Exploratory investigation of virtual lesions in gastrointestinal endoscopy using a novel phase-shift method for three-dimensional shape measurement.

Accurate measurement of the size of lesions or distances between any two points during endoscopic examination of the gastrointestinal tract is difficult owing to the fisheye lens used in endoscopy. To overcome this issue, we developed a phase-shift method to measure three-dimensional (3D) data on a curved surface, which we present herein. Our system allows the creation of 3D shapes on a curved surface by the phase-shift method using a stripe pattern projected from a small projecting device to an object. For evaluation, 88 measurement points were inserted in porcine stomach tissue, attached to a half-pipe jig, with an inner radius of 21 mm. The accuracy and precision of the measurement data for our shape measurement system were compared with the data obtained using an Olympus STM6 measurement microscope. The accuracy of the path length of a simulated protruded lesion was evaluated using a plaster model of the curved stomach and graph paper. The difference in height measures between the measurement microscope and measurement system data was 0.24 mm for the 88 measurement points on the curved surface of the porcine stomach. The error in the path length measurement for a lesion on an underlying curved surface was <1% for a 10-mm lesion. The software was developed for the automated calculation of the major and minor diameters of each lesion. The accuracy of our measurement system could improve the accuracy of determining the size of lesions, whether protruded or depressed, regardless of the curvature of the underlying surface.

CONUT score as a predictor for anamorelin efficacy in patients with cancer cachexia receiving chemotherapy.

BACKGROUND: Anamorelin is expected to improve cancer cachexia by increasing lean body mass (LBM) due to increased appetite and protein synthesis. However, the effect of anamorelin on cancer cachexia in real-world practice is unclear. The purpose of this study was to evaluate the efficacy and safety of anamorelin and to identify predictors of efficacy on treatment with anamorelin. METHODS: We retrospectively analyzed data from patients with cancer cachexia treated with chemotherapy between May 2021 and August 2022. Efficacy of anamorelin was evaluated using LBM, with "12-week sustained effective response" to anamorelin treatment defined as maintenance or an increase in LBM for 12 weeks. We examined factors associated with "12-week sustained effective response" to anamorelin treatment using a multivariable logistic model that included controlling nutritional status (CONUT) score, an objective assessment of nutritional disorders, and the modified Glasgow prognostic score (mGPS), which scores the cachexia status of cancer patients. To assess patient subjective quality of life (QOL) changes related to eating after starting anamorelin treatment, we used a questionnaire (QOL-ACD appetite-related items: Q8, 9, 11). Adverse events were evaluated in accordance with the Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0. RESULTS: On analysis of data from 40 patients, 23 patients showed a 12-week sustained effective response to anamorelin (57.5%). At 12 weeks, LBM significantly increased by 1.63 ± 3.73 kg (mean ± SD). Multivariable logistic analysis revealed that a low CONUT score was significantly associated with "12-week sustained effective response" to anamorelin treatment (adjusted odds ratio: 13.5, 95% confidence intervals: 2.2-84.2, P = 0.004). QOL assessment showed a trend toward increased appetite and enjoyment of meals after anamorelin initiation. Five patients (12.5%) had an increase in HbA1c of more than 1.0% during the 12 weeks after the start of anamorelin. No patient had QT interval prolongation or grade 3 or higher hepatic transaminase elevation. CONCLUSION: Anamorelin may maintain or increase LBM with tolerable safety in patients with cancer cachexia undergoing chemotherapy. A low CONUT score, despite meeting criteria for cancer cachexia, is suggested as a predictor for the efficacy of anamorelin, indicating that patients with a low CONUT score may benefit from early introduction of anamorelin.

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.

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.

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.

Pretherapeutic factors predicting conversion surgery in unresectable pancreatic ductal adenocarcinoma: A retrospective study.

Recently, conversion surgery (CS) has been reported to improve the prognosis in patients with unresectable pancreatic ductal adenocarcinoma (UR-PDAC) with a favorable response to intense chemotherapy or chemoradiotherapy. However, few pretherapeutic parameters predict the attainability of CS in patients with UR-PDAC. The present study aimed to explore the pretherapeutic predictors for the attainability of CS in patients with UR-PDAC. The present study retrospectively evaluated 130 patients with UR-PDAC treated at Gifu University Hospital (Gifu, Japan) from January 2015 to December 2021. Survival analysis was performed using the Simon and Makuch-modified Kaplan-Meier method. The hazard ratio (HR) was estimated using a time-varying Cox regression model. The association between each predictor and CS was evaluated using the univariate analysis and age-adjusted Fine-Gray sub-distribution hazard model. The bootstrap bias-corrected area under the receiver operating characteristic curve analysis for predicting CS was used to assess the cut-off values for each predictor. The cumulative incidence rate was calculated with CS as the outcome when divided into two groups based on the cut-off value of each pretherapeutic predictor. Among the 130 patients included in the analysis, only 14 (11%) underwent CS. The median survival time was significantly longer in patients who underwent CS compared with patients without CS (56.3 vs. 14.1 months; P<0.001). The age-adjusted Fine-Gray sub-distribution hazard regression showed that the total protein (TP) [HR 2.81, 95% confidence interval (CI) 1.19-6.65; P=0.018], neutrophil-to-lymphocyte ratio (NLR) (HR 0.53, 95% CI 0.31-0.90; P=0.020), and lymphocyte-to-monocyte ratio (LMR) (HR 1.28, 95% CI 1.07-1.53; P=0.006) were significantly associated with CS. Moreover, TP ≥6.8, NLR <2.84 and LMR ≥3.87 were associated with a higher cumulative incidence of CS. In conclusion, pretherapeutic TP, NLR and LMR are clinically feasible biomarkers for predicting the attainability of CS in patients with UR-PDAC.

Radiomics Features Using Dual-energy CT for Lymph Nodes After Preoperative Chemotherapy for Esophageal Cancer.

BACKGROUND/AIM: Progress has been made in a triplet preoperative chemotherapy regimen for advanced esophageal cancer. We performed a preliminary investigation of the radiomics features of pathological lymph node metastasis after neoadjuvant chemotherapy using dual-energy computed tomography (DECT). PATIENTS AND METHODS: From January to December 2022, 36 lymph nodes from 10 patients with advanced esophageal cancer who underwent contrast-enhanced DECT after neoadjuvant chemotherapy and radical surgery in our department were studied. Radiomics features were extracted from iodine-based material decomposition images at the portal venous phase constructed by DECT using MATLAB analysis software. Receiver operating characteristic (ROC) analysis and cut-off values were determined for the presence or absence of pathological metastasis. RESULTS: ROC for the short axis of the pathologically positive lymph nodes showed an AUC of 0.713. Long run emphasis (LRE) within gray-level run-length matrix (GLRLM) was confirmed with a high AUC of 0.812. Sensitivity and specificity for lymph nodes with a short axis >10 mm were 0.222 and 1, respectively. Sensitivity and specificity for LRE within GLRLM were 0.722 and 0.833, respectively. Sensitivity and specificity for small zone emphasis (SZE) within gray-level size zone matrix (GLSZM) were 0.889 and 0.667, and zone percentage (ZP) values within GLSZM were 0.722 and 0.778, respectively. Discrimination of existing metastases using radiomics showed significantly higher sensitivity compared to lymph node short axis >10 mm (odds ratios of LRE, SZE, and ZP: 9.1, 28, and 9.1, respectively). CONCLUSION: Evaluation of radiomics analysis using DECT may enable a more detailed evaluation of lymph node metastasis after neoadjuvant chemotherapy.

Proposal for Classifying the Emetogenicity of Oral Anticancer Agents with a Focus on PARP Inhibitors: A Prospective, Observational, Multicenter Study (JASCC-CINV 2002).

Background: Olaparib and niraparib (poly adenosine diphosphate [ADP]-ribose polymerase [PARP] inhibitors) have significant antitumor action in patients with ovarian cancer. However, the incidence of nausea and vomiting among patients on these drugs in clinical trials is rather high. There are no guidelines on antiemetic treatment for nausea caused by oral anticancer agents. This study aimed to investigate the incidence of nausea and vomiting caused by PARP inhibitors and the actual situation of antiemetic therapy in patients with gynecologic cancer. Methods: Patients with gynecologic cancer who were scheduled to receive PARP inhibitors were enrolled. Data on PARP inhibitor-induced nausea and vomiting were collected from patient diaries for 21 days. The primary endpoint was the incidence of vomiting during the 21 days after starting olaparib and niraparib. Results: Overall, between January 2020 and March 2023, 134 patients were enrolled. Of the 129 patients who were evaluated, 28 (21.7%) received prophylactic antiemetics for 21 days, and 101 (78.3%) did not. The overall incidence of PARP inhibitor-induced vomiting was 16.3%. The incidence of vomiting in the group that did not receive antiemetic prophylaxis was 13.9%. On dividing the group that did not receive antiemetic prophylaxis into the olaparib and niraparib subgroups, the incidence of vomiting was found to be 18.6% for the olaparib group and 10.3% for the niraparib group. Conclusion: The incidence of emesis without antiemetic prophylaxis among patients on olaparib and niraparib ranged from 10% to 30%. Therefore, olaparib and niraparib can be classified in the low emetogenic risk and prophylactic antiemetic therapy at the time of treatment initiation may be unnecessary.

Endothelial Glycocalyx in the Peripheral Capillaries is Injured Under Oxaliplatin-Induced Neuropathy.

Oxaliplatin, a platinum-based anticancer drug, is associated with peripheral neuropathy (oxaliplatin-induced peripheral neuropathy, OIPN), which can lead to worsening of quality of life and treatment interruption. The endothelial glycocalyx, a fragile carbohydrate-rich layer covering the luminal surface of endothelial cells, acts as an endothelial gatekeeper and has been suggested to protect nerves, astrocytes, and other cells from toxins and substances released from the capillary vessels. Mechanisms underlying OIPN and the role of the glycocalyx remain unclear. This study aimed to define changes in the three-dimensional ultrastructure of capillary endothelial glycocalyx near nerve fibers in the hind paws of mice with OIPN. The mouse model of OPIN revealed disruption of the endothelial glycocalyx in the peripheral nerve compartment, accompanied by vascular permeability, edema, and damage to the peripheral nerves. To investigate the potential treatment interventions, nafamostat mesilate, a glycocalyx protective agent was used in tumor-bearing male mice. Nafamostat mesilate suppressed mechanical allodynia associated with neuropathy. It also prevented intra-epidermal nerve fiber loss and improved vascular permeability in the peripheral paws. The disruption of endothelial glycocalyx in the capillaries that lie within peripheral nerve bundles is a novel finding in OPIN. Furthermore, these findings point toward the potential of a new treatment strategy targeting endothelial glycocalyx to prevent vascular injury as an effective treatment of neuropathy as well as of many other diseases. PERSPECTIVE: OIPN damages the endothelial glycocalyx in the peripheral capillaries, increasing vascular permeability. In order to prevent OIPN, this work offers a novel therapy approach that targets endothelial glycocalyx.

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.

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.

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.

Efficacy and Safety of Oxaliplatin-based Regimens as First-line Chemotherapy in Elderly Patients With Metastatic Colorectal Cancer.

BACKGROUND/AIM: Metastatic colorectal cancer (mCRC) is mainly a disease of the elderly. The aim of this retrospective study was to investigate the efficacy and safety of oxaliplatin-based regimens as first-line chemotherapy in elderly patients with mCRC. PATIENTS AND METHODS: We recruited mCRC patients aged ≥75 years who were treated with oxaliplatin-based chemotherapy as first-line therapy from October 2011 to November 2020. Primary outcome was median progression-free survival (PFS) and incidence of adverse events, while secondary outcomes included overall survival (OS), relative dose intensity (RDI) and tumor response rate. RESULTS: The study enrolled 41 patients with mCRC aged ≥75 years. Median PFS and OS were 9.3 months and 38.9 months, respectively. Median rate of starting dose per standard dose and median RDI of L-OHP were 94.6% [interquartile range (IQR)=80.0-100] and 52.4% (IQR=30.2-71.1), respectively. The most common adverse events of grade ≥3 were neutropenia (21.4%), high blood pressure (16.7%), and anorexia (14.3%). CONCLUSION: Although the RDI of L-OHP drug was low, the PFS, OS, and incidence of adverse events were similar to previous reports of oxaliplatin-based regimens not limited to the elderly. Oxaliplatin-based regimens as first-line chemotherapy may be safely and effectively adapted to patients aged ≥75 years with mCRC by continuing chemotherapy with implementation of a reduction and discontinuation of anticancer drugs depending on adverse events.

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.

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 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.

Distinct Frontoparietal Brain Dynamics Underlying the Co-Occurrence of Autism and ADHD.

Previous diagnostic systems precluded the co-existence of autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD) in one person; but, after many clinical reports, the diagnostic criteria were updated to allow their co-occurrence. Despite such a clinical change, the neurobiological bases underpinning the comorbidity remain poorly understood, and whether the ASD+ADHD condition is a simple overlap of the two disorders is unknown. Here, to answer this question, we compared the brain dynamics of high-functioning ASD+ADHD children with age-/sex-/IQ-matched pure ASD, pure ADHD, and typically developing (TD) children. Regarding autistic traits, the socio-communicational symptom of the ASD+ADHD children was explained by the same overstable brain dynamics as seen in pure ASD. In contrast, their ADHD-like traits were grounded on a unique neural mechanism that was unseen in pure ADHD: the core symptoms of pure ADHD were associated with the overly flexible whole-brain dynamics that were triggered by the unstable activity of the dorsal-attention network and the left parietal cortex; by contrast, the ADHD-like cognitive instability of the ASD+ADHD condition was correlated with the atypically frequent neural transition along a specific brain state pathway, which was induced by the atypically unstable activity of the frontoparietal control network and the left prefrontal cortex. These observations need to be validated in future studies using more direct and comprehensive behavioral indices, but the current findings suggest that the ASD+ADHD comorbidity is not a mere overlap of the two disorders. Particularly, its ADHD-like traits could represent a unique condition that would need a specific diagnosis and bespoke treatments.

Effects of interprofessional conferences on intensive care units: comparing lengths of stay in the intensive care unit before and after the introduction of interprofessional conferences.

Objective: This study evaluated the effects of interprofessional conferences on intensive care units (ICUs) by comparing related outcomes before and after their introduction. Patients and Methods: This study was conducted at a single center and included ICU patients admitted between April 2017 and March 2019. Interprofessional conferences include physicians, nurses, physical therapists, nutritionists, and pharmacists. Data were extracted from the available medical records. The primary outcome measure was ICU length of stay (LOS). The secondary outcome measures were hospital LOS and any rehabilitation and nutrition begun within 48 hours of ICU admission. Outcomes before and after the introduction of the interprofessional conferences were compared. The adjusted variables were sex, age, body mass index, ICU readmission, health outcomes, Barthel index at admission, and disease (classified according to the International Statistical Classification of Diseases and Related Health Problems 10th edition). Results: We included 1,765 ICU patients admitted between April 2017 and March 2019. There were 898 patients in the "pre-interprofessional conference introduction" group (before group) and 867 in the "post-interprofessional conference introduction" group (after group). The ICU LOS (regression coefficient: -0.08; 95% confidence interval [CI]: -0.13 to -0.04) and hospital LOS (regression coefficient: -2.96; 95% CI: -5.20 to -0.72) were significantly shorter in the after group. Moreover, the proportion of patients who commenced nutrition (odds ratio [OR]: 1.45; 95% CI: 1.14 to 1.84) and rehabilitation (OR: 0.77; 95% CI: 0.51 to 1.17) within 48 hours of ICU admission was significantly higher in the after group. Conclusions: Introduction of interprofessional conferences effectively reduced ICU and hospital LOSs and improved likelihood of commencing nutrition and rehabilitation within 48 hours of ICU admission.