Evaluation of starch granules based on hydroxypropylcellulose as a substitute for excipient lactose.

BACKGROUND: The improvement in flowability and adhesion of starch powder (SP) is essential for using starch as an excipient for lactose intolerant patients. In this study, we attempted to evaluate the usefulness of hydroxypropylcellulose with molecular weight 80,000 (HPC-80) in the preparation of the starch granules (SG) as a substitute for excipient lactose. METHODS: Hydroxypropylcellulose with molecular weight 30,000 (HPC-30) and HPC-80 were used as binders to prepare the SG, and defined as HPC-30-SG and HPC-80-SG, respectively. Mean particle size (D50) was measured according to the Method, Optical Microscopy of Particle Size Determination in Japanese Pharmacopoeia, Eighteenth Edition, and storage stability were evaluated by measuring of the physical properties after vortexing the granules for 180 s (physical impact). The product loss rate was calculated from the weight change of the various excipients before and after the one dose packaging (ODP). RESULTS: The D50 of SP (30 µm) was smaller than that of the lactose powder (115 µm). The granulation with 0.75-3% HPC-30 and HPC-80 increased the particle size of SP, and the D50 in 1.5% HPC-30-SG (255 µm) and HPC-80-SG (220 µm) were higher than that of lactose. The excipient was removed from the heat seal of the ODP, and upon visual inspection, a large amount of starchy material was observed to be adhering to the paper in the SP. On the other hand, the low recovery rate in SP was attenuated by the granulation with HPC-30 and HPC-80. In the both HPC-30 and HPC-80, the improvement in recovery rate reached a plateau at 1.5%, and the levels of recovery rate was similar to that of lactose. The recovery rate in the 0.75-3% HPC-30-SG and 0.75% HPC-80-SG were decreased by the physical impact, however, the recovery rate and amount of 1.5% and 3% HPC-80-SG were not affected by the physical impact, and these levels were similar to that of lactose. CONCLUSIONS: The use of HPC-80 as a binder of SG was found to produce a higher quality granule product than conventional HPC-based SG. This finding is useful in streamlining the preparation of starch-based powdered medicine in clinical applications.

Incidence of serious infections in the working-age Japanese adult population with rheumatoid arthritis treated with tumor necrosis factor-α inhibitors and interleukin-6 inhibitors: A nationwide retrospective cohort study.

AIM: This retrospective cohort study aimed to compare the risk of serious infections in patients with rheumatoid arthritis (RA) treated with tumor necrosis factor-α inhibitors (TNFαi) and interleukin-6 inhibitors (IL-6i), with no prior use of biological disease-modifying antirheumatic drugs (bDMARDs). METHODS: We employed the nationwide insurance claims database encompassing the years 2005 to 2018 in Japan. The inclusion criteria specified patients who were prescribed any type of bDMARDs, including TNFαi and IL-6i. The following exclusion criteria were applied: missing prescription dates, RA not diagnosed, below 16 years of age, bDMARDs prescribed within 6 months of registration, RA diagnosed post-bDMARDs prescription, and incidence of serious infections within 2 weeks before bDMARDs therapy. We applied stabilized inverse probability weights and utilized a Cox regression model to estimate the risk of serious infections associated with TNFαi and IL-6i. RESULTS: The cohort of 2493 patients with RA was categorized into a TNFαi group and an IL-6i group of 2018 and 475 participants, respectively. The median follow-up duration (interquartile range) was 347 (147-820) days in the TNFαi group and 369 (149-838) days in the IL-6i group. In the inverse probability-weighted cohort, the incidence rates (95% confidence interval) of serious infections were 2.13 (1.65-2.71) and 3.25 (2.15-4.69) per 100 person-years for the TNFαi and IL-6i groups, respectively. The hazard ratio (95% confidence interval) comparing the TNFαi group to the IL-6i group was 0.66 (0.36-1.20, p = 0.168). DISCUSSION: The results underscore the lack of evidence to preferentially favor either TNFαi or IL-6i as later-line therapy in the management of bDMARDs-naive RA to mitigate the risk of serious infections.

Predictors of olaparib discontinuation owing to adverse drug events in patients with ovarian, peritoneal, or fallopian tube cancer: a retrospective observational study.

We investigated predictors of olaparib discontinuation owing to adverse effects. Patients with ovarian, peritoneal, or fallopian tube cancers treated with olaparib at Osaka Medical and Pharmaceutical University Hospital between April 2018 and September 2022 were included in this study. The exclusion criteria were as follows: discontinuation of treatment due to disease progression, use of anaemia medications, and use of cytochrome P450 (CYP3A4) inhibitors. The follow-up period was 90 d. Of the 46 eligible patients, 21 patients discontinued olaparib, including 15 patients with grade 3 or higher anaemia, eight patients with grade 3 or higher neutropenia, and four patients with non-haematological toxicity (including multiple onset). Multivariate logistic regression analysis showed that grade 4 neutropenia and anaemia progression to grades 2-3 due to chemotherapy administered before olaparib administration were predictors of olaparib discontinuation. The severity of neutropenia and anaemia due to chemotherapy before olaparib administration may be a potential marker for its discontinuation.

CT-derived skeletal muscle change before immunotherapy predicts survival of advanced gastric cancer: associations with inflammatory markers and liver lipid metabolism.

BACKGROUND: Skeletal muscle (SM) is a key factor in cancer treatment. However, it is unclear whether pretreatment SM change affects the outcome of immune checkpoint inhibitors (ICIs) therapy in gastric cancer (GC). METHODS: Advanced GCs treated with ICIs were retrospectively investigated. SM evaluated by psoas muscle area at the third lumbar vertebra was measured on CT acquired within 1 month from the start of ICIs therapy (CT-1), and on CT acquired 2.8 ± 0.84 months before CT-1. Monthly change rate of SM (MCR-SM) was defined as the change rate of SMs between those two CTs divided by the period between those CTs (month). Monthly change rate of body weight (MCR-BW) during the same period was also calculated. They were compared with disease-specific survival (DSS) and progression-free survival (PFS). MCR-SM was compared with pretreatment markers including neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), monocyte-to-lymphocyte ratio (MLR), C-reactive protein (CRP), and liver-to-spleen CT attenuation ratio (LSR) as a marker of liver lipid metabolism. RESULTS: This study enrolled eighty-three GC patients. MCR-SM significantly correlated with DSS and PFS (P < 0.0001, 0.001, respectively), whereas MCR-BW did not. Kaplan-Meier analyses demonstrated that higher MCR-SM (MCR-SM ≥ -0.7185%) significantly associated with better DSS and PFS (P = 0.0002, 0.03, respectively). Patients with positive MCR-SM showed significantly lower NLR, MLR, and CRP than those with negative (P = 0.01, 0.006, 0.003, respectively). MCR-SM showed a significant positive correlation with LSR (P = 0.007, R = 0.30). CONCLUSIONS: Pretreatment SM loss, associated with high systemic inflammation and hepatic fat accumulation, related to poor outcome of ICIs therapy in GC.

A case of rectal metastasis of prostate cancer mimicking extramural growth-type rectal tumor.

Rectal metastases of prostate cancer are rare and may be difficult to diagnose. In this report, we describe a case in which an extramural growth-type rectal tumor was resected and pathologically diagnosed as prostate cancer metastasis. A 70-year-old man on hormone therapy for prostate cancer with seminal vesicle invasion and pelvic lymph node metastasis was referred to our department after an imaging scan showed an extramural growth-type rectal tumor. Endoscopic ultrasound-guided fine needle aspiration was considered for diagnosis, but the patient preferred an early resection without the exam, so surgery was performed. Histopathological examination revealed that the lesion was in the adventitia of the rectum and metastasis of prostate cancer. Metastatic lesions of prostate cancer are not indicated for resection. A detailed preoperative study with the possibility of prostate cancer metastasis in mind is necessary because it is relevant to choosing the treatment strategy.

Intraoperative assessment of blood flow using transabdominal ultrasound during laparoscopic surgery of celiac artery compression syndrome.

Surgical treatment of celiac artery (CA) compression syndrome (CACS) is to release the median arcuate ligament (MAL) by removing the abdominal nerve plexus surrounding CA. In laparoscopic surgery of CACS, objective intraoperative assessment of blood flow in CA is highly desirable. We herein demonstrate a case of laparoscopic surgery of CACS with use of intraoperative transabdominal ultrasound. A 52-year-old woman was presented with epigastric pain and vomiting after eating. Contrast-enhanced computed tomography demonstrated significant stenosis at the origin of CA. Doppler study of CA was also performed, and she was diagnosed as CACS. Laparoscopic surgery was performed, and the MAL was divided. And then, Doppler study using intraoperative transabdominal ultrasound confirmed the successful decompression of CA. This patient was discharged on postoperative day 11, and her symptoms was improved. Intraoperative assessment of blood flow in CA using transabdominal ultrasound was a simple and useful method for laparoscopic surgery of CACS.

Stage IV and recurrent colorectal cancer cured following multimodal therapy: A case series.

The treatment strategies for colorectal cancer (CRC) with distant metastasis or metastatic recurrence after resection of the primary tumor are controversial. In the present study, four cases of patients with advanced CRC with distant metastasis who achieved disease-free survival (DFS) for >5 years and were deemed potentially cured were reported. Case 1 was that of a 53-year-old male patient with rectal cancer and liver metastases (pT3N2bM1, pStage IV), and case 2 was that of a 58-year-old female patient with descending colon cancer (pT3N1M1, pStage IV) who had lung metastases at surgery and postoperatively. Both patients achieved DFS for >5 years after simultaneous or staged partial hepatectomy or pneumonectomy followed by chemotherapy. Case 3 was that of a 75-year-old male patient with transverse colon cancer (pT3N1M0, pStage IIIB) and case 4 was that of a 73-year-old male patient with sigmoid colon cancer (pT3N0M0, pStage IIA). These cases developed liver metastases after resection of the primary tumour and were subsequently treated with chemotherapy before or after partial hepatectomy. DFS for >5 years was achieved. All four patients were considered cured. The data revealed that even patients with CRC and distant metastases can potentially be cured following multidisciplinary treatment. In the present case report, the factors that enabled these patients to be considered cured were discussed and the aim was to improve the treatment strategy to cure CRC with distant metastasis or recurrence.

Clinical and preclinical evidence that angiotensin-converting enzyme inhibitors and angiotensin receptor blockers prevent diabetic peripheral neuropathy.

Given possible involvement of the central and peripheral angiotensin system in pain processing, we conducted clinical and preclinical studies to test whether pharmacological inhibition of the angiotensin system would prevent diabetic peripheral neuropathy (DPN) accompanying type 2 diabetes mellitus (T2DM). In the preclinical study, the nociceptive sensitivity was determined in leptin-deficient ob/ob mice, a T2DM model. A clinical retrospective cohort study was conducted, using the medical records of T2DM patients receiving antihypertensives at three hospitals for nearly a decade. In the ob/ob mice, daily treatment with perindopril, an angiotensin-converting enzyme inhibitor (ACEI), or telmisartan, an angiotensin receptor blocker (ARB), but not amlodipine, an L-type calcium channel blocker (CaB), significantly inhibited DPN development without affecting the hyperglycemia. In the clinical study, the enrolled 7464 patients were divided into three groups receiving ACEIs, ARBs and the others (non-ACEI, non-ARB antihypertensives). Bonferroni's test indicated significantly later DPN development in the ARB and ACEI groups than the others group. The multivariate Cox proportional analysis detected significant negative association of the prescription of ACEIs or ARBs and ß-blockers, but not CaBs or diuretics, with DPN development. Thus, our study suggests that pharmacological inhibition of the angiotensin system is beneficial to prevent DPN accompanying T2DM.

Platelet count and dose, but not comorbidities, predict severe neutropenia in cabazitaxel-treated prostate cancer patients: A retrospective observational study.

OBJECTIVE: To determine the safety of cabazitaxel and predictors of severe neutropenia caused by cabazitaxel in a patient population that includes those with comorbidities. MATERIALS AND METHODS: Of 42 prostate cancer patients treated with cabazitaxel at Osaka Medical and Pharmaceutical University Hospital between September 2014 and June 2022, 33 were included in this study, whereas 6 patients who were outpatients and 3 who were discharged early within 7 days upon patient request were excluded. Logistic regression analysis was used to examine predictors of severe neutropenia. RESULTS: Of the 33 eligible patients, 24 had comorbidities, with hypertension being the most common (n = 19), followed by dyslipidemia (n = 14) and diabetes (n = 11). There was no statistically significant difference in the rate of severe neutropenia due to any of the comorbidities, depending on the presence or absence of the comorbidity. However, the rate of severe neutropenia was significantly higher in patients with baseline platelet levels < 22.4×104/µL and those receiving cabazitaxel doses > 34 mg/body. In the final model adjusted for age, body mass index, C-reactive protein, and monocyte count, lower baseline platelet levels and higher doses of cabazitaxel were also predictors of the development of severe neutropenia. CONCLUSION: Comorbidities such as hypertension, dyslipidemia, diabetes mellitus, cerebrovascular disease, chronic kidney disease, liver dysfunction, and cardiac disease did not affect the incidence of severe neutropenia in patients receiving cabazitaxel. The baseline platelet count and the dose of cabazitaxel were also suggested to be markers for the development of severe neutropenia.

Risk of infection from glucocorticoid and methotrexate interaction in patients with rheumatoid arthritis using biologics: A retrospective cohort study.

AIMS: This retrospective cohort study aimed to evaluate the effect of the interaction between methotrexate and glucocorticoids on the risk of developing bacterial infections in patients with rheumatoid arthritis (RA) using biological disease-modifying antirheumatic drugs (bDMARDs). METHODS: We used the 2005-2018 JMDC claims database, a nationwide claims database in Japan. From the database of 7 175 048 patients, study patients were obtained by applying the following exclusion criteria: no use of bDMARDs; without information on the date of prescription; without RA as a disease; other than the new users of bDMARDs; and age <18 years. The exposures were glucocorticoids and methotrexate, and the outcome was bacterial infection. The interaction effects were examined using multivariate Cox regression analysis. Bacterial infections were identified according to antibiotic prescription and International Statistical Classification of Diseases and Related Health Problems, 10th revision codes. RESULTS: A total of 2837 RA patients were identified, with a median age of 50 years. The incidence of infection was 16.8% (95% confidence interval: 15.5-18.3). The interaction term for the doses of glucocorticoids and methotrexate was significant. Additionally, a higher dose of glucocorticoid was a significant risk factor for developing bacterial infections on the side of high doses of methotrexate. The incidence of bacterial infections tended to increase significantly with increasing methotrexate doses coprescribed with glucocorticoids ≥5 mg or glucocorticoid doses coprescribed with methotrexate ≥8 mg. CONCLUSION: Our results indicate a potential association between methotrexate dose and bacterial infections during bDMARDs administration with glucocorticoids in patients with RA.

Apparent diffusion coefficient by magnetic resonance cholangiopancreatography is useful for grading cholecystitis and surgery planning.

INTRODUCTION: Laparoscopic cholecystectomy is a standard procedure for treating cholescytitis, but severe inflammation may cause complications. Our previous study showed that the apparent diffusion coefficient (ADC) values could predict difficult surgery. In the present study, relevance of ADC values in grading the severity of cholecystitis was pathologically investigated. METHODS: We retrospectively analyzed a total of 50 patients who underwent laparoscopic cholecystectomy or laparotomic cholecystectomy/choledocholithotomy. The degree of inflammation in the neck of the gall bladder was pathologically graded into three tiers (grade 1, mild; grade 2, moderate; grade 3, severe), and ulceration, lymphoid follicle formation, and wall thickness of the gallbladder neck were recorded. All factors were statistically compared with the measured ADC values. RESULTS: The ADC value was significantly lower in the severe inflammation group ( grade 3) than in the weak inflammation group (grades 1 and 2) (1.93 ± 0.22 vs 2.38 ± 0.67, respectively; P = .02). Ulceration and wall thickness in the gallbladder neck were significantly correlated with ADC values (P = .04 and .006, respectively), and lymphoid follicle formation was marginally correlated with ADC values (P = .06). The diagnostic utility of the ADC values decreased as the interval between imaging and cholecystectomy increased. [Correction added on 19 October 2022, after first online publication: [On the first sentence of the Results section, (grades 2 and 3) for weak inflammation group has been changed to (grades 1 and 2).] CONCLUSION: ADC values were inversely associated with the pathologic intensity of cholecystitis. We recommend that the ADC value be measured before surgery, so that the procedure can be accordingly planned.

Adverse event profiles of microscopic colitis in the Japanese Adverse Drug Event Report (JADER) database.

Microscopic colitis (MC) is a chronic inflammatory bowel disease that is characterized by nonbloody watery diarrhea. The epidemiology in Japan differs from that in Europe and the United States, but little information is available from epidemiological surveys of MC in Japan. This study aimed to provide a new hypothesis regarding the factors associated with MC by using the Japanese Adverse Drug Event Report (JADER) database. "Colitis microscopic" (preferred term code: 10056979) cases entered into the JADER database between 2004 and 2021 were analyzed. Of the 246,997 cases in the JADER database, 161 cases were observed to be associated with MC. A Weibull analysis revealed that the median onset duration of MC (interquartile range) was 72.5 (36.0‒125.5) days in lansoprazole users and 116.0 (60.3‒1089.0) days in aspirin users. A multiple logistic regression analysis revealed that MC was significantly associated with the female sex, as well as ages ≥ 60 years and drugs including lansoprazole, aspirin, and nicorandil. A subset analysis revealed that MC was positively associated with obesity in female cases. Our study cannot demonstrate a causal inference between MC and each drug; however, the findings suggest that MC was associated with nicorandil as well as with lansoprazole and aspirin.

Biologic Disease-Modifying and Other Anti-Rheumatic Drugs Use in Patients with Moderate-to-Severe Juvenile Idiopathic Arthritis Based on a Japanese Nationwide Claims Database.

Purpose: Biologic disease-modifying anti-rheumatic drugs (bDMARDs) are highly effective and safe against juvenile idiopathic arthritis (JIA), which is classified into systemic JIA (sJIA) and the other JIA categories (non-sJIA) according to differences in clinical symptoms and pathophysiology. The purpose of the current study was to investigate trends in patterns of prescribing bDMARDs for moderate-to-severe JIA using a relatively large sample size in Japan. Patients and Methods: A descriptive epidemiological study based on a nationwide claims database in Japan was conducted from 2012 to 2018 using the "JMDC Claims Database" to explain annual changes based on the number of patients prescribed bDMARDs. Study drugs were identified based on the Anatomical Therapeutic Chemical codes, such as methotrexate, glucocorticoids, non-steroidal anti-inflammatory drugs, and bDMARDs. Results: From a database of 6,862,244 patients, the following exclusion criteria were applied: aged ≥16 years, without "M08" in their ICD-10 code as disease, and missing the information of prescription date in the database during the study period, resulting in a final number of 111 JIA patients. We found an increasing trend for adalimumab and tocilizumab and a decreasing trend for methotrexate. Differences in medication use between sJIA and non-sJIA patients were also evident, being consistent with national and international guidelines. Conclusion: Although the introduction of bDMARDs has markedly improved the efficacy of JIA therapy, there are still many short- and long-term safety issues to be examined, including the risk of infection and potential risk of associated malignancy. Future studies are needed to clarify these issues.

[Analysis of Factors Affecting Proteinuria Onset Timing in Patients Treated with Bevacizumab].

Bevacizumab (BV) is a recombinant and humanized monoclonal antibody that inhibits vascular endothelial growth factor. BV is used to treat various types of cancer. Proteinuria is a characteristic adverse event that occurs as a result of treatment with BV. However, the onset timing of proteinuria after BV administration remains unclear. In the present study, we examined the risk factors affecting the timing of proteinuria onset upon BV administration. Medical records of 135 patients (62 males and 73 females; mean age: 67.8±10.7 years) treated with BV were reviewed at the Kindai University Nara Hospital from April 2011 to December 2019. Proteinuria was identified in 44.4% (60/135) of the studied patients. The time to the first onset of proteinuria was significantly shorter in the administration of doses of BV (≥10) and history of diabetes mellitus. The median cumulative dose associated with the onset of proteinuria was 30.0 (16.1-58.8) mg/kg. When this cumulative dose was compared with 10 mg/kg, no significant difference was observed (p=0.319). The present study demonstrated that the administration of doses of BV (≥10) and history of diabetes mellitus are one of the main risk factors for early-onset proteinuria. These findings may be useful for the future treatment of early-onset proteinuria in patients treated with BV.

Prescribing Trends of Biologic Disease-Modifying Anti-rheumatic Drugs Using a Claims Database from 6 Million People in Japan.

BACKGROUND AND OBJECTIVE: Biologic disease-modifying anti-rheumatic drugs (bDMARDs) are used either when conventional synthetic DMARDs are ineffective or when disease activity is high and with poor prognostic factors, based on various clinical guidelines. The purpose of this study was to investigate the prescribing trends of bDMARDs for patients with rheumatoid arthritis in Japan, and to clarify whether the pharmacological therapy of bDMARDs is administered based on guidelines. METHODS: We conducted a descriptive epidemiological study from 2012 to 2018 using the JMDC Claims Database, a nationwide claims database, and described the annual changes based on the number of patients prescribed bDMARDs. Anti-rheumatic drugs were identified based on the Anatomical Therapeutic Chemical codes, including methotrexate, glucocorticoids, non-steroidal anti-inflammatory drugs and bDMARDs. RESULTS: From the database including 6,862,244 people, the data of 6407 patients with rheumatoid arthritis were extracted. The present study demonstrated that the proportion of patients prescribed bDMARDs was 1.0 per 1000 people, with those aged ≥ 65 years being the most common age group. The proportion of patients with rheumatoid arthritis who were prescribed bDMARDs increased significantly over time (p < 0.0001). Additionally, the concomitant proportions of methotrexate (p < 0.0001), non-steroidal anti-inflammatory drugs (p < 0.0001) and glucocorticoids (p = 0.0001) prescribed with bDMARDs decreased significantly over time. CONCLUSIONS: The increase in bDMARD monotherapy may be attributed to the new bDMARDs that have been launched sequentially; furthermore, physicians have come to recognise monotherapy as the mainstay of treatment. Future studies must accumulate evidence on the long-term efficacy and safety of bDMARDs.

Multiple Domains in the Rhizobial Type III Effector Bel2-5 Determine Symbiotic Efficiency With Soybean.

Bradyrhizobium elkanii utilizes the type III effector Bel2-5 for nodulation in host plants in the absence of Nod factors (NFs). In soybean plants carrying the Rj4 allele, however, Bel2-5 causes restriction of nodulation by triggering immune responses. Bel2-5 shows similarity with XopD of the phytopathogen Xanthomonas campestris pv. vesicatoria and possesses two internal repeat sequences, two ethylene (ET)-responsive element-binding factor-associated amphiphilic repression (EAR) motifs, a nuclear localization signal (NLS), and a ubiquitin-like protease (ULP) domain, which are all conserved in XopD except for the repeat domains. By mutational analysis, we revealed that most of the putative domains/motifs in Bel2-5 were essential for both NF-independent nodulation and nodulation restriction in Rj4 soybean. The expression of soybean symbiosis- and defense-related genes was also significantly altered by inoculation with the bel2-5 domain/motif mutants compared with the expression upon inoculation with wild-type B. elkanii, which was mostly consistent with the phenotypic changes of nodulation in host plants. Notably, the functionality of Bel2-5 was mostly correlated with the growth inhibition effect of Bel2-5 expressed in yeast cells. The nodulation phenotypes of the domain-swapped mutants of Bel2-5 and XopD indicated that both the C-terminal ULP domain and upstream region are required for the Bel2-5-dependent nodulation phenotypes. These results suggest that Bel2-5 interacts with and modifies host targets via these multiple domains to execute both NF-independent symbiosis and nodulation restriction in Rj4 soybean.

Relationship between renal dysfunction and electrolyte abnormalities in hematopoietic stem cell transplant patients treated with foscarnet.

This study aimed to investigate the relationship between renal dysfunction and electrolyte abnormalities, which are adverse events of foscarnet used for cytomegalovirus infection. Of the Ninety hematopoietic stem cell transplantation patients, 32 who met the selection criteria were enrolled in this retrospective study. The study patients were divided into two groups according to whether they developed renal dysfunction. The incidences of hypocalcemia, hypokalemia, and hypomagnesemia with an increase of grade 2 or higher in the renal dysfunction group were 45.5%, 18.2%, and 27.3%, respectively. Additionally, in the renal dysfunction group, a significant correlation was observed between creatinine and calcium (r = -0.458, p = 0.0244) and between creatinine and potassium (r = -0.520, p = 0.0092). This study shows that renal dysfunction and electrolyte abnormalities may be closely related in HSCT patients receiving foscarnet; thus, it is a report that may contribute to the safety of continuous foscarnet treatment.

Development of imaging biomarker for esophageal cancer using intravoxel incoherent motion MRI.

BACKGROUND: Intravoxel incoherent motion MRI (IVIM-MRI) can quantify micro-perfusion at the capillary level in the tissue. The purpose of this study is to measure tumor perfusion using IVIM-MRI, and evaluate its value as a biomarker to predict prognosis in esophageal squamous cell carcinoma (ESCC) patients. METHODS: 109 ESCC patients (93 men and 16 women; median age: 72) who underwent IVIM-MRI prior to treatment between February 2018 and August 2020 were retrospectively investigated. Both mean apparent diffusion coefficient (ADC) value and mean perfusion-related parameter (PP) value of the primary tumor were measured using three b values of 0, 400, and 1000 s/mm2 based on the IVIM model. We analyzed associations of these parameters with clinical stage and disease-specific survival (DSS). RESULTS: Lower ADC and PP values of the tumor were significantly associated with the higher clinical T stage (p < 0.0001, p < 0.0001, respectively). In Kaplan-Meier analyses, patients with lower PP value tumors (< 18.94, median) had significantly worse DSS (p < 0.0001), while tumor ADC value did not show a significant correlation with DSS. In a multivariate analysis, PP value of the tumor was an independent prognostic factor for DSS (p = 0.0027). CONCLUSIONS: Quantification of tumor perfusion using IVIM-MRI can be a non-invasive prognostic biomarker of ESCC, reflecting clinical stage and survival.

Surface Modification Using Assisting Electrodes in Wire Electrical Discharge Machining for Silicon Wafer Preparation.

This paper outlines notable advances in the wire electrical discharge machining of polycrystalline silicon workpieces for wafer preparation. Our use of assisting electrodes permits the transfer of aluminum particles to the machined surface of the polycrystalline silicon workpieces, to enhance conductivity and alter surface topography regardless of the silicon's crystallographic structure and diamond-type lattice. This in-process surface modification technique was shown to promote material removal and simultaneously preserve the integrity of the machined surfaces with preferable surface textures. In the validation experiment, the 25 mm-thick assisting electrodes deposited a notable concentration of aluminium on the machined surface (~3.87 wt %), which greatly accelerated the rate of material removal (~9.42 mg/s) with minimal surface roughness (Sa ~5.49 µm) and moderate skewness (-0.23). The parameter combination used to obtain the optimal surface roughness (Sa 2.54 µm) was as follows: open voltage (80 V), electrical resistance (1.7 Ω), pulse-on time (30 µs), and electrode thickness (15 mm). In multiple objective optimization, the preferred parameter combination (open voltage = 80 V, resistance = 1.4 Ω, pulse-on time = 60 µs, and assisting electrode thickness = 25 mm) achieved the following appreciable results: surface modification of 3.26 ± 0.61 wt %, material removal rate of 7.08 ± 2.2 mg/min, and surface roughness of Sa = 4.3 ± 1.67 µm.

Properties and Classification of Diamond-Like Carbon Films.

Diamond-like carbon (DLC) films have been extensively applied in industries owing to their excellent characteristics such as high hardness. In particular, there is a growing demand for their use as protective films for mechanical parts owing to their excellent wear resistance and low friction coefficient. DLC films have been deposited by various methods and many deviate from the DLC regions present in the ternary diagrams proposed for sp3 covalent carbon, sp2 covalent carbon, and hydrogen. Consequently, redefining the DLC region on ternary diagrams using DLC coatings for mechanical and electrical components is urgently required. Therefore, we investigate the sp3 ratio, hydrogen content, and other properties of 74 types of amorphous carbon films and present the classification of amorphous carbon films, including DLC. We measured the sp3 ratios and hydrogen content using near-edge X-ray absorption fine structure and Rutherford backscattering-elastic recoil detection analysis under unified conditions. Amorphous carbon films were widely found with nonuniform distribution. The number of carbon atoms in the sp3 covalent carbon without bonding with hydrogen and the logarithm of the hydrogen content were inversely proportional. Further, we elucidated the DLC regions on the ternary diagram, classified the amorphous carbon films, and summarized the characteristics and applications of each type of DLC.