Cyanopyridoimidazole/1,2-Aminothiol Click Reaction: A Novel Bioorthogonal Reaction for Synthesis of Radiotracers.

We herein described the design and synthesis of the cyanopyridoimidazoles (CPIs) as new bioorthogonal click reagents toward 1,2-aminothiol groups. Kinetic and density functional theory-based studies of the synthetic compounds revealed that incorporating an electron-withdrawing substituent into the CPI scaffold lowers its lowest unoccupied molecular orbital energy, consequently increasing reactivity. Optimized CPI 8a showed rapid reactivity and high stability in physiological conditions and has been demonstrated to be suitable for various radiotracer synthetic methods. Based on the new bioorthogonal reaction, a [67Ga]Ga-labeled prostate-specific membrane antigen-targeted probe was successfully prepared for in vivo imaging of prostate cancer in an animal model.

LDL Receptor-Related Protein 1B Polymorphisms Associated with Increased Risk of Lymph Node Metastasis in Oral Cancer Group with Diabetes Mellitus.

Oral cancer ranks fourth among malignancies among Taiwanese men and is the eighth most common cancer among men worldwide in terms of general diagnosis. The purpose of the current study was to investigate how low-density lipoprotein receptor-related protein 1B (LDL receptor related protein 1B; LRP1B) gene polymorphisms affect oral squamous cell carcinoma (OSCC) risk and progression in individuals with diabetes mellitus (DM). Three LRP1B single-nucleotide polymorphisms (SNPs), including rs10496915, rs431809, and rs6742944, were evaluated in 311 OSCC cases and 300 controls. Between the case and control groups, we found no evidence of a significant correlation between the risk of OSCC and any of the three specific SNPs. Nevertheless, in evaluating the clinicopathological criteria, individuals with DM who possess a minimum of one minor allele of rs10496915 (AC + CC; p = 0.046) were significantly associated with tumor size compared with those with homozygous major alleles (AA). Similarly, compared to genotypes homologous for the main allele (GG), rs6742944 genotypes (GA + AA; p = 0.010) were more likely to develop lymph node metastases. The tongue and the rs6742944 genotypes (GA + AA) exhibited higher rates of advanced clinical stages (p = 0.024) and lymph node metastases (p = 0.007) when compared to homozygous alleles (GG). LRP1B genetic polymorphisms appear to be prognostic and diagnostic markers for OSCC and DM, as well as contributing to genetic profiling research for personalized medicine.

Molecular subtypes of breast cancer predicting clinical benefits of radiotherapy after breast-conserving surgery: a propensity-score-matched cohort study.

BACKGROUND: Based on the molecular expression of cancer cells, molecular subtypes of breast cancer have been applied to classify patients for predicting clinical outcomes and prognosis. However, further evidence is needed regarding the influence of molecular subtypes on the efficacy of radiotherapy (RT) after breast-conserving surgery (BCS), particularly in a population-based context. Hence, the present study employed a propensity-score-matched cohort design to investigate the potential role of molecular subtypes in stratifying patient outcomes for post-BCS RT and to identify the specific clinical benefits that may emerge. METHODS: From 2006 to 2019, the present study included 59,502 breast cancer patients who underwent BCS from the Taiwan National Health Insurance Research Database. Propensity scores were utilized to match confounding variables between patients with and without RT within each subtype of breast cancer, namely luminal A, luminal B/HER2-negative, luminal B/HER2-positive, basal-like, and HER2-enriched ones. Several clinical outcomes were assessed, in terms of local recurrence (LR), regional recurrence (RR), distant metastasis (DM), disease-free survival (DFS), and overall survival (OS). RESULTS: After post-BCS RT, patients with luminal A and luminal B/HER2-positive breast cancers exhibited a decrease in LR (adjusted hazard ratio [aHR] = 0.18, p < 0.0001; and, 0.24, p = 0.0049, respectively). Furthermore, reduced RR and improved DFS were observed in patients with luminal A (aHR = 0.15, p = 0.0004; and 0.29, p < 0.0001), luminal B/HER2-negative (aHR = 0.06, p = 0.0093; and, 0.46, p = 0.028), and luminal B/HER2-positive (aHR = 0.14, p = 0.01; and, 0.38, p < 0.0001) breast cancers. Notably, OS benefits were found in patients with luminal A (aHR = 0.62, p = 0.002), luminal B/HER2-negative (aHR = 0.30, p < 0.0001), basal-like (aHR = 0.40, p < 0.0001), and HER2-enriched (aHR = 0.50, p = 0.03), but not luminal B/HER2-positive diseases. Remarkably, when considering DM, luminal A patients who received RT demonstrated a lower cumulative incidence of DM than those without RT (p = 0.02). CONCLUSION: In patients with luminal A breast cancer who undergo BCS, RT could decrease the likelihood of tumor metastasis. After RT, the tumor's hormone receptor status may predict tumor control regarding LR, RR, and DFS. Besides, the HER2 status of luminal breast cancer patients may serve as an additional predictor of OS after post-BCS RT. However, further prospective studies are required to validate these findings.

18 F-FDG PET/CT imaging for haemophilic arthropathy compared with clinical, radiological and power Doppler sonographic characteristics of 20 haemophilia patients.

INTRODUCTION AND OBJECTIVES: Repeated joint bleeding in haemophilia patients may lead to haemophilic arthropathy with marked inflammation and synovitis. This study investigated the potential of 18 F-fluorodeoxyglucose positron emission tomography-computed tomography (18 F-FDG PET/CT) as a novel diagnostic method for haemophilic arthropathy. MATERIALS AND METHODS: We recruited 20 adult haemophilia patients who reported history of hemarthroses in the shoulder, elbow, hip, knee, or ankle joints. All joints were assessed by power Doppler ultrasonography and radiography, and graded by hyperaemia score and Pettersson score, respectively. Joint pain was evaluated by visual analogue score (VAS). Range of motion (ROM), Haemophilia Joint Health Score (HJHS) and annual joint bleeding rate (AJBR) were recorded. Finally, all participants had whole-body 18 F-FDG PET/CT, and maximum standardized uptake value (SUVmax) of the joints being studied was measured. RESULTS: Thirteen patients had severe haemophilia, and seven had moderate haemophilia. The mean age was 36 years. PET SUVmax showed significant correlations with VAS, ROM, Pettersson score, hyperaemia score, HJHS score and AJBR in all large joints except hip. Joints with pain, hyperaemia and radiographic changes were found to have higher SUVmax than those without these features. Using Youden's index, the optimal cut-off value for early radiographical arthropathy was found to be between 1.9 and 2.0. CONCLUSION: Our study indicates that 18 F-FDG PET/CT imaging correlated well with various conventional diagnostic techniques. It also demonstrated high sensitivity and specificity for early radiographic arthropathy. 18 F-FDG PET/CT imaging may quantitatively evaluate disease activity of most large joints in a single examination and help detect early haemophilic arthropathy.

IRAK2, an Immune and Radiation-Response Gene, Correlates with Advanced Disease Features but Predicts Higher Post-Irradiation Local Control in Non-Metastatic and Resected Oral Cancer Patients.

Gene Ontology (GO) analysis can provide a comprehensive function analysis for investigating genes, allowing us to identify the potential biological roles of genes. The present study conducted GO analysis to explore the biological function of IRAK2 and performed a case analysis to define its clinical role in disease progression and mediating tumor response to RT. Methods: We performed a GO enrichment analysis on the RNA-seq data to validate radiation-induced gene expression. A total of 172 I-IVB specimens from oral squamous cell carcinoma patients were collected for clinical analysis, from which IRAK2 expression was analyzed by immunohistochemistry. This was a retrospective study conducted between IRAK2 expression and the outcomes of oral squamous cell carcinoma patients after radiotherapy treatment. We conducted Gene Ontology (GO) analysis to explore the biological function of IRAK2 and performed a case analysis to define its clinical role in mediating tumor response to radiotherapy. GO enrichment analysis to validate radiation-induced gene expression was performed. Clinically, 172 stage I-IVB resected oral cancer patients were used to validate IRAK2 expression in predicting clinical outcomes. GO enrichment analysis showed that IRAK2 is involved in 10 of the 14 most enriched GO categories for post-irradiation biological processes, focusing on stress response and immune modulation. Clinically, high IRAK2 expression was correlated with adverse disease features, including pT3-4 status (p = 0.01), advanced overall stage (p = 0.02), and positive bone invasion (p = 0.01). In patients who underwent radiotherapy, the IRAK2-high group was associated with reduced post-irradiation local recurrence (p = 0.025) compared to the IRAK2-low group. IRAK2 plays a crucial role in the radiation-induced response. Patients with high IRAK2 expression demonstrated more advanced disease features but predicted higher post-irradiation local control in a clinical setting. These findings support IRAK2 as a potential predictive biomarker for radiotherapy response in non-metastatic and resected oral cancer patients.

Evaluation of Chelator-to-Antibody Ratio on Development of 89Zr-iPET Tracer for Imaging of PD-L1 Expression on Tumor.

89Zr-iPET has been widely used for preclinical and clinical immunotherapy studies to predict patient stratification or evaluate therapeutic efficacy. In this study, we prepared and evaluated 89Zr-DFO-anti-PD-L1-mAb tracers with varying chelator-to-antibody ratios (CARs), including 89Zr-DFO-anti-PD-L1-mAb_3X (tracer_3X), 89Zr-DFO-anti-PD-L1-mAb_10X (tracer_10X), and 89Zr-DFO-anti-PD-L1-mAb_20X (tracer_20X). The DFO-anti-PD-L1-mAb conjugates with varying CARs were prepared using a random conjugation method and then subjected to quality control. The conjugates were radiolabeled with 89Zr and evaluated in a PD-L1-expressing CT26 tumor-bearing mouse model. Next, iPET imaging, biodistribution, pharmacokinetics, and ex vivo pathological and immunohistochemical examinations were conducted. LC-MS analysis revealed that DFO-anti-PD-L1-mAb conjugates were prepared with CARs ranging from 0.4 to 2.0. Radiochemical purity for all tracer groups was >99% after purification. The specific activity levels of tracer_3X, tracer_10X, and tracer_20X were 2.2 ± 0.6, 8.2 ± 0.6, and 10.5 ± 1.6 µCi/µg, respectively. 89Zr-iPET imaging showed evident tumor uptake in all tracer groups and reached the maximum uptake value at 24 h postinjection (p.i.). Biodistribution data at 168 h p.i. revealed that the tumor-to-liver, tumor-to-muscle, and tumor-to-blood uptake ratios for tracer_3X, tracer_10X, and tracer_20X were 0.46 ± 0.14, 0.58 ± 0.33, and 1.54 ± 0.51; 4.7 ± 1.3, 7.1 ± 3.9, and 14.7 ± 1.1; and 13.1 ± 5.8, 19.4 ± 13.8, and 41.3 ± 10.6, respectively. Significant differences were observed between tracer_3X and tracer_20X in the aforementioned uptake ratios at 168 h p.i. The mean residence time and elimination half-life for tracer_3X, tracer_10X, and tracer_20X were 25.4 ± 4.9, 24.2 ± 6.1, and 25.8 ± 3.3 h and 11.8 ± 0.5, 11.1 ± 0.7, and 11.7 ± 0.6 h, respectively. No statistical differences were found between-tracer in the aforementioned pharmacokinetic parameters. In conclusion, 89Zr-DFO-anti-PD-L1-mAb tracers with a CAR of 1.4-2.0 may be better at imaging PD-L1 expression in tumors than are traditional low-CAR 89Zr-iPET tracers.

Impact of Hypertensive Disorders of Pregnancy on the Risk of Stroke Stratified by Subtypes and Follow-Up Time.

BACKGROUND AND PURPOSE: Hypertensive disorders of pregnancy (HDP) comprise 4 subtypes. Previous studies have not investigated the relationship between stroke risk, different HDP subtypes, and follow-up time, which was the purpose of this study. METHODS: Data of 17 588 women aged 18 to 45 years who had a history of HDP in Taiwan from 2000 to 2017 was retrospectively reviewed. After matching with confounders, 13 617 HDP women and 54 468 non-HDP women were recruited. RESULTS: HDP women had an adjusted hazard ratio (aHR) of 1.71 (95% CI, 1.46-2.00) for stroke, and 1.60 (1.35-1.89) and 2.98 (2.13-4.18) for ischemic and hemorrhagic stroke, respectively (P<0.001 for all). The overall stroke risk in the HDP group was still 2.04 times 10 to 15 years after childbirth (1.47-2.83, P<0.001). Although the risks of both ischemic and hemorrhagic stroke persisted, their risk time trends were different. The risk of ischemic stroke reached peak during 1 to 3 years after childbirth with an aHR of 2.14 (1.36-3.38), while hemorrhagic stroke risk gradually increased and had an aHR of 4.64 (2.47-8.73) after 10 to 15 years of childbirth (both P<0.001). Among the 4 HDP subtypes, chronic hypertension with superimposed preeclampsia had the highest stroke risk (aHR=3.86, 1.91-7.82, P<0.001), followed by preeclampsia-eclampsia (aHR=2.00, 1.63-2.45, P<0.001), and gestational hypertension (aHR=1.68, 1.13-2.52, P<0.05); chronic preexisting hypertension had the lowest stroke risk (aHR=1.27, 0.97-1.68, P>0.05). Furthermore, multiple HDP combined with preeclampsia had aHR of 5.48 (1.14-26.42, P<0.05). CONCLUSIONS: The effect of HDP on the risk of future stroke persisted for up to 17 years, both for ischemic and hemorrhagic strokes. The presence of multiple HDP and preeclampsia further increase the stroke risk.

The Long-Term Analgesic Effectiveness of Platelet-Rich Plasma Injection for Carpal Tunnel Syndrome: A Cross-Sectional Cohort Study.

OBJECTIVE: Interest in perineural platelet-rich-plasma (PRP) injections for the treatment of carpal tunnel syndrome (CTS) has increased in recent years. However, evidence supporting the long-term effectiveness of PRP is lacking. Therefore, the aim of our cross-sectional cohort study was to investigate the long-term results of PRP injections for CTS. METHODS: Eighty-one patients diagnosed with CTS of any grade who received a single PRP injection at least 2 years prior were enrolled. Through structured telephone interviews, all patients were asked of their post-injection outcomes compared to their pre-injection condition. Symptom relief ≥50%, compared to the pre-injection condition, was considered an effective outcome. Binary logistic regression was applied to analyze each baseline variable as a regressor for determining the prognostic outcome factors. RESULTS: In total, 70% of patients reported positive outcomes ≥2 years post-injection. Shorter duration of symptoms before treatment (odds ratio: 0.991; 95% confidence interval [CI] 0.983-0.999; P = .023) and lower electrodiagnostic severity of CTS were the main prognostic factors for an effective outcome (mild grade vs severe grade, odds ratio: 17.652; 95% CI 1.43-221.1; P = .025). Although there was a trend toward positive outcomes at longer follow-up durations (2-3 years vs 3-4 years vs 4-5 years), the difference was not statistically significant. CONCLUSIONS: A single perineural PRP injection has a long-term analgesic effect on CTS, especially in mild-to-moderate cases.

Impact of 23-valent pneumococcal polysaccharide vaccination on the frequency of pneumonia-related hospitalization and survival in elderly patients with prostate cancer: A seven-year nationwide matched cohort study.

BACKGROUND: The 23-valent pneumococcal polysaccharide vaccine (PPSV23) is indicated for adults who have a high risk of pneumonia; however, its effectiveness in patients with prostate cancer who are at a risk of pneumonia because of age and cancer treatments, including androgen-deprivation therapy, is unknown. METHODS: Between 2000 and 2010, 38,735 patients with prostate cancer were diagnosed in Taiwan. After exclusions and exact matching for age, previous pneumonia, and influenza vaccination, 2188 vaccinated patients and 2188 unvaccinated patients were recruited. The incidence density of all-cause bacterial pneumonia hospitalizations was analyzed. RESULTS: Over 7 years of follow-up, patients who received the PPSV23 had a significantly lower incidence density, with 142.8 per 1000 person-years versus 162.0 per 1000 person-years for unvaccinated patients. More patients in the vaccinated cohort were never hospitalized for pneumonia compared with those in the unvaccinated cohort (64.2% vs 62.2%, respectively). After adjusting for the Charlson comorbidity index, cancer treatment modalities, and socioeconomic levels, the risk of pneumonia-related hospitalization in the PPSV23 vaccination cohort was 0.48 times lower than that in the unvaccinated cohort (adjusted incidence rate ratio, 0.48; P = .046). For patients who received the influenza vaccination, subgroup analysis demonstrated that PPSV23 vaccination significantly decreased the risk (adjusted incidence rate ratio, 0.45; P < .001). Compared with unvaccinated controls, PPSV23-vaccinated patients had a lower cumulative incidence for the first occurrence of pneumonia-related hospitalization (34.49% vs 36.36%; P = .178) and higher overall survival (47.5% and 42.3%, respectively; P < .001). CONCLUSIONS: Vaccination of elderly patients who have prostate cancer with the relatively common and inexpensive PPSV23 can decrease the risk of pneumonia and prolong survival.

Long-term outcome after perineural injection with 5% dextrose for carpal tunnel syndrome: a retrospective follow-up study.

OBJECTIVE: Perineural injection therapy with 5% dextrose water is progressively becoming a mainstream method for treating carpal tunnel syndrome. However, its long-term outcome is still unknown. Hence, the purpose of this retrospective study was to investigate the long-term outcome after perineural injection therapy using 5% dextrose water. METHODS: A total of 185 patients diagnosed with carpel tunnel syndrome at least 1 year post-therapy were enrolled. All the patients underwent ultrasound-guided perineural injection therapy using 10 ml of 5% dextrose water at the outpatient department. In a structured telephone interview, the patients were asked about the outcome post-therapy compared with pre-injection. A symptom relief ≥50% indicated effective outcome, and a symptom relief <50% was indicative of a poor outcome. RESULTS: In total, 88.6% patients reported an effective outcome, and 11.4% rated the outcome as poor, after a mean of 2.2 injections with a mean of 1-3 years' post-injection follow-up. The outcome was significantly related with severity level, and the patients that reported a poor outcome had a significantly higher incidence of severe grade compared with those who reported an effective outcome (52.4% vs 31.7%, P = 0.03). Patients with mild, moderate and severe grades, respectively, required an average of 1.7 (0.1), 2.4 (0.2) and 2.6 (0.3) injections to reach an effective outcome (P = 0.006) (severe vs mild, P = 0.008; moderate vs mild, P = 0.062). CONCLUSION: Perineural injection therapy is a novel approach for treatment of carpal tunnel syndrome with safe and outstanding long-term effects.

Osteoporosis and the risk of temporomandibular disorder in chronic obstructive pulmonary disease.

INTRODUCTION: Chronic obstructive pulmonary disease (COPD) is a major cause of chronic morbidity and mortality worldwide. The coexistence of COPD and temporomandibular disorder (TMD) has been noted, and dysfunctional mastication resulting from TMD can worsen individuals' nutritional status. This association between COPD and TMD has been rarely discussed in previous studies. Therefore, this study aimed to determine whether osteoporosis increases the risk of TMD in COPD and whether anti-osteoporosis medications can prevent TMD. MATERIALS AND METHODS: This retrospective nationwide population-based study utilized the Taiwan National Health Insurance Research Database. We enrolled 52,652 COPD patients between 2000 and 2015: 13,163 with osteoporosis and 39,489 without osteoporosis. Groups of COPD patients with and without osteoporosis were age- and sex-matched. A multivariable Cox proportional hazards regression model was used to evaluate the risk of TMD development in COPD patients with and without osteoporosis over 15 years. RESULTS: There was a higher risk of TMD occurrence in COPD patients with osteoporosis than in those without osteoporosis (adjusted hazard ratio 2.564, P < 0.001) after adjusting for demographic variables and associative comorbidities. Osteoporosis, hypertension, vertebral compression fracture, and nonpsychotic mental disorders were risk factors contributing to TMD development in patients with COPD. Anti-osteoporosis medications were associated with the prevention of TMD development concomitant with osteoporosis and COPD (adjusted hazard ratio 0.617, P = 0.004). CONCLUSIONS: Patients with COPD and osteoporosis are at a higher risk of developing TMD, and anti-osteoporosis medications can prevent the development of TMD in this context.

The Efficacy of Hyaluronic Acid for Carpal Tunnel Syndrome: A Randomized Double-Blind Clinical Trial.

OBJECTIVES: To investigate the effect of hyaluronic acid (HA) in patients diagnosed with mild or moderate carpal tunnel syndrome (CTS). DESIGN: A prospective randomized, double-blinded control study with 6 months of follow-up. SETTING: Rehabilitation outpatient clinic of one single medical center. SUBJECTS: Thirty-five participants with mild or moderate CTS. METHODS: Participants were enrolled and randomly assigned to HA or control groups. The HA group received one ultrasound-guided perineural injection of 2.5 mL HA while the control group received 2.5 mL normal saline injection through in-plane, long-axis approach to separate the median nerve from the flexor retinaculum via nerve hydrodissection. Boston Carpal Tunnel Syndrome Questionnaire (BCTQ) scores were the primary outcome, while secondary outcomes included the numeric rating scale (NRS), electrophysiological domains, and the cross-sectional area of the median nerve. The assessment was conducted prior to injection and during the second week and 1-, 3-, and 6-months post-injection. RESULTS: Thirty-two patients (17 wrists in HA group and 15 wrists in control group) completed the study. Compared with the control group, the HA group did not show significantly superior outcomes, except in BCTQ and NRS at the second week post-injection (all P < .0125). CONCLUSIONS: A single ultrasound guided perineural HA injection may have short-term therapeutic efficacy for mild or moderate CTS; however, the 2-weeks superior efficacy was not beneficial for chronic neuropathy. Further studies with larger sample sizes are required to verify its therapeutic efficacy.

Prognostic factors in carpal tunnel syndrome treated with 5% dextrose perineural injection: A retrospective study.

Background: Perineural injection therapy with 5% dextrose water (D5W) is a potential and innovative treatment with long-term efficacy for carpal tunnel syndrome (CTS). However, the prognostic factors of this management are lacking; hence, the aim of this retrospective study was to identify the prognostic factors of D5W perineural injection therapy for mild-to-moderate CTS. Methods: A total of 52 patients (52 wrists) diagnosed with mild-to-moderate CTS and treated with a single ultrasound-guided 5cc D5W perineural injection were retrospectively reviewed. Patient-reported injection outcomes (visual analog scale, VAS) at 6 months post-injection were categorized into two groups; (1) Good outcome, when symptom relief ≥50% compared to pre-injection and (2) Poor outcome, when symptom relief < 50% compared to pre-injection. Significant variables between groups were entered into a binary logistic regression with forward stepwise regression to determine the prognostic factors for these outcomes. Results: The treatment outcome was significantly related to body height and sensory nerve conduction velocity (SNCV) (159.1 ± 1.0 vs. 155.0 ± 1.8, p=0.04; 33.6 ± 0.8 vs. 28.3 ± 1.2, p=0.001, good vs. poor outcomes). However, only SNCV remained significantly correlated with the outcomes after conducting stepwise logistic regression (ORs: 1.201; 95% CI 1.05-1.38; p=0.01). Conclusions: SNCV was found to be a significant prognostic factor of treatment outcome for patients with mild-to-moderate CTS 6 months after a D5W perineural injection.

Comparison of short- and long-axis nerve hydrodissection for carpal tunnel syndrome: A prospective randomized, single-blind trial.

Background: This study is to compare the efficacy of short-axis hydrodissection with long-axis hydrodissection for patients with mild-to-moderate carpal tunnel syndrome (CTS). Methods: Forty-seven patients with mild-to-moderate CTS were enrolled in a prospective, randomized, single-blinded, controlled trial (6 months follow-up). With ultrasound guidance, patients in both groups (short-axis or long-axis groups) were injected with normal saline (5 mL per session). Assessments were performed before and 2 weeks after the injection, as well as at 1, 3, and 6 months post-intervention. The primary outcome measure was the Boston Carpal Tunnel Syndrome Questionnaire (BCTQ) score and secondary outcomes included the cross-sectional area of the median nerve and electrophysiological studies. Results: Forty-four patients (21 wrists in the short-axis group and 23 wrists in the long-axis group) completed the study. Compared with the baseline, both groups showed improved BCTQ and cross-sectional area at all follow-up assessments (p<0.05). The short-axis group was not more effective except significant improvements in BCTQ-severity and BCTQ-function 1 month post-injection compared to the long-axis group (p = 0.031 and p = 0.023, respectively). Conclusions: Both short- and long-axis hydrodissection were effective for patients with mild-to-moderate CTS and the short-axis approach was not more effective than long-axis injection. Further studies with larger sample sizes, multiple injections, and larger injection volume are encouraged in the future.

One-Year Efficacy of Platelet-Rich Plasma for Moderate-to-Severe Carpal Tunnel Syndrome: A Prospective, Randomized, Double-Blind, Controlled Trial.

OBJECTIVE: To assess the therapeutic effect of platelet-rich plasma (PRP) for moderate-to-severe carpal tunnel syndrome (CTS). DESIGN: A prospective, randomized, double-blinded, controlled trial (1-year follow-up). SETTING: Outpatient of local medical center settings. PARTICIPANTS: Patients (N=26) who were diagnosed with bilateral moderate-to-severe CTS (total 52 wrists) were included. For each patient, one wrist was randomized into either the PRP or control group and the contralateral wrist of the same patient was allocated to another group. Twenty-four patients were included in the final data analysis. INTERVENTIONS: The wrists in the PRP group received a single ultrasound-guided dose of PRP injection (3.5mL), and the control group received a single ultrasound-guided injection with normal saline (3.5mL). MAIN OUTCOME MEASURES: The Boston Carpal Tunnel Syndrome Questionnaire (BCTQ) scores were used as the primary outcome. Secondary outcomes encompassed the cross-sectional area of the median nerve and electrophysiological study. Assessments were conducted prior to injection and 1, 3, 6, and 12 months postinjection. RESULTS: Compared to the control group, the PRP group exhibited significant improvements in BCTQ severity scores at all time points, BCTQ functional scores at the sixth month, and cross-sectional area at the 12th month postinjection (P<.0125). CONCLUSIONS: A single dose of ultrasound-guided perineural PRP injection can provide therapeutic effect for 1 year postinjection.

Outcome predictors of platelet-rich plasma injection for moderate carpal tunnel syndrome.

INTRODUCTION: Platelet-rich plasma (PRP) injection is effective for mild-to-moderate carpal tunnel syndrome (CTS), and physicians have been using PRP injections to treat CTS. However, the predictive factors of PRP injections have not been evaluated. This retrospective study sought to identify the predictive factors of PRP injections in patients with moderate CTS. METHODS: Seventy-one patients with moderate CTS receiving single PRP injections were enrolled. The outcomes at the third- and sixth-month postinjection visits were categorised into good and poor groups according to the following: (1) good outcome, with visual analogue scale (VAS) score decrease ≧50% and (2) poor outcome, with VAS score decrease <50% of preinjection scores. Significant variables between groups were entered into a binary logistic regression to determine the predictive factors. RESULTS: The baseline body weight (BW), distal motor latency (DML), sensory nerve conduction velocity (SNCV), and cross-sectional area (CSA) of the median nerve were significantly different between the groups in the third month. The odds ratios (ORs) of all features were significant, except for SNCV (BW, OR: 0.911; P = .016; DML, OR: 0.383; P = .028; CSA, OR: 0.694; P = .003), and they remained significant in the sixth month (BW, OR: 0.909; P = .004; DML, OR: 0.530; P = .011; CSA, OR: 0.828; P = .032). CONCLUSION: Lower BW, DML, and CSA values of the median nerve predict better outcomes after perineural injection of PRP for moderate CTS at the 3- and 6-month follow-ups.

Increased risk of shoulder calcific tendinopathy in diabetes mellitus: A nationwide, population-based, matched cohort study.

BACKGROUND: Calcific tendinopathy of the rotator cuff is a common cause of painful disability in the shoulder with unclear aetiology. Diabetes mellitus (DM) is associated with calcific tendinopathy; however, large epidemiological data are lacking. Thus, we conducted a nationwide population-based matched cohort study to investigate the risk for calcific tendinopathy of the shoulder in diabetic patients. METHODS: The National Health Insurance Research Database of Taiwan was used to include 42 915 patients newly diagnosed with DM between 1 January 2000 and 31 December 2015 and randomly extract the data of 171 660 individuals, as a matched control group. All individuals were followed-up until the development of calcific tendinopathy or the end of 2015. RESULTS: Overall, 122 patients from the DM group (0.284%) developed calcific tendinopathy compared with 340 individuals from the non-DM group (0.198%). The Kaplan-Meier analysis indicated that patients with DM had a higher risk of calcific tendinopathy since the eighth year of follow-up (log-rank test, P = .006). Cox proportional hazard regression revealed that the adjusted hazard ratio of calcific tendinopathy in diabetic patients to that in non-diabetic patients was 1.276 (95% confidence interval 1.037-1.571, P = .002). Moreover, the stratified analysis disclosed that DM was a strong independent risk factor for calcific tendinopathy irrespective of the existing comorbidities. CONCLUSIONS: This study demonstrated that patients with DM had a 27% increased risk of developing calcific tendinopathy of the shoulder, 8 years after initially being diagnosed with DM.

Translating Research for the Radiotheranostics of Nanotargeted 188Re-Liposome.

Nanoliposomes are one of the leading potential nano drug delivery systems capable of targeting chemotherapeutics to tumor sites because of their passive nano-targeting capability through the enhanced permeability and retention (EPR) effect for cancer patients. Recent advances in nano-delivery systems have inspired the development of a wide range of nanotargeted materials and strategies for applications in preclinical and clinical usage in the cancer field. Nanotargeted 188Re-liposome is a unique internal passive radiotheranostic agent for nuclear imaging and radiotherapeutic applications in various types of cancer. This article reviews and summarizes our multi-institute, multidiscipline, and multi-functional studied results and achievements in the research and development of nanotargeted 188Re-liposome from preclinical cells and animal models to translational clinical investigations, including radionuclide nanoliposome formulation, targeted nuclear imaging, biodistribution, pharmacokinetics, radiation dosimetry, radiation tumor killing effects in animal models, nanotargeted radionuclide and radio/chemo-combination therapeutic effects, and acute toxicity in various tumor animal models. The systemic preclinical and clinical studied results suggest 188Re-liposome is feasible and promising for in vivo passive nanotargeted radionuclide theranostics in future cancer care applications.

Molecular Imaging and Preclinical Studies of Radiolabeled Long-Term RGD Peptides in U-87 MG Tumor-Bearing Mice.

The Arg-Gly-Asp (RGD) peptide shows a high affinity for αvß3 integrin, which is overexpressed in new tumor blood vessels and many types of tumor cells. The radiolabeled RGD peptide has been studied for cancer imaging and radionuclide therapy. We have developed a long-term tumor-targeting peptide DOTA-EB-cRGDfK, which combines a DOTA chelator, a truncated Evans blue dye (EB), a modified linker, and cRGDfK peptide. The aim of this study was to evaluate the potential of indium-111(111In) radiolabeled DOTA-EB-cRGDfK in αvß3 integrin-expressing tumors. The human glioblastoma cell line U-87 MG was used to determine the in vitro binding affinity of the radiolabeled peptide. The in vivo distribution of radiolabeled peptides in U-87 MG xenografts was investigated by biodistribution, nanoSPECT/CT, pharmacokinetic and excretion studies. The in vitro competition assay showed that 111In-DOTA-EB-cRGDfK had a significant binding affinity to U-87 MG cancer cells (IC50 = 71.7 nM). NanoSPECT/CT imaging showed 111In-DOTA-EB-cRGDfK has higher tumor uptake than control peptides (111In-DOTA-cRGDfK and 111In-DOTA-EB), and there is still a clear signal until 72 h after injection. The biodistribution results showed significant tumor accumulation (27.1 ± 2.7% ID/g) and the tumor to non-tumor ratio was 22.85 at 24 h after injection. In addition, the pharmacokinetics results indicated that the 111In-DOTA-EB-cRGDfK peptide has a long-term half-life (T1/2λz = 77.3 h) and that the calculated absorbed dose was safe for humans. We demonstrated that radiolabeled DOTA-EB-cRGDfK may be a promising agent for glioblastoma tumor imaging and has the potential as a theranostic radiopharmaceutical.

The Effectiveness of Platelet-Rich Plasma and Radial Extracorporeal Shock Wave Compared with Platelet-Rich Plasma in the Treatment of Moderate Carpal Tunnel Syndrome.

OBJECTIVES: To evaluate the combination effect of platelet-rich plasma (PRP) and extracorporeal shock wave therapy (ESWT) for moderate carpal tunnel syndrome (CTS), compared with PRP alone. DESIGN: A randomized, double-blinded, placebo-controlled trial. SETTING: A single medical center in Taiwan. PATIENTS: Patients diagnosed with moderate CTS. INTERVENTIONS: All subjects were administered one dose of ultrasound-guided PRP injection at baseline. After two weeks, one session of rESWT was completed in the intervention group, whereas the control group received one session of sham rESWT. Evaluations were performed at baseline and one, three, and six months post-PRP injection. OUTCOME MEASURES: The Boston Carpal Tunnel Syndrome Questionnaire (BCTQ) was measured as the primary outcome. Electrophysiological study and cross-sectional area (CSA) of the median nerve were used as secondary outcomes. RESULTS: All 40 enrolled subjects (male/female: 4/36) completed the study, resulting in an analysis of 32 wrists per group (total: N = 64 wrists). Compared with the control group, the intervention group did not show statistically significantly superior outcomes, except in BCTQs at one month (mean change ± SE = -11.47 ± 1.18 vs -7.06 ± 1.26, P = 0.013) and distal motor latency at three months (mean change ± SE = -0.59 ± 0.09 vs -0.30 ± 0.09, P = 0.031). CONCLUSIONS: Combined PRP and one-session rESWT was not superior to PRP alone in treating moderate CTS. Further studies with multiple sessions of ESWT and longer follow-up periods are needed to verify the clinical efficacy of ESWT.