A preliminary investigation of dissociation between subjective cognitive complaints and objective cognitive impairments in female patients with fibromyalgia: a role of information processing speed.

OBJECTIVES: Fibromyalgia (FM) is a chronic condition characterised by widespread pain, and cognitive difficulties represent one of the most common symptoms of FM. However, subjective cognitive complaints (SCC) may not necessarily indicate significant abnormalities in objective cognitive performances, and there is limited research investigating the relationship between these two aspects. This study thus aims to analyse the differences between SCC and objective cognitive performance in FM patients and to explore their associations. METHODS: A total of 32 FM female patients (age: 50.91±7.06; years since diagnosis: 4.34±4.53) recruited in this study underwent a comprehensive assessment covering four domains: pain, depression, trait anxiety, SCC, and objective cognitive functions (memory, executive function, and information processing speed). RESULTS: Eighty-seven percent of patients experienced significant negative impacts from pain; meanwhile, 91% and 62% showed marked tendencies towards trait anxiety and depression, respectively. Additionally, 56% of patients reported significantly higher levels of SCC. However, less than one-third of patients demonstrated impairments in various cognitive functions. SCC significantly correlated with pain intensity, depression, information processing speed, and trait anxiety, with pain intensity being a significant predictor (R2=.30). Furthermore, patients with significant SCC exhibited more abnormalities in pain, information processing speed, and trait anxiety compared to those without significant SCC. CONCLUSIONS: SCC may not necessarily correlate with objective cognitive impairments and might be specifically linked to defective information processing speed. It thus merits that clinical assessments for FM patients should incorporate measurements of information processing speed to gain a comprehensive understanding of SCC in FM patients.

Indigenizing and co-producing the ACGME anesthesiology milestone in Taiwan: a Delphi study and subgroup analysis.

BACKGROUND: To implement the ACGME Anesthesiology Milestone Project in a non-North American context, a process of indigenization is essential. In this study, we aim to explore the differences in perspective toward the anesthesiology competencies among residents and junior and senior visiting staff members and co-produce a preliminary framework for the following nation-wide survey in Taiwan. METHODS: The expert committee translation and Delphi technique were adopted to co-construct an indigenized draft of milestones. Descriptive analysis, chi-square testing, Pearson correlation testing, and repeated-measures analysis of variance in the general linear model were employed to calculate the F values and mean differences (MDs). RESULTS: The translation committee included three experts and the consensus panel recruited 37 participants from four hospitals in Taiwan: 9 residents, 13 junior visiting staff members (JVSs), and 15 senior visiting staff members (SVSs). The consensus on the content of the 285 milestones was achieved after 271 minor and 6 major modifications in 3 rounds of the Delphi survey. Moreover, JVSs were more concerned regarding patient care than were both residents (MD = - 0.095, P < 0.001) and SVSs (MD = 0.075, P < 0.001). Residents were more concerned regarding practice-based learning improvement than were JVSs (MD = 0.081; P < 0.01); they also acknowledged professionalism more than JVSs (MD = 0.072; P < 0.05) and SVSs (MD = 0.12; P < 0.01). Finally, SVSs graded interpersonal and communication skills lower than both residents (MD = 0.068; P < 0.05) and JVSs (MD = 0.065; P < 0.05) did. CONCLUSIONS: Most ACGME anesthesiology milestones are applicable and feasible in Taiwan. Incorporating residents' perspectives may bring insight and facilitate shared understanding to a new educational implementation. This study helped Taiwan generate a well-informed and indigenized draft of a competency-based framework for the following nation-wide Delphi survey.

Lysosomal-targeted doxorubicin delivery using RBC-derived vesicles to overcome drug-resistant cancer through mitochondrial-dependent cell death.

Multidrug resistance (MDR) is a major challenge in cancer chemotherapy. Nanoparticles as drug delivery systems (DDSs) show promise for MDR cancer therapy. However, current DDSs require sophisticated design and construction based on xenogeneic nanomaterials, evoking feasibility and biocompatibility concerns. Herein, a simple but versatile biological DDS (bDDS) composed of human red blood cell (RBC)-derived vesicles (RDVs) with excellent biocompatibility was surface-linked with doxorubicin (Dox) using glutaraldehyde (glu) to form Dox-gluRDVs that remarkably suppressed MDR in uterine sarcoma through a lysosomal-mitochondrial axis-dependent cell death mechanism. Dox-gluRDVs can efficiently deliver and accumulate Dox in lysosomes, bypassing drug efflux transporters and facilitating cellular uptake and retention of Dox in drug-resistant MES-SA/Dx5 cells. The transfer of lysosomal calcium to the mitochondria during mitochondria-lysosome contact due to lysosomal Dox accumulation may result in mitochondrial ROS overproduction, mitochondrial membrane potential loss, and activation of apoptotic signaling for the superior anti-MDR activity of Dox-gluRDVs in vitro and in vivo. This work highlights the great promise of RDVs to serve as a bDDS of Dox to overcome MDR cancers but also opens up a reliable strategy for lysosomal-mitochondrial axis-dependent cell death for fighting against other inoperable cancers.

Longitudinal Trajectory of Opioid Prescribing and its Associated Serious Adverse Events: A Population-Wide Cohort Study in Taiwan.

Chronic opioid prescribing (COP) for noncancer pain is highly restricted in Taiwan, but tramadol is not listed in the regulation on chronic prescribing. This study investigated the trajectories of COP in noncancer pain when considering tramadol in Taiwan and identified the risk of serious adverse events. This population-wide longitudinal cohort study used the Taiwan National Health Insurance claims records from 2001 to 2016. Adults prescribed opioids (including tramadol) and without cancer were selected. Patients who received COP (opioid supply days for 28 days or continuous opioid supply for 14 days) in the first patient quarter were included, and serious adverse events were identified. Group-based trajectory models were applied to identify patients with a similar trajectory of quarterly COP. The Cox proportional hazard model was applied to assess the association between adverse events and patients' trajectories. Of the 2,360,358 noncancer opioid users, 476,934 (20.2%) received COP in the first quarter. Four groups of COP trajectory were identified, and 59,310 (12.8%) patients received COP quarterly over 2 years. Patients categorized into the trajectory of long-term COP had a significantly higher crude incidence rate of cardiovascular death, seizure, and hypoglycemia. Still, there is no newly developed opioid use disorder. There was a substantial underestimate in COP in Taiwan when tramadol was not considered. Notably, 10% of them could receive COP for over 2 years. The result raises concern about unmet pain management needs and the limited accessibility of alternative treatments for noncancer pain.

Development of the Chronic Pain Cognition Scale: A Culture-Sensitive Pain Measurement in Chinese.

Purpose: People with pain problems are highly vulnerable to cultural disparities, and it is imperative to reduce these inequalities. This cross-sectional study aimed to develop a culturally sensitive Chronic Pain Cognition Scale (CPCS) for Chinese-/Chinese dialect-speaking populations and investigate its psychometric properties. Patients and Methods: Adult patients with chronic low back pain or chronic neck pain who visited pain clinics at a medical center in northern Taiwan were enrolled. Participants completed the demographic, intensity of pain, and two other related sensations, "Sng ()" and "Ma ()", often reported in Chinese-speaking populations, CPCS, Chronic Pain Acceptance Questionnaire-8, and Pain Self-Efficacy Questionnaire. Results: 200 patients were included. Patients' mean age was 64.84 ± 14.33, 126 (63.0%) were female, and 83 (41.5%) had 13+ years of education. The average duration of pain was 77.25 ± 97.46 months, the intensity of pain was 6.04 ± 2.50, Ma was 3.43 ± 3.24, and Sng was 4.54 ± 3.14. The CPCS comprised four factors: pain impact (how pain impact one's life), losing face (how one being disrespected due to pain), helplessness, and avoidance, with good structural validity and adequate reliability (Cronbach α, 0.60-0.81) and satisfactory criterion-related validity. Moreover, losing face, an essential concept in Chinese relationalism, was significantly related to pain, Sng, and Ma (r = 0.19, 0.15 and 0.16), but not to pain acceptance or self-efficacy, indicating a culturally specific element in pain measurement. Conclusion: The CPCS has good psychometric properties and is suitable for evaluating chronic pain in the clinical setting, and might be generalizable to other Chinese-/Chinese dialect-speaking populations.

The impact of shoulder pathologies on job discontinuation and return to work: a pilot ultrasonographic investigation.

BACKGROUND: Ultrasound imaging has emerged as one of the most useful tools for evaluating shoulder disorders. To date, the association between shoulder ultrasonography and a patient's work status has rarely been explored by antecedent studies. AIM: This study aimed to investigate the association between sonographically diagnosed shoulder pathologies and job discontinuation and return to work. DESIGN: A cross-sectional study. SETTING: Outpatient clinic in the university hospital. POPULATION: Fifty-nine patients who were older than 20 years of age and had worked in a full-time job within the past three years. METHODS: All participants underwent clinical evaluation using the visual analog scale (for pain), Shoulder Pain and Disability Index, Pittsburgh Sleep Quality Index, and shoulder ultrasound examination. The work-related ergonomic risks, including dealing with heavy objects, repeated use and requiring forceful motion of the affected upper extremity, were assessed. The ultrasound-identified shoulder pathologies associated with job discontinuation, that is, sick leave due to painful shoulder for more than two consecutive months, were considered as the primary outcome. In the job discontinuation subgroup, we further investigated the association between return to work and the clinical/sonographic findings. RESULTS: Univariate analysis revealed a positive association between job discontinuation and shoulder surgery or work types requiring forceful upper-limb movements. Multivariate analysis demonstrated that job discontinuation was positively associated with supraspinatus tendon full-thickness tears (risk ratio, 8.80; 95% CI, 1.77-10.56; P=0.018). Of the patients who received shoulder surgery, 46.6% had recurrent rotator cuff tears. Return to work was likely to be related to pain scores during overhead activities and shoulder function impairment but not to sonographic findings. CONCLUSIONS: Job discontinuation is associated with shoulder surgery, work that necessitates forceful upper-extremity movements and supraspinatus tendon full-thickness tears detected by ultrasound. CLINICAL REHABILITATION IMPACT: Sonographic findings should not be used as the only standard for evaluating the patient's work capability.

Enhancing diagnosis and treatment of superior cluneal nerve entrapment: cadaveric, clinical, and ultrasonographic insights.

OBJECTIVES: Low back pain is a prevalent public health issue caused by superior cluneal nerve (SCN) entrapment. This study aimed to explore the course of SCN branches, cross-sectional area (CSA) of the nerves, and effects of ultrasound-guided SCN hydrodissection. METHODS: SCN distance relative to the posterior superior iliac spines was measured and compared with ultrasound findings in asymptomatic volunteers. The CSA of the SCN, pressure-pain threshold, and pain measurements were obtained from asymptomatic controls and patients with SCN entrapment at various time points after hydrodissection (with 1 mL of 50% dextrose, 4 mL of 1% lidocaine, and 5 mL of 1% normal saline) in the short-axis view. RESULTS: Twenty sides of 10 formalin-fixed cadavers were dissected. The SCN locations on the iliac crest did not differ from the ultrasound findings in 30 asymptomatic volunteers. The average CSA of the SCN across different branches and sites ranged between 4.69-5.67 mm2 and did not vary across different segments/branches or pain statuses. Initial treatment success was observed in 77.7% (n = 28) of 36 patients receiving hydrodissection due to SCN entrapment. A group with initial treatment success experienced symptom recurrence in 25% (n = 7) of cases, and those with recurrent pain had a higher prevalence of scoliosis than those without symptom recurrence. CONCLUSIONS: Ultrasonography effectively localizes SCN branches on the iliac crest, whereby increased nerve CSA is not useful for diagnosis. Most patients benefit from ultrasound-guided dextrose hydrodissection; however, those with scoliosis may experience symptom recurrence and whether structured rehabilitation can reduce recurrence post-injection should be considered as one perspective in future research. Trial registration ClinicalTrials.gov (NCT04478344). Registered on 20 July 2020, https://clinicaltrials.gov/ct2/show/NCT04478344?cond=Superior+Cluneal+Nerve&cntry=TW&draw=2&rank=1 . Critical relevance statement Ultrasound imaging accurately locates SCN branches on the iliac crest, while enlargement of the CSA is not useful in diagnosing SCN entrapment; however, approximately 80% of SCN entrapment cases respond positively to ultrasound-guided dextrose hydrodissection.

Long-term work quality of patients with mild traumatic brain injury: The associations with postconcussion symptoms.

Return to work (RTW) has always been a determinant functional outcome in patients with mild traumatic brain injury (MTBI). However, the quality of long-term RTW was still unclear. This study thus aims to examine long-term work quality and to reveal its associating factors. A total of 110 patients with MTBI was prospectively recruited. Post-concussion symptoms (PCS) and RTW were evaluated by the Checklist of Post-Concussion Symptoms (CPCS) and Work Quality Index (WQI) respectively at one-week and long-term evaluation (M = 2.90 years, SD = 1.29) post-injury. Only 16% of patients can successfully RTW at one-week post-injury, while 69% of patients have retained their jobs at long-term evaluations. Importantly, 12% of patients had to work under the adverse impacts of PCS at one-week after MTBI, and long-term WQI was significantly associated with PCS at one-week post-injury. Almost 1/3 of patients still had unfavorable long-term work quality even though they could return to work. Thus, a careful evaluation of the early PCS endorsement and work quality for patients with MTBI is merited.

Global series: Complex regional pain syndrome: abstracts from the International Association for the Study of Pain complex regional pain syndrome SIG virtual symposia 2021.

The aim of this IASP complex regional pain syndrome (CRPS) SIG Global Series 2021 was to bring together clinicians including those from developing countries to better understand the clinical presentation of complex regional pain syndrome in countries with less well-published patient populations. The purpose was to learn from each other about the range of treatments, successful outcomes, and challenges experienced. These meeting proceedings comprise abstracts from nine countries that span 4 continents and are summaries of online presentations delivered by speakers representing these countries over the course of 2 symposia. The symposia were attended by a global audience of approximately 360 people. Patients with CRPS were described and treated by clinicians from countries across Asia (Pakistan, Jordan, South Korea, Taiwan, and Singapore), South America (Brazil and Peru), Africa (South Africa), and Europe (Norway). This reflects that CRPS exists across borders, ethnicities, and cultures. These proceedings provide a broader perspective within the international pain community about how we can better understand and treat CRPS across the globe.

Effects of Goal-Directed Hemodynamic Therapy Using a Noninvasive Finger-Cuff Monitoring Device on Intraoperative Cerebral Oxygenation and Early Delayed Neurocognitive Recovery in Patients Undergoing Beach Chair Position Shoulder Surgery: A Randomized Controlled Trial.

BACKGROUND: Perioperative cerebral desaturation events (CDEs) and delayed neurocognitive recovery are common among patients undergoing beach chair position (BCP) shoulder surgery and may be caused by cerebral hypoperfusion. This study tested the hypothesis that the application of goal-directed hemodynamic therapy (GDHT) would attenuate these conditions. METHODS: We randomly assigned 70 adult patients undergoing BCP shoulder surgery to GDHT group or control at a 1:1 ratio. Cerebral oxygenation was monitored using near-infrared spectroscopy, and GDHT was administered using the ClearSight pulse wave analysis system. The primary outcome was CDE duration, whereas the secondary outcomes were CDE occurrence, delayed neurocognitive recovery occurrence, and Taiwanese version of the Quick Mild Cognitive Impairment (Qmci-TW) test score on the first postoperative day (T 2 ) adjusted for the baseline score (on the day before surgery; T 1 ). RESULTS: CDE duration was significantly shorter in the GDHT group (0 [0-0] vs 15 [0-75] min; median difference [95% confidence interval], -8 [-15 to 0] min; P = .007). Compared with the control group, fewer patients in the GDHT group experienced CDEs (23% vs 51%; relative risk [95% confidence interval], 0.44 [0.22-0.89]; P = .025) and mild delayed neurocognitive recovery (17% vs 40%; relative risk [95% confidence interval], 0.60 [0.39-0.93]; P = .034). The Qmci-TW scores at T 2 adjusted for the baseline scores at T 1 were significantly higher in the GDHT group (difference in means: 4 [0-8]; P = .033). CONCLUSIONS: Implementing GDHT using a noninvasive finger-cuff monitoring device stabilizes intraoperative cerebral oxygenation and is associated with improved early postoperative cognitive scores in patients undergoing BCP shoulder surgery.

Prenatal diagnosis of ALPL gene mutations in recurrent fetal skeletal dysplasia.

OBJECTIVE: One multiparity women had recurrent pregnancies of skeletal dysplasia. The karyotype and array-comparative genomic hybridization were unremarkable. Thus, trio whole exome sequencings were suggested. CASE REPORT: The ALPL gene mutations were identified. Maternal heterozygous deletion on Chr1: 21880592 (GRCh37) TA->T, paternal heterozygous insertion on Chr1 21894597, 21894598 (GRCh37) G->GC, T->TAA, and the compound heterozygous mutation were noted on her third pregnancy. The prenatal ultrasound findings and ALPL variants were compatible with the diagnosis of hypophosphatasia. Sanger sequencings were performed and found their normal phenotype daughter carried the same heterozygous mutation with her mother. The mother was then incidentally found her fourth pregnancy; unfortunately, the fetus was prenatally diagnosed of hypophosphatasia with the compound heterozygous mutations. CONCLUSION: The whole exome sequencing could assist to find the disease-causing variants, which may not be identified through routine prenatal diagnosis. With the precise diagnosis, we could provide the counseling for prenatal or pre-implantation diagnosis.

Effects of local anesthetics and contrast agents on musculoskeletal regenerative medicine procedures.

In regenerative medicine, cells, tissues and organs are often replaced, engineered or regrown in order to restore their function after they have been damaged or lost. Local anesthetics, corticosteroids and contrast agents are commonly employed for both diagnostic and therapeutic objectives in interventional pain and musculoskeletal treatments for regenerative medicine. There is growing evidence that routine injectables promote catabolism and disease processes. Thus, understanding the effects of these compounds on regenerative medicine injectates and target tissues such as tenocytes, chondrocytes, nucleus pulposus and ligamentous tissue is critical. This review includes the current research on the effects of local anesthetics and contrast agents, as well as their use and recommendations in regenerative medicine operations.

In regenerative medicine, various human organs are often modified to restore their function after being damaged. Various substances are commonly injected in pain and musculoskeletal treatments for regenerative medicine. A growing body of literature indicates that common injectable substances may promote cellular destruction and pathologies. Therefore, understanding their effects on various musculoskeletal tissue and cellular components is critical. This review includes the current research on the effects of local anesthetics and contrast agents, as well as their use and recommendations in regenerative medicine operations.

Ultrasound imaging for inguinal hernia: a pictorial review.

Inguinal hernia is the most prevalent type of abdominal wall hernia. Indirect inguinal hernia is twice as common as direct inguinal hernia. Computed tomography and magnetic resonance imaging can be used to evaluate inguinal hernia, but these modalities are greatly limited by their cost and availability. Ultrasonography has emerged as the most convenient imaging tool for diagnosing inguinal hernia due to its advantages, such as portability and absence of radiation. The present pictorial review presents an overview on the use of ultrasonography in the evaluation of inguinal hernia with a particular emphasis on the regional anatomy, relevant scanning tips, identification of subtypes, postoperative follow-up, and diagnosis of pathologies mimicking inguinal hernia.

Ultrasound Imaging, Guidance, and Treatment for Shoulder-related Pain Syndrome: A Bibliometric Analysis.

BACKGROUND: Ultrasound imaging is shown to be superior to other imaging tools for the evaluation of shoulder disorders in a primary care settings. In addition to its diagnostic utility, ultrasound diathermy is useful as a deep heat modality for the management of shoulder pain. OBJECTIVE AND STUDY DESIGN: In this study, we analyzed the bibliometric data of publications that have focused on ultrasound imaging/therapy for shoulder-related pain syndrome. METHODS: We searched the Web of Science (WoS) database for articles published between January 1, 1976, and June 24, 2022. The CiteSpace Version 6.1R2 software was used to analyze publication output, authoritative journals/countries/institutions/authors, keywords, references, and citations. RESULTS: We analyzed 1185 articles in this study and observed a significant trend of an increase in publications per year (beta coefficient 1.8165, R2 = 0.7519, P < 0.001). The maximum number of relevant citations was identified in 2009, and these declined in subsequent years. The Journal of Ultrasound in Medicine, the United States of America, and the League of European Research Universities were identified as the journal, country, and institution with the highest number of publications, respectively. Keyword analysis revealed that "ultrasonography" showed the strongest citation bursts, followed by "arthroscopic findings" and "painful shoulders." LIMITATIONS: We only analyzed publications indexed in the WoS because most indicators required for bibliometric analysis can be efficiently extracted from its website. CONCLUSION: This study highlights a significant trend of an increase in the number of publications focused on ultrasound imaging for shoulder-related pain syndrome. Ultrasound was shown to be a highly popular imaging modality among health care practitioners for the evaluation of shoulder disorders. Randomized controlled trials and state-of-the-art reviews are warranted to boost the citation count and conclusively establish the role of ultrasound applications in patients with shoulder pain syndrome.

Changes in the quick mild cognitive impairment test over time: A normative study in an adult sample in Taiwan.

BACKGROUND: The Quick Mild Cognitive Impairment (Qmci) test has been suggested to be an easy-to-use and precise screening tool for detecting postoperative cognitive dysfunction (POCD). To provide essential information for future POCD studies in Taiwan, the present study provided data regarding the Taiwan version of the Qmci (Qmci-TW) test conducted in the normative Taiwanese population and changes in them over time. METHODS: The present study recruited adult native Taiwanese volunteers without known neurologic or psychiatric diseases. All enrolled participants received protocolized serial Qmci-TW test at baseline, 2-day follow-up, and 6-month follow-up. RESULTS: In total, 30 participants, 15 men and 15 women, were enrolled in this study. The baseline Qmci-TW score ranged from 55 to 80, with a mean of 68.9 and a standard deviation (SD) of 7. At 2-day follow-up, the mean Qmci-TW test score was significantly higher (by 5.3; SD = 7.3) than that at baseline (P = 0.001). At 6-month follow-up, the mean Qmci-TW score was 71.3 (SD = 6.1), with no significant difference compared with that at baseline. The decline in Qmci-TW scores by > 9 points on postoperative day 1 and by > 11 points at 6-month follow-up was the criterion for POCD. CONCLUSION: The present study provided data regarding the Qmci-TW test conducted in the normative Taiwanese population and its time trajectory during the 6-month follow-up.

Elevated tau and ß-amyloid in the serum of fibromyalgia patients.

OBJECTIVE: Fibromyalgia (FM) is a chronic widespread pain syndrome. Although its mechanism remains relatively unknown, accelerated neurodegeneration in the brain has been reported in patients with FM. Sleep disturbance can increase the risk of neurocognitive disorders, which are associated with tau and beta-amyloid (Aß) protein accumulation. We hypothesize neurodegeneration in patients with FM may be associated with sleep disturbance. METHODS: In this case-control study, we analyzed serum tau and Aß levels and their association with symptom profiles for patients with FM, by recruiting 22 patients with FM and 22 age-matched healthy participants. The visual analog scale, Fibromyalgia Impact Questionnaire, pressure pain threshold test, Pittsburgh Sleep Quality Index (PSQI), Beck Depression Inventory-II, Beck Anxiety Inventory, and serum tau and beta-amyloid-42 (Aß-42) levels were recorded. The Mann-Whitney test was conducted to compare questionnaire and protein level results between the groups. Pearson correlation test was conducted to investigate the correlation of questionnaire scores with tau and Aß-42 levels in patients with FM. The significance level was set at P < .05. RESULTS: Serum tau and Aß-42 levels were significantly higher in patients with FM than in controls. A positive correlation between serum tau levels and PSQI scores was observed in patients with FM (r = 0.476, P = .025). We found that only sleep disturbance in patients with FM was significantly associated with higher serum tau levels among all symptom scores. CONCLUSIONS: We suggest sleep disturbance may play a vital role in the pathomechanism of accelerated neurodegeneration in FM.

Impact of expanded strong opioid availability on opioid prescription patterns in patients with cancer: A population-wide cohort study in Taiwan.

Background One of the major barriers to adequate cancer pain management in Taiwan is the limited prescription options regarding strong opioids. Internationally recommended strong opioids, including oxycodone and hydromorphone, were not introduced in Taiwan until late 2014. We analysed the patterns in opioid prescription for cancer pain management, after the introduction of new opioid options. Methods All inpatient and outpatient clinical visits from January 1, 2012, to December 31, 2017, with the diagnosis of cancer and the analgesic prescriptions were collected from the database of National Health Insurance, Taiwan, and analysed. Opioids were grouped into strong opioids, weak opioids, and guideline non-recommended opioids. Findings A total of 1, 292, 905 patients with cancers were included. Approximately 50% of patients used analgesics, 50% of which were opioids; the proportions were stable during the study period. The annual cumulative opioid use per patient (defined daily dose, DDD) significantly decreased from 36•41±102•59 (Mean±SD) in 2012 to 32•42±100•99 in 2017 (p < •001). The annual cumulative strong opioid use per patient increased significantly from 17•54±89•23 in 2012 to 19•28±94•97 in 2017 (+9•90%, p < •001). In parallel, the annual cumulative weak opioids use per patient decreased from 18•64±40•81 in 2012 to 13•04±26•79 in 2017 (-30•04%, p < •001). Among extended-release strong opioids, the use of transdermal fentanyl significantly decreased after oxycodone and hydromorphone were introduced (p < •001). Interpretation Increased therapeutic options in strong opioid prescriptions led opioid prescription patterns to evolve towards international cancer pain management guidelines. In addition, increased accessibility to a wider range of different strong opioids may facilitate more efficient opioid titration and rotation - and thus decrease, not increase, the opioid usage. Funding This study was supported by Ministry of Science and Technology, Taiwan (MOST-106-2314-B-002-213 and MOST-108-2314-B-002-072-MY3), Ministry of Health and Welfare, Taiwan (MOHW109-TDU-B-211-114002), National Taiwan University Hospital, Taipei, Taiwan (NTUH-103-002314 and NTUH. 105-S2954), and National Center of Excellence for Clinical Trial & Research, National Taiwan University Hospital, Taipei, Taiwan (NCTRC201208 and NCTRC201603).

Influence of scalp block on oncological outcomes of high-grade glioma in adult patients with and without isocitrate dehydrogenase-1 mutation.

High-grade gliomas are notorious for a high recurrence rate even after curative resection surgery. Studies regarding the influence of scalp block on high-grade gliomas have been inconclusive, possibly because the condition's most important genetic mutation profile, namely the isocitrate dehydrogenase 1 (IDH1) mutation, had not been analyzed. Therefore, we conducted a single-center study including patients with high-grade glioma who underwent tumor resection between January 2014 and December 2019. Kaplan-Meier survival analysis revealed that scalp block was associated with longer progression-free survival (PFS; 15.17 vs. 10.77 months, p = 0.0018), as was the IDH1 mutation (37.37 vs. 10.90 months, p = 0.0149). Multivariate Cox regression analysis revealed that scalp block (hazard ratio: 0.436, 95% confidence interval: 0.236-0.807, p = 0.0082), gross total resection (hazard ratio: 0.405, 95% confidence interval: 0.227-0.721, p = 0.0021), and IDH1 mutation (hazard ratio: 0.304, 95% confidence interval: 0.118-0.784, p = 0.0138) were associated with better PFS. Our results demonstrate that application of scalp block, regardless of IDH1 profile, is an independent factor associated with longer PFS for patients with high-grade glioma.

The structure-based cancer-related single amino acid variation prediction.

Single amino acid variation (SAV) is an amino acid substitution of the protein sequence that can potentially influence the entire protein structure or function, as well as its binding affinity. Protein destabilization is related to diseases, including several cancers, although using traditional experiments to clarify the relationship between SAVs and cancer uses much time and resources. Some SAV prediction methods use computational approaches, with most predicting SAV-induced changes in protein stability. In this investigation, all SAV characteristics generated from protein sequences, structures and the microenvironment were converted into feature vectors and fed into an integrated predicting system using a support vector machine and genetic algorithm. Critical features were used to estimate the relationship between their properties and cancers caused by SAVs. We describe how we developed a prediction system based on protein sequences and structure that is capable of distinguishing if the SAV is related to cancer or not. The five-fold cross-validation performance of our system is 89.73% for the accuracy, 0.74 for the Matthews correlation coefficient, and 0.81 for the F1 score. We have built an online prediction server, CanSavPre ( http://bioinfo.cmu.edu.tw/CanSavPre/ ), which is expected to become a useful, practical tool for cancer research and precision medicine.

RBC-derived vesicles as a systemic delivery system of doxorubicin for lysosomal-mitochondrial axis-improved cancer therapy.

Introduction: Chemotherapeutic drugs are the main intervention for cancer management, but many drawbacks impede their clinical applications. Nanoparticles as drug delivery systems (DDSs) offer much promise to solve these limitations. Objectives: A novel nanocarrier composed of red blood cell (RBC)-derived vesicles (RDVs) surface-linked with doxorubicin (Dox) using glutaraldehyde (glu) to form Dox-gluRDVs was investigated for improved cancer therapy. Methods: We investigated the in vivo antineoplastic performance of Dox-gluRDVs through intravenous (i.v.) administration in the mouse model bearing subcutaneous (s.c.) B16F10 tumor and examined the in vitro antitumor mechanism and efficacy in a panel of cancer cell lines. Results: Dox-gluRDVs can exert superior anticancer activity than free Dox in vitro and in vivo. Distinct from free Dox that is mainly located in the nucleus, but instead Dox-gluRDVs release and efficiently deliver the majority of their conjugated Dox into lysosomes. In vitro mechanism study reveals the critical role of lysosomal Dox accumulation-mediated mitochondrial ROS overproduction followed by the mitochondrial membrane potential loss and the activation of apoptotic signaling for superior anticancer activity of Dox-gluRDVs. Conclusion: This work demonstrates the great potential of RDVs to serve a biological DDS of Dox for systemic administration to improve conventional cancer chemotherapeutics.