Albumin-conjugated PEG liposome enhances tumor distribution of liposomal doxorubicin in rats

To evaluate the effect of coupling of recombinant human serum albumin (rHSA) onto the surface of poly(ethylene glycol)-modified liposorne (PEG liposome) on the in vivo disposition characteristics of liposomal doxorubicin (DXR), the pharmacokinetics and tissue distribution of DXR were evaluated after intravenous administration of rHSA-modified PEG (rHSA/PEG) liposomal DXR into tumor-bearing rats. rHSA/PEG liposome prepared using a hetero-bifunctional cross-linker, N- succinimidyl 3-(2-pyridyldithio) propionate (SPDP), efficiently encapsulated DXR (over 95%). rHSA/PEG liposomal DXR showed longer blood-circulating property than PEG liposornal DXR and the hepatic and splenic clearances of rHSA/PEG liposornal DXR were significantly smaller than those of PEG liposomal DXR. It was also demonstrated that the disposition of DXR to the heart, one of the organs for DXR-related side-effects, was significantly smaller than free DXR. Furthermore, the tumor accumulation of rHSA/PEG liposomal DXR was significantly larger than that of PEG liposomal DXR. The &#34;therapeutic index&#34;, a criterion for therapeutic outcome, for rHSA/PEG fiposornal DXR was significantly higher than PEG liposomal DXR. These results clearly indicate that rHSA-conjugation onto the surface of PEG liposome would be a useful approach to increase the effectiveness and safety of PEG liposomal DXR.</p

Association between the Beighton Score and Stress Ultrasonographic Findings of the Anterior Talofibular Ligament in Healthy Young Women: A Cross-Sectional Study

The Beighton score (BS) is widely used to evaluate generalized joint laxity. However, the association between the BS and lateral ankle laxity is unclear. This study compared the ultrasonographic (US) findings of the anterior talofibular ligament (ATFL) between high- (≥6) and low- (≤3) BS groups of healthy young women. The ATFL lengths of healthy young women were measured in the stress and nonstress positions using the previously reported technique from March 2021 to January 2022. The ATFL ratio (ratio of stress to nonstress ATFL length) was used as an indicator of lateral ankle laxity. The anterior drawer test (ADT) was performed. The correlation between the BS and US findings was also examined. A total of 20 (high-BS group) and 61 (low-BS group) subjects with a mean age of 23.8 ± 1.0 years were included. The high-BS group showed a higher grade of ADT than the low-BS group. No significant differences were found in the nonstress and stress ATFL lengths and ATFL ratio (1.10 ± 0.05 vs. 1.09 ± 0.05, p = 0.19) between the groups. No correlation was found between the BS and US findings. In conclusion, this study did not detect significant differences in the US findings of the ATFL between the high- and low-BS groups

Fixation of an Osteochondral Lesion of the Femoral Intercondylar Groove Using Autogenous Osteochondral Grafts and Bioabsorbable Pins in a Patient with Open Physes: A Case Report

Osteochondral lesion (OCL) of the patellofemoral (PF) joint is not an uncommon cause of knee pain, and surgery is needed when conservative treatment fails. However, there is a lack of evidence regarding the optimal surgical treatment for OCL of the PF joint. Fixation of OCLs using autogenous osteochondral grafts has been reported to be effective for OCL of the knee. However, in this surgical technique, the biomechanical strength of osteochondral grafts may not be sufficient in patients with open physes due to the specific quality of the cartilage and subchondral bone given their age. There is a lack of studies reporting fixation of the OCL located in the PF joint using autogenous osteochondral grafts. We herein report a case of OCL of the femoral intercondylar groove where autogenous osteochondral grafts augmented with bioabsorbable pins were used to fix the lesion in a 14-year-old patient with open physes. Preoperative MRI revealed a completely detached OCL of the intercondylar groove (36 mm &times; 20 mm). Although a total of four osteochondral grafts were harvested from the non-weightbearing area of the lateral femoral condyle, cartilage detached from one of the grafts. The quality of the osteochondral grafts was considered to be insufficient for stabilization of the OCL; thus, two bioabsorbable pins were additionally inserted following fixation of the lesion using three osteochondral grafts. After two years of follow-up, postoperative functional scores were favorable without knee pain. The present case suggests that fixation of the OCL using autogenous osteochondral grafts may not be appropriate for young patients with open physes

Influence of the Tibial Tunnel Angle and Posterior Tibial Slope on &ldquo;Killer Turn&rdquo; during Posterior Cruciate Ligament Reconstruction: A Three-Dimensional Finite Element Analysis

This study aimed to evaluate the influence of various posterior tibial slopes (PTSs) and tibial tunnel angles (TTAs) on &ldquo;killer turn&rdquo; in posterior cruciate ligament (PCL) reconstruction by using three-dimensional finite element analysis (FEA). The study models were created using computed tomography images of a healthy young Asian male. Using SolidWorks, PCL grafts and tibial bone tunnels at different tibial drilling angles (30&deg;, 45&deg;, 60&deg;) were developed. Anterior opening wedge high tibial osteotomy (aOW-HTO) was performed to evaluate the influence of the PTS (+8&deg;, +4&deg;, native, &minus;4&deg;, &minus;8&deg;). An FEA was performed utilizing the ANSYS software program. In the same PTS model, the peak of the equivalent Von Mises stress in PCL grafts decreased as the angle of the TTA increased. In the same TTA model, the peak of the Von Mises in PCL grafts decreased as the PTS angle increased. The &ldquo;high-contact stress area&rdquo; (contact stress greater than 10 MPa) was diminished when the TTA and PTS were increased. aOW-HTO was used to steepen the PTS, and a larger TTA may reduce the stress at the &ldquo;killer turn&rdquo; during PCL reconstruction. In conclusion, the study findings suggest that using aOW-HTO to steepen the PTS and a larger TTA may reduce the stress at the &ldquo;killer turn&rdquo; during PCL reconstruction. The usefulness and safety of this surgical procedure need to be evaluated in future clinical studies

On-demand Inhaled Corticosteroid and Fast-onset Beta-2 Agonist Combination Therapy Versus Conventional Treatment for Mild to Moderate Asthma: A Non-inferiority, Network Meta-analysis

The aim of this study was to assess the non-inferiority of on-demand (OD) inhaled corticosteroid (ICS) and fast-onset beta-2 agonist (FOBA) combination therapy. Although the guidelines recommend regular inhalation of ICS and long-acting beta-2 agonist (LABA), we investigated whether OD-ICS/FOBA is as effective as regular inhalation. A network meta-analysis of randomized controlled trials was conducted to inspect the non-inferiority of OD-ICS/FOBA efficacy compared with conventional best practice, i.e. regular low – to medium-dose ICS with or without LABA, plus OD short-acting beta-2 agonist (REG-ICS+OD-SABA or REG-ICS/LABA+OD-SABA) in patients with mild to moderate asthma. PubMed, the Cochrane library database, and Scopus were searched to identify relevant articles. Outcome measures were the incidence of asthma exacerbation or aggravation. A network meta-analysis was performed to estimate risk ratios (RRs) with 95% confidence intervals (CIs) and the probability of being the best treatment for the outcome. Four randomized controlled trials of treatment for mild to moderate asthma met the criteria and were included in the study. We could not demonstrate non-inferiority of OD-ICS/FOBA to REG-ICS+OD-SABA (RR, 1.17; 95% CI, 0.61 to 2.26) or to REG-ICS/LABA+OD-SABA (RR, 1.47; 95% CI, 0.79 to 2.71) for mild to moderate asthma. The probability of being the best treatment to reduce asthma exacerbation or aggravation was 10.5% for OD-ICS/FOBA, 10.3% for REG-ICS+OD-SABA, and 79.3% for REG-ICS/LABA+OD-SABA. Surface under the cumulative ranking (SUCRA) curves were 0.4, 0.2 and 0.9 for OD-ICS/FOBA, REG-ICS+OD-SABA, and REG-ICS/LABA+OD-SABA, respectively. Although non-inferiority of OD-ICS/FOBA to conventional best practice was not shown, SUCRA was higher for OD-ICS/FOBA than for REG-ICS+OD-SABA. From these results, we propose that OD-ICS/FOBA can be an effective alternative to REG-ICS+OD-SABA to reduce asthma exacerbation or aggravation in patients with mild to moderate asthma

Meta-analysis of Low-versus High-dose Benralizumab in Adults with Uncontrolled Eosinophilic Asthma

The aim of the present study was to assess the non-inferiority of low-dose benralizumab relative to high-dose benralizumab as a treatment option for uncontrolled eosinophilic asthma through a meta-analysis of efficacy and safety in randomized controlled trials (RCTs). PubMed, the Cochrane Library Database, and Scopus were searched to identify relevant articles. Outcome measures were a change in the Asthma Control Questionnaire-6 (ACQ-6) score and the exacerbation rate. In addition, the meta-analysis assessed the incidence of adverse events, injection site reactions, and pyrexia or influenza-like illness. Two RCTs with two doses of benralizumab (20 and 100mg) and a placebo for the treatment of uncontrolled eosinophilic asthma met the criteria and were included in the present study. Non-inferiority of low-dose (20mg) versus high-dose (100mg) benralizumab was shown for the change in ACQ-6 score, exacerbation rate, and the incidence of adverse events, injection site reactions, and pyrexia or influenza-like illness. Although not significant, the incidence of pyrexia or influenza-like illness was lower in patients treated with low-dose benralizumab. These results suggest that low-dose (20mg) benralizumab is effective for symptom control and reduction of exacerbation rate in uncontrolled eosinophilic asthma, with lower treatment costs

On-Demand Inhaled Corticosteroid and Fast-Acting Beta-2 Agonist Combination Therapy Versus Regular Inhaled Corticosteroid Plus Rescue Bronchodilator in Adults with Mild Asthma: A Network Meta-Analysis

The aim of this study was to assess the non-inferiority of on-demand (OD) inhaled corticosteroid (ICS) and fast-acting beta-2 agonist (FABA) combination therapy. Although regular inhalation of low-dose ICS and OD short-acting beta-2 agonist (REG-ICS+OD-SABA) is said to be effective therapy for mild asthma, we investigated whether OD-ICS/FABA is as effective as REG-ICS+OD-SABA. A network meta-analysis of randomized controlled trials was conducted to examine non-inferiority by comparing the efficacy of NON-REG+OD-ICS/FABA with REG-ICS+OD-SABA for mild asthma. We also assessed the superiority of NON-REG+OD-ICS/FABA to OD-SABA without any regular treatment (NON-REG+OD-SABA). PubMed, the Cochrane library database, and Scopus were searched to identify relevant articles with an outcome measure of the incidence of asthma control. A network meta-analysis was performed and the summary effect size was expressed as the mean difference (MD) with 95% confidence intervals (CIs). The probability of being the best treatment for the outcome and the surface under the cumulative ranking curves were also calculated. Three randomized controlled trials of treatment for mild asthma met the criteria and were included in the study. Non-inferiority of NON-REG+OD-ICS/FABA to REG-ICS+OD-SABA (MD, -0.17; 95% CI, -0.41 to 0.07) and superiority of NON-REG+OD-ICS/FABA to NON-REG+OD-SABA (MD, -0.29; 95% CI, -0.49 to -0.08) were shown in patients with mild asthma. The respective probabilities of being the best treatment for asthma control were 91.2%, 8.8% and 0.2% for NON-REG+OD-ICS/FABA, REG-ICS+OD-SABA, and NON-REG+OD-SABA, respectively, and the surface under the cumulative ranking curves were 1.0, 0.5, and 0.1, respectively. These results suggest that NON-REG+OD-ICS/FABA is an effective alternative to REG-ICS+OD-SABA for asthma control in patients with mild asthma

Fertility-sparing radical resection of juvenile clear cell adenocarcinoma of the cervix by pneumovaginal endoscopic surgery

Vaginoscopy has been mainly used diagnostically due to the lack of adequate equipment for performing complicated surgeries (Johary et al., 2015). However, herein, we report therapeutic vaginal endoscopic surgery (pneumovaginoscopy) for secondary malignant vaginal tumors using the vNOTES technique and devices (Kita et al., 2021; Yokoe et al., 2022).To our knowledge, this report and surgical video demonstrate the first case of successful fertility-sparing R0 tumor resection of a rare primary cervical clear cell adenocarcinoma using pneumovaginoscopy.A 12-year-old girl was referred to our outpatient clinic with a chief complaint of a genital tumor and possible clear cell carcinoma on biopsy. There was no history of diethylstilbestrol exposure. MRI and CT images suggested a polypoid cervical tumor without metastatic lesions. Therefore, we performed therapeutic pneumovaginoscopic surgery with diagnostic laparoscopy and hysteroscopy.The cervical tumor was resected completely, and hysteroscopy and laparoscopy revealed no abnormalities. The total surgical time was 123 min, and the blood loss volume was minimal. R0 resection was achieved microscopically.Postoperatively, we performed a partial cervical resection around the first surgical scar to confirm no residual tumor.There were no postoperative complications, and a 2-year follow-up revealed no recurrence.The standard treatment for early-stage cervical cancer (IA2-IB1) remains radical hysterectomy with pelvic lymphadenectomy. However, fertility-sparing minimally invasive surgery has recently been introduced for clear cell adenocarcinoma of the cervix (Su et al., 2020). Our report supports the possibility of this minimally invasive surgery under exceptional conditions. This study was approved by the ethics committee of Kansai Medical University. Written and signed informed consent was obtained from the patient’s legal guardian

Effect of a leukotriene receptor antagonist on cough receptor sensitivity and allergen-induced cough in a patient with atopic cough variant asthma

A 24-year-old female patient with chronic dry cough, without wheezing and other symptoms, was diagnosed as atopic cough variant asthma (CVA) sensitized with house dust (HD) mite. To investigate the effect of a leukotriene (LT) receptor antagonist (pranlukast hydrate, ONON 450 mg/day), cough score, respiratory function, cough receptor sensitivity to capsaicin, airway inflammation evaluated by hypertonic saline inhalation and airway reactivity to histamine were studied before and after treatment for 4 weeks. Furthermore, the effect of a LT receptor antagonist on HD allergen-induced bronchoconstrictive and cough responses was investigated. Treatment with a LT receptor antagonist resulted in disappearance of cough, improvement of respiratory function, decrease in eosinophil percentage in induced sputum and increase in capsaicin and histamine threshold. Although bronchoprovocation with HD extract induced an immediate bronchoconstriction followed by cough responses before treatment, inhibition of both bronchoconstrictive and cough responses was observed after treatment. These results suggest that LT is involved in the mechanism of cough in this patient with atopic CVA

Association between Casual Serum Triglyceride Levels and Bone Resorption Activity in Japanese Middle-aged and Elderly Women

High serum triglyceride (TG) levels may lower bone fracture risk, but the association between serum TG and bone resorption activity is unclear. The aim of the present study was to analyze this association using casual serum TG levels in patients with and without accelerated bone resorption. A case-control study was performed in 39 patients with accelerated bone resorption and in 69 controls, treated between April 2011 and March 2016 at the Internal Medicine Clinic. Bone resorption activity was assessed by urinary N-telopeptide of type I collagen (uNTx; a marker of bone resorption), which is routinely measured at the Internal Medicine Clinic. Cases were female outpatients aged ≥40 years in whom uNTx levels were ≥54.3nmol bone collagen equivalent (BCE)/mmol creatinine. Subjects with casual serum TG levels ＞150mg/dl were diagnosed with potential hypertriglyceridemia (PHTG). Propensity score-adjusted multinomial logistic regression was performed to estimate the odds ratios (ORs) and corresponding 95% confidence intervals (CIs) for PHTG in cases compared with controls. Correlations between uNTX and casual serum TG levels in all patients were evaluated using multivariate regression. The prevalence of PHTG was significantly lower in cases than in controls (OR 0.20; 95% CI 0.05-0.65; P=0.006). uNTx levels were negatively associated with casual serum TG levels in all patients (r=-0.07, P=0.046). These results suggest that serum TG levels are negatively associated with bone resorption activity. Reduced bone resorption activity may explain, in part, the reduced fracture risk in Japanese middle-aged and elderly female patients with hypertriglyceridemia