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In Japan, the hinotori™ Surgical Robot System obtained pharmaceutical approval for use in colorectal cancer surgery in October 2022. This system has an operating arm with eight axes, adjustable arm base, and flexible three-dimensional viewer, which are expected to be advantageous in colorectal cancer surgery. A 55-year-old man presented to our hospital with melena and was diagnosed with cStage IIA (cT3N0M0) rectal cancer. The patient underwent intersphincteric resection using hinotori™ Surgical Robot System. Appropriate port placement was available for rectal manipulation, lymph node dissection, and arm base angle adjustment. Herein, we report the world's first rectal cancer surgery using the hinotori™ Surgical Robot System with TaTME by two teams.

The volume and toxicity of radioactive waste can be decreased by separating the components of high-level liquid waste according to their properties. An impregnated silica-based adsorbent was prepared in this study by combining N,N,N′,N′,N″,N″-hexa-n-octylnitrilotriacetamide (HONTA) extractant, N′,N′-di-n-hexyl-thiodiglycolamide (Crea) extractant, and macroporous silica polymer composite particles (SiO2–P). The performance of platinum-group metals adsorption and separation on prepared (HONTA + Crea)/SiO2–P adsorbent was then assessed together with that of co-existing metal ions by batch-adsorption and chromatographic separation studies. From the batch-adsorption experiment results, (HONTA + Crea)/SiO2–P adsorbent showed high adsorption performance of Pd(II) owing to an affinity between Pd(II) and Crea extractant based on the Hard and Soft Acids and Bases theory. Additionally, significant adsorption performance was observed toward Zr(IV) and Mo(VI). Compared with studies using the Crea extractant, the high adsorption performance of Zr(IV) and Mo(VI) is attributed to the HONTA extractant. As revealed from the chromatographic experiment results, most of Pd(II) was recovered from the feed solution using 0.2 M thiourea in 0.1 M HNO3. Additionally, the possibility of recovery of Zr(IV), Mo(VI), and Re(VII) was observed using the (HONTA + Crea)/SiO2–P adsorbent.

Introduction: Head and neck photoimmunotherapy (HN-PIT) uses a combination of drugs and laser illumination to specifically destroy tumor cells. Lemierre’s syndrome is an infectious disease with severe systemic symptoms caused by prior infection in the pharyngeal region, leading to thrombophlebitis. Here, we report a case of Lemierre’s syndrome that developed after HN-PIT for recurrent nasopharyngeal carcinoma. Case Presentation: A 68-year-old male with nasopharyngeal carcinoma (squamous cell carcinoma) underwent HN-PIT after local recurrence with chemoradiation therapy. Three months after HN-PIT, the patient developed fever and neck pain, which led to a diagnosis of Lemierre’s syndrome. The patient was treated with antibiotics and anticoagulants for at least 1 month. The patient’s general condition and inflammatory findings on blood sampling showed gradual improvement, and a follow-up cervicothoracic computed tomography imaging showed that the venous thrombus had been obscured and the patient was doing well. Conclusion: HN-PIT is a high-risk procedure for the development of Lemierre’s syndrome due to irradiation-induced mucositis, and anticipating the development of Lemierre’s syndrome during HN-PIT is important.

Background: A novel treatment has been developed to reconstruct large skin defects caused by the excision of giant congenital melanocytic nevi. It involves the reimplantation of high-hydrostatic pressurized nevus tissue as a cell-inactivated autologous scaffold for dermal regeneration, followed by the implantation of cultured epithelial autografts on the regenerated dermis. Because this treatment has shown promise in a first-in-human clinical trial which used a prototype pressure machine, a novel pressure device was specifically designed for clinical use. Methods: In a prospective investigator-initiated clinical trial involving three patients, we evaluated the safety and efficacy of the skin regeneration treatment using a pressure device. All three patients underwent surgical excision of the nevus tissue, primary reimplantation of the inactivated nevus tissue, and secondary implantation of cultured epithelial autografts. Results: Engraftment of inactivated nevus tissue and cultured epithelial autografts was successful in all three cases, with over 90% epithelialization at 8 weeks post-surgery. No serious adverse events or device malfunction were observed during the trial. Conclusion: The novel pressure device safely and effectively enabled dermal regeneration using the nevus tissue as an autologous scaffold. This innovative approach offers several advantages, including reduced invasiveness due to minimal sacrifice of normal skin for skin grafting and high curative potential resulting from full-thickness removal of the nevus tissue.

Transoral robotic surgery (TORS) and transoral videolaryngoscopic surgery (TOVS) are minimally invasive procedures for early-stage head and neck cancers. However, due to its unique nature, transoral resection often leads to skeletal and anatomical disorders. We describe a case in which TORS was used in a 71-year-old man with a skeletal disorder, spastic stridor, and a T2N1M0 stage I p16-positive oropharyngeal carcinoma. Prior to the procedure, he underwent right cervical dissection (levels II–IV). Although he had an oblique neck, the right side of his neck was naturally hyperextended because the dissection was performed on the right side. The right facial, lingual, and external carotid arteries were ligated in preparation for TORS. Postoperative pathological examination revealed no extranodal involvement of the metastatic lymph nodes. A two-stage TOVS procedure was performed for the oropharyngeal tumor, in which the surgeon was required to be positioned at the patient’s head to allow direct manipulation. This makes the neck and oral cavity more susceptible to the skeletal effects. In contrast, in TORS, the da Vinci insertion angle can be set to match the angle of the neck, allowing surgeons to operate with less skeletal influence. TORS is more useful in this setting.

Abstract Background The hinotori™ Surgical Robot System was approved for use in colorectal cancer surgery in Japan in 2022. This robot has advantages, such as an operation arm with eight axes, an adjustable arm base, and a flexible three-dimensional viewer, and is expected to be utilized in rectal cancer surgery. Herein, we report the world's first surgery for rectal cancer using the hinotori™ Surgical Robot System. Case presentation A 71-year-old woman presented to our hospital with bloody stools. A colonoscopy revealed type 2 advanced cancer in the rectum, and a histological examination exposed a well-differentiated adenocarcinoma. Abdominal enhanced computed tomography divulged rectal wall thickening without significant swelling of the lymph nodes or distant metastasis. Pelvic magnetic resonance imaging showed tumor invasion beyond the intrinsic rectal muscle layer. The patient was diagnosed with cStage IIa (cT3N0M0) rectal cancer and underwent low anterior resection using the hinotori™ Surgical Robot System. Based on an adequate simulation, surgery was safely performed with appropriate port placement and arm base-angle adjustment. The operating time was 262 min, with a cockpit time of 134 min. Subsequently, the patient was discharged 10 days postoperatively without complications. The pathological diagnosis was pStage IIA (cT3N0M0) and the circumferential resection margin was 6 mm. Conclusions We report the first case of low anterior resection for rectal cancer using the hinotori™ Surgical Robot System, in which a safe and appropriate oncological surgery was performed.

Background: The impact of coronary bifurcation angle (BA) on incomplete stent apposition (ISA) after crossover stenting followed by side branch (SB) intervention has not been established. Methods: A total of 100 crossover stentings randomly treated with proximal optimization technique followed by short balloon dilation in the SB (POT-SBD group, 48 patients) and final kissing balloon technique (KBT group, 52 patients) were analyzed in the PROPOT trial. Major ISA with maximum distance > 400 μm and its location was determined using optical coherence tomography before SB intervention and at the final procedure. The BA was defined as the angle between the distal main vessel and SB. Optimal POT was determined when the difference in stent volume index between the proximal and distal bifurcation was greater than the median value (0.86 mm3/mm) before SB intervention. Result: Major ISA was more frequently observed in the POT-SBD than in the KBT group (35% versus 17%, p

Abstract Metamagnetic shape memory alloys (MMSMAs) are attractive functional materials owing to their unique properties such as magnetostrain, magnetoresistance, and the magnetocaloric effect caused by magnetic‐field‐induced transitions. However, the energy loss during the martensitic transformation, that is, the dissipation energy, Edis, is sometimes large for these alloys, which limits their applications. In this paper, a new Pd2MnGa Heusler‐type MMSMA with an extremely small Edis and hysteresis is reported. The microstructures, crystal structures, magnetic properties, martensitic transformations, and magnetic‐field‐induced strain of aged Pd2MnGa alloys are investigated. A martensitic transformation from L21 to 10M structures is seen at 127.4 K with a small thermal hysteresis of 1.3 K. The reverse martensitic transformation is induced by applying a magnetic field with a small Edis (= 0.3 J mol−1 only) and a small magnetic‐field hysteresis (= 7 kOe) at 120 K. The low values of Edis and the hysteresis may be attributed to good lattice compatibility in the martensitic transformation. A large magnetic‐field‐induced strain of 0.26% is recorded, indicating the proposed MMSMA's potential as an actuator. The Pd2MnGa alloy with low values of Edis and hysteresis may enable new possibilities for high‐efficiency MMSMAs.

A simple solvothermal reaction was used to prepare a 3-aminopropyl-functionalized silica-gel-based adsorbent for adsorbing Pd(II) from the nitric acid solution. Scanning electron microscopy, fourier transform infrared spectroscopy, and thermogravimetry analysis were performed on the as-synthesized adsorbent to demonstrate the successful introduction of Schiff base groups. Batch experiments were used to investigate the effects of contact time, nitric acid concentration, solution temperature, and adsorption capacity. It is worth noting that the prepared adsorbent exhibited a higher affinity toward Pd(II) with the uptake approximately 100% even in a 2 M HNO3 solution. At an equilibrium time of 5 h, the maximum adsorption capacity of Pd(II) was estimated to be 0.452 mmol/g. The adsorbed Pd(II) could be completely eluted by dissolving 0.2 M thiourea solution in 0.1 M HNO3. Using a combination of particle-induced X-ray emission analysis and an X-ray photoelectron spectrometer, the adsorbed Pd was found to be uniformly distributed on the surface of the prepared adsorbent and the existing species were Pd(II) and zero-valent Pd(0). Due to the desirable performances, facile preparation method, and abundant raw material source, the prepared adsorbent demonstrated a high application potential in the recovery of Pd(II) from simulated high-level liquid waste treatment.

The post-acute sequelae of SARS-CoV-2 (PASC) pose a threat to patients’ health-related quality of life (HRQOL). Here, the impact of COVID-19 on HRQOL and the clinical factors associated with impaired HRQOL were examined. Discharged COVID-19 patients were assessed at 3 and 6 months after disease onset. The patients completed a medical examination and the SF-36 questionnaire at these two time points and underwent pulmonary function testing at 6 months after disease onset. All had undergone computed tomography (CT) imaging upon hospital admission. Of the 74 included patients, 38% reported respiratory symptoms at 3 months, and 26% reported respiratory symptoms at 6 months after disease onset. The aggregated SF-36 scores declined in the role/social component summary (RCS), a category related to social activity. Patients with lower RCS tended to have respiratory sequelae or a relatively lower forced vital capacity. The CT score that reflected the extent of COVID-19 pneumonia was inversely correlated with the RCS score (3 months, p = 0.0024; 6 months, p = 0.0464). A high CT score (≥10 points) predicted a low RCS score at 6 months (p = 0.013). This study highlights the impairment of RCS and its associations with respiratory sequelae. The study also emphasizes the importance of radiological findings in predicting long-term HRQOL outcomes after COVID-19.

Abstract Background Few cases have been reported of colorectal cancer with inferior mesenteric artery (IMA) branching abnormalities; therefore, the lymphatic flow in such cases remains unknown. We report the first case of locally advanced rectal cancer in which the IMA arose from the superior mesenteric artery (SMA) in which we achieved to visualize the lymphatic flow. Case presentation A 65-year-old woman complaining of bloody stools was investigated in our hospital and suspected with rectal cancer. Colonoscopy and abdominal enhanced computed tomography (CT) revealed a circumscribed, localized ulcerative tumor in the rectum. 3-Dimensional contrast-enhanced computed tomography (3D-CT) showed that the IMA arose from the SMA. The patient was diagnosed with rectal cancer (cT3N0M0, cStage IIa) and laparoscopic low anterior resection was performed. The sigmoid colon was resected using the medial approach. Only the plexus of the colic branch of the lumbar splanchnic nerve was observed at the site where the root of the IMA usually exists and showed interruption of the indocyanine green (ICG) fluorescence-illuminated lymphatics. The root of the IMA was ligated, and Japanese D3 lymphadenectomy was performed, preserving the accessory middle colic artery. All fluorescent lymph nodes were resected. The pathological diagnosis was pT4aN1aM0 stage IIIb. The patient’s postoperative course was uneventful. Adjuvant chemotherapy was administered, and the patient was recurrence-free at 1.5 years after surgery. Conclusions We were able to perform safe and appropriate surgery oncologically, despite abnormal vascular anatomy, due to preoperative identification using 3D-CT and intraoperative navigation using ICG administration.

Abstract Background Carnitine is related to malaise, and cisplatin is associated with decreased carnitine. The purpose of this study was to elucidate the effects of one course of induction chemotherapy (IC) for head and neck cancer on blood carnitine levels, focusing on free carnitine (FC). Methods This single-center prospective study investigated 20 patients diagnosed with primary head and neck cancer who underwent IC with cisplatin, docetaxel, and 5-fluorouracil. FC, acylcarnitine (AC), and total carnitine (TC) levels were measured before starting therapy and on Days 7 and 21 after starting IC. In addition, malaise was evaluated before and after therapy using a visual analog scale (VAS). Results All subjects were men and the most common primary cancer site was the hypopharynx (9 patients). FC levels before starting therapy and on Days 7 and 21 were 47.7 ± 2.2 μM/mL, 56.7 ± 2.2 μM/mL, and 41.1 ± 1.9 μM/mL, respectively. Compared with the baseline before starting therapy, FC had significantly decreased on Day 21 (p = 0.007). AC levels before starting therapy and on Days 7 and 21 were 12.5 ± 1.2 μM/mL, 13.6 ± 1.4 μM/mL, and 10.7 ± 0.7 μM/mL, respectively. TC levels before starting therapy and on Days 7 and 21 were 60.2 ± 2.5 μM/mL, 70.2 ± 3.3 μM/mL, and 51.7 ± 2.3 μM/mL, respectively. No significant differences in AC, TC or VAS were seen before the start of therapy and on Day 21. Conclusions After IC, a latent decrease in FC occurred without any absolute deficiency or subjective malaise.

A hydrophobic ionic liquid including an amino moiety ([DiOcAPmim][NTf2]) was synthesized. Its extraction behaviors towards Pd(II), Ru(III), Rh(III) were investigated in nitric acid aqueous solution as a function of contact time, effect of concentration of nitric acid, effect of temperature, and effect of co-existing metal ions. The extraction kinetics of Pd(II) was fairly fast and extraction equilibrium can be attained within only 5 min under the [HNO3] = 2.05 M. When [HNO3]< 1 M, the extraction percentage of Pd(II), Ru(III), Rh(III) were all above 80%. When [HNO3] reached 2 M, all of the extraction percentage decreased and in an order of Pd(II)>Ru(III)>Rh(III). When [HNO3]> 2 M, the extraction performance gradually recovered. The effect of temperature can slightly affect the extraction performance of Pd(II). Furthermore, in simulated high-level liquid waste, [DiOcAPmim][NTf2] showed a better preference towards Pd(II) under the interference of various other co-existing metal ions.

Objectives: In 2014, the Japan narrow-band imaging expert team (JNET) proposed the first unified colorectal narrow-band imaging magnifying classification system, the JNET classification. The clinical usefulness of this system has been well established in JNET member institutions, but its suitability for use by “non-expert physicians” (physicians with no expertise in the use of JNET classification) remains unclear. This study aimed to examine the clinical usefulness of the JNET classification by “non-expert physicians”. Methods: We retrospectively analyzed 852 consecutive patients who underwent screening colonoscopy following a positive fecal occult blood test between January 2017 and May 2018. Endoscopic results from colon polyp diagnosis by physicians who started using the JNET classification (JNET group) were compared with those of physicians who did not (control group). Mann-Whitney U test and Fisher's exact test were used to compare continuous and categorical variables, respectively. Results: The median patient age was 68 years, and the male-to-female ratio was 1:0.84. When no lesions were found, the median withdrawal time was significantly different between groups (JNET group: 12 min; control group: 15 min; P < 0.01). The number of resected adenomas per colonoscopy was significantly higher in the JNET group (1.7) than in the control group (1.2; P < 0.01). Among the resected lesions, 8.9% in the JNET group and 17% in the control group were non-neoplastic lesions that did not require resection (P < 0.01). Conclusions: Colon polyp diagnosis using the JNET classification can reduce unnecessary resection during magnifying colonoscopy when conducted by “non-expert physicians”.

Objective: To explore the prevalence and clinical implications of the mirror and TV signs in the moderate to advanced stages of Alzheimer’s disease (AD) and dementia with Lewy bodies (DLB). Methods: We retrospectively examined the prevalence of clinical and psychiatric symptoms including the mirror and TV signs in 200 subjects with AD and 200 with DLB and evaluated the relationships among the symptoms. Results: The mirror sign was found in 3.0% of AD and 4.5% of DLB subjects. The TV sign was found in 1.5% of AD and 4.0% of DLB subjects. The prevalence of the mirror and TV signs was not significantly different between the AD and DLB groups. Visual hallucination, visual illusion, misidentification of person, and sleep talking were significantly more frequent in DLB than in AD subjects. The mirror sign was significantly associated with lower Mini-Mental State Examination scores, whereas the TV sign was significantly associated with the misidentification of person. Conclusions: Both the mirror and TV signs were rare even in the moderate to advanced stages of AD and DLB. The mirror sign may be independent from other delusional misidentification syndromes (DMSs). Being associated mainly with global cognitive decline, the mirror sign is unlikely attributed to any specific cognitive impairment or the dysfunction of localized brain areas. In contrast, the TV sign was significantly more often coexistent with the misidentification of person, suggesting that the TV sign may partly share common neuropsychological mechanisms with DMSs.

Background and Aim Endoscopic stone removal has some complications. Although the life expectancy of elderly patients has increased dramatically worldwide, little information is available on the necessity of complete endoscopic stone removal in extremely elderly patients. This study aimed to evaluate the safety and efficacy of complete endoscopic stone removal in extremely elderly patients. Methods All extremely elderly patients (>90 years) who underwent endoscopic stone removal for choledocholithiasis at our hospital between January 2012 and January 2017 were retrospectively evaluated. The included patients were divided into complete stone removal and incomplete stone removal groups. Complication rate, overall survival (OS), and disease‐specific survival (DSS) rates were compared between the two groups. Results Overall, 73 patients were included in this study. The median number of stones was one (range, 0–10) and two (range, 1–12) (P = 0.043), while the median diameter of the largest stones was 9 (range, 0–27) and 14 (range, 5–46) mm (P = 0.001) in the complete and incomplete stone removal groups, respectively. During the follow‐up period, OS was 60% and 39% and DSS was 95% and 97% in the complete and incomplete stone removal groups, respectively. Kaplan–Meier analysis found no significant difference in OS and DSS between the two groups (P = 0.052 and P = 0.646, respectively). Conclusion Complete stone removal might not always be necessary in extremely elderly patients aged ≥90 years.

Abstract Background The progress of electronic health technologies and biobanks holds enormous promise for efficient research. Evidence shows that studies based on sharing and secondary use of data/samples have the potential to significantly advance medical knowledge. However, sharing of such resources for international collaboration is hampered by the lack of clarity about ethical and legal requirements for transfer of data and samples across international borders. Main text Here, the International Clinical Trial Center Network (ICN) reports the legal and ethical requirements governing data and sample exchange (DSE) across four continents. The most recurring requirement is ethical approval, whereas only in specific conditions approval of national health authorities is required. Informed consent is not required in all sharing situations. However, waiver of informed consent is only allowed in certain countries/regions and under certain circumstances. The current legal and ethical landscape appears to be very complex and under constant evolution. Regulations differ between countries/regions and are often incomplete, leading to uncertainty. Conclusion With this work, ICN illuminates the unmet need for a single international collaborative framework to facilitate DSE. Harmonising requirements for global DSE will reduce inefficiency and waste in research. There are many challenges to realising this ambitious vision, including inconsistent terminology and definitions, and heterogeneous and dynamic legal constraints. Here, we identify areas of agreement and significant difference as a necessary first step towards facilitating international collaboration. We propose the establishment of a working group to continue the comparison across jurisdictions, create a standardised glossary and define a set of basic principles and fundamental requirements for DSE.

Objectives: The aim of this study was to identify the predictive factors for suboptimal result in side branch (SB) in chronic total occlusion (CTO) bifurcation lesions and clinical outcomes of patients with suboptimal result in SB. Background: There is little evidence on the optimal strategy for bifurcation lesions in CTO. Methods: We retrospectively reviewed 314 consecutive bifurcation lesions in CTO with SB ≥ 2.5 mm in 3 hospitals from March 2010 to June 2018. Patients were divided into the two groups based on the suboptimal SB treatment (SST) and optimal SB treatment (OST) groups. The baseline characteristics, procedural and clinical outcomes were compared between the two groups. This study also evaluated the predictors of suboptimal result in SB. Results: Suboptimal result in SB occurred in 47 cases. Presence of stenosis in SB, bifurcations located within the occluded segment and sub-intimal tracking at SB ostium was an independent predictor of suboptimal result in SB. The cumulative incidence of target lesion revascularization (TLR) in all lesions was not significantly different between the two groups, however, TLR in right coronary artery (RCA) was significantly higher in the SST group. In the Cox regression analysis, suboptimal result in SB in RCA and sub-intimal tracking were independent predictors of TLR for MB. In patients with bifurcations located within the occluded segment, usage of two-stent technique was significantly lower in the SST group. Conclusions: Meticulous procedures are required for SB preservation to improve not only SB prognosis but also MB, especially in RCA.

The additive manufacturing of ceramics offers a reliable and repeatable method for fabricating parts with complex geometries. To compete with conventional ceramic forming methods, the time and cost associated with material and process optimization for ceramic stereolithography should be improved. Computational analysis methods can be utilized to reduce the number of experimental steps required for material and process optimization. This work used the discrete element method and ray tracing analyses to predict suitable material parameters and processing conditions for ceramic stereolithography. The discrete element method was used to create alumina particle dispersion models to predict suitable paste compositions, and ray tracing was used to predict suitable laser power and scan speed to achieve a sufficient curing depth for stereolithography processing. The predicted conditions of paste composition and processing parameters were comparable to experimental values, reducing the number of experimental iterations required for process optimization. Furthermore, suitable processing parameters for high-speed fabrication by stereolithography was predicted, achieving a processing speed much faster than previously reported ceramic stereolithography. The reduction in process optimization timeline, and the increase in fabrication speed, could increase the appeal of ceramic stereolithography to industry.

Abstract t(17;19)(q21‐q22;p13), responsible for TCF3‐HLF fusion, is a rare translocation in childhood B‐cell precursor acute lymphoblastic leukemia(BCP‐ALL). t(1;19)(q23;p13), producing TCF3‐PBX1 fusion, is a common translocation in childhood BCP‐ALL. Prognosis of t(17;19)‐ALL is extremely poor, while that of t(1;19)‐ALL has recently improved dramatically in intensified chemotherapy. In this study, TCF3‐HLF mRNA was detectable at a high level during induction therapy in a newly diagnosed t(17;19)‐ALL case, while TCF3‐PBX1 mRNA was undetectable at the end of induction therapy in most newly diagnosed t(1;19)‐ALL cases. Using 4 t(17;19)‐ALL and 16 t(1;19)‐ALL cell lines, drug response profiling was analyzed. t(17;19)‐ALL cell lines were found to be significantly more resistant to vincristine (VCR), daunorubicin (DNR), and prednisolone (Pred) than t(1;19)‐ALL cell lines. Sensitivities to three (Pred, VCR, and l‐asparaginase [l‐Asp]), four (Pred, VCR, l‐Asp, and DNR) and five (Pred, VCR, l‐Asp, DNR, and cyclophosphamide) agents, widely used in induction therapy, were significantly poorer for t(17;19)‐ALL cell lines than for t(1;19)‐ALL cell lines. Consistent with poor responses to VCR and DNR, gene and protein expression levels of P‐glycoprotein (P‐gp) were higher in t(17;19)‐ALL cell lines than in t(1;19)‐ALL cell lines. Inhibitors for P‐gp sensitized P‐gp‐positive t(17;19)‐ALL cell lines to VCR and DNR. Knockout of P‐gp by CRISPRCas9 overcame resistance to VCR and DNR in the P‐gp‐positive t(17;19)‐ALL cell line. A combination of cyclosporine A with DNR prolonged survival of NSG mice inoculated with P‐gp‐positive t(17;19)‐ALL cell line. These findings indicate involvement of P‐gp in resistance to VCR and DNR in Pgp positive t(17;19)‐ALL cell lines. In all four t(17;19)‐ALL cell lines, RAS pathway mutation was detected. Furthermore, among 16 t(1;19)‐ALL cell lines, multiagent resistance was usually observed in the cell lines with RAS pathway mutation in comparison to those without it, suggesting at least a partial involvement of RAS pathway mutation in multiagent resistance of t(17;19)‐ALL.

Removal of borate in mine drainages by co-precipitation with hydroxyapatite (HAp) was developed from a laboratory scale to a pilot scale. Weakly acidic initial pH facilitated to enhance dissolution of Ca(OH)2 and decrease the dissolved carbonate concentration, leading to efficient immobilization of borate and arsenate. The NH4H2PO4 lowered best the equilibrium B concentration among different phosphate sources, avoiding the lattice strain of HAp. The added molar ratio of P/Ca significantly influenced the decreasing behavior of the B concentration, showing the optimal value of 0.3. In case of P/Ca larger than 0.30, the excess concentration of PO43- was probably adsorbed on Ca(OH)2 particles to prevent the dissolution, resulting in inhibiting the formation of HAp. In case of P/Ca smaller than 0.30, the production of HAp was limited, leading to less immobilized borate. All the optimized conditions as above were applied to the pilot scale with a 250 L reactor, where borate concentration was effectively reduced in also both batch and continuous tests.

Medical products comprising human cells, genes, and tissues have been developed for clinical applications worldwide, and their developmental environment has been established. These products can be imported and exported, but marketing authorization regulations are complicated among regions. This investigation was conducted to identify the characteristics of medical products comprising human cells, genes, and tissues. We used website data, books from survey companies, and reports from public agencies to conduct two investigations. We used website data to conduct a general information survey of 143 cell-therapy and gene-therapy products sold in 24 countries and public assessment reports to individually survey non-clinical and clinical developments of 18 cell-therapy and gene-therapy products developed in Japan and the European Union (EU). The first survey revealed that the numbers of products used in orthopedic surgery and dermatology have increased since 2000, and the numbers of hematological products have increased since 2011. The second investigation revealed that fewer orphaned products were developed in Japan than in the EU. The most appropriate dose was 1.2 × 108 cells per injection per adult. Clinical trials to determine the most appropriate dose were conducted in the EU but not in Japan. No non-clinical immunogenicity tests for autogenous products were conducted in Japan or the EU. Pharmacokinetics tests were not individually performed for sheet-form products. Both in vivo and in vitro pharmacological tests were more likely to be conducted in the EU, while only one or the other was conducted in Japan. Furthermore, in Japan, carcinogenicity tests were performed based on non-clinical technical guidance, while in the EU, these tests were determined according to each product's features. Fewer clinical trials were performed, and fewer subjects per product were used in Japan than in the EU. Many aspects of the clinical and non-clinical development of medical products comprising human cells, genes, and tissues differ between Japan and the EU. Analyzing these differences will enable the safe and rapid distribution of these products to clinical sites.

Objectives. Our aim was to evaluate the safety and efficacy of biodegradable polymer everolimus-eluting stents (BP-EES) compared with durable polymer everolimus-eluting stents (DP-EES) in midterm. Background. There are few data about midterm clinical outcomes of BP-EES compared with DP-EES. Methods and Results. Between January 2016 and December 2017, 395 consecutive patients were treated with BP-EES and 391 consecutive patients were treated with DP-EES in Nagoya Heart Center. The primary endpoint was a 3-year cumulative incidence of target lesion failure (TLF) defined as cardiac death, target vessel myocardial infarction (MI), and clinical indicated target lesion revascularization (TLR). Moreover, clinical indicated target vessel revascularization (TVR) and definite stent thrombosis (ST) were also evaluated as the secondary endpoints. After propensity score matching, 327 patients were selected in each group. At 3 years, the cumulative incidence of TLF was 4.5% in the BP-EES group versus 6.5% in DP-EES (adjusted HR 0.67 (95% CI 0.33–1.30), log-rank P=0.23). Regarding the individual components of the TLF at 3 years, the cumulative incidence of target vessel MI was significantly lower in BP-EES than in DP-EES (0% versus 1.9%: adjusted HR 0.83 (95% CI 0.71–0.97), log-rank P=0.01), but there was no difference between BP-EES and DP-EES in the incidence of cardiac death and clinically indicated TLR. The cumulative 3-year incidence of definite ST was significantly lower in BP-EES than in DP-EES (0% versus 1.6%, log-rank P=0.02). Conclusions. There were no significant differences of TLF between BP-EES and DP-EES within 3 years. In this study, BP-EES seems to prevent definite ST and be safer than DP-EES in midterm.

Autologous nerve grafting is widely accepted as the gold standard treatment for segmental nerve defects. To overcome the inevitable disadvantages of the original method, alternative methods such as the tubulization technique have been developed. Several studies have investigated the characteristics of an ideal nerve conduit in terms of supportive cells, scaffolds, growth factors, and vascularity. Previously, we confirmed that biological scaffold-free conduits fabricated from human dermal fibroblasts promote nerve regeneration in a rat sciatic nerve injury model. The purpose of this study is to evaluate the feasibility of biological scaffold-free conduits composed of autologous dermal fibroblasts using a large-animal model. Six male beagle dogs were used in this study. Eight weeks before surgery, dermal fibroblasts were harvested from their groin skin and grown in culture. Bio 3D conduits were assembled from proliferating dermal fibroblasts using a Bio 3D printer. The ulnar nerve in each dog’s forelimb was exposed under general anesthesia and sharply cut to create a 5 mm interstump gap, which was bridged by the prepared 8 mm Bio 3D conduit. Ten weeks after surgery, nerve regeneration was investigated. Electrophysiological studies detected compound muscle action potentials (CMAPs) of the hypothenar muscles and motor nerve conduction velocity (MNCV) in all animals. Macroscopic observation showed regenerated ulnar nerves. Low-level hypothenar muscle atrophy was confirmed. Immunohistochemical, histological, and morphometric studies confirmed the existence of many myelinated axons through the Bio 3D conduit. No severe adverse event was reported. Hypothenar muscles were re-innervated by regenerated nerve fibers through the Bio 3D conduit. The scaffold-free Bio 3D conduit fabricated from autologous dermal fibroblasts is effective for nerve regeneration in a canine ulnar nerve injury model. This technology was feasible as a treatment for peripheral nerve injury and segmental nerve defects in a preclinical setting.

A 62-year-old Japanese female was referred to our hospital with gastrointestinal bleeding. Although small-bowel bleeding was suspected, no bleeding source was identified by enhanced computed tomography (CT), video capsule endoscopy (VCE), and double-balloon enteroscopy (DBE). Five years later, the patient had recurrent intermittent bloody stools with a significant decrease in hemoglobin levels. Although no active bleeding was observed on antegrade DBE, we detected a pulsatile submucosal uplift accompanied by a small red patch on the top of the uplift in the jejunum. Arteriovenous malformation (AVM) was suspected as the cause of small-bowel bleeding. Multiple-phase CT showed a number of small vascular ectasias during the arterial phase in the jejunum, and we confirmed the presence of multiple AVMs in the jejunum by selective angiography. To identify the location of the lesions and determine the minimal surgical margins, we performed intraoperative selective angiography with indocyanine green (ICG) injection. This technique allowed us to clearly observe the region and perform segmental small-bowel resection with minimal surgical margin. The patient reported that she has had no gastrointestinal bleeding at the two years follow-up visit.

No real-world, long-term outcomes of immunotherapy with nivolumab for recurrent or metastatic squamous cell carcinoma of the head and neck (R/M SCCHN) have yet been reported. Furthermore, the prognostic impact of the best overall response (BOR) of this therapy remains unclear. We conducted a multi-institutional cohort study of the long-term efficacy and safety of this therapy and investigated prognostic factors associated with survival. Further, we evaluated the relationship between BOR and survival. Median follow-up time was 25.9 months. Median overall survival (OS) was 9.6 months, and two-year survival rate was 25.0%. Median progression-free survival (PFS) was 3.7 months, and two-year PFS rate was 19.6%. BOR was assessed as complete response (CR) in 6%, partial response (PR) in 13%, stable disease (SD) in 30%, and progressive disease (PD) in 52% of the patients. Overall response rate was 18%, and disease control rate was 48%. For immune-related adverse events (irAEs), 38 irAEs were detected in 29 patients. On multivariate analysis, the development of irAEs was significantly associated with better OS and PFS. Better BOR was significantly associated with longer OS and PFS. These findings demonstrate the long-term efficacy and safety of nivolumab therapy for R/M SCCHN in a real-world setting. The magnitude of BOR and the development of irAEs might be useful surrogate markers of survival.

The magnetization, electric resistivity, and magnetoresistance properties of Pd 2 Mn 1 . 4 Sn 0 . 6 Heusler alloys were investigated. The Curie temperature of the parent phase, martensitic transformation temperatures, and magnetic field dependence of the martensitic transformation temperatures were determined. The magnetoresistance was investigated from 10 to 290 K, revealing both intrinsic and extrinsic magnetoresistance properties for this alloy. A maximum of about − 3 . 5 % of intrinsic magnetoresistance under 90 kOe and of about − 30 % of extrinsic magnetoresistance under 180 kOe were obtained. Moreover, the thermal transformation arrest phenomenon was confirmed in the Pd 2 Mn 1 . 4 Sn 0 . 6 alloy, and an abnormal heating-induced martensitic transformation (HIMT) behavior was observed.

BACKGROUND:Following the amendment of the Pharmaceutical Affairs Law in Japan in 2003 researchers were permitted to begin investigator-initiated trials (IITs). In subsequent years, however, the number of IITs remained low. In other countries in Asia as well as in Europe, North America, and South Africa, the number of IITs has increased over the past decade. The differences in the characteristics of IITs between Japan and other countries are unknown. Some studies have analyzed the characteristics of all clinical trials according to registry databases, but there has been less research focusing on IITs. AIMS:The purpose of this study is to analyze the characteristics of IITs in the ClinicalTrials.gov registry and in the three Japanese registries, to identify differences in IITs between Japan and other countries. METHODS:Using Thomson Reuters Pharma™, trials sponsored by academia and government as IITs in 2010 and registered in ClinicalTrials.gov were identified. IITs from 2004 to 2012 in Japan were identified in the three Japanese registries: the University Hospital Medical Information Network Clinical Trials Registry, the Japan Pharmaceutical Information Center Clinical Trials Information, and the Japan Medical Association Center for Clinical Trials, Clinical Trials Registry. Characterization was made of the trial purposes, phases, participants, masking, arms, design, controls, and other data. RESULTS:New and revised IITs registered in ClinicalTrials.gov during 2010 averaged about 40% of all sponsor-identified trials. IITs were nearly all early-phase studies with small numbers of participants. A total of 56 Japanese IITs were found over a period of 8 years, and these were also almost nearly all early-phase studies with small numbers of participants. CONCLUSION:There appear to be no great differences between Japan and other countries in terms of characteristics of IITs. These results should prompt a new review of the IIT environment in Japan.