Clinical characterization of patients with gBRCA1/2 mutation-positive unresectable pancreatic cancer: a multicenter prospective study.

BACKGROUND: Accumulating evidence has demonstrated platinum-based chemotherapy followed by maintenance therapy with a poly Adenosine diphosphate (ADP)-ribose polymerase inhibitor (olaparib) show benefits in unresectable pancreatic cancer with a germline (g)BRCA1/2 mutation. Evaluation of the germline BRCA1 and BRCA2 mutation is essential for making decisions on a treatment strategy for patients with unresectable pancreatic cancer. However, the detection rates of germline BRCA1 and BRCA2 mutations and efficacy of maintenance with olaparib remain undetermined, prospectively, in Japan. METHODS & RESULTS: In this prospective analysis, the rate of germline BRCA1 and BRCA2 mutations and efficacy of chemotherapy were analyzed in 136 patients with pancreatic cancer who underwent BRACAnalysis® (85 patients) or FoundationOne® CDx (51 patients) between January 2020 and July 2022. A total of six patients (4.4%) had a germline BRCA1 and BRCA2 mutation. Five patients were treated with modified FOLFIRINOX and one with fluorouracil and oxaliplatin. All patients continued platinum-based chemotherapy for ˃4 months and were subsequently treated with olaparib as a maintenance therapy. The response rate to platinum-based chemotherapy in the germline BRCA1 and BRCA2 mutation-positive group was significantly better than that of the germline BRCA1 and BRCA2 mutation-negative group (66% vs 23%, P = 0.04). All patients harbouring a germline BRCA1 and BRCA2 mutation were able to switch to olaparib. The median progression-free survival using olaparib was 5.7 months (range 3.0-9.2). CONCLUSIONS: The rate of germline BRCA1 and BRCA2 mutations found in patients with unresectable pancreatic cancer was comparable to those of previous studies.An analysis of germline BRCA1 and BRCA2 mutations has benefits for all patients with unresectable pancreatic cancer with regard to decisions on therapeutic strategies in a clinical practice setting.

The emerging emetogenicity of trifluridine/tipiracil (TAS­102) from patient self-reporting: a multicenter, prospective, observational study.

BACKGROUND: Trifluridine/tipiracil (TAS-102) is an oral anticancer drug with adequate efficacy in unresectable colorectal cancer, but frequently also induces chemotherapy-induced nausea and vomiting (CINV). To investigate the occurrence of CINV and antiemetic therapy in patients with colorectal cancer treated with TAS-102 (JASCC-CINV 2001). METHODS: We conducted a multicenter, prospective, observational study in patients with colorectal cancer who received TAS-102 without dose reduction for the first time. Primary endpoint was the incidence of vomiting during the overall period. Secondary endpoints were the incidence of nausea, significant nausea, anorexia, other adverse events (constipation, diarrhea, insomnia, fatigue, dysgeusia) and patient satisfaction. Patient diaries were used for primary and secondary endpoints. All adverse events were subjectively assessed using PRO-CTCAE ver 1.0. and CTCAE ver 5.0. RESULTS: Data from 100 of the 119 enrolled patients were analyzed. The incidence of vomiting, nausea, and significant nausea was 13%, 67%, and 36%, respectively. The incidence of vomiting in patients with and without prophylactic antiemetic therapy were 20.8% and 10.5%, respectively. Prophylactic antiemetics were given to 24% of patients, of whom 70% received D2 antagonists. Multivariate Cox proportional hazards analysis showed that experience of CINV in previous treatment tended to be associated with vomiting (hazard ratio [HR]: 7.13, 95% confidence interval [CI]: 0.87-58.5, P = 0.07), whereas prophylactic antiemetic administration was not (HR: 1.61, 95 CI: 0.50-5.21, P = 0.43). With regard to patient satisfaction, the proportion of patients who were "very satisfied," "satisfied," "slightly satisfied" or "somewhat satisfied" was 81.8%. CONCLUSIONS: The low incidence of vomiting and high patient satisfaction suggest that TAS-102 does not require the use of uniform prophylactic antiemetic treatments. However, patients with the experience of CINV in previous treatment might require prophylactic antiemetic treatment.

Prognostic impact of severe neutropenia in colorectal cancer patients treated with TAS-102 and bevacizumab, addressing immortal-time bias.

BACKGROUND: Several studies have reported an association between severe neutropenia and long-term survival in patients treated with trifluridine-tipiracil (TAS-102). Because some of these studies failed to address immortality time bias, however, their findings should be interpreted with caution. Additionally, the association between severe neutropenia and survival in patients receiving TAS-102 in combination with bevacizumab (Bmab) remains unclear. PATIENTS AND METHODS: We conducted a single-center retrospective cohort study in patients with colorectal cancer who received Bmab + TAS-102. We compared overall survival (OS) between patients who developed grade ≥ 3 neutropenia during the treatment period and those who did not. To account for immortal time bias, we used two approaches, time-varying Cox regression and landmark analysis. RESULTS: Median OS was 15.3 months [95% CI: 14.1-NA] in patients with grade ≥ 3 neutropenia and 10.0 months [95% CI: 8.1-NA] in those without. In time-varying Cox regression, onset grade ≥ 3 neutropenia was significantly related to longer survival after adjustment for age and modified Glasgow Prognostic Score. Additionally, 30-, 60-, 90-, and 120-day landmark analysis showed that grade ≥ 3 neutropenia was associated with longer survival after adjustment for age and modified Glasgow Prognostic Score, with respective HRs of 0.30 [0.10-0.90], 0.65 [0.30-1.42], 0.39 [0.17-0.90], and 0.41 [0.18-0.95]. CONCLUSION: We identified an association between long-term survival and the development of severe neutropenia during the early cycle of Bmab + TAS-102 using an approach that addressed immortality time bias.

Efficacy and safety of 5HT3RA, DEX, and NK1RA for the prevention of FOLFIRINOX-induced nausea and vomiting in patients with pancreatic cancer: a retrospective cohort study.

PURPOSE: Modified FOLFIRINOX (mFFX), a standard chemotherapy regimen for advanced pancreatic cancer (APC), is expected to be associated with a higher risk of chemotherapy-induced nausea and vomiting (CINV). Herein, we conducted a retrospective cohort study to evaluate the efficacy and safety of a three-drug combination of 5-hydroxytryptamine-3 receptor antagonists (5HT3RA), dexamethasone (DEX), and neurokinin 1 receptor antagonists (NK1RA) for the prevention of CINV during mFFX therapy. METHODS: This study enrolled patients with APC who received mFFX as initial therapy with a combination of 5HT3RA, DEX, and NK1RA as antiemetic prophylaxis. The primary endpoint was the complete response (CR) rate during cycle 1, which was defined as no emetic episodes and no rescue medication use during the overall period (0-120 h). Safety was also evaluated with a focus on hyperglycemia, which is a concern in patients with APC. RESULTS: Seventy patients were eligible for this retrospective analysis. The CR rate during the overall period was 51.4%. Significant nausea, defined as grade 2 or higher, peaked to 77.1% on days 4-5, but remained above 65% until day 7. Hyperglycemia occurred in 37.1% of patients, and 34.3% were grade 3 hyperglycemia. CONCLUSIONS: CINV induced by mFFX was poorly controlled even with prophylactic antiemetic therapy using 5HT3RA, DEX, and NK1RA, and was found to persist beyond 5 days. Enhanced antiemetic measures for mFFX are desirable. However, in patients with diabetes mellitus complications, sparing of steroids and glycemic control should be considered.

The influence of temperature on the metabolic activity of CYP2C9, CYP2C19, and CYP3A4 genetic variants in vitro.

1. Temperature is considered to affect the activity of drug-metabolizing enzymes; however, no previous studies have compared temperature dependency among cytochrome P450 genetic variants. This study aimed to analyse warfarin 7-hydroxylation by CYP2C9 variants; omeprazole 5-hydroxylation by CYP2C19 variants; and midazolam 1-hydroxylation by CYP3A4 variants at 34 °C, 37 °C, and 40 °C.2. Compared with that seen at 37 °C, the intrinsic clearance rates (Vmax/Km) of CYP2C9.1 and .2 were decreased (76 ∼ 82%), while that of CYP2C9.3 was unchanged at 34 °C. At 40 °C, CYP2C9.1, .2, and .3 exhibited increased (121%), unchanged and decreased (87%) intrinsic clearance rates, respectively. At 34 °C, the clearance rates of CYP2C19.1A and .10 were decreased (71 ∼ 86%), that of CYP2C19.1B was unchanged, and those of CYP2C19.8 and .23 were increased (130 ∼ 134%). At 40 °C, the clearance rates of CYP2C19.1A, .1B, .10, and .23 remained unaffected, while that of CYP2C19.8 was decreased (74%). At 34 °C, the clearance rates of CYP3A4.1 and .16 were decreased (79 ∼ 84%), those of CYP3A4.2 and .7 were unchanged, and that of CYP3A4.18 was slightly increased (112%). At 40 °C, the clearance rate of CYP3A4.1 remained unaffected, while those of CYP3A4.2, .7, .16, and .18 were decreased (58 ∼ 82%).3. These findings may be clinically useful for dose optimisation in patients with hypothermia or hyperthermia.

Assessment of satisfaction with antiretroviral drugs and the need for long-acting injectable medicines among people living with HIV in Japan and its associated factors: a prospective multicenter cross-sectional observational study.

BACKGROUND: Long-acting injectable formulations for HIV infection have been approved and are now available in Japan. Although not currently recommended as first-line drugs in Japanese or overseas guidelines, use of such formulations may increase, in accordance with patient conditions and preference. We determine the level of satisfaction with current anti-HIV drugs and analyzed the preferences of patients who favor long-acting injectable drugs based on their satisfaction level with the present anti-HIV drugs. METHODS: People living with HIV (PLWH) who had received antiretroviral therapy (ART) for at least one month and consented to the study between 1 April and 31 December 2021 were included in a survey conducted using a self-administered questionnaire. The content of the survey included satisfaction with seven items (tablet size, ease and feeling when taking the medicine, color, taste, portability, daily oral therapy, and co-payment) related to the anti-HIV drugs they were taking and their need for future drugs (dosage form, frequency of dosing, long-acting injectable, etc.). In addition, factors related to the need for long-acting injectable medications were analyzed with regard to the relationship with satisfaction with anti-HIV drugs. RESULTS: Overall, 667 patients available for analysis were included in this study. Satisfaction with anti-HIV drugs was highest with regard to "co-payment" and lowest with "daily oral therapy". Regarding the need for long-acting injectable medications, logistic regression analysis indicated that tablet size and daily oral therapy were significant predictors of patient preference for a once-every-eight-weeks intramuscular formulation in terms of their requirement for long-acting injectable medications (tablet size, OR = 2.14, 95%CI 1.030-4.430, p = 0.042; and daily oral therapy, OR = 1.75, 95%CI 1.010-3.030, p = 0.044). CONCLUSIONS: Patients currently receiving anti-HIV drugs who express dissatisfaction with tablet size and daily oral therapy may prefer a long-acting injectable formulation, taking into consideration patient age, employment status, ART history, frequency of daily dosage and concomitant medications other than ART.

The apple gene responsible for columnar tree shape reduces the abundance of biologically active gibberellin.

Ectopic expression of the apple 2-oxoglutarate-dependent dioxygenase (DOX, 2ODD) gene, designated MdDOX-Co, is thought to cause the columnar shape of apple trees. However, the mechanism underlying the formation of such a unique tree shape remains unclear. To solve this problem, we demonstrated that Arabidopsis thaliana overexpressing MdDOX-Co contained reduced levels of biologically active gibberellin (GA) compared with wild type. In summary: (i) with biochemical approaches, the gene product MdDOX-Co was shown to metabolize active GA A4 (GA4 ) to GA58 (12-OH-GA4 ) in vitro. MdDOX-Co also metabolized its precursors GA12 and GA9 to GA111 (12-OH-GA12 ) and GA70 (12-OH-GA9 ), respectively; (ii) Of the three 12-OH-GAs, GA58 was still active physiologically, but not GA70 or GA111 ; (iii) Arabidopsis MdDOX-Co OE transformants converted exogenously applied deuterium-labeled (d2 )-GA12 to d2 -GA111 but not to d2 -GA58 , whereas transformants converted applied d2 -GA9 to d2 -GA58 ; (iv) GA111 is converted poorly to GA70 by GA 20-oxidases in vitro when GA12 is efficiently metabolized to GA9 ; (v) no GA58 was detected endogenously in MdDOX-Co OE transformants. Overall, we conclude that 12-hydroxylation of GA12 by MdDOX-Co prevents the biosynthesis of biologically active GAs in planta, resulting in columnar phenotypes.

Asymmetric Cationic Polymerization of Benzofuran through a Reversible Chain-Transfer Mechanism: Optically Active Polybenzofuran with Controlled Molecular Weights.

Benzofuran (BzF) is a prochiral, 1,2-disubstituted, unsymmetric cyclic olefin that can afford optically active polymers by asymmetric polymerization, unlike common acyclic vinyl monomers. Although asymmetric cationic polymerization of BzF was reported by Natta et al. in the 1960s, the polymer structure has not been clarified, and there are no reports on molecular weight control. Herein, we report dual control of the optical activity and molecular weight of poly(BzF) using thioether-based reversible chain-transfer agents for asymmetric cationic polymerization with ß-amino acid derivatives as chiral additives and aluminum chloride as a catalyst. This asymmetric moderately living cationic polymerization leads to an increase in molecular weight and specific optical rotation with monomer conversion. In addition, asymmetric block polymers consisting of opposite absolute configurational segments were synthesized using both enantiomers sequentially as chiral additives. Finally, a comprehensive analysis of the polymerization products and the model reaction revealed that the optical activity of poly(BzF) originates from the threo-diisotactic structure, which occurs by regio-, trans-, and enantioselective propagation.

One-Day Versus Three-Day Dexamethasone with NK1RA for Patients Receiving Carboplatin and Moderate Emetogenic Chemotherapy: A Network Meta-analysis.

BACKGROUND: The dexamethasone (DEX)-sparing strategy, which limits administration of DEX to day one, is reportedly non-inferior to conventional antiemetic regimens comprising multiple-day DEX. However, the usefulness of the DEX-sparing strategy in triplet antiemetic prophylaxis (neurokinin-1 receptor antagonist [NK1RA] + serotonin receptor antagonist [5HT3RA] + DEX) for carboplatin and moderate emetogenic chemotherapy (MEC) has not been clarified. PATIENTS AND METHODS: We systematically reviewed randomized controlled trials that examined the efficacy of antiemetics for preventing chemotherapy-induced nausea and vomiting associated with carboplatin and MEC. We conducted a network meta-analysis to compare the antiemesis efficacy of three-day DEX with NK1RA (3-DEX + NK1RA) and one-day DEX with NK1RA (1-DEX + NK1RA). The primary outcome was complete response during the delayed phase (CR-DP). The secondary outcome was no nausea during the delayed phase (NN-DP). RESULTS: Seventeen trials involving 4534 patients were included. The proportion who experienced CR-DP was 82.5% (95% credible interval [CI], 73.9-88.6) and 73.5% (95% CI, 62.8-80.9) among those who received 3-DEX + NK1RA and 1-DEX + NK1RA, respectively. There was no significant difference between the two regimens. However, 3-DEX + NK1RA tended to be superior to 1-DEX + NK1RA, with an absolute risk difference of 9.0% (95% CI, -2.3 to 21.1) in CR-DP and 24.7% (95% CI: -14.9 to 54.6) in NN-DP. 3-DEX + NK1RA also tended to be superior to 1-DEX + NK1RA in patients who received carboplatin-based chemotherapy, for whom the absolute risk difference was 12.3% (95% CI, -3.2 to 30.7). CONCLUSIONS: Care is needed when administering the DEX-sparing strategy in combination with NK1RA to patients receiving carboplatin and non-carboplatin MEC.

Effects of ingestion of isomaltulose beverage on plasma volume and thermoregulatory responses during exercise in the heat.

PURPOSE: Isomaltulose is a low glycemic and insulinaemic carbohydrate increasingly used as an alternative sweetener in commercial beverages. While isomaltulose beverages can improve hydration status compared to sucrose-based beverages, it remains unclear if ingestion of an isomaltulose beverage prior to exercise in the heat may improve plasma volume (PV) and thermoregulatory responses. METHODS: Twelve endurance-trained men consumed a 1L carbohydrate beverage containing either 6.5%-sucrose (SUC) or 6.5%-isomaltulose (ISO) 60 min prior to 5 successive, 15-min bouts of moderate-intensity (60% of their pre-determined maximum oxygen uptake) in the heat (32 °C, 50% relative humidity), each separated by a 5 min rest. A 6th bout was performed, wherein the participant adjusted running speed to maximize distance covered within the 15-min period. The change (Δ) in PV, heart rate (HR), body core (rectal and gastrointestinal) and skin temperatures, and whole-body sweat loss were assessed during each exercise bout. RESULTS: Ingestion of ISO induced a higher ΔPV at 4th bout only (P < 0.001) and lower HR (P = 0.032, main effect of beverage) during exercise compared to those of SUC. Body core and skin temperatures and whole-body sweat loss did not differ between conditions (all P ≥ 0.192, interaction effect). Running distance covered in final exercise bout tended to increase (~ 5%) in ISO versus SUC (P = 0.057, d = 0.64). CONCLUSIONS: Relative to a sucrose-based beverage, ISO ingestion prior to exercise in the heat reduced cardiovascular strain by preserving PV and attenuating HR, albeit with no corresponding benefit on thermoregulatory function. The former response may facilitate improvements in exercise performance.

Association of albumin-bilirubin score in patients with colorectal cancer receiving later-line chemotherapy with regorafenib.

BACKGROUND: Regorafenib is recognized as a later-line standard treatment in patients with metastatic colorectal cancer (mCRC). In this study, we examined the association of the albumin-bilirubin (ALBI) score in patients with mCRC receiving later-line chemotherapy with regorafenib. PATIENTS AND METHODS: We retrospectively analyzed data from patients with mCRC treated with regorafenib in a later line between January 2013 and December 2019. Patients were divided into a Normal-ALBI group (ALBI grade 1) and a High-ALBI group (ALBI grades 2 and 3). Primary endpoint was median overall survival (OS) and secondary endpoints were median time to treatment failure (TTF) and incidence of adverse events (AEs). RESULTS: Data from 60 patients were analyzed (Normal-ALBI group: 32 patients and High-ALBI group: 28 patients). Median OS [10.23 vs. 3.70 months, hazard ratio (HR): 1.79, 95% confidence interval (CI) 1.02-3.13, p = 0.041] and median TTF (2.27 vs. 1.78 months, HR: 1.78, 95%CI 1.02-3.09, p = 0.042) were significantly longer in the Normal-ALBI group than High-ALBI group. On Cox proportional hazard analysis, ALBI score was significantly correlated with OS. The incidence of liver dysfunction (grade ≥ 2) was significantly higher in the High-ALBI than the Normal-ALBI group (42.9% vs. 15.6%, p = 0.041), whereas other AEs were comparable between the two groups. CONCLUSION: ALBI was strongly associated with the prognosis of patients with mCRC treated with regorafenib and with the occurrence of liver-related adverse events. These findings may imply that patients with a high ALBI score should not be treated with regorafenib.

Bevacizumab in Combination with TAS-102 Improves Clinical Outcomes in Patients with Refractory Metastatic Colorectal Cancer: A Retrospective Study.

OBJECTIVE: TAS-102 is effective for treating patients with metastatic colorectal cancer (mCRC). This study determined whether combining bevacizumab (Bmab) with TAS-102 improves clinical outcomes in refractory mCRC. PATIENTS AND METHODS: We retrospectively analyzed data from Japanese patients with refractory mCRC who received TAS-102 (35 mg/m2 , twice a day) with (T-B group) or without Bmab (TAS-102 monotherapy; T group) between July 2014 and December 2018. The primary endpoint was median overall survival (OS), and secondary endpoints were median time to treatment failure, overall response rate, and the incidence of adverse events. Clinical outcomes were compared using propensity score matched analysis. RESULTS: Data from 57 patients were analyzed (T-B group: 21 patients, T group: 36 patients). Median OS was significantly longer in the T-B group than the T group (14.4 months vs. 4.5 months, p < .001). Cox proportional hazard analysis showed that combination therapy with Bmab was significantly correlated with OS. Propensity score matched analysis confirmed that the median OS was significantly longer in the T-B group than the T group (14.4 months vs. 6.1 months, p = .006) and that there was a significant correlation between Bmab and OS. The incidence of hypertension (grade ≥2) as an adverse event was significantly higher in the T-B group than the T group (23.8% vs. 0.0%, p = .005), whereas other adverse events were comparable between the two groups. CONCLUSION: Treatment with Bmab in combination with TAS-102 is significantly associated with improved clinical outcomes in patients with mCRC refractory to standard therapies. IMPLICATIONS FOR PRACTICE: Combining bevacizumab (Bmab) with TAS-102 significantly improved overall survival and several prognostic indicators in patients with metastatic colorectal cancer (mCRC) refractory to standard therapies, with manageable toxicities. Treatment with Bmab in combination with TAS-102 is significantly associated with improved clinical outcomes in patients with mCRC.

[Good's syndrome developing hemophagocytic lymphohistiocytosis following thymectomy].

This report presents the case of a 68-year-old female patient previously diagnosed with thymoma by her local doctor. She was referred to our hospital for surgery, and the thymoma was removed and diagnosed as a World Health Organization (WHO) classification type AB thymoma. After surgery, she experienced general malaise, a loss of appetite, and weight loss, so she visited our hospital in May 2019. A blood test showed hypogammaglobulinemia and low B lymphocytes. A bone marrow examination revealed no morphological abnormalities. Flow cytometric analysis indicated a marked decrease in both the B cell-related surface markers CD19 and CD20 and the T cell-related surface marker CD4, and the CD4/CD8 ratio was also low. She was diagnosed with Good's syndrome, and immunoglobulin replacement therapy was administered. She subsequently developed hemophagocytic lymphohistiocytosis (HLH) due to infection and was treated according to the HLH2004 protocol, but she finally succumbed to multiple organ damage as a result of sepsis. Given that Good's syndrome is associated with both humoral and cellular immune dysfunctions, affected patients tend to develop severe infections and have a poor prognosis. In such cases, early detection, regular immunoglobulin replacement therapy, and infection prevention therapies are important.

Stretching After Heat But Not After Cold Decreases Contractures After Spinal Cord Injury in Rats.

BACKGROUND: Contractures are a prevalent and potentially severe complication in patients with neurologic disorders. Although heat, cold, and stretching are commonly used for treatment of contractures and/or spasticity (the cause of many contractures), the sequential effects of these modalities remain unclear. QUESTIONS/PURPOSES: Using an established rat model with spinal cord injury with knee flexion contracture, we sought to determine what combination of heat or cold before stretching is the most effective for treatment of contractures derived from spastic paralyses and investigated which treatment leads to the best (1) improvement in the loss of ROM; (2) restoration of deterioration in the muscular and articular factors responsible for contractures; and (3) amelioration of histopathologic features such as muscular fibrosis in biceps femoris and shortening of the joint capsule. METHODS: Forty-two adolescent male Wistar rats were used. After spasticity developed at 2 weeks postinjury, each animal with spinal cord injury underwent the treatment protocol daily for 1 week. Knee extension ROM was measured with a goniometer by two examiners blinded to each other's scores. The muscular and articular factors contributing to contractures were calculated by measuring ROM before and after the myotomies. We quantitatively measured the muscular fibrosis and the synovial intima length, and observed the distribution of collagen of skeletal muscle. The results were confirmed by a blinded observer. RESULTS: The ROM of heat alone (34° ± 1°) and cold alone (34° ± 2°) rats were not different with the numbers available from that of rats with spinal cord injury (35° ± 2°) (p = 0.92 and 0.89, respectively). Stretching after heat (24° ± 1°) was more effective than stretching alone (27° ± 3°) at increasing ROM (p < 0.001). Contrastingly, there was no difference between stretching after cold (25° ± 1°) and stretching alone (p = 0.352). Stretching after heat was the most effective for percentage improvement of muscular (29%) and articular (50%) factors of contractures. Although quantification of muscular fibrosis in the rats with spinal cord injury (11% ± 1%) was higher than that of controls (9% ± 0.4%) (p = 0.01), no difference was found between spinal cord injury and each treatment protocol. The total synovial intima length of rats with spinal cord injury (5.9 ± 0.2 mm) became shorter than those of the controls (7.6 ± 0.2 mm) (p < 0.001), and those of stretching alone (6.9 ± 0.4 mm), stretching after heat (7.1 ± 0.3 mm), and stretching after cold (6.7 ± 0.4 mm) increased compared with rats with spinal cord injury (p = 0.01, p = 0.001, and p = 0.04, respectively). The staining intensity and pattern of collagen showed no difference among the treatment protocols. CONCLUSIONS: This animal study implies that heat or cold alone is ineffective, and that stretching is helpful for the correction of contractures after spinal cord injury. In addition, we provide evidence that heat is more beneficial than cold to increase the effectiveness of stretching. CLINICAL RELEVANCE: Our findings tend to support the idea that stretching after heat can improve the loss of ROM and histopathologic features of joint tissues. However, further studies are warranted to determine if our findings are clinically applicable.

TGA and NMR relaxation measurement of nonmesoporous silica to investigate the amount of hydrolysis product in acetylsalicylic acid adsorbed on silica.

This study investigated a crucial surface property of silica that contributes to the chemical stability of acetylsalicylic acid (ASA) physically adsorbed on silica. Hydrophilic nonmesoporous types of silica were selected, and the number of hydroxyl groups on silica (N(OH)) was evaluated using thermogravimetric analysis (TGA). The ASA-containing silica was stored at 40 °C in drying conditions, and the amount of ASA degradation was quantified based on salicylic acid. From the scatterplots between the number of hydroxyl groups per unit weight (specific surface area (SSA) × N(OH)) and the amount of ASA degradation, it was clarified that in ASA adsorbed on silica, the ASA chemical stability was determined by the formula (the SSA × N(OH)). In addition, a time-domain nuclear magnetic resonance measurement verified the N(OH) result by estimating the interaction between the silica surface and water in an aqueous silica suspension. The N(OH) result was found to be reasonable.

Exploring Physical Activity Levels in Patients with Cardiovascular Disease-A Preliminary Study.

Increased physical activity may prevent disease onset and severity in individuals with cardiovascular disease. However, studies evaluating physical activity in people with cardiovascular disease are limited. This prospective observational study aimed to objectively assess the level of physical activity in patients with cardiovascular disease and determine the actual extent of physical activity in their daily lives. Participants aged 20 years or older with cardiovascular disease at a cardiology clinic were included. Physical activity was measured using an activity meter with a three-axis acceleration sensor. Overall, 58 patients were included in the study. Household activities were found to be more frequent sources of physical activity. The step count was related to age and housework, while total physical activity and household activity were related to age and work. Locomotive activity was related to sex and housework. Total physical and household activities tended to decrease with age. These findings indicate the influence of work and household chores on physical activity and suggest that physical activity may be underestimated if household activity is not also assessed. These fundamental findings may provide clinical evidence to underpin physical activity for patients with cardiovascular disease.

Serum Soluble IL-2 Receptors Are Elevated in Febrile Illnesses and Useful for Differentiating Clinically Similar Malignant Lymphomas from Kikuchi Disease: A Cross-Sectional Study.

Background: The use of serum soluble interleukin 2 receptor (sIL-2R) for the diagnosis of febrile illnesses has not been examined. In this study, febrile patients were classified according to etiology and disease, and serum sIL-2R levels were evaluated. We determined whether serum sIL-2R is a useful marker for differentiating between malignant lymphoma (ML) and non-ML patients and between patients with ML and Kikuchi disease, which present similar clinical manifestations. Methods: This study was a cross-sectional study and included 344 patients with uncomplicated hemophagocytic syndrome, who had a fever of 38 °C or higher within 1 week of admission to our institution. Patient serum sIL-2R was measured, and the serum sIL-2R values are shown as median and IQR. Results: Serum sIL-2R increased above the upper reference limit in all disease groups with fever. The serum sIL-2R level in ML patients (n = 13) was 4760 (2120-6730) U/mL and significantly higher (p < 0.001) than the level of 998 (640-1625) U/mL in non-ML patients (n = 331). The serum sIL-2R level in ML patients (n = 13) was also significantly higher (p < 0.001) compared with that in patients with Kikuchi disease (n = 20; 705 (538-1091) U/mL). Conclusions: Serum sIL-2R tends to exceed the upper reference limit in patients with febrile illnesses. We conclude that the measurement of serum sIL-2R is useful for differentiating ML from non-ML and ML from Kikuchi disease.

Development of artificial intelligence-based slow-motion echocardiography and clinical usefulness for evaluating regional wall motion abnormalities.

The diagnostic accuracy of exercise stress echocardiography (ESE) for myocardial ischemia requires improvement, given that it currently depends on the physicians' experience and image quality. To address this issue, we aimed to develop artificial intelligence (AI)-based slow-motion echocardiography using inter-image interpolation. The clinical usefulness of this method was evaluated for detecting regional wall-motion abnormalities (RWMAs). In this study, an AI-based echocardiographic image-interpolation pipeline was developed using optical flow calculation and prediction for in-between images. The accuracy for detecting RWMAs and image readability among 25 patients with RWMA and 25 healthy volunteers was compared between four cardiologists using slow-motion and conventional ESE. Slow-motion echocardiography was successfully developed for arbitrary time-steps (e.g., 0.125×, and 0.5×) using 1,334 videos. The RWMA detection accuracy showed a numerical improvement, but it was not statistically significant (87.5% in slow-motion echocardiography vs. 81.0% in conventional ESE; odds ratio: 1.43 [95% CI: 0.78-2.62], p = 0.25). Interreader agreement analysis (Fleiss's Kappa) for detecting RWMAs among the four cardiologists were 0.66 (95%CI: 0.55-0.77) for slow-motion ESE and 0.53 (95%CI: 0.42-0.65) for conventional ESE. Additionally, subjective evaluations of image readability using a four-point scale showed a significant improvement for slow-motion echocardiography (2.11 ± 0.73 vs. 1.70 ± 0.78, p < 0.001).In conclusion, we successfully developed slow-motion echocardiography using in-between echocardiographic image interpolation. Although the accuracy for detecting RWMAs did not show a significant improvement with this method, we observed enhanced image readability and interreader agreement. This AI-based approach holds promise in supporting physicians' evaluations.