patients (93%) with Judkin left (3.5 to 5) diagnostic catheters and in 11 patients (79%) with Judkin right (4) diagnostic catheters. The second-line catheter of choice was the Amplatz left (AL) 1 catheter for the right coronary artery and AL 2 for the left coronary artery. Procedural success was achieved in all 5 patients who underwent post-TAVR PCI without procedural or in-hospital complications. The use of a Guideliner microcatheter facilitated stent delivery in one patient. CONCLUSIONS: Coronary angiography or PCI following TAVR with a MCV device is feasible and safe, but requires understanding of the three-dimensional geometry of the prosthetic valve and its relationship to the coronary ostia.

Risk factors for nonresponsive hydration in patients with spinal cerebrospinal fluid leakage.

BACKGROUND: Spinal cerebrospinal fluid (CSF) leakage is frequently encountered clinically after lumbar puncture or spontaneous events. Although some patients recover without treatment or after intensive hydration, some require an epidural blood patch (EBP). The risks of nonresponsive hydration remain unknown. Therefore, we identified the risk factors for patients with spinal CSF leakage nonresponsive to hydration. METHODS: We retrospectively reviewed patients diagnosed with spinal CSF leakage between January 2010 and March 2021. Clinical data, including patient age, sex, etiology, and radiological indications in magnetic resonance imaging, were compared between patients who were responsive and non-responsive to hydration. RESULTS: Of the 74 patients with spinal CSF leakage, 25 were responsive to hydration and 49 required EBP. Patients who were nonresponsive to hydration were older (39.27 vs. 34.32 years, P = 0.01), had a higher percentage of spontaneous intracranial hypotension (93.88% vs. 68.00%, P = 0.005), had more spinal CSF leakage (12.04 vs. 8.04, P = 0.01), and had a higher percentage of dural sinus engorgement (81.63% vs. 60.00%, P = 0.044). Spontaneous intracranial hypotension (odds ratio [OR]: 4.63; 95% confidence interval [CI]: 1.00-21.38) and having ≥9 spinal CSF leakages (OR: 3.29; 95% CI: 1.08-10.01), as indicated by magnetic resonance myelography, are considered risk factors for noneffective hydration. CONCLUSIONS: Patients with spinal CSF leakage who have spontaneous intracranial hypotension and those with ≥9 spinal CSF leakages are considered at risk for noneffective hydration. EBP should be considered early in these patients.

Internal iliac artery preservation outcomes of endovascular aortic repair for common iliac aneurysm: iliac branch device versus crossover chimney technique.

OBJECTIVES: To compare the outcomes of using iliac branch devices (IBD) and the crossover chimney (COCh) technique for preserving the internal iliac artery (IIA) during endovascular aortic repair in patients with common iliac aneurysm (CIA). METHODS: From February 2010 to July 2016, we recruited 61 consecutive and elective patients. Thirty of them received the IBD, and the remaining 31 received the COCh. Their medical chart was reviewed retrospectively, and computed tomographic angiography was performed at 3, 6, and 12 months postoperatively and then yearly as a follow-up. RESULTS: The median follow-up time was 19.72 ± 5.45 months. The technical success rate reached 100% in both groups. The 12-month and 24-month primary IIA patency rates between IBD and COCh group were 90.00% versus 93.54% (p = 0.67) and 83.33% versus 93.54% (p = 0.25). The numbers of stents were 1.00 ± 0.00 and 1.93 ± 0.24 in the IBD and COCh group (p < 0.001). No significant difference was observed for the incidence of type 1a (IBD/COCh = 3.33%/6.45%, p > 0.99) and type 2 endoleak (IBD/COCh = 13.33%/12.90%, p > 0.99) between two groups. Neither type 1b or type 3 endoleak nor delayed aortic rupture appeared in our series. The postoperative complication rates did not exhibit significant differences either. Free from reintervention was also similar in both groups (IBD/COCh = 22.50 ± 4.62/23.00 ± 3.87 months, p = 0.64). CONCLUSIONS: The IBD and COCh techniques exhibited similar success rates and IIA patency rates at the 24-month follow-up. Both these techniques are feasible for the preservation of IIA in patients with CIA.

Real-world evidence on the safety and effectiveness of fingolimod in patients with multiple sclerosis from Taiwan.

BACKGROUND/PURPOSE: Multiple sclerosis is classified as a rare disease in Taiwan. This study evaluated the safety and effectiveness of fingolimod in patients with relapsing-remitting multiple sclerosis (RRMS) from routine clinical practice in Taiwan. METHODS: In this retrospective, multicentre, observational study, we collected clinical data of patients treated with fingolimod 0.5 mg/day in routine clinical practice between September 2012 and December 2015. Primary outcome was the overall safety of fingolimod; secondary outcome was the annualized relapse rate (ARR). RESULTS: Overall, 62/69 (86.1%) patients were on fingolimod by the end of data collection period. Mean age (±standard deviation [SD]) at inclusion was 37.7 ± 10.10 years; mean duration of MS was 5.4 ± 4.52 years and mean duration of fingolimod exposure was 135.8 patient-years. The most common adverse events (AEs) were bradycardia (21.7%; first-dose related), upper respiratory tract infection, dizziness, and hypoaesthesia (numbness) (11.6% each), followed by urinary tract infection and back pain (7.2% each). Seven patients had liver enzyme-related AEs. Eight patients had absolute lymphocyte counts <0.2 × 103/uL over the study period. One patient developed second degree AV block after first-dosing. Serious AEs were observed in 11 patients (15.9%; mild-to-moderate). No newly developed macular oedema was detected. The ARR was 0.3 ± 0.74 in fingolimod-treated patients and 66.7% of patients were relapse-free. The mean (SD) change from baseline in expanded disability status scale score was -0.30 ± 1.353. CONCLUSION: Fingolimod 0.5 mg/day treatment with an average of 2 years of exposure was associated with a manageable safety profile, and maintained/improved effectiveness in RRMS patients from Taiwan.

Disinfection efficiency of hospital infectious disease wards with chlorine dioxide and hypochlorous acid.

The disinfection efficiencies of two chemical disinfectants, chlorine dioxide and weak acid hypochlorous water (WAHW), were examined in the soiled room and dishwashing room of a hospital infectious disease ward in Taiwan. The investigations were conducted in two seasons, namely winter and summer, in order to examine the correlation between the bioaerosol concentration and the environmental factors. In addition, a single-daily disinfection mode (SM) and a twice-daily disinfection mode (TM) were applied in this study. The results showed that the bacteria and fungi colony counts were strongly correlated with the temperature. Both disinfectants reduced the bacteria and fungi concentrations in the considered rooms. However, of the two disinfectants, the ClO2 showed a stronger disinfection effect than the WAHW. It means that when using ClO2 as the disinfectant, the disinfection efficiency of the TM treatment mode is significantly better than that of the SM treatment mode. But, when using WAHW as the disinfectant, no significant difference is found between the disinfection efficiencies of the two methods. Overall, the results showed that the application of ClO2 twice daily provided the most effective means of satisfying the Taiwan EPA guidelines for the indoor air quality of hospital medical wards.

Cytokine Signature of Dengue Patients at Different Severity of the Disease.

Clinical presentations of dengue fever (DF) are diverse and non-specific, causing unpredictable progression and outcomes. Its progression and severity have been associated with cytokine levels alteration. In this study, dengue patients were classified into groups following the 2009 WHO dengue classification scheme to investigate the cytokine signature at different severity of the disease: dengue without warning sign symptoms (A); dengue with warning signs (B); severe dengue (C); other fever (OF) and healthy (Healthy). We analyzed 23 different cytokines simultaneously, namely IL-1b, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12p70, IL-17A, IL-33, CD14, CD54, CD62E, CD62L, CD62p, CD106, CD121b, CD154, CD178, GM-CSF, IFN-g, MIF, ST2 and TNF from patients admitted to National Cheng Kung University Hospital during the 2015 Taiwan dengue outbreak. Cytokines TNF, CD54, CD62E, CD62L, CD62P, GM-CSF, IL-1b, IL-2, IL-6, IL-8, IL-10, IL-12p70, IL-17A, INF-g and MIF were elevated while CD106, CD154, IL-4 and L-33 were decreased when compared to the control. IL-10 demonstrated to be a potential diagnostic marker for DF (H and A group; AUC = 0.944, H and OF group; AUC = 0.969). CD121b demonstrated to be predictive of the SD (A and B group; AUC = 0.744, B and C group; AUC = 0.775). Our results demonstrate the cytokine profile changes during the progression of dengue and highlight possible biomarkers for optimizing effective intervention strategies.

Two-photon fluorescence and second harmonic generation hyperspectral imaging of old and modern spruce woods.

Spruce is the commonly-used tonewood for the top plate of violin-family instruments, such as violins and cellos. The wood properties can critically determine the acoustic quality. It's been shown the wood of famous old instruments differ from modern ones due to chemical treatment and aging. To reveal the differences microscopically in both spatial and spectral domains, a two-photon hyperspectral system has been applied to investigate the autofluorescence and second harmonic generation within wood samples. Not only the cellular structures were observed through optical sectioning, but the spectral variations were revealed among different age wood samples and different cellular structures.

Women had favourable reverse left ventricle remodelling after TAVR.

BACKGROUND: Being woman is associated with higher survival rates after transcatheter aortic valve replacement (TAVR) despite the increase in periprocedural complications. The left ventricle (LV) remodelling process that follows TAVR is considered to play an important role. We aim to investigate whether gender difference affects the process of LV remodelling after TAVR. MATERIALS AND METHODS: A total of 100 patients (50 men and 50 women) after TAVR were enrolled. Echocardiography was performed at baseline before the TAVR procedure and repeated upon discharge, and at three, nine and 12 months post-TAVR. RESULTS: Women exhibited an early regression of LV mass and the LV mass index (LVMi) decreased 12.0% from 148.3 ± 48.0 to 130.5 ± 43.7 g/m2 at just a median of 17 days after the procedure (P < .001). Almost one-half of the LVMi regression occurred by 17 days post-TAVR and the LVMi regressed 22.0% by 12 months post-TAVR. In contrast, the regression of LVMi in men seemed to be more gradual and the significant regression of LVMi from baseline began to be observed since three months later after TAVR. The LVMi reduction at nine months was 11.5% and achieved 15.4% over one year. Multivariable logistic regression analysis showed only the female sex, better LVEF and greater baseline LVMi were independently associated with greater LVMi regression after TAVR, indicating female gender is an independent predictor for favourable LV remodelling after TAVR. CONCLUSION: In conclusion, female patients with AS had favourable reverse remodelling with greater and earlier LV mass regression post-TAVR compared with the male patients.