The Effectiveness of 23-valent Pneumococcal Polysaccharide Vaccine on Elderly Colorectal Cancer Long-Term Survivors: A population-based exact-matched cohort study.

Colorectal cancer (CRC) long-term survivor is a rapid enlarging group. However, the effectiveness of 23-valent pneumococcal polysaccharide vaccine (PPSV23) on this group is unknown. This nationwide population-based study in Taiwan was designed to examine the effect of PPSV23 on incidence rate ratio (IRR) of pneumonia hospitalization, cumulative incidence, and overall survival rate for these long-term CRC survivors. This cohort study was based on the Taiwan Cancer Registry and Taiwan National Health Insurance Research Database from 2000-2017. After individual exact matching to covariates with 1:1 ratio, there were a total of 1,355 vaccinated and 1,355 unvaccinated survivors. After adjusted by multivariate Poisson regression model, vaccinated group had a non-significantly lower pneumonia hospitalization risk than unvaccinated, with an adjusted IRR of 0.879 (p = .391). Besides, vaccinated group had both lower cumulative incidence rate and higher overall survival time than unvaccinated.

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.

Association of spironolactone use with risk of urinary tract cancer in the general population: A matched population-based cohort study.

PURPOSE: The correlation between spironolactone usage and cancer risk has sparked interest. The objective of this study is to examine the association between spironolactone use and the incidence of urinary tract cancer in the general population. METHODS: We conducted a matched population-based cohort study. The study population was obtained from the Taiwan National Health Insurance Research Database (TNHIRD) during the period from 2000 to 2016. The multivariate Cox proportional hazard model was performed to examine the impact of spironolactone use on the risk of urinary tract cancer. A total of 8,608 individuals exposed to spironolactone were exact matched by 1:1 ratio with unexposed controls on factors including age, gender, comorbidities, CCI scores and socioeconomic status. The incidences of urinary tract cancer, including prostate, renal and bladder cancer, were estimated in both spironolactone exposed and non-exposed cohorts. RESULTS: After adjusting for confounding variables, the multivariate Cox regression analysis showed no significant association between spironolactone exposure and urinary tract cancer incidence, including bladder (adjusted hazard ratio [aHR] = 1.19, 95% confidence interval [CI] = 0.72-1.96, p = 0.50), renal (aHR = 1.75, 95% CI = 0.99-3.07, p = 0.053), and prostate cancer (aHR = 0.67, 95% CI = 0.43-1.04, p = 0.07). When the population was stratified into low (cumulative dose < = 29,300 mg) and high (cumulative dose >29,300 mg) dose of spironolactone, only high dose of spironolactone use was significantly associated with a reduced risk of prostate cancer (aHR = 0.45, 95% CI = 0.23-0.89, p = 0.02), while being associated with an elevated risk of renal cancer (aHR = 2.09, 95% CI = 1.07-4.08, p = 0.03). However, no clear cumulative dose-response relationship was observed in theses associations. CONCLUSIONS: High cumulative dose of spironolactone may be potentially associated with a decreased incidence of prostate cancer and an increased incidence of renal cancer, while no significant association was observed with bladder cancer incidence. However, given the lack of support from the dose-response pattern, the available evidence is inconclusive to establish a definitive association between spironolactone use and urinary tract cancer.

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.

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.

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.

Hazard-based risk grouping effectively stratifying breast cancer patients in post-irradiation long-term heart diseases: a population-based cohort study.

Background: Even though advanced radiotherapy techniques provide a better protective effect on surrounding normal tissues, the late sequelae from radiation exposure to the heart are still considerable in breast cancer patients. The present population-based study explored the role of cox-regression-based hazard risk grouping and intended to stratify patients with post-irradiation long-term heart diseases. Materials and methods: The present study investigated the Taiwan National Health Insurance (TNHI) database. From 2000 to 2017, we identified 158,798 breast cancer patients. Using a propensity score match of 1:1, we included 21,123 patients in each left and right breast irradiation cohort. Heart diseases, including heart failure (HF), ischemic heart disease (IHD), and other heart diseases (OHD), and anticancer agents, including epirubicin, doxorubicin, and trastuzumab, were included for analysis. Results: Patients received left breast irradiation demonstrated increased risks on IHD (aHR, 1.16; 95% CI, 1.06-1.26; p < 0.01) and OHD (aHR, 1.08; 95% CI, 1.01-1.15; p < 0.05), but not HF (aHR, 1.11; 95% CI, 0.96-1.28; p = 0.14), when compared with patients received right breast irradiation. In patients who received left breast irradiation dose of >6,040 cGy, subsequent epirubicin might have a trend to increase the risk of heart failure (aHR, 1.53; 95% CI, 0.98-2.39; p = 0.058), while doxorubicin (aHR, 0.59; 95% CI, 0.26-1.32; p = 0.19) and trastuzumab (aHR, 0.93; 95% CI, 0.33-2.62; p = 0.89) did not. Older age was the highest independent risk factor for post-irradiation long-term heart diseases. Conclusion: Generally, systemic anticancer agents are safe in conjunction with radiotherapy for managing post-operative breast cancer patients. Hazard-based risk grouping may help stratify breast cancer patients associated with post-irradiation long-term heart diseases. Notably, radiotherapy should be performed cautiously for elderly left breast cancer patients who received epirubicin. Limited irradiation dose to the heart should be critically considered. Regular monitoring of potential signs of heart failure may be conducted.

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.

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.

Clinical outcomes of benign brain tumors treated with single fraction LINAC-based stereotactic radiosurgery: Experience of a single institute.

Objectives: Accelerator-based stereotactic radiosurgery (SRS) is a noninvasive and effective treatment modality widely used for benign brain tumors. This study aims to report 20-year treatment outcomes in our institute. Materials and Methods: From May 2001 to December 2020, 127 patients treated with LINAC-based single-fraction SRS for their benign brain lesions were included. A neurosurgeon and two radiation oncologists retrospectively reviewed all data. Computed tomography (CT) simulation was performed after head-frame fixation under local anesthesia. All planning CT images were co-registered and fused with gadolinium-enhanced magnetic resonance imaging taken within 3 months for lesions targeting and critical organs delineation. The marginal dose was prescribed at 60%-90% isodose lines, respectively, to cover ≥95% planning target volume. Outcome evaluations included clinical tumor control rate (TCR), defined as the need for salvage therapy, and radiological response, defined as no enlargement of >2 cm in the maximal diameter. Overall survival (OS) and adverse reaction (defined according to CTCAE 5.0) were also analyzed. Results: The present study included 76 female and 51 male patients for analysis. The median age was 59 years (range, 20-88 years). Their diagnoses were vestibular schwannoma (VS, n = 54), nonvestibular cranial nerve schwannoma (n = 6), meningioma (n = 50), and pituitary adenoma (n = 17). Totally 136 lesions were treated in a single fraction, predominantly skull base tumors, accounting for 69.1%. Median and mean follow-up duration was 49 and 61 months (range, 1-214 months), Overall TCR was 92.9%. The 5-year disease-specific TCR for VS, nonvestibular schwannoma, meningioma, and pituitary adenoma were 97.4%, 91.7%, 93.8%, and 83.3%. Salvage therapy was indicated for eight patients at 4-110 months after SRS. Among symptomatic patients, post-SRS symptom(s) was improved, stable, and worse in 68.2%, 24.3%, and 3.6%, respectively. Radiological response rate for 111 evaluable patients was 94.6% (shrinkage, 28.8%; stable, 65.8%). OS was 96.1% without treatment-related mortality. One patient with post-SRS cranial nerve injury (0.8%, involving the trigeminal nerve, grade 2 toxicities). No grade 3-4 acute or late toxicity was found. Conclusion: Our results suggested that LINAC-based SRS effectively controls tumor growth and tumor-related neurological symptoms for patients with benign brain tumors. SRS is less aggressive, associated with low neurological morbidity and no mortality. Continuous follow-up is indicated to conclude longer outcomes.

Impact of preeclampsia/eclampsia on hemorrhagic and ischemic stroke risk: A 17 years follow-up nationwide cohort study.

BACKGROUND AND PURPOSES: The long-term risk of stroke in women with preeclampsia/eclampsia is a concerning issue. In this study we further investigated different stroke subtypes and differentiated follow-up time intervals. METHODS: Between 2000 and 2017, 1,384,427 pregnant women were registered in the National Health Insurance Research Database in Taiwan. After excluding women with previous stroke history and exact matching with all confounders, 6,053 women with preeclampsia/eclampsia and 24,212 controls were included in the analysis sample. RESULTS: Over the 17-year follow-up, the adjusted hazard ratio (aHR) for stroke in women with preeclampsia/eclampsia was 2.05 (95% confidence interval, CI = 1.67-2.52, p<0.001). The 17 years overall aHR of both ischemic and hemorrhagic stroke were 1.98 and 3.45, respectively (p<0.001). The stroke subtypes, hemorrhagic and ischemic, had different time trend risks, and hemorrhagic stroke risks kept higher than that of ischemic stroke. The aHR of ischemic stroke reached a peak during 1-3 years after childbirth (aHR = 3.09). The aHR of hemorrhagic stroke reached a peak during 3-5 years (aHR = 7.49). CONCLUSIONS: Stroke risk persisted even after decades, for both ischemic and hemorrhagic subtypes. Women with preeclampsia/eclampsia history should be aware of the long-term risk of stroke.

Efficacy of a Novel Intra-Articular Administration of Platelet-Rich Plasma One-Week Prior to Hyaluronic Acid versus Platelet-Rich Plasma Alone in Knee Osteoarthritis: A Prospective, Randomized, Double-Blind, Controlled Trial.

Recent studies have suggested that the combined injection of platelet-rich plasma (PRP) and hyaluronic acid (HA) may have additive benefits for knee osteoarthritis over PRP alone, but there is insufficient evidence to support this combined injection. Moreover, the simultaneous injection of PRP and HA may offset the combined effect. Hence, the aim of this prospective, randomized, double-blind study was to assess their combined efficacy with a novel injection protocol. Forty-six study subjects with unilateral knee osteoarthritis were randomized to receive either a single-dose injection of HA (intervention group) or normal saline (control group) 1 week after a single-dose injection of leukocyte-poor PRP. The Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and static balance and the risk of falls measured by Biodex Balance System were, respectively, the primary and secondary outcome measures. Evaluations were performed at baseline, 1 month, 3 months, 6 months, and 12 months post-injection. The intervention group exhibited significant declines in WOMAC pain, stiffness, and total scores, as well as static balance, compared to the control group (p < 0.05). These randomized double-blind control trials, with novel protocol of intra-articular injection of PRP 1-week prior to HA, provide greater symptom relief and improve static balance compared to PRP alone in patients with knee osteoarthritis.

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 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.

Chronic low back pain is associated with impaired bed turning ability: Evaluation by a mobility detection system.

BACKGROUND: We aimed to assess and compare kinetics and kinematic variables of bed turning ability using a mobility detection system in patients with and without chronic low back pain and to observe the impacts of the disease on bed turning kinetics and kinematics. METHODS: Thirty-five patients with chronic low back pain were enrolled and compared to healthy controls (n = 34). Pain scores and disability level were assessed by Numeric Pain Rating Scale and the function questionnaires including Oswestry Disability Index and Roland Morris Disability Questionnaire. Bed turning ability was tested using the Mobile Detection System. Univariate and multivariate regression analysis were applied to compare the differences between groups. FINDINGS: Patients with chronic low back pain had significantly lower turning over and back force/weight ratio (p < 0.001) than those healthy controls. Turning over time was significantly longer in patients with Numeric Rating Scale score 3 than in those with Numeric Rating Scale score 2 (p = 0.015). Turning over and back force were significantly higher in male patients and patients with higher BMI after adjusting BMI and sex, respectively (all p < 0.001). When turning back, chronic low back pain patients with Numeric Rating Scale scores of 3 had lower turning back force/weight ratio than those with Numeric Rating Scale scores of 2 (p = 0.014). Male patients had higher turning back force/weight ratio after adjusting pain score (p = 0.001). INTERPRETATION: The novel Mobility Detection System can provide more objective assessments of bed turning kinetics and kinematics in patients with chronic low back pain.

Effectiveness of individual audio-visual coaching, respiratory modulated stereotactic body radiotherapy for localized hepatocellular carcinoma: Analysis of 29 cases from a single academic radiotherapy center.

OBJECTIVES: Recently, Stereotactic Body Radiotherapy (SBRT) has been suggested for managing hepatocellular carcinoma (HCC) curatively. Thus, we conducted this clinical study to evaluate retrospectively the effect of individualized audio-visual (AV) coaching, respiratory modulated SBRT. MATERIALS AND METHODS: Between 2014 and 2018, 29 patients with inoperable Barcelona Clinic Liver Cancer (BCLC) stage 0-B HCC received AV coaching, respiratory-modulated SBRT. We constructed a task-oriented multidisciplinary team to establish a standard operation process of respiratory modulation procedures and developed our AV coaching devices. In the training period, a goodness-of-fit test was applied individually. SBRT was delivered with a total dose of 40-54 Gy in 5-6 fractions individually. Freedom from local progression (FFLP) and overall survival (OS) were estimated using SPSS (version 17, SPSS Inc., Chicago, IL, USA) life tables. RESULTS: The patient characteristics were as follows: 32.7 ± 16 mm in maximum tumor diameter (range 11-94); BCLC stage 0: 3.4%, BCLC A: 48.3%, BCLC B: 48.3%; Child-Pugh classification A: 86.2%, Child-Pugh classification B: 13.8%, and a median of 2 prior liver-directed treatments (range 0-7). One-, 2-, and 3-year rates of FFLP of SBRT were 96.6%, 96.6%, and 96.6%, respectively. One-, 2-, and 3-year rates of OS were 81.5%, 72.4%, and 67.2%, respectively. No adverse event (AE) occurred in 41.4% of patients, 48.3% developed grade (G) 1-2 AE, 10.3% had G3 AE and none had G4-5 AE. CONCLUSION: Respiration-modulated SBRT is a promising noninvasive treatment option for patients with inoperable and localized HCC. Our data show that SBRT provides comparable tumor control to historical curative options like surgery and radiofrequency ablation of localized tumors. Thus, we are conducting a further prospective clinical trial with the intent to demarcate the clinical effectiveness of SBRT in a larger population of patients with HCC.

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.

IRAK2, an IL1R/TLR Immune Mediator, Enhances Radiosensitivity via Modulating Caspase 8/3-Mediated Apoptosis in Oral Squamous Cell Carcinoma.

Predicting and overcoming radioresistance are crucial in radiation oncology, including in managing oral squamous cell carcinoma (OSCC). First, we used RNA-sequence to compare expression profiles of parent OML1 and radioresistant OML1-R OSCC cells in order to select candidate genes responsible for radiation sensitivity. We identified IRAK2, a key immune mediator of the IL-1R/TLR signaling, as a potential target in investigating radiosensitivity. In four OSCC cell lines, we observed that intrinsically low IRAK2 expression demonstrated a radioresistant phenotype (i.e., OML1-R and SCC4), and vice versa (i.e., OML1 and SCC25). Next, we overexpressed IRAK2 in low IRAK2-expression OSCC cells and knocked it down in high IRAK2-expression cells to examine changes of irradiation response. After ionizing radiation (IR) exposure, IRAK2 overexpression enhanced the radiosensitivity of radioresistant cells and synergistically suppressed OSCC cell growth both in vitro and in vivo, and vice versa. We found that IRAK2 overexpression restored and enhanced radiosensitivity by enhancing IR-induced cell killing via caspase-8/3-dependent apoptosis. OSCC patients with high IRAK2 expression had better post-irradiation local control than those with low expression (i.e., 87.4% vs. 60.0% at five years, P = 0.055), showing that IRAK2 expression was associated with post-radiation recurrence. Multivariate analysis confirmed high IRAK2 expression as an independent predictor for local control (HR, 0.11; 95% CI, 0.016 - 0.760; P = 0.025). In conclusion, IRAK2 enhances radiosensitivity, via modulating caspase 8/3-medicated apoptosis, potentially playing double roles as a predictive biomarker and a novel therapeutic target in OSCC.

Long-term effect of botulinum toxin A on the hip and spine in cerebral palsy: A national retrospective cohort study in Taiwan.

OBJECTIVES: To investigate the effect of botulinum toxin A (BTA) on the development of hip dislocation and scoliosis, surgical rates for hip and spine, and mortality in cerebral palsy (CP). STUDY DESIGN: A cohort study was conducted using CP data from a Taiwan National Insurance Health Research Database. Diagnoses were defined using the International Classification of Diseases codes, 9th revision. Adjusted hazard ratios for outcomes were calculated using Cox regression analysis and adjusted for the following variables: BTA injection, sex, age, severities of CP, comorbidities, location, urbanization level, and level of care. RESULTS: A total of 1,405 CP children (670 female vs. 735 male), 281 in the BTA group and 1,124 in the controls, were followed-up for a mean of 5 years 4 months. There were no significant differences in the outcomes in both groups, in the incidence rates of hip dislocation and scoliosis, nor in the surgical rates for hip and spine surgery. Mortality rate in the BTA group was 0.49 times lower than that in the controls (p = 0.001). Moderate to severe types of CP had higher incidence rates of hip dislocation, scoliosis, hip surgery, spine surgery, and mortality. CONCLUSION: Moderate to severe types of CP had poorer outcomes in all aspects, including a higher risk of hip dislocation, scoliosis, surgical rate for hip and spine, and mortality. Although BTA injection in children with CP proved to not significantly reduce hip dislocation and scoliosis, it is considered safe as an anti-spasticity treatment and may be beneficial for survival.

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.