Fibrinogen Aα-chain amyloidosis outbreaks in Japanese squirrels (Sciurus lis): a potential disease model.

Fibrinogen Aα-chain amyloidosis is a hereditary systemic amyloidosis characterized by glomerular amyloid depositions, which are derived from the fibrinogen Aα-chain variant in humans. Despite its unique pathology, the pathogenic mechanisms of this disease are only partially understood. This is in part because comparative pathological studies on fibrinogen Aα-chain amyloidosis are currently unavailable as there is a lack of reported cases in animals other than humans. In this study, mass spectrometry-based proteomic analyses of Japanese squirrels (Sciurus lis) that died in five Japanese zoos showed that they developed glomerular-associated fibrinogen Aα-chain amyloidosis with an extremely high incidence rate (29/38 cases, 76.3%). The condition was found to be age-dependent in the Japanese squirrels, with 89% of individuals over 4 years of age affected. Mass spectrometry revealed that the C-terminal region of the fibrinogen Aα-chain was involved in amyloidogenesis in Japanese squirrels as well as humans. No gene variations were identified between amyloid-positive and amyloid-negative squirrels, which contrasted with the available data for humans. The results indicate that fibrinogen Aα-chain amyloidosis is a senile amyloidosis in Japanese squirrels. The results have also provided comparative pathological support that the amyloidogenic C-terminal region of the fibrinogen Aα-chain is involved in the characteristic glomerular pathology, regardless of the animal species. This study elucidates the potential causes of death in Japanese squirrels and will contribute to future comparative pathological studies of fibrinogen Aα-chain amyloidosis. © 2023 The Pathological Society of Great Britain and Ireland.

Clinical outcomes of patients diagnosed with cancer of unknown primary or malignancy of undefined primary origin who were referred to a regional cancer center.

BACKGROUND: A regional cancer hospital has been identified to be crucial in the management of malignancies of undefined primary origin (MUO) and cancer of unknown primary (CUP). This hospital primarily consists of oncologists with expertise in CUP, pathologists, and interventional radiologists. Early consultation or referral of MUO and CUP to a cancer hospital is deemed important. METHODS: This study retrospectively collected and analyzed the clinical, pathological, and outcome data of all patients (n = 407) referred to the Aichi Cancer Center Hospital (ACCH) in Japan over an 8-year period. RESULTS: In total, 30% of patients were referred for a second opinion. Among 285 patients, 13% had non-neoplastic disease or confirmed primary site and 76% had confirmed CUP (cCUP), with 29% of cCUP being identified as favorable risk. In 155 patients with unfavorable-risk CUP, 73% had primary sites predicted by immunohistochemistry (IHC) and distribution of metastatic sites, whereas 66% of them received site-specific therapies based on the predicted primary sites. The median overall survival (OS) was found to be poor in patients with MUO (1 month) and provisional CUP (6 months). In addition, the median OS of 206 patients with cCUP treated at the ACCH was 16 months (favorable risk, 27 months; unfavorable risk, 12 months). No significant difference was noted in OS between patients with non-predictable and predictable primary-sites (13 vs 12 months, p = 0.411). CONCLUSION: The outcome of patients with unfavorable-risk CUP remains to be poor. Site-specific therapy based on IHC is not recommended for all patients with unfavorable-risk CUP.

Mitral valve leaflet stiffness predicts residual mitral regurgitation after transcatheter edge-to-edge mitral valve repair.

BACKGROUND: Residual regurgitation after transcatheter edge-to-edge mitral valve repair (TMVR) is a predictor of poor prognosis in patients with functional mitral regurgitation (FMR). This study sought to identify the mitral valve (MV) parameters measured by three-dimensional transesophageal echocardiography (3D-TEE) and MV leaflet features that predict residual mitral regurgitation (MR) after TMVR in patients with FMR. METHODS: Consecutive patients with FMR who underwent TMVR were classified into two groups based on the degree of residual MR just after TMVR: < 2+ in the optimal MR reduction group and ≥ 2+ in the suboptimal MR reduction group. The two groups were compared with respect to 3D-TEE parameters and the MV leaflet features, including the following parameters: stiffness, defined as a leaflet that remains at a fixed angle even during diastole, and thickness, measured in both clear and rough zones. RESULTS: Thirty-four of 46 patients (74%) were classified as the optimal MR reduction group. Multivariable analysis showed that anterior mitral leaflet + posterior mitral leaflet length/anteroposterior annulus diameter (p = .044) and MV leaflet stiffness (p = .007) were independent predictors of residual MR. CONCLUSION: MV leaflet stiffness and the ratio of MV leaflet lengths to the annulus diameter may be good predictors of residual MR after TMVR in patients with FMR.

High-fat diet-induced obesity accelerates the progression of spontaneous osteoarthritis in Senescence-Accelerated Mouse Prone 8 (SAMP8).

OBJECTIVES: Aging and obesity are major risk factors for osteoarthritis (OA), a widespread disease currently lacking efficient treatments. Senescence-accelerated mouse prone 8 (SAMP8) display early-onset aging phenotypes, including OA. This study investigates the impacts of high-fat diet (HFD)-induced obesity on OA development in SAMP8. METHODS: SAMP8 at five weeks were fed either a normal chow diet or an HFD for ten weeks to induce obesity. Parameters related to obesity, liver function, and lipid and glucose metabolism were analyzed. At 14 weeks of age, knee joint pathology, bone mineral density, and muscle strength were assessed. Immunohistochemistry and TUNEL staining were performed to evaluate markers for cartilage degeneration and chondrocyte apoptosis. RESULTS: At 14 weeks of age, HFD-induced obesity increased liver and adipose tissue inflammation in SAMP8 without further exacerbating diabetes. Histological scoring revealed aggravated cartilage, menisci deterioration, and synovitis, while no further loss of bone mineral density or muscle strength was observed. Increased chondrocyte apoptosis was detected in knee joints following HFD feeding. CONCLUSIONS: Ten weeks of HFD feeding promotes spontaneous OA progression in 14-week-old SAMP8, potentially via liver damage subsequent chondrocyte apoptosis. This aging-obese mouse model may prove valuable for further exploration of spontaneous OA pathophysiology.

The impact of combined PD-L1 positive score on clinical response to nivolumab in patients with advanced esophageal squamous cell carcinoma.

BACKGROUND: Nivolumab is recommended for patients with advanced esophageal squamous cell carcinoma (aESCC) refractory or intolerant to fluoropyrimidine- and platinum-based chemotherapy regardless of the tumor proportion score (TPS). However, the role of combined positive score (CPS) in predicting nivolumab efficacy remains unclear. We aimed to study whether TPS or CPS is a more suitable biomarker for predicting nivolumab efficacy in these patients. METHODS: We retrospectively collected data from patients with aESCC treated with fluoropyrimidines and platinum and subsequently received nivolumab monotherapy between January 1, 2014 and September 15, 2020. Next, we evaluated the efficiencies of TPS and CPS in predicting the clinical response to nivolumab using PD-L1 IHC 22C3 pharmDx assay. RESULTS: This study included 50 patients (CPS groups: ≥ 10/1-10/ < 1, n = 24/18/8, respectively; TPS groups, ≥ 10%/1%-10%/ < 1%, n = 17/8/25, respectively). The median progression-free survival was 3.2, 2.5, and 1.5 months in the ≥ 10, 1-10 [hazard ratio (HR) vs. CPS of ≥ 10 group, 1.01; p = 0.98; adjusted HR, 1.33; p = 0.56], and < 1 CPS groups (HR vs. CPS of ≥ 10 group, 3.44; p = 0.006; adjusted HR, 1.67; p = 0.41), respectively. For the patients with CPS of ≥ 10/1-10/ < 1 and TPS of ≥ 10%/1%-10%/ < 1%, the objective response rate was 30%/25%/0% and 36%/0%/19% and the disease control rate was 60%/50%/12% (p = 0.06) and 65%/40%/38% (p = 0.30), respectively. CONCLUSIONS: This study suggests that a CPS of < 1 is not a strong predictor of efficacy but can predict the absence of response to nivolumab in patients with aESCC.

Effect of cholesterol on the lactosylceramide domains in phospholipid bilayers.

Lactosylceramide (LacCer) in the plasma membranes of immune cells is an important lipid for signaling in innate immunity through the formation of LacCer-rich domains together with cholesterol (Cho). However, the properties of the LacCer domains formed in multicomponent membranes remain unclear. In this study, we examined the properties of the LacCer domains formed in Cho-containing 1-palmitoyl-2-oleoyl phosphatidylcholine (POPC) membranes by deuterium solid-state NMR and fluorescence lifetimes. The potent affinity of LacCer-LacCer (homophilic interaction) is known to induce a thermally stable gel phase in the unitary LacCer bilayer. In LacCer/Cho binary membranes, Cho gradually destabilized the LacCer gel phase to form the liquid-ordered phase by its potent order effect. In the LacCer/POPC binary systems without Cho, the 2H NMR spectra of 10',10'-d2-LacCer and 18',18',18'-d3-LacCer probes revealed that LacCer was poorly miscible with POPC in the membranes and formed stable gel phases without being distributed in the liquid crystalline domain. The lamellar structure of the LacCer/POPC membrane was gradually disrupted at around 60°C, whereas the addition of Cho increased the thermal stability of the lamellarity. Furthermore, the area of the LacCer gel phase and its chain order were decreased in the LacCer/POPC/Cho ternary membranes, whereas the liquid-ordered domain, which was observed in the LacCer/Cho binary membrane, was not observed. Cho surrounding the LacCer gel domain liberated LacCer and facilitated forming the submicron to nano-scale small domains in the liquid crystalline domain of the LacCer/POPC/Cho membranes, as revealed by the fluorescence lifetimes of trans-parinaric acid and trans-parinaric acid-LacCer. Our findings on the membrane properties of the LacCer domains, particularly in the presence of Cho, would help elucidate the properties of the LacCer domains in biological membranes.

The Prognostic Impact of KRAS G12C Mutation in Patients with Metastatic Colorectal Cancer: A Multicenter Retrospective Observational Study.

BACKGROUND: KRAS is one of the most frequently mutated oncogenes in colorectal cancer (CRC). Recently, a novel therapy targeting KRAS G12C mutation has demonstrated promising activities for corresponding advanced solid tumors, including metastatic CRC (mCRC). However, the prognostic impact of the KRAS G12C mutation remains unclear in patients with mCRC. MATERIALS AND METHODS: We retrospectively reviewed medical records of patients with mCRC who received first-line chemotherapy between January 2005 and December 2017 at four large oncology facilities in Japan. Survival outcomes were compared between patients with KRAS G12C and those with non-G12C mutations. RESULTS: Among 2,457 patients with mCRC, 1,632 met selection criteria, and of these, 696 had KRAS exon 2 mutations, including 45 with KRAS G12C mutation tumors. Patient characteristics were not significantly different between the KRAS G12C and non-G12C groups. At a median follow-up of 64.8 months, patients with the KRAS G12C mutation showed significantly shorter first-line progression-free survival (PFS; median, 9.4 vs. 10.8 months; p = .015) and overall survival (OS; median, 21.1 vs. 27.3 months; p = .015) than those with non-G12C mutations. Multivariate analysis also showed that KRAS G12C mutation was significantly associated with shorter PFS (hazard ratio [HR], 1.43; 95% confidence interval [CI], 1.04-1.96, p = .030) and OS (HR, 1.42; 95% CI, 1.01-2.00; p = .044). CONCLUSION: We demonstrate that, compared with non-G12C mutations, KRAS G12C mutation is significantly correlated with shorter first-line PFS and OS. These findings indicate the relevance of a stratified treatment targeting KRAS G12C mutation in mCRC. IMPLICATIONS FOR PRACTICE: Among patients with KRAS exon 2 mutated metastatic colorectal cancer (mCRC), median progression-free survival (PFS) and overall survival (OS) were 9.4 and 21.1 months, respectively, for G12C mutation and 10.8 and 27.3 months, respectively, for patients with non-G12C mutations, indicating significantly shorter PFS (hazard ratio [HR], 1.47; 95% confidence interval [CI], 1.08-2.01; p = .015) and OS (HR, 1.50; 95% CI, 1.08-2.08; p = .015) in patients with G12C mutation than in those with non-G12C mutations. Furthermore, multivariate analysis showed that KRAS G12C mutation was independently associated with shorter first-line PFS and OS. Thus, these findings underscore the relevance of a stratified treatment targeting KRAS G12C mutation in mCRC.

Challenges in the diagnosis and management of central line-associated blood stream infection due to Exophiala dermatitidis in an adult cancer patient.

BACKGROUND: Exophiala (Wangiella) dermatitidis is a clinically relevant black yeast. Although E. dermatitidis rarely causes human infection, it can cause superficial and deep-seated infections, and cutaneous and subcutaneous diseases. Cases of fungemia and central line-associated bloodstream infections due to E. dermatitidis are extremely uncommon, and their clinical manifestations and prognosis are still not well-known. Herein, we report a case of central line-associated bloodstream infections in a patient with cancer. These infections were caused by melanized yeast that was finally identified as E. dermatitidis via internal transcribed spacer sequencing and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. CASE PRESENTATION: A 75-year-old man with thoracic esophageal cancer and early gastric cancer presented with a 1-day history of fever during his hospitalization at our hospital. A central venous port was placed in the patient for total parenteral nutrition. Two E. dermatitidis isolates were recovered from two blood samples drawn at different times from a peripheral vein and this central venous port. The isolate was identified as E. dermatitidis by internal transcribed spacer sequencing and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. The central venous port was removed, and the patient was administered micafungin and voriconazole. Although the minimum inhibitory concentrations of E. dermatitidis for voriconazole and minimum effective concentrations for micafungin were 2 µg/mL and 4 µg/m, respectively, the bacteremia was successfully treated. CONCLUSIONS: Although no clear treatment guidelines have been proposed for E. dermatitidis infections, immediate removal of central venous catheters is the key to improving central line-associated bloodstream infections.

Impact of the SARS-CoV-2 Pandemic on Primary Percutaneous Coronary Intervention for Patients with ST-Elevation Myocardial Infarction.

During the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, patients with ST-elevation myocardial infarction (STEMI) should be treated as possibly infected individuals. Therefore, more time is considered necessary to conduct primary percutaneous coronary intervention (PCI). In this study, we sought to evaluate the impact of the SARS-CoV-2 pandemic on primary PCI for STEMI. Between March 2019 and March 2021, 259 patients with STEMI underwent primary PCI. Patients were divided into 2 groups: the pre-pandemic group (March 2019-February 2020) and the pandemic group (March 2020-February 2021). The patient demographics, reperfusion time including onset-to-door time, door-to-balloon time (DTBT), computed tomography (CT), peak creatinine phosphokinase (CPK), and 30-day mortality rate were investigated. The mean age of the patients was 70.4 ± 12.9 years, and 71.6% were male. There were 117 patients before the pandemic and 142 during the pandemic. The median DTBT was 29 (21.25-41.25) minutes before the pandemic and 48 minutes (31-73 minutes) during the pandemic (P < 0.001). The median door-to-catheter-laboratory time was 13.5 (10-18.75) minutes before the pandemic and 29.5 (18-47.25) minutes during the pandemic (P < 0.001). CT evaluation was performed before PCI in 39 (33.3%) patients and 63 (44.4%) patients (P = 0.08); their peak CPK levels were 1480 (358-2737.5) IU and 1363 (621-2722.75) IU (P = 0.56), and the 30-day mortality rates were 4.3% and 2.1% (P = 0.48), respectively. The SARS-CoV-2 pandemic changed the diagnostic procedure in the emergency department and affected the DTBT in patients with STEMI. Nonetheless, no adverse effects on the 30-day mortality rate were observed.

Bifurcation Intervention in Single Coronary Artery.

A 77-year-old man was referred to our hospital for angina on effort. Coronary angiography and computed tomography demonstrated a single coronary artery arising from the right sinus of Valsalva. The left circumflex coronary artery (LCx) anomalously deriving near from the ostium of right coronary artery exhibited severe stenosis in the bifurcation of the obtuse marginal branch. Although the bifurcation lesion still remains a therapeutic challenge for guide extension catheter (GEC)-based percutaneous coronary intervention, under the guidance of intravascular ultrasound imaging, we successfully implanted an everolimus-eluting stent at the bifurcated LCx lesion and performed kissing balloon inflation using 0.014- and 0.010-inch systems through GECs.

Rotational Atherectomy Followed by Drug-Coated Balloon Dilation in Possible Coronary Sequelae of Kawasaki Disease.

Rotational atherectomy with/without low-pressure balloon dilation has been a mainstay of interventional treatment for stenosis due to the coronary sequelae of Kawasaki disease (KD). Here, we report a restenosis case of probable coronary sequelae of KD treated with rotational atherectomy with low-pressure 2.5-mm balloon dilation 6 months previously. Under the guidance of optical frequency domain imaging, we performed rotational atherectomy followed by 2.5-mm drug-coated balloon (DCB) dilation for an atherosclerotic restenosis at the inlet of a calcified aneurysm in the proximal left anterior descending coronary artery. Coronary angiography 6 months later showed no apparent progression of vessel narrowing, and we could defer repeat intervention. The present case suggests that rotational atherectomy followed by DCB dilation could be an alternative revascularization therapy of choice in coronary KD sequelae complicated with atherosclerosis.

Lactic acid fermentation of kamaboko, a heated Alaska pollock surimi, enhances angiotensin I-converting enzyme inhibitory activity via fish protein hydrolysis.

To enhance the value of surimi, efforts have been made to develop a fermentation method with lactic acid bacteria (LAB) to proteolyze fish protein. However, fermenting unheated surimi poses a spoilage risk due to its high bacterial content. Surimi heat treatment can prevent spoilage, but gel formation induced by heating introduces another technical issue: it hinders uniform fermentation. Thus, this study aims to observe the proteolysis and enhance the functionality of seafood product through lactic acid fermentation of kamaboko, a heated surimi. Upon analyzing the kamaboko fermented with Lactobacillus helveticus JCM1004, we observed that LAB produced protease, resulting in the degradation of myosin heavy chain and actin during fermentation. Lactic acid fermentation significantly augmented the peptide content of kamaboko, subsequently elevating the angiotensin Ⅰ-converting enzyme (ACE) inhibitory activity in 200-fold diluted extract of fermented kamaboko to approximately 70% and higher. Notably, our investigation revealed that proteolysis was confined to the surface of kamaboko, as evidenced by SDS-PAGE analysis. This observation implies that the surface area of kamaboko influences the ACE inhibitory activity. Through a comparative analysis of various bacterial strains, we demonstrated that the increase in ACE inhibitory activity is contingent on the protease generated by LAB. These results suggest that LAB-mediated proteolysis of fish proteins liberates bioactive peptides, thereby manifesting in the ACE inhibitory activity. In summary, this study underscores that the fermentation of kamaboko employing proteolytic LAB holds promise in the development of novel functional seafood products.

Mitral regurgitation outcomes after transcatheter atrial septal defect closure.

BACKGROUND: Worsening mitral regurgitation (MR) is a complication of intervention for atrial septal defect (ASD). Little is known about mitral valve (MV) characteristics associated with worsening MR. We aimed to elucidate MR outcomes and predictors of worsening MR after transcatheter ASD closure. METHODS: We analyzed changes in MR from prior to transcatheter ASD closure to 6 months after the procedure and predictors of worsening MR via baseline transthoracic echocardiography in 238 patients (64.7% females; mean age, 53 ± 22 years). RESULTS: Worsening MR was defined as worsening to moderate in patients with less than or equal to mild MR at baseline or vena contracta width increasing of ≥2 mm by 6-month follow-up in patients with moderate MR. Worsening MR was observed in 29 patients (12.2%). The associated echocardiographic findings were pseudoprolapse, hamstringing, stiffness, and anteroposterior and intercommissural mitral annulus diameter in the univariable logistic regression analysis (all P < 0.05). Multivariable analysis after adjusting for age; long-standing persistent atrial fibrillation; and ASD size showed that models combining MV leaflet findings such as pseudoprolapse or hamstringing, or anterior leaflet stiffness with the ratio of the sum of anterior and posterior leaflet lengths to intercommissural mitral annulus diameter were statistically significant for predicting worsening MR (R2 = 0.393, P < 0.001 and R2 = 0.385, P < 0.001, respectively). CONCLUSIONS: Worsening MR after transcatheter ASD closure might depend on MV leaflet findings and annulus size in patients with long-standing persistent atrial fibrillation.

Chronological improvement of survival in patients with advanced gastric cancer over 15 years.

Background: Recent trials have reported a median overall survival (OS) of 11-17 months in patients with advanced gastric cancer (AGC). However, it is unclear how recently approved drugs contribute to patient prognosis. Objectives: We aimed to evaluate the characteristics and survival in patients with AGC over the past 15 years. Design: Retrospective study. Methods: We evaluated data of 1355 patients with AGC who received first-line chemotherapy between January 2005 and March 2019 at a single institution. We compared the characteristics and survival rates across four periods: January 2005-December 2007 (period A), January 2008-February 2011 (period B), March 2011-May 2015 (period C), and June 2015-March 2019 (period D). The median follow-up duration was 13.1 months, with 312, 333, 393, and 317 patients in periods A, B, C, and D, respectively. Results: There were no significant differences in patient characteristics between the four periods, except for the proportion of patients who underwent prior gastrectomy and human epidermal growth factor receptor 2 (HER2) testing. Patients in period D had significantly longer OS than those in period A [median: 15.7 versus 12.4 months; adjusted hazard ratio (aHR): 0.79; p = 0.02]. The mean OS in patients with liver metastasis (LM) in period D was remarkably longer than that in patients in period A (median: 19.3 versus 12.4 months; aHR: 0.61; p < 0.01), while that in patients with peritoneal metastasis showed limited improvement. Conclusion: Clinical strategy changes, including gastrectomy, HER2 testing, and approval of new drugs, may be associated with improved OS in patients with AGC. In the last 4 years, a remarkable improvement has been observed in patients with LM.

Safety and Efficacy of Gemcitabine Plus Cisplatin Against Recurrent/Metastatic Nasopharyngeal Carcinoma: A Retrospective Study.

BACKGROUND/AIM: Although gemcitabine plus cisplatin (GC) prolongs survival in patients with recurrent or metastatic nasopharyngeal carcinoma (R/M NPC) compared with fluorouracil plus cisplatin, no study has evaluated the efficacy and safety of GC in nonendemic regions, including Japan, yet. Therefore, we assessed the safety and efficacy of GC in Japanese patients with R/M NPC. PATIENTS AND METHODS: We retrospectively reviewed patients with R/M NPC who received GC treatment at the Aichi Cancer Center Hospital from January 2017 to March 2020. The main eligibility criteria were histologically confirmed NPC, Eastern Cooperative Oncology Group performance status (ECOG PS) of 0-2, and locally recurrent disease unsuitable for local treatment or metastatic disease. The regimen was administered every 3 weeks (gemcitabine, 1,000 mg/m2 on days 1 and 8; cisplatin, 80 mg/m2 on day 1). RESULTS: Fourteen patients (median age, 58 years) were included in the study. Two patients had an ECOG PS of 2 and 11 exhibited nonkeratinizing histology. Of the eight patients with measurable lesions, one exhibited complete response and seven exhibited partial response, with an objective response rate of 75%. Median progression-free survival and overall survival were 7.7 and 24.2 months, respectively. Common grade 3 or 4 adverse events included neutropenia (64%), thrombocytopenia (14%), and febrile neutropenia (14%). The median relative dose intensity of gemcitabine and cisplatin was 62% and 60%, respectively. No treatment-related deaths occurred. CONCLUSION: The GC regimen demonstrates promising activity and is tolerable in Japanese patients with R/M NPC.

[A Bibliometric Analysis of Research Paper Productivity of Japanese Pharmacy Schools].

Since the early 2000s, Japan has been frequently noted as being the only country among about 20 major countries where the publication of academic papers has stagnated. During this period, there have been major changes especially with regards to the Japanese pharmacy schools, such as the shift to a six-year schooling system and the rapid increase in the number of private pharmacy schools. However, few studies have focused on academic productivity specifically among pharmacy schools. Therefore, this study analyzed the outputs associated with the publication of peer-reviewed scholarly articles in Scopus search engine per faculty member in pharmacy schools nationwide in 2020. Professors, associate professors, and lecturers were considered as faculty members. The average number of papers published per the faculty member was 3.13 for national and public universities and 1.15 for private universities, with a significant difference between these universities. Dividing the pharmacy schools of private universities into schools established in and after 2003 and schools established before that, the production coefficient of the former was 0.98 and that of the latter was 1.33. Newly established pharmacy schools were thus found to be slightly less productive in terms of published papers than traditional schools. The paper productivity of private university pharmacy schools is stagnant; the increase in the number of private schools that have adopted a six-year schooling system has contributed to large extent to the creation of clinically competent pharmacists, but it has also brought to light concerns related to the decline in basic research capabilities of Japanese pharmaceutical academia.

Long-term conservative treatment outcomes for midshaft clavicle fractures: a 10-to-30-year follow-up.

BACKGROUND: Few reports exist on the long-term outcomes of midshaft clavicle fracture conservative treatments. Therefore, this study investigated the long-term outcome of this treatment in patients with midshaft clavicle fractures. METHODS: Patients were treated conservatively for midshaft clavicle fractures with a figure-of-eight bandage between 10 and 30 years ago. Subsequently, a telephone survey was used to follow-up these patients, and 38 were successfully evaluated. The mean term after trauma was 17.0 years. Afterward, the American Shoulder and Elbow Surgeons Shoulder (ASES) score and Shoulder pain and disability index (SPADI) on the affected and unaffected sides were calculated based on the filled questionnaires. We defined patients whose ASES and SPADI on the affected side were worse than the unaffected side as the symptomatic group. Furthermore, plain radiographs measured proportional changes in clavicular length and displacement. RESULTS: The ASES scores of the affected side were significantly lower than those of the unaffected side, and the SPADI of the affected side was significantly higher than that of the unaffected side. Furthermore, the symptomatic group's proportional changes in clavicular length and displacement were significantly larger than the asymptomatic group. CONCLUSION: The affected shoulder side was more symptomatic than the unaffected side 10 to 30 years after the trauma when midshaft clavicle fractures were treated conservatively. Moreover, several patients became symptomatic for fractures with a larger proportional change in clavicular length or displacement.

Efficacy and safety of guide extension catheter in balloon pulmonary angioplasty for treatment of complex lesions in chronic thromboembolic pulmonary hypertension.

BACKGROUND: Balloon pulmonary angioplasty (BPA) is used for treatment of inoperable chronic thromboembolic pulmonary hypertension (CTEPH) and residual pulmonary hypertension after pulmonary endarterectomy (PEA) to improve hemodynamics, right ventricular function, and exercise capacity. However, the effectiveness and safety of guide extension catheters for BPA treatment in patients with CTEPH have not been demonstrated. METHODS: We retrospectively analyzed 91 lesions in 55 sessions of 28 patients with CTEPH who underwent BPA using a guide extension catheter. The purpose (backup, coaxial, and extension), efficacy, and safety of the guide extension catheters were explored. The efficacy of the guide extension catheter was assessed based on the success of the procedures and safety was evaluated based on procedure-related complications. RESULTS: Regarding the intended use, a guide extension catheter was used to strengthen the backup force of the guiding catheter in 52% of cases, extend the tip of the catheter in 38% of cases, and maintain the coaxiality of the guiding catheter in 10% of cases. Procedural success was achieved in 92.7% of 55 sessions and in 95.6% of 91 lesions. Complex lesions had a lower success rate than simple lesions (p = 0.04). Regarding safety concerns, complications were observed in 5 of 55 sessions (9.1%) and 6 of 91 lesions (6.6%). Only one case of pulmonary artery dissection using a guide extension catheter was reported. Except for this one case, extension catheter-related complications were not observed. CONCLUSIONS: A guide extension catheter can be used safely in BPA procedures with anatomically complex pulmonary artery branches and complex lesions by increasing backup support.

Pulmonary artery blood flow dynamics in chronic thromboembolic pulmonary hypertension.

Chronic thromboembolic pulmonary hypertension is caused by incomplete resolution and organization of thrombi. Blood flow dynamics are involved in thrombus formation; however, only a few studies have reported on pulmonary artery blood flow dynamics in patients with chronic thromboembolic pulmonary hypertension. Furthermore, the effects of treatment interventions on pulmonary artery blood flow dynamics are not fully understood. The aim of the study was to evaluate pulmonary artery blood flow dynamics in patients with chronic thromboembolic pulmonary hypertension before and after pulmonary endarterectomy and balloon pulmonary angioplasty, using computational fluid dynamics. We analyzed patient-specific pulmonary artery models of 10 patients with chronic thromboembolic pulmonary hypertension and three controls using computational fluid dynamics. In patients with chronic thromboembolic pulmonary hypertension, flow velocity and wall shear stress in the pulmonary arteries were significantly decreased, and the oscillatory shear index and blood stagnation volume were significantly increased than in controls. Pulmonary endarterectomy induced redistribution of pulmonary blood flow and improved blood flow dynamics in the pulmonary artery. Balloon pulmonary angioplasty improved pulmonary blood flow disturbance, decreased blood flow stagnation, and increased wall shear stress, leading to vasodilatation of the distal portion of the pulmonary artery following balloon pulmonary angioplasty treatment.