Safety of a short-term infusion of fosnetupitant in patients with gastrointestinal and breast cancer: a prospective study.

BACKGROUND: Fosnetupitant, a neurokinin-1 receptor antagonist, is used to prevent chemotherapy-induced nausea and vomiting (CINV) in patients undergoing highly emetogenic chemotherapy (HEC) or moderately emetogenic chemotherapy (MEC). Previous phase III trials demonstrated the non-inferiority of its 30-minute infusion to fosaprepitant in efficacy and a favorable safety profile. METHODS: This was a single-arm, phase II study to investigate the safety of a 15-minute infusion of fosnetupitant in patients with gastrointestinal and breast cancer. Patients who had received their dose of fosnetupitant in a 30-minute infusion without developing an allergic reaction were eligible and received their next fosnetupitant dose for 15 minutes. The primary endpoint was the incidence of an allergic reaction during the first 15-minutes infusion, and the secondary endpoints were the incidence of injection site reaction (ISR), the incidence of a grade ≥ 3 treatment-related adverse event (TRAE) with fosnetupitant, and complete response (CR) rate. RESULTS: The study period was from February 17, 2023 to June 20, 2023. In an exploratory analysis, medical records from the end of the study period to December 31, 2023 were retrospectively evaluated to assess the time-saving effect and safety of the short-term infusion of fosnetupitant. Fifty-six patients with gastrointestinal and 14 patients with breast cancer were enrolled, one of whom with breast cancer did not receive study treatment at her own request. No allergic reactions occurred during the 15-minutes infusion. Furthermore, there were no allergic reactions across all 280 short-term injections (Table 1). Additionally, no ISR or grade 3 or higher TRAE were reported. The CR rate was 87.0%. CONCLUSION: Short-term infusion of fosnetupitant, administered over 15 minutes, was demonstrated to be safe and effective for patients receiving HEC or MEC (Japan Registry of Clinical Trials Trial ID: jRCT1041220144).

Clinical outcomes of patients diagnosed with cancer of unknown primary or malignancy of undefined primary origin who were referred to a regional cancer center.

BACKGROUND: A regional cancer hospital has been identified to be crucial in the management of malignancies of undefined primary origin (MUO) and cancer of unknown primary (CUP). This hospital primarily consists of oncologists with expertise in CUP, pathologists, and interventional radiologists. Early consultation or referral of MUO and CUP to a cancer hospital is deemed important. METHODS: This study retrospectively collected and analyzed the clinical, pathological, and outcome data of all patients (n = 407) referred to the Aichi Cancer Center Hospital (ACCH) in Japan over an 8-year period. RESULTS: In total, 30% of patients were referred for a second opinion. Among 285 patients, 13% had non-neoplastic disease or confirmed primary site and 76% had confirmed CUP (cCUP), with 29% of cCUP being identified as favorable risk. In 155 patients with unfavorable-risk CUP, 73% had primary sites predicted by immunohistochemistry (IHC) and distribution of metastatic sites, whereas 66% of them received site-specific therapies based on the predicted primary sites. The median overall survival (OS) was found to be poor in patients with MUO (1 month) and provisional CUP (6 months). In addition, the median OS of 206 patients with cCUP treated at the ACCH was 16 months (favorable risk, 27 months; unfavorable risk, 12 months). No significant difference was noted in OS between patients with non-predictable and predictable primary-sites (13 vs 12 months, p = 0.411). CONCLUSION: The outcome of patients with unfavorable-risk CUP remains to be poor. Site-specific therapy based on IHC is not recommended for all patients with unfavorable-risk CUP.

The relationship between chronic kidney disease and denosumab-induced hypocalcemia in high-age osteoporotic patients.

PURPOSE: A few studies have reported the safety of the treatment of elderly osteoporotic patients with chronic kidney disease (CKD) and the possibility of hypocalcemia. The aim of the present study was to examine the relationship between the incidence of hypocalcemia and the CKD stage in elderly osteoporotic patients treated with denosumab. MATERIALS AND METHODS: This study was designed as a parallel-group comparison study between the denosumab-associated hypocalcemia (DAH) groups: the concentration of serum calcium was under 8.6 mg/dl and the normal calcium (NC) groups: the concentration of serum calcium was over 8.6 mg/dl. Fifty-two subjects over 70 years old were enrolled in this study, with 16 patients classified into the DAH group and 36 patients assigned to the NC group. All patients were further classified into two subgroups according to their age, into an around 75 years group to clarify the relevance of old age and an around 85 years group and also into a mild CKD group and a moderate CKD group by based on estimated glomerular filtration (eGFR). Serum calcium concentration, tartrate-resistant acid phosphatase (TRACP-5b), and type 1 procollagen N terminal propeptide (P1NP) were measured, and adverse drug reactions were evaluated. RESULTS: The eGFR and serum calcium were significantly lower in the DAH group than in the NC group in the starting phase. Moreover, TRACP-5b was significantly higher in the DAH group than in the NC group in the starting phase. There were no significant differences in P1NP. The incidence of hypocalcemia was significantly higher in the around 85 groups than in the around 75 groups. The frequency of hypocalcemia was also significantly higher in the severe CKD group than in the mild CKD group. CONCLUSION: Advanced age combined with low eGFR and low serum Ca status appear to be associated with the incidence of hypocalcemia when using denosumab for the treatment of osteoporosis.

[Regorafenib versus S-1 plus Bevacizumab for Metastatic Colorectal Cancer as Salvage Line-A Phase â ¡ Study (OGSG1301)].

BACKGROUND: Regorafenib(Rego)is the salvage line standard treatment for metastatic colorectal cancer(mCRC), which often causes severe toxicities, such as hand-foot syndrome. Previously, we reported that in phase Ⅱ study, S-1 plus bevacizumab( Bev)(SB)showed favorable anticancer activity and feasibility as a salvage line. The aim of this study was to evaluate 2 treatments for mCRC as salvage line. PATIENTS AND METHODS: In this multicenter phase Ⅱ study, the patients were randomly assigned(1:1)to the Rego or SB group. In the Rego group, Rego 160 mg/kg body weight was orally administered every 28 days for 21 days. In the SB group, S-1 was orally administered every 42 days for 28 days, according to body surface area, and Bev 5 mg/kg was administered by intravenous infusion on days 1, 15, and 29. Administration of S-1 every 21 days for 14 days and Bev 7.5 mg/kg on day 1 was also permitted. The primary endpoint was overall survival(OS), and the planned sample size was 86. RESULTS: This study was ended prematurely due to poor accrual. Overall, 8 patients were enrolled from 6 institutions between Oct 2013 and May 2015. Although 4 patients were assigned to each group, one patient in the Rego group was excluded after enrollment. The median OS in the Rego and SB groups was 30.2 months and 6.6 months, respectively(hazard ratio: 0.205, p=0.123). The median progression-free survival in the Rego and SB groups was 3.7 months and 1.6 months, respectively. The disease control rate in the Rego and SB groups was 100% and 75%, respectively. The Grade 3 or 4 adverse events were increased, including AST/ALT(n=1, 25%), hyponatremia(n=1, 25%), hand-foot syndrome(n=1, 25%), hypertension(n=1, 25%), and proteinuria(n=1, 25%)in the Rego group and colitis( n=1, 25%)in the SB group; the treatment was discontinued. CONCLUSION: Despite the fact that data could only be collected from a small number of patients, SB is not recommended as salvage line for mCRC.

[A Case of Remnant Gastric Cancer Occurring 12 Years after Surgery That Was Successfully Treated with Radiation Therapy].

A 59-year-old woman had a history of distal gastrectomy and D2 dissection in May 200X for advanced gastric cancer(GC) in the antrum area. The pathological stage was poorly differentiated, T2(SS), N2, H0, P0, CY0, M0, pStage ⅢA. After administration of S-1 for 1 year as adjuvant chemotherapy, the patient underwent surveillance with no recurrence. However, remnant GC was diagnosed in April 200X+12. Considering that there was no indication for curative resection due to severe invasion of the proper hepatic artery, gastrojejunostomy was performed for the anastomotic stenosis. Although the patient was administered 3 courses of S-1 plus oxaliplatin therapy as first-line treatment, partial response was not achieved. Therefore, chemoradiotherapy(CRT)with capecitabine was administered for local tumor control. Complete response was achieved, and the patient underwent surveillance with no recurrence 16 months after the recurrence. There were no serious acute adverse events(AEs)during CRT and late AEs after CRT. The patient was successfully treated with CRT for locally advanced remnant GC. Although there is no standard treatment for locally advanced remnant GC, this case showed the effectiveness of CRT.

Magnetic Hyperthermia Using Self-Controlled Heating Elements Consisting of Fe-Al Milling Alloy Induces Cancer Cell Apoptosis while Preserving Skeletal Muscle.

Necrosis-inducing anticancer drugs enhance high-mobility group box 1 (HMGB1) release during cell necrosis, and HMGB1-induced autophagy in skeletal muscle induces muscle atrophy. We evaluated the efficacy of magnetic hyperthermia therapy (MHT) using a low-energy magnetic field and self-controlled heating elements in tumor treatment. MHT-induced apoptosis by heating mouse subcutaneous tumors at 43°C using a heat-controlling iron-aluminum (Fe-Al) milling alloy. In contrast, MHT using Fe line-induced necrosis by heating to approximately 100°C. Furthermore, MHT with Fe-Al milling alloy reduced stemness. In hyperthermia using age line or Fe-Al milling alloy, both of them provided histological degeneration in skeletal muscle; however, qualitative differences were observed. MHT using Fe-line induced pronounced autophagy, decrease of myosin heavy chain content, and increase in serum HMGB1. In contrast, MHT using Fe-Al milling alloy induced heat shock protein 90 but no autophagy and decreased serum HMGB1. Therefore, MHT using Fe-Al milling alloy might be a good method for local treatment of tumors to reduce skeletal muscle atrophy.

Unmodulated 40 Hz Stimulation as a Therapeutic Strategy for Aging: Improvements in Metabolism, Frailty, and Cognitive Function in Senescence-Accelerated Prone 10 Mice.

With aging populations in many countries, including Japan, efforts to mitigate the aging-related decline in physical function have gained importance not only for improving individual quality of life but also for mitigating the effects of this loss of function on society. Impaired glucose tolerance, muscle weakness, and cognitive decline are well-known effects of aging. These interrelated factors can create a vicious cycle because impaired glucose tolerance can accelerate muscle weakness and cognitive decline. Unmodulated 40 Hz (u40Hz) stimulation is imperceptible to the human ear and has been reported to improve cognitive function in humans and mice. However, research on the effects of u40Hz stimulation is still limited. This study aimed to report the effects of u40Hz stimulation on glucose tolerance and muscle strength in senescence-accelerated prone (SAMP)-10 mice, a model of accelerated aging. SAMP-10 mice underwent five weeks of u40Hz stimulation followed by glucose-tolerance tests, cognitive and behavioral assessments, and frailty evaluations. In comparison with the control group, the u40Hz-stimulation group showed mitigation of age-related decline in glucose tolerance, a better frailty index (FI), and notably preserved muscle strength. Microarray analysis of stimulated muscle tissue revealed significant upregulation of ß-oxidation genes and genes functioning downstream of peroxisome proliferator-activated receptor gamma, and significant downregulation of clock genes. These findings indicate the beneficial effects of u40Hz stimulation on glucose tolerance, muscle strength, and cognitive function, warranting further research in this area.

Trifluridine/tipiracil with and without ramucirumab for advanced gastric cancer: a comparative observational study.

The combination of trifluridine/tipiracil hydrochloride (FTD/TPI) plus ramucirumab has demonstrated clinical activity in patients with advanced gastric cancer (AGC). We evaluated the efficacy and safety of this combination compared with those of FTD/TPI monotherapy in patients with AGC. We retrospectively reviewed data of patients with AGC who received FTD/TPI plus ramucirumab or FTD/TPI monotherapy as third- or later-line treatment. This study included 36 patients treated with FTD/TPI plus ramucirumab and 70 patients receiving FTD/TPI monotherapy. The objective response rate (ORR) and disease control rate (DCR) were 25.8% and 58.1%, respectively, in the FTD/TPI plus ramucirumab group and 5.0% and 38.3%, respectively, in the FTD/TPI group (ORR, P = 0.007; DCR, P = 0.081). The median progression-free survival (PFS) was significantly longer in the FTD/TPI plus ramucirumab group (median PFS, 2.9 vs. 1.8 months; hazard ratio [HR]: 0.52; P = 0.001). A numerical survival benefit was also observed (median overall survival, 7.9 months vs. 5.0 months; HR: 0.68, P = 0.089). In the multivariate analysis, PFS was significantly longer in the FTD/TPI plus ramucirumab group than in the FTD/TPI monotherapy group (HR: 0.61, P = 0.030). The incidence of febrile neutropenia was higher in the FTD/TPI plus ramucirumab group than in the FTD/TPI group (13.8% vs. 2.9%); however, no new safety signals were identified. Compared with FTD/TPI monotherapy, FTD/TPI plus ramucirumab offers clinical benefits with acceptable toxicity in heavily pretreated patients with AGC. Further investigation via randomized trials is warranted to confirm these findings.

Chronological improvement of survival in patients with advanced gastric cancer over 15 years.

Background: Recent trials have reported a median overall survival (OS) of 11-17 months in patients with advanced gastric cancer (AGC). However, it is unclear how recently approved drugs contribute to patient prognosis. Objectives: We aimed to evaluate the characteristics and survival in patients with AGC over the past 15 years. Design: Retrospective study. Methods: We evaluated data of 1355 patients with AGC who received first-line chemotherapy between January 2005 and March 2019 at a single institution. We compared the characteristics and survival rates across four periods: January 2005-December 2007 (period A), January 2008-February 2011 (period B), March 2011-May 2015 (period C), and June 2015-March 2019 (period D). The median follow-up duration was 13.1 months, with 312, 333, 393, and 317 patients in periods A, B, C, and D, respectively. Results: There were no significant differences in patient characteristics between the four periods, except for the proportion of patients who underwent prior gastrectomy and human epidermal growth factor receptor 2 (HER2) testing. Patients in period D had significantly longer OS than those in period A [median: 15.7 versus 12.4 months; adjusted hazard ratio (aHR): 0.79; p = 0.02]. The mean OS in patients with liver metastasis (LM) in period D was remarkably longer than that in patients in period A (median: 19.3 versus 12.4 months; aHR: 0.61; p < 0.01), while that in patients with peritoneal metastasis showed limited improvement. Conclusion: Clinical strategy changes, including gastrectomy, HER2 testing, and approval of new drugs, may be associated with improved OS in patients with AGC. In the last 4 years, a remarkable improvement has been observed in patients with LM.

Safety and Efficacy of Gemcitabine Plus Cisplatin Against Recurrent/Metastatic Nasopharyngeal Carcinoma: A Retrospective Study.

BACKGROUND/AIM: Although gemcitabine plus cisplatin (GC) prolongs survival in patients with recurrent or metastatic nasopharyngeal carcinoma (R/M NPC) compared with fluorouracil plus cisplatin, no study has evaluated the efficacy and safety of GC in nonendemic regions, including Japan, yet. Therefore, we assessed the safety and efficacy of GC in Japanese patients with R/M NPC. PATIENTS AND METHODS: We retrospectively reviewed patients with R/M NPC who received GC treatment at the Aichi Cancer Center Hospital from January 2017 to March 2020. The main eligibility criteria were histologically confirmed NPC, Eastern Cooperative Oncology Group performance status (ECOG PS) of 0-2, and locally recurrent disease unsuitable for local treatment or metastatic disease. The regimen was administered every 3 weeks (gemcitabine, 1,000 mg/m2 on days 1 and 8; cisplatin, 80 mg/m2 on day 1). RESULTS: Fourteen patients (median age, 58 years) were included in the study. Two patients had an ECOG PS of 2 and 11 exhibited nonkeratinizing histology. Of the eight patients with measurable lesions, one exhibited complete response and seven exhibited partial response, with an objective response rate of 75%. Median progression-free survival and overall survival were 7.7 and 24.2 months, respectively. Common grade 3 or 4 adverse events included neutropenia (64%), thrombocytopenia (14%), and febrile neutropenia (14%). The median relative dose intensity of gemcitabine and cisplatin was 62% and 60%, respectively. No treatment-related deaths occurred. CONCLUSION: The GC regimen demonstrates promising activity and is tolerable in Japanese patients with R/M NPC.

Quantitative flow ratio versus fractional flow reserve for Heart Team decision-making in multivessel disease: the randomised, multicentre DECISION QFR trial.

BACKGROUND: Vessel-level physiological data derived from pressure wire measurements are one of the important determinant factors in the optimal revascularisation strategy for patients with multivessel disease (MVD). However, these may result in complications and a prolonged procedure time. AIMS: The feasibility of using the quantitative flow ratio (QFR), an angiography-derived fractional flow reserve (FFR), in Heart Team discussions to determine the optimal revascularisation strategy for patients with MVD was investigated. METHODS: Two Heart Teams were randomly assigned either QFR- or FFR-based data of the included patients. They then discussed the optimal revascularisation mode (percutaneous coronary intervention [PCI] or coronary artery bypass grafting [CABG]) for each patient and made treatment recommendations. The primary endpoint of the trial was the level of agreement between the treatment recommendations of both teams as assessed using Cohen's kappa. RESULTS: The trial included 248 patients with MVD from 10 study sites. Cohen's kappa in the recommended revascularisation modes between the QFR and FFR approaches was 0.73 [95% confidence interval {CI} : 0.62-0.83]. As for the revascularisation planning, agreements in the target vessels for PCI and CABG were substantial for both revascularisation modes (Cohen's kappa=0.72 [95% CI: 0.66-0.78] and 0.72 [95% CI: 0.66-0.78], respectively). The team assigned to the QFR approach provided consistent recommended revascularisation modes even after being made aware of the FFR data (Cohen's kappa=0.95 [95% CI:0.90-1.00]). CONCLUSIONS: QFR provided feasible physiological data in Heart Team discussions to determine the optimal revascularisation strategy for MVD. The QFR and FFR approaches agreed substantially in terms of treatment recommendations.

[Elderly Bochdalek hernia found out by intestinal obstruction].

A 78-year-old man, who had been pointed out elevation of the diaphragm by chest radiography, visited local physician complaining of abdominal pain and vomiting. He was referred to our hospital and was diagnosed as intestinal obstruction. The patient had neither respiratory symptoms nor findings of peritonitis. The radiography revealed intestinal gas with neveau formation in the left thorax. The computed tomography showed dilatation of the stomach and small intestine, and a diaphragmatic hernia was suspected. Although conservative treatment was started, radiographic and laboratory findings got worse on the 5th hospital day. The patient underwent surgery for a left diaphragmatic hernia with the intestinal obstruction. Diagnosis of Bochdalek hernia with hernia sac was established. The content of hernia was the perforated small intestine. Postoperative course was almost uneventful, and the patient was discharged on the 35th postoperative day without pyothorax. In treatment of adult Bochdalek hernia, early surgery is important because patients with incarceration or perforation often experience severe postoperative complication.

Differential Efficacy of Targeted Monoclonal Antibodies in Left-Sided Colon and Rectal Metastatic Cancers.

BACKGROUND: The recommended first-line chemotherapy for RAS/BRAF wild-type metastatic colorectal cancer (mCRC) is bevacizumab (BEV)-containing therapy for right-sided colon cancer (R) and antiepidermal growth factor receptor antibody (anti-EGFR)-containing therapy for left-sided colon cancer (L) or rectal cancer (RE). However, anatomical or biological heterogeneity reportedly exists between L and RE. Therefore, we aimed to compare the efficacies of anti-EGFR and BEV therapies for L and RE, respectively. METHODS: We retrospectively reviewed 265 patients with KRAS (RAS)/BRAF wild-type mCRC treated with fluoropyrimidine-based doublet chemotherapy plus anti-EGFR or BEV as the first-line treatment at a single institution. They were divided into 3 groups: R, L, and RE. Overall survival (OS), progression-free survival (PFS), objective response rate, and conversion surgery rate were analyzed. RESULTS: Forty-five patients had R (anti-EGFR/BEV: 6/39), 137 patients had L (45/92), and 83 patients had RE (25/58). In patients with R, both median (m) PFS and OS were superior with BEV therapy (mPFS, anti-EGFR vs. BEV: 8.7 vs. 13.0 months, hazard ratio [HR]: 3.90, P = .01; mOS, 17.1 vs. 33.9 months, HR: 1.54, P = .38). In patients with L, better mPFS and comparable mOS with anti-EGFR therapy were observed (mPFS, 20.0 vs. 13.4 months, HR: 0.68, P = .08; mOS, 44.8 vs. 36.0 months, HR: 0.87, P = .53), whereas, in patients with RE, comparable mPFS and worse mOS with anti-EGFR therapy were observed (mPFS, 17.2 vs. 17.8 months, HR: 1.08, P = .81; mOS, 29.1 vs. 42.2 months, HR: 1.53, P = .17). CONCLUSIONS: Efficacies of anti-EGFR and BEV therapies may differ between patients with L and RE.

Comparison of the Effects on Rib Fracture between the Traditional Japanese Medicine Jidabokuippo and Nonsteroidal Anti-Inflammatory Drugs: A Randomized Controlled Trial.

Jidabokuippo is a traditional Japanese medicine used for contusion-induced swelling and pain. This open multicenter randomized study was designed to compare the efficacies of jidabokuippo and nonsteroidal anti-inflammatory drugs (NSAIDs) in patients with rib fracture by analyzing the treatment duration. Our study involved 170 rib fracture patients capable of oral ingestion divided randomly into 2 groups: the jidabokuippo and NSAID groups. We compared the duration of treatment and healthcare expenditure between these 2 groups. Medication was continued in both groups until the visual analogue scale score decreased to less than 50% of the pretreatment score. We excluded the patients in whom medication was prematurely discontinued. We analyzed 81 patients belonging to the jidabokuippo and NSAIDs groups. No significant intergroup differences were observed in age, gender, severity (injury severity score), and presence/absence of underlying disease. The treatment duration was significantly shorter in the jidabokuippo group than in the NSAIDs group (P = 0.0003). Healthcare expenditure was significantly lower in the jidabokuippo group than in the NSAIDs group (P < 0.0001). Our results suggest that compared to NSAIDs, jidabokuippo can shorten the duration of treatment in patients with rib fracture and is a promising analgesic agent based on the medical economic viewpoint.

Inhibitory effects of secoiridoids from the roots of Gentiana straminea on stimulus-induced superoxide generation, phosphorylation and translocation of cytosolic compounds to plasma membrane in human neutrophils.

Gentiana straminea Maxim. has been used widely as a traditional Chinese medicine for the treatment of rheumarthritis, icterepatitis, constipation, pain and hypertension. Five secoiridoids, gentiopicroside (GTP), 6'-O-(2-hydroxy-3-O-ß-D-glucopyranosyl-benzoyl)-sweroside (HGBS), 6'-O-ß-D-glucosylgentiopicroside (GGTP), sweroside (SW) and swertiamarin (STM) were isolated from the roots of G. straminea. The effect of these secoiridoids on stimulus-induced superoxide generation in human neutrophils was assayed by measuring the reduction of ferricytochrome c. Tyrosyl or serine/threonine phosphorylation of neutrophil proteins, and translocation of the cytosolic compounds to the cell membrane were also investigated using specific monoclonal antibodies. The five secoiridoids used in the present experiment suppressed N-formyl-methionyl-leucyl-phenylalanine (fMLP)-induced superoxide generation in a concentration dependent manner. GTP and HGBS also suppressed phorbol 12-myristate 13-acetate (PMA) and arachidonic acid (AA)-induced superoxide generation. However, the other three secoiridoids showed no effect on PMA- and AA-induced superoxide generation. fMLP-, PMA- and AA-induced tyrosyl or serine/threonine phosphorylation and translocation of the cytosolic proteins to the cell membrane were suppressed in parallel with the suppression of the stimulus-induced superoxide generation.

Percutaneous aspiration embolectomy is beneficial for pulmonary thromboembolism in adult patients with Fontan circulation.

In patients with acute pulmonary thromboembolism (PTE), increased pulmonary vascular resistance (PVR) due to thrombus sometimes causes hemodynamic instability, requiring reperfusion therapy with drugs, surgery, or catheterization. In particular, patients with Fontan circulation, which is strongly affected by PVR, are prone to hemodynamic instability. Moreover, these patients sometimes have bleeding complications such as hemoptysis and intrathoracic adhesions, following multiple prior thoracotomies, making it difficult to choose pharmacotherapy. Percutaneous aspiration embolectomy (PAE) is a useful treatment option because it minimizes bleeding complications, is less invasive, and more rapid than surgery, and is easy to perform. Herein, we report two cases of Fontan patients having PTE treated with PAE. In Case 1, a 21-year-old man with a history of a Fontan procedure suddenly developed acute PTE, for which anticoagulants were administered immediately. However, his condition was refractory to treatment and he underwent PAE on the third day of illness. In Case 2, a 28-year-old woman with a history of Fontan procedure who had been on anticoagulants, developed acute PTE on the ninth postpartum day, and underwent PAE on the day of onset. In both cases, the respiratory condition improved, and re-treatment for PTE was not required. Learning objective: Fontan patients with acute pulmonary thromboembolism often require reperfusion therapy because they can easily become hemodynamically unstable due to increased pulmonary vascular resistance. For them, who often have adhesions following multiple prior thoracotomies and bleeding complications, percutaneous aspiration embolectomy may be effective as it has minimal bleeding risk and is minimally invasive, rapid, and straightforward.

A prospective analysis of concentration of 25-OHD between northern and southern district in Japan in year-round study.

Although osteoporotic patients have already been recognized as having a low-volume vitamin D status, the concentration of active vitamin D precursor has not been studied in detail. This trial aimed to clarify the concentration of 25-hydroxyvitamin D (25-OHD), which is a natural type of vitamin D and compare between 2 separate areas in Japan. To compare and clarify the concentration of 25-OHD between 2 separate areas, Japanese patients who were diagnosed as having osteoporosis based on bone mineral density were studied. We analyzed 2 different hospitals' patients whose residence is separated into a northern district (Akita city: north latitude 39" 43') and a southern district (Shizuoka city: north latitude 34" 58'). Both of them have completely different daylight hours. Three-hundred sixty eight patients (174 in Akita, 194 in Shizuoka) were enrolled in this trial to compare the differences of concentration of 25-OHD by Welch's t t-test. There were significant differences in the concentration of 25-OHD and age between them. Akita patients were significantly higher than that of Shizuoka patients despite Shizuoka having much daylight hours of Akita. In conclusion, there might be no relationship between the concentration of 25 OHD and exposure to sunlight.

Characteristics of the aortic root morphology in conotruncal anomaly of the congenital heart disease.

BACKGROUND: Aortopathy is a well-known feature of conotruncal anomalies, but it remains unknown whether valve-sparing aortic root replacement, such as the David procedure, is feasible in young patients with severe aortic regurgitation. We assessed the aortic valve complex and aortic root morphology in patients with conotruncal anomalies using echocardiography. Furthermore, we evaluated the relevant factors associated with aortopathy in this population. METHODS: A total of 172 adult patients with conotruncal anomalies were enrolled in this study. Dimensions of the aortic valve complex were measured at the level of the sinus of Valsalva (SV) and sinotubular junction (STJ). The geometric height (GH), effective height (EH), and coaptation length (CL) were also assessed to analyze the aortic valve complex in detail. RESULTS: Sixteen of 172 patients were excluded due to poor imaging; 105 patients with tetralogy of Fallot, 24 with double outlet right ventricle, and 27 with transposition of the great arteries totaling 156 patients (32+/-11 years old) were included in the analysis. The patients were divided into four groups: Group 1 (98 patients) had no dilatation of SV or STJ; Group 2 (32 patients) had dilated SV and STJ; Group 3 (14 patients) had dilated SV; and Group 4 (12 patients) had dilated STJ. GH and EH in Group 2 were also highest among the four, whereas CL was not significantly shortened. Multivariate analysis revealed that male sex, age, and conduit repair were risk factors for aortopathy in this population. CONCLUSIONS: Patients with dilated SV and STJ (Group 2) were the most common among the patients with aortopathy (Groups 2, 3, and 4). The aortic valve leaflets themselves were enlarged, and the poor coaptation of the valve tips was compensated in spite of aortic root dilatation, which plays an important role in preventing severe aortic regurgitation in this population. Overall, valve-sparing aortic valve replacement is more feasible in the young populations than we expected.

Heart Team risk assessment with angiography-derived fractional flow reserve determining the optimal revascularization strategy in patients with multivessel disease: Trial design and rationale for the DECISION QFR randomized trial.

In patients with multivessel disease (MVD), functional information on lesions improves the prognostic capability of the SYNTAX score. Quantitative flow ratio (QFR®) is an angiography-derived fractional flow reserve (FFR) that does not require a pressure wire or pharmacological hyperemia. We aimed to investigate the feasibility of QFR-based patient information in Heart Teams' discussions to determine the optimal revascularization strategy for patients with MVD. We hypothesized that there is an acceptable agreement between treatment recommendations based on the QFR approach and recommendation based on the FFR approach. The DECISION QFR study is a prospective, multicenter, randomized controlled trial that will include patients with MVD who require revascularization. Two Heart Teams comprising cardiologists and cardiac surgeons will be randomized to select a revascularization strategy (percutaneous coronary intervention or coronary artery bypass graft) according to patient information either based on QFR or on FFR. All 260 patients will be assessed by both teams with reference to the anatomical and functional SYNTAX score/SYNTAX score II 2020 derived from the allocated physiological index (QFR or FFR). The primary endpoint of the trial is the level of agreement between the treatment recommendations of both teams, assessed using Cohen's κ. As of March 2022, the patient enrollment has been completed and 230 patients have been discussed in both Heart Teams. The current trial will indicate the usefulness of QFR, which enables a wireless multivessel physiological interrogation, in the discussions of Heart Teams to determine the optimal revascularization strategy for MVD.

The Effects of Trends in Osteoporosis Treatment on the Incidence of Fractures.

OBJECTIVE: This study focused on the trends in antiosteoporosis drug preferences and compared the incidence of fractures between patients treated orally and those who were exposed to an awareness campaign and assigned to intravenous/subcutaneous treatment. METHODS: Our hospital registry included 1,716 osteoporotic women who were over 65 years of age without preexisting vertebral and nonvertebral fractures over 1 year before this study, with bone mineral density (BMD) < -2.5 standard deviation (SD) and fracture assessment tool (FRAX) score > 20%, who were given 1,337 oral and 379 intravenous/subcutaneous prescriptions to treat their osteoporosis. Self-administered surveys (2012, 2013, 2014, 2015, and 2016) collected data on trends of preferences among nine drugs and fracture prevention using relative risk reduction (RRR). RESULTS: The number of patients taking oral prescriptions decreased gradually from 2012 to 2016, while the number of patients treated with intravenous and subcutaneous injections increased. The incidence of fracture was lower in patients receiving intravenous and subcutaneous injections than in patients taking oral medications. CONCLUSION: These findings indicate a decrease in oral prescriptions for osteoporosis treatment and that treatment for osteoporosis using intravenous or subcutaneous injections of antiosteoporosis drugs is more effective for preventing fractures.