Pharmacist-initiated interventions to test quantitative bone mineral density and prescribe osteoporosis medications to prevent steroid-induced osteoporosis.

Fragility fractures associated with glucocorticoid-induced osteoporosis (GIO) can markedly impair quality of life. However, only 20% of patients are treated in compliance with the relevant management guidelines, and bone mineral density analysis with dual-energy X-ray absorptiometry (DXA) is only rarely performed. We report the intervention methods suggested by pharmacists and describe their efficacy. Patients who visited the outpatient clinic of the General Medicine Department of Ogaki Municipal Hospital and received steroids were enrolled. The rates of DXA implementation and compliance with GIO pharmacotherapy guidelines before and after pharmacist to physician-suggested interventions were compared. Guideline compliance was defined as prescription of osteoporosis drugs to patients with a score of ≥3. Administered prophylaxes and bone mineral density were subsequently assessed. The before and after intervention DXA rates were 1% (1/100 patients) and 96.0% (96/100 patients; P<0.01), respectively. Overall, 96.9% (93/96) of the patients met the GIO criteria for pharmacotherapy initiation (score ≥3), and the guideline compliance rates before and after the intervention were 39.8% (37/93) and 93.5% (87/93; P<0.01), respectively. Of the 56 patients who did not receive prophylaxis, 52 were recommended treatment, yielding an acceptance rate of 82.7% (43/52). Among the 37 patients receiving prophylaxis, 20 (54.1%) had a DXA-related young adult mean of ≤70%, of whom 11 (55.0%) agreed to drug therapy. The acceptance rate of pharmacotherapy recommendations for patients not receiving prophylaxis was higher than that for those receiving prophylaxis (P=0.03). Pharmacist-initiated interventions for GIO facilitates the administration of appropriate pharmacotherapy.

A phase II trial of paclitaxel plus biweekly cetuximab for patients with recurrent or metastatic head and neck cancer previously treated with both platinum-based chemotherapy and anti-PD-1 antibody.

BACKGROUND: An important unmet need for new treatment options remains for patients with recurrent or metastatic head and neck squamous cell carcinoma (R/M-HNSCC) previously treated with both platinum-based chemotherapy and anti-programmed cell death protein 1 (PD-1) antibody. Retrospective studies suggest that previous treatment with immune checkpoint inhibitor might augment the efficacy of subsequent chemotherapy. Here, we conducted a phase II trial aimed to evaluate the efficacy and safety of paclitaxel plus biweekly cetuximab for patients in this setting. PATIENTS AND METHODS: This was a single-arm, multicenter, phase II trial. Key eligibility criteria were R/M-HNSCC, and previous treatment with both platinum-based chemotherapy and PD-1 antibody. Paclitaxel plus biweekly cetuximab consisted of weekly paclitaxel 100 mg/m2 (days 1, 8, 15) and biweekly cetuximab 500 mg/m2 (days 1, 15) with a cycle of 28 days until progression or unacceptable toxicity. Primary endpoint was objective response rate (ORR). Secondary endpoints included progression-free survival (PFS), overall survival (OS), disease control rate (DCR), and adverse events (AEs) (Common Terminology Criteria for Adverse Events version 5.0). RESULTS: Between August 2020 and August 2022, 35 patients were enrolled, of whom 33 were assessable for response. ORR was 69.6% (95% confidence interval 51.2% to 84.4%). With a median follow-up period for survivors of 16.6 months, median PFS and OS were 5.5 and 13.3 months, respectively. DCR was 93.7%. Twenty-three patients (65%) experienced grade 3 or 4 AEs, including neutropenia (34%), infection (14%), leukopenia (11%), mucositis (8%), and pneumonitis (8%). Eight patients discontinued study treatment due to treatment-related AEs, and no treatment-related death was observed. CONCLUSIONS: Paclitaxel plus biweekly cetuximab showed highly encouraging efficacy and manageable toxicities in R/M-HNSCC patients previously treated with both platinum-based chemotherapy and PD-1 antibody. This combination therapy warrants further investigation in this setting.

Amivantamab plus lazertinib versus osimertinib in first-line EGFR-mutant advanced non-small-cell lung cancer with biomarkers of high-risk disease: a secondary analysis from MARIPOSA.

BACKGROUND: Amivantamab-lazertinib significantly prolonged progression-free survival (PFS) versus osimertinib in patients with epidermal growth factor receptor (EGFR)-mutant advanced non-small-cell lung cancer [NSCLC; hazard ratio (HR) 0.70; P < 0.001], including those with a history of brain metastases (HR 0.69). Patients with TP53 co-mutations, detectable circulating tumor DNA (ctDNA), baseline liver metastases, and those without ctDNA clearance on treatment have poor prognoses. We evaluated outcomes in these high-risk subgroups. PATIENTS AND METHODS: This analysis included patients with treatment-naive, EGFR-mutant advanced NSCLC randomized to amivantamab-lazertinib (n = 429) or osimertinib (n = 429) in MARIPOSA. Pathogenic alterations were identified by next-generation sequencing (NGS) of baseline blood ctDNA with Guardant360 CDx. Ex19del and L858R ctDNA in blood was analyzed at baseline and cycle 3 day 1 (C3D1) with Biodesix droplet digital polymerase chain reaction (ddPCR). RESULTS: Baseline ctDNA for NGS of pathogenic alterations was available for 636 patients (amivantamab-lazertinib, n = 320; osimertinib, n = 316). Amivantamab-lazertinib improved median PFS (mPFS) versus osimertinib for patients with TP53 co-mutations {18.2 versus 12.9 months; HR 0.65 [95% confidence interval (CI) 0.48-0.87]; P = 0.003} and for patients with wild-type TP53 [22.1 versus 19.9 months; HR 0.75 (95% CI 0.52-1.07)]. In patients with EGFR-mutant, ddPCR-detectable baseline ctDNA, amivantamab-lazertinib significantly prolonged mPFS versus osimertinib [20.3 versus 14.8 months; HR 0.68 (95% CI 0.53-0.86); P = 0.002]. Amivantamab-lazertinib significantly improved mPFS versus osimertinib in patients without ctDNA clearance at C3D1 [16.5 versus 9.1 months; HR 0.49 (95% CI 0.27-0.87); P = 0.015] and with clearance [24.0 versus 16.5 months; HR 0.64 (95% CI 0.48-0.87); P = 0.004]. Amivantamab-lazertinib significantly prolonged mPFS versus osimertinib among randomized patients with [18.2 versus 11.0 months; HR 0.58 (95% CI 0.37-0.91); P = 0.017] and without baseline liver metastases [24.0 versus 18.3 months; HR 0.74 (95% CI 0.60-0.91); P = 0.004]. CONCLUSIONS: Amivantamab-lazertinib effectively overcomes the effect of high-risk features and represents a promising new standard of care for patients with EGFR-mutant advanced NSCLC.

Translational insights and overall survival in the U31402-A-U102 study of patritumab deruxtecan (HER3-DXd) in EGFR-mutated NSCLC.

BACKGROUND: Human epidermal growth factor receptor 3 (HER3) is broadly expressed in non-small-cell lung cancer (NSCLC) and is the target of patritumab deruxtecan (HER3-DXd), an antibody-drug conjugate consisting of a HER3 antibody attached to a topoisomerase I inhibitor payload via a tetrapeptide-based cleavable linker. U31402-A-U102 is an ongoing phase I study of HER3-DXd in patients with advanced NSCLC. Patients with epidermal growth factor receptor (EGFR)-mutated NSCLC that progressed after EGFR tyrosine kinase inhibitor (TKI) and platinum-based chemotherapy (PBC) who received HER3-DXd 5.6 mg/kg intravenously once every 3 weeks had a confirmed objective response rate (cORR) of 39%. We present median overall survival (OS) with extended follow-up in a larger population of patients with EGFR-mutated NSCLC and an exploratory analysis in those with acquired genomic alterations potentially associated with resistance to HER3-DXd. PATIENTS AND METHODS: Safety was assessed in patients with EGFR-mutated NSCLC previously treated with EGFR TKI who received HER3-DXd 5.6 mg/kg; efficacy was assessed in those who also had prior PBC. RESULTS: In the safety population (N = 102), median treatment duration was 5.5 (range 0.7-27.5) months. Grade ≥3 adverse events occurred in 76.5% of patients; the overall safety profile was consistent with previous reports. In 78/102 patients who had prior third-generation EGFR TKI and PBC, cORR by blinded independent central review (as per RECIST v1.1) was 41.0% [95% confidence interval (CI) 30.0% to 52.7%], median progression-free survival was 6.4 (95% CI 4.4-10.8) months, and median OS was 16.2 (95% CI 11.2-21.9) months. Patients had diverse mechanisms of EGFR TKI resistance at baseline. At tumor progression, acquired mutations in ERBB3 and TOP1 that might confer resistance to HER3-DXd were identified. CONCLUSIONS: In patients with EGFR-mutated NSCLC after EGFR TKI and PBC, HER3-DXd treatment was associated with a clinically meaningful OS. The tumor biomarker characterization comprised the first description of potential mechanisms of resistance to HER3-DXd therapy.

Comprehensive validation of early diagnostic algorithms for myocardial infarction in the emergency department.

OBJECTIVE: To comprehensively evaluate diagnostic algorithms for myocardial infarction using a high-sensitivity cardiac troponin I (hs-cTnI) assay. PATIENTS AND METHODS: We prospectively enrolled patients with suspected myocardial infarction without ST-segment elevation from nine emergency departments in Japan. The diagnostic algorithms evaluated: (i) based on hs-cTnI alone, such as the European Society of Cardiology (ESC) 0/1-h or 0/2-h and High-STEACS pathways; or (ii) used medical history and physical findings, such as the ADAPT, EDACS, HEART, and GRACE pathways. We evaluated the negative predictive value (NPV), sensitivity as safety measures, and proportion of patients classified as low or high-risk as an efficiency measure for a primary outcome of type 1 myocardial infarction or cardiac death within 30 days. RESULTS: We included 437 patients, and the hs-cTnI was collected at 0 and 1 hours in 407 patients and at 0 and 2 hours in 394. The primary outcome occurred in 8.1% (33/407) and 6.9% (27/394) of patients, respectively. All the algorithms classified low-risk patients without missing those with the primary outcome, except for the GRACE pathway. The hs-cTnI-based algorithms classified more patients as low-risk: the ESC 0/1-h 45.7%; the ESC 0/2-h 50.5%; the High-STEACS pathway 68.5%, than those using history and physical findings (15-30%). The High-STEACS pathway ruled out more patients (20.5%) by hs-cTnI measurement at 0 hours than the ESC 0/1-h and 0/2-h algorithms (7.4%). CONCLUSIONS: The hs-cTnI algorithms, especially the High-STEACS pathway, had excellent safety performance for the early diagnosis of myocardial infarction and offered the greatest improvement in efficiency.

Gastric functional monitoring by gastric electrical impedance tomography (gEIT) suit with dual-step fuzzy clustering.

Gastric Function has been successfully estimated by gastric electrical impedance tomography (gEIT) Suit with dual-step fuzzy clustering. The gEIT Suit which are made of elastic cloth with dual-planar electrodes and compact data acquisition (DAQ) system measures gastric impedance Z to visualize the gastric conductivity distribution σ. The dual-step fuzzy clustering extracts the clustered gastric conductivity distribution kσ, which accurately estimates the gastric function. The gEIT Suit with dual-step fuzzy clustering are applied to eight healthy persons during liquid meal consumption to estimate the gastric function under gastric accommodation phase of 200, 400 and 600 mL based on the gastric emptying phase. As the results, the gEIT Suit successfully estimate the gastric function. By the measured impedance Z, the subjects have a mean temporal impedance [Formula: see text]= - 9.27 [Ohm] and p-value of that [Formula: see text] p(Z) = 0.0013[-]as the t-test result. In the case of gastric conductivity distribution σ, the subjects have a value of spatial mean conductivity distribution ⟨σ⟩ = 0.23[-] and p-value of that ⟨σ⟩ p(σ) = 0.0140[-]. Lastly, in the case gastric volume V, subjects have a gastric volume V = 12.44 [%] and p-value p(V) = 0.0664[-].

Expression of Vincristin-induced Peripheral Neuropathy Related to Different Administration Methods.

Vincristine (VCR) is an important drug used in R-CHOP regimens for the treatment of non-Hodgkin's lymphoma. The purpose of this study was to examine whether the administration method affects the incidence of VCR-induced peripheral neuropathy. We investigated the ratio of VCR-induced peripheral neuropathy during rapid intravenous infusion and intravenous drip infusion. A total of 71 patients who had received six or more courses of R-CHOP from January, 2015 to December, 2016 at Komaki City Hospital and Ogaki Municipal Hospital were retrospectively investigated. Peripheral neuropathy was observed in 27/39 patients (69 %) and 24/32 (75 %) in rapid intravenous infusion and intravenous drip infusion of VCR, respectively (P = 0.79). Peripheral neuropathy was observed at a high frequency in this study. Additionally, there was no difference in frequency of peripheral neuropathy due to the difference in administration method. In both groups, the degree of peripheral neuropathy was grade 1 and grade 2 in most patients. However, in rapid intravenous infusion, grade 3 peripheral neuropathy was observed. Some cases required dose reduction and discontinuation in rapid intravenous infusion. In contrast, there were no discontinuing patients in the intravenous drip infusion. Therefore, it was suggested that intravenous drip infusion of VCR reduced serious peripheral neuropathy because the ratio requiring dose reduction and discontinuation was less than that in the rapid group. In conclusion, this study is informative as there are few reports focusing on the administration method of vincristine.

Correlation between magnesium pre-loading and cisplatin-induced nephrotoxicity in 5-fluorouracil/cisplatin combination therapy for esophageal cancer.

The use of cisplatin may cause nephrotoxicity in patients. Hydration solutions supplemented with magnesium could reduce cisplatin-induced nephrotoxicity. In this study, we evaluated the preventive effect of magnesium pre-loading on cisplatin-induced nephrotoxicity in patients with esophageal cancer. We retrospectively evaluated the prevalence of, and risk factors for, nephrotoxicity in 160 patients with esophageal cancer treated with the 5-fluorouracil/cisplatin regimen from 2014 to 2016 with and without magnesium supplementation. Significant differences were observed between the magnesium and non-magnesium groups in terms of frequency of estimated creatinine clearance of grade 2 or higher that was at 4% (n = 3) and 13% (n = 10) (p = 0.027), respectively. The logistic regression analysis revealed that eCcr of grade 2 or higher was significantly associated with the non-magnesium regimen (odds ratio (OR), 4.175; 95% confidence interval (CI) = 1.061-16.430; p = 0.041) and age ≥ 65 years (OR, 13.951; 95% CI = 1.723-112.974; p = 0.014). This study suggests that 20 mEq magnesium pre-loading significantly reduces the prevalence of cisplatin-induced nephrotoxicity. Furthermore, when cisplatin is administered to individuals older than 64 years, a close observation for the onset of cisplatin-induced nephrotoxicity is crucial.

Open-label phase II study of the efficacy of nivolumab for cancer of unknown primary.

BACKGROUND: Cancer of unknown primary (CUP) has a poor prognosis. Given the recent approval of immune checkpoint inhibitors for several cancer types, we carried out a multicenter phase II study to assess the efficacy of nivolumab for patients with CUP. PATIENTS AND METHODS: Patients with CUP who were previously treated with at least one line of systemic chemotherapy constituted the principal study population. Previously untreated patients with CUP were also enrolled for exploratory analysis. Nivolumab (240 mg/body) was administered every 2 weeks for up to 52 cycles. The primary endpoint was objective response rate in previously treated patients as determined by blinded independent central review according to RECIST version 1.1. RESULTS: Fifty-six patients with CUP were enrolled in the trial. For the 45 previously treated patients, objective response rate was 22.2% [95% confidence interval (CI), 11.2% to 37.1%], with a median progression-free survival and overall survival of 4.0 months (95% CI, 1.9-5.8 months) and 15.9 months (95% CI, 8.4-21.5 months), respectively. Similar clinical benefits were also observed in the 11 previously untreated patients. Better clinical efficacy of nivolumab was apparent for tumors with a higher programmed death-ligand 1 expression level, for those with a higher tumor mutation burden, and for microsatellite instability-high tumors. In contrast, no differences in efficacy were apparent between tumor subgroups based on estimated tissue of origin. Adverse events were consistent with the known safety profile of nivolumab. No treatment-related death was observed. CONCLUSIONS: Our results demonstrate a clinical benefit of nivolumab for patients with CUP, suggesting that nivolumab is a potential additional therapeutic option for CUP.

Association between Decreased Social Participation and Depressive Symptom Onset among Community-Dwelling Older Adults: A Longitudinal Study during the COVID-19 Pandemic.

OBJECTIVES: The coronavirus disease (COVID-19) pandemic has imposed restrictions on people's social behavior. However, there is limited evidence regarding the relationship between changes in social participation and depressive symptom onset among older adults during the pandemic. We examined the association between changes in social participation and the onset of depressive symptoms among community-dwelling older adults during the COVID-19 pandemic. DESIGN: This was a longitudinal study. SETTING: Communities in Minokamo City, a semi-urban area in Japan. PARTICIPANTS: We recruited community-dwelling older adults aged ≥ 65 years using random sampling. Participants completed a questionnaire survey at baseline (March 2020) and follow-up (October 2020). MEASUREMENTS: Depressive symptoms were assessed using the Two-Question Screen. Based on their social participation status in March and October 2020, participants were classified into four groups: "continued participation," "decreased participation," "increased participation," and "consistent non-participation." RESULTS: A total of 597 older adults without depressive symptoms at baseline were analyzed (mean age = 79.8 years; 50.4% females). Depressive symptoms occurred in 20.1% of the participants during the observation period. Multivariable Poisson regression analysis showed that decreased social participation was significantly associated with the onset of the depressive symptoms, compared to continued participation, after adjusting for all covariates (incidence rate ratio = 1.59, 95% confidence interval = 1.01-2.50, p = 0.045). CONCLUSION: Older adults with decreased social participation during the COVID-19 pandemic demonstrated a high risk of developing depressive symptoms. We recommend that resuming community activities and promoting the participation of older adults, with sufficient consideration for infection prevention, are needed to maintain mental health among older adults.

Hepatocellular uptake index obtained with gadoxetate disodium-enhanced magnetic resonance imaging in the assessment future liver remnant function after major hepatectomy for biliary malignancy.

BACKGROUND: Functional assessment of the future liver remnant (FLR) after major hepatectomy is essential but often difficult in patients with biliary malignancy, owing to obstructive jaundice and portal vein embolization. This study evaluated whether a novel index using gadoxetate disodium-enhanced MRI (EOB-MRI) could predict posthepatectomy liver failure (PHLF) after major hepatectomy for biliary malignancy. METHODS: The remnant hepatocellular uptake index (rHUI) was calculated in patients undergoing EOB-MRI before major hepatectomy for biliary malignancy. Receiver operating characteristic (ROC) curve analyses were used to evaluate the accuracy of rHUI for predicting PHLF grade B or C, according to International Study Group of Liver Surgery criteria. Multivariable logistic regression analyses comprised stepwise selection of parameters, including rHUI and other conventional indices. RESULTS: This study included 67 patients. The rHUI accurately predicted PHLF (area under the curve (AUC) 0.896). A cut-off value for rHUI of less than 0.410 predicted all patients who developed grade B or C PHLF. In multivariable analysis, only rHUI was an independent risk factor for grade B or C PHLF (odds ratio 2.0 × 103, 95 per cent c.i. 19.6 to 3.8 × 107; P < 0.001). In patients who underwent preoperative portal vein embolization, rHUI accurately predicted PHLF (AUC 0.885), whereas other conventional indices, such as the plasma disappearance rate of indocyanine green of the FLR and FLR volume, did not. CONCLUSION: The rHUI is potentially a useful predictor of PHLF after major hepatectomy for biliary malignancy.

Messenger RNA expression and localization of xenin in the gastrointestinal tract in sheep.

The present study aimed to determine the primary sequence of ovine xenin and clarify the mRNA expression and peptide localization of xenin in the gastrointestinal tract in sheep. The colocalization of xenin and glucose-dependent insulinotropic polypeptide was also compared in the antrum and duodenum. Analysis of the nucleotide sequence of ovine xenin revealed a high degree (97.9%) of sequence homology of the sequence between sheep and cattle, and the amino acids sequence determined for ovine xenin coincided (100%) with that of other mammalian species. Real-time quantitative PCR for ovine xenin did not show regional difference in the mRNA expression ratio of xenin. In contrast to the real-time quantitative PCR results, anti-xenin positive cells were abundantly localized in the abomasal antrum (P < 0.01) and at a lesser amount in the duodenum, but no antixenin positive cells were observed in the other regions. Anti-xenin single-positive cells were in a majority in the abomasal antrum, whereas anti-xenin single-positive cells, and anti-GIP single-positive cells, and double-positive cells were even colocalized in the duodenum. These results suggest that abomasal antrum is a major source of xenin in the ovine gastrointestinal tract.

Effect of therapeutic plasma exchange on phenytoin plasma concentration in patients receiving intravenous fosphenytoin therapy.

We report for patients with encephalitis treated with plasma exchange (PE) and fosphenytoin. In patient 1, phenytoin levels decreased on the maintenance dose, and the phenytoin concentration was <10 µg/mL on day 12 of administration. In patient 2, the phenytoin levels was <10 µg/mL on day 4. Increasing the fosphenytoin dose pushed the phenytoin level into therapeutic range. There were no differences between the areas under the concentration-time curve of phenytoin with and without PE. We previously reported a decline in phenytoin levels after prolonged use of fosphenytoin. Therefore, dose adjustment of fosphenytoin in patients undergoing PE may be unnecessary.

Histopathological study of carcinoma showing thymus-like differentiation (CASTLE).

INTRODUCTION: Carcinoma showing thymus-like differentiation (CASTLE) is a rare tumour that mainly arises from the thyroid gland, or occasionally, from the head and neck. Although the 10-year survival rate of patients with CASTLE is approximately 80%, local recurrence and distant metastasis are observed in some cases. A recent systematic review for CASTLE indicated that the prognostic factors are treatment-dependent, and postoperative radiotherapy significantly improves patient survival. CASE REPORT: Herein, we describe and compare three cases of CASTLE, including a case with distant metastasis despite administering postoperative chemotherapy. Thus, the mechanisms underlying metastasis of CASTLE are unclear. This case study helps to elucidate the histopathological risk factors of metastasis in CASTLE. DISCUSSION: We found that prominent lymphovascular invasion and higher proliferative activities might be risk factors of metastasis in CASTLE. In addition, we have summarised the cytological, morphological, and immunohistochemical features of CASTLE for an accurate diagnosis.

Histamine-2 receptor antagonists (H2RA) may negatively impact ADL assessment in patients on a convalescent rehabilitation ward.

Background/aim: In the convalescent rehabilitation ward, many elderly patients undergo rehabilitation. Histamine-2 receptor antagonists (H2RA), which is a one of the acid secretion inhibitors, is frequently prescribed for the patients as a peptic ulcer prevention measure. At present, H2RA are reported as being associated with factors that reduce cognitive function. However, little is known about the relationship H2RA and rehabilitation outcome. Therefore, this study examined the relationship between H2RA use and Functional Independence Measure (FIM) gain, which determines rehabilitation outcomes for patients admitted to the convalescent rehabilitation ward. Patients and methods: We retrospectively investigated FIM gain on discharge by both the administration group (H2RA (+)) (n = 118) and non-administration group (H2RA (-)) (n = 118). Results: The FIM gain scores of Motor FIM total, Cognition FIM total, and Total FIM were significantly lower in H2RA (+) than in H2RA (-) (Motor FIM total: 8.0 [4.0-16.0] [Inter-Quartile Range] vs. 12.0 [5.0-19.2], p =0.0217, Cognition FIM total: 3.0 [1.0-6.0] vs. 5.0 [2.0-7.0], p =0.0120, Total FIM: 11.5 [4.8-20.2] vs. 17.0 [8.0-27.0], p =0.0089). Conclusion: The administration of H2RA to elderly patients undergoing rehabilitation may prevent cognitive function maintenance or recovery by rehabilitation.