Controlled crystallisation of porous crystals of luminescent platinum(II) complexes by electronic tuning of ancillary ligands.

Porous molecular crystals (PMCs) have gained significant importance as next-generation functional porous materials. However, the selective crystallisation of the PMC phase remains a challenge. Herein, we have systematically controlled the stability of the luminescent PMC phase prepared using the luminescent Pt(II) complex [Pt(pbim)(N^O)] (pbim = 2-phenylbenzimidazolate, N^O = N-heteroaryl carboxylate) with Pt⋯Pt electronic interactions. The PMC phase formation varied significantly among the complexes depending on the heteroaryl group of the ancillary N^O ligand; the oxazolyl-bearing complex did not form a PMC phase, whereas the pyrazyl- and 5-fluoropyridyl-bearing complexes spontaneously formed a porous structure. This difference was rationalised by the π-stacking capability of the heteroaryl group of the ancillary ligand. Furthermore, owing to the presence of the one-dimensional Pt⋯Pt chains in this PMC phase, the photophysical properties of PMCs resulting from the Pt⋯Pt interactions were also significantly changed by the ancillary ligands.

Anthracycline-based hepatic arterial infusion chemotherapy achieved 17 months of disease regression in a patient with breast cancer liver metastases resistant to multiple systemic chemotherapies.

Hepatic arterial infusion chemotherapy (HAIC) for liver metastases (LMs) from breast cancer is not a standard of care, but its effectiveness in patients with extensive LMs who cannot tolerate systemic therapy has been reported. Herein, we report a case of breast cancer LMs that were controlled by anthracycline-based HAIC. A 46-year-old woman with estrogen receptor-positive, human epidermal growth factor receptor 2-negative metastatic breast cancer who had multiple LMs and bone metastases underwent seven lines of systemic therapy (paclitaxel/bevacizumab for 38 months; letrozole, nivolumab/fulvestrant, eribulin, gemcitabine/vinorelbine, high-dose toremifene/abemaciclib, and capecitabine for 21 months in total). However, owing to its adverse effects and the continued progression of the LMs, systemic therapy was switched to HAIC (40 mg/body epirubicin on day 1, 4 mg/body mitomycin C on days 1 and 15, and 500 mg/body 5-fluorouracil on days 1, 8, and 15; 28-day courses). In response to HAIC, the LMs remarkably regressed and were controlled for 17 months without severe adverse effects. HAIC was stopped when multiple brain metastases arose, and the patient died 2 months later. This case suggests that HAIC is a reasonable option for patients with extensive LMs, even in the late stage of treatment. HAIC recipients should be carefully selected through multidisciplinary discussions as the survival benefits of HAIC over systemic treatment remain unclear. Our findings identify a potential window for the use of traditional chemotherapeutic agents such as anthracyclines. Novel strategies to improve drug delivery are warranted in the future.

A case of rapidly progressing sarcomatous intrahepatic cholangiocarcinoma with suddenly appearing lymph node metastasis.

BACKGROUND: The sarcomatous variant of carcinoma is relatively rare in intrahepatic cholangiocarcinoma (ICC). Sarcomatous ICC (SICC) is associated with a poorer prognosis compared with ICC. SICC is rarely diagnosed before surgery due to non-descriptive findings; it progresses rapidly, resulting in miserable prognosis. Here, we report a case of rapidly progressing SICC that showed a clinically significant tumor growth rate. CASE PRESENTATION: A 77-year-old woman who had undergone ileocecal resection for cecal cancer 5 years previously was found to have elevated levels of the tumor marker carbohydrate antigen 19-9. Although an abdominal computed tomography (CT) scan did not detect any liver mass lesions until 3 months before this serum examination, the subsequent CT scan revealed a hypodensity 20 mm mass lesion in the right anterior section. Contrast-enhanced CT and magnetic resonance imaging revealed peripheral enhancement in the arterial-to-equilibrium phase. Fluorodeoxyglucose positron emission tomography revealed uptake in the lesion. None of the imaging modalities showed lymph node swelling or distant metastases. She underwent hepatectomy under the diagnosis of ICC or an atypical metastasis from previous cecal cancer. Although preoperative images showed no suspicious lymph node metastasis 3 weeks prior, the hilar lymph node swelled 3 cm and contained adenocarcinoma. Consequently, the patient underwent right anterior sectionectomy and lymph node dissection of the hepatoduodenal ligament. Histopathological examination revealed that the liver tumor was a poorly differentiated adenocarcinoma with sarcomatous pattern. While the patient received adjuvant gemcitabine and S-1 therapy, lymph node metastasis appeared in the mediastinum 13 months after the surgery. She received gemcitabine + cisplatin + S-1 therapy but died 20 months after surgery. CONCLUSION: SICC and lymph node metastasis clinically appeared within 3 months and 3 weeks, respectively. Suspected ICC that rapidly progresses should be considered SICC and treated with early resection. SICC is often missed in clinical diagnosis and has a poor prognosis, even after curative resection. While an alternative strategy involving preoperative biopsy and neoadjuvant therapy may be beneficial, it should be approached with discretion due to the potential risks of tumor progression and peritoneal dissemination.

Predictive Value of Aortic Valve Calcium Volume Measured by Computed Tomography for Paravalvular Leakage After Transcatheter Aortic Valve Implantation.

Paravalvular leakage (PVL) is a complication of transcatheter aortic valve implantation (TAVI) for aortic stenosis, leading to an adverse prognosis. We investigated whether aortic valve calcium volume (Ca-Vol) measured by preoperative cardiac computed tomography had a predictive value for PVL after TAVI using a third-generation self-expandable valve.We retrospectively analyzed 59 consecutive patients who underwent TAVI using a third-generation self-expandable valve. We measured Ca-Vol in the aortic valve and each cusp (non-coronary cusp [NCC], right-coronary cusp [RCC], and left-coronary cusp [LCC]). We divided the patients into 2 groups: a PVL group (32.2%) and a non-PVL group (67.8%). Total Ca-Vol was significantly higher in the PVL group than in the non-PVL group (P < 0.001). Ca-Vol in each cusp was also significantly higher in the PVL group ([NCC] P < 0.001, [RCC] P = 0.001, [LCC] P < 0.001). Univariate logistic regression analysis for PVL indicated that the total and per-cusp Ca-Vols were predictors for PVL (total, odds ratio [OR] 4.0, P < 0.001; NCC, OR 12.5, P = 0.002; RCC, OR 16.0, P = 0.008; LCC, OR 44.5, P < 0.001).Receiver operating characteristic curve analysis of Ca-Vol for predicting PVL revealed the optimal cut-off values of Ca-Vol were 2.4 cm3 for the total, 0.74 cm3 for NCC, 0.73 cm3 for RCC, and 0.56 cm3 for LCC (area under the curve, 0.85, 0.79, 0.76, and 0.83, respectively).Preoperative total, NCC, RCC, and LCC calcium volumes were significant predictors for PVL after TAVI using third-generation self-expandable valves.

Multimodality Risk Assessment of Patients with Ischemic Heart Disease Using Deep Learning Models Applied to Electrocardiograms and Chest X-rays.

Comprehensive management approaches for patients with ischemic heart disease (IHD) are important aids for prognostication and treatment planning. While single-modality deep neural networks (DNNs) have shown promising performance for detecting cardiac abnormalities, the potential benefits of using DNNs for multimodality risk assessment in patients with IHD have not been reported. The purpose of this study was to investigate the effectiveness of multimodality risk assessment in patients with IHD using a DNN that utilizes 12-lead electrocardiograms (ECGs) and chest X-rays (CXRs), with the prediction of major adverse cardiovascular events (MACEs) being of particular concern.DNN models were applied to detection of left ventricular systolic dysfunction (LVSD) on ECGs and identification of cardiomegaly findings on CXRs. A total of 2107 patients who underwent elective percutaneous coronary intervention were categorized into 4 groups according to the models' outputs: Dual-modality high-risk (n = 105), ECG high-risk (n = 181), CXR high-risk (n = 392), and No-risk (n = 1,429).A total of 342 MACEs were observed. The incidence of a MACE was the highest in the Dual-modality high-risk group (P < 0.001). Multivariate Cox hazards analysis for predicting MACE revealed that the Dual-modality high-risk group had a significantly higher risk of MACE than the No-risk group (hazard ratio (HR): 2.370, P < 0.001), the ECG high-risk group (HR: 1.906, P = 0.010), and the CXR high-risk group (HR: 1.624, P = 0.018), after controlling for confounding factors.The results suggest the usefulness of multimodality risk assessment using DNN models applied to 12-lead ECG and CXR data from patients with IHD.

Calcium-Phosphorus Product Is Associated with Adverse Prognosis in Hospitalized Patients with Heart Failure and Chronic Kidney Disease.

It has been reported that high levels of calcium-phosphorus (Ca-P) product are an indicator of coronary calcification and mortality risk in patients undergoing chronic hemodialysis. In the present study, we aimed to evaluate the significance of Ca-P product to predict the prognosis of patients with heart failure (HF) and chronic kidney disease (CKD). We conducted a prospective observational study of 793 patients with decompensated HF and CKD, and measured the value of Ca-P product. The cut-off value was obtained from the survival classification and regression tree (CART) analysis to predict post-discharge all-cause mortality and/or worsening HF, and the patients were divided into 2 groups: a high group (Ca-P product > 28, n = 594) and a low group (Ca-P product ≤ 28, n = 199). We compared the patient baseline characteristics and post-discharge prognosis between the 2 groups. The age as well as the prevalence of male sex, ischemic etiology, and anemia were significantly higher in the low group than in the high group. In contrast, there was no difference in echocardiographic parameters between the 2 groups. In the Kaplan-Meier analysis (mean follow-up 1089 days), all-cause mortality and/or worsening HF event rates were higher in the low group than in the high group (log-rank P = 0.001). In the multivariable Cox proportional hazard analysis, lower Ca-P product was found to be an independent predictor of all-cause mortality and/or worsening HF (hazard ratio 0.981, P = 0.031). Lower Ca-P product predicts adverse prognosis in patients with HF and CKD.

Geriatric Nutritional Risk Index predicts bleeding event in patients with heart failure.

AIMS: We aimed to elucidate the association between malnutrition and the occurrence of bleeding events in patients with heart failure. METHODS AND RESULTS: We evaluated the nutritional status of patients with heart failure [n = 2044, median (inter-quartile range) age 69.0 (59.0-78.0) years, 1209 (59.1%) males] using the Geriatric Nutritional Risk Index (GNRI). The primary endpoint was a composite of bleeding events such as haemorrhagic stroke or gastrointestinal bleeding. According to the survival classification and regression tree analysis, the accurate cut-off point of GNRI for predicting the primary endpoint was 106.2. We divided the patients into two groups based on GNRI levels: high GNRI group (GNRI ≥ 106.2, n = 606, 29.6%) and low GNRI group (GNRI < 106.2, n = 1438, 70.4%). We compared the patients' characteristics and prognosis between the two groups. The low GNRI group was older [72.0 (63.0-79.0) vs. 63.0 (53.0-73.0) years, P < 0.001] and had a lower prevalence of male sex (56.9% vs. 64.5%, P = 0.001). There were no differences in the use of antiplatelet agents and anticoagulants between the two groups. Levels of B-type natriuretic peptide were higher [321.1 (123.3-667.4) vs. 111.6 (42.6-235.4) pg/mL, P < 0.001] and levels of haemoglobin were lower [12.4 (10.8-13.7) vs. 14.2 (12.9-15.4) g/dL, P < 0.001] in the low GNRI group. The Kaplan-Meier analysis demonstrated that bleeding event rates were higher in the low GNRI group (log-rank P < 0.001). The multivariable Cox proportional hazard analysis revealed that low GNRI (hazard ratio 1.952, 95% confidence interval 1.002-3.805, P = 0.049) was associated with bleeding events. CONCLUSIONS: Heart failure patients with poor nutritional status, determined by GNRI under 106.2, experienced high bleeding event rates. Comprehensive management is required to avoid bleeding event in those populations.

Perioperative immunosuppressive therapy and coronary ostial angioplasty for unstable angina with Takayasu arteritis.

A young female patient with Takayasu arteritis presented with unstable angina due to bilateral coronary artery involvement. Steroid pulse therapy and subsequent prednisolone administration were started, but early coronary artery bypass grafting was required because of the multiple angina attacks at rest, with a prednisolone dose of 22.5 mg (0.45 mg/kg/day). Since the left internal thoracic artery which was grafted to the left anterior descending artery resulted in graft failure a few days after the surgery, the immunosuppressive therapy was intensified with the addition of tocilizumab and methotrexate. After controlling the disease activity, coronary ostial angioplasty using external iliac artery grafts was successfully performed, with a prednisolone dose of 15 mg (0.3 mg/kg/day). Ten months after the operation, the patient has been free from chest pain. The present case demonstrated the importance of adequate preoperative immunosuppressive therapy, even when early surgical intervention is required. Learning objective: There are no established treatment regimens for immunosuppressive management in cases of Takayasu arteritis (TAK) requiring immediate surgical intervention. Even when early surgery is required, it is important to reduce disease activity with appropriate preoperative immunosuppressive therapy using steroids in addition to biological agents, such as tocilizumab. Coronary ostial angioplasty is the effective surgical revascularization technique for TAK with coronary artery involvement.

A Case of Giant Goiter Associated with Airway Stenosis Caused by Long-Term Intravenous Epoprostenol Therapy for Idiopathic Pulmonary Arterial Hypertension.

Idiopathic pulmonary arterial hypertension is a progressive and life-threatening disease with pulmonary vasculature remodeling, leading to right-sided heart failure. Epoprostenol (prostaglandin I2) is highly recommended for patients with severe pulmonary arterial hypertension (PAH) categorized by the World Health Organization as functional class III or IV. It has been reported that prostaglandin I2 analogs can cause thyroid gland swelling and abnormal thyroid function. A 34-year-old woman was diagnosed with idiopathic pulmonary arterial hypertension and started receiving continuous intravenous epoprostenol. Three years after starting epoprostenol, she began complaining of neck swelling and was diagnosed with Graves' disease. The patient's thyroid function was controlled by thiamazole and levothyroxine; nevertheless, her thyroid gland enlargement worsened as the epoprostenol dose was titrated. After 20 years, she developed respiratory failure with a giant goiter leading to airway stenosis, and she passed away. The pathological autopsy confirmed a massive goiter associated with hyperthyroidism and airway stenosis. We experienced a case of idiopathic pulmonary hypertension with a giant goiter and airway stenosis after long-term intravenous epoprostenol therapy.

Experimental evaluation of pathogenicity and acquired immunity of Eimeria species, E. uekii and E. raichoi, infecting Japanese rock ptarmigans in a subspecies of the birds.

Japanese rock ptarmigans (Lagopus muta japonica) are birds that inhabit only alpine regions of central Honshu Island, Japan, known as the Japanese Alps. The number of these birds has recently declined, and in situ and ex situ national conservation programs for Japanese rock ptarmigans have been initiated. The infections of Eimeria spp. as protozoan parasites of the phylum Apicomplexa, E. uekii and E. raichoi, were frequently reported in the birds. However, the virulence of these Eimeria parasites has not been determined. Here, we analyzed the pathogenicity of these Eimeria parasites using experimental infections of a subspecies model of Japanese rock ptarmigans, Svalbard rock ptarmigans (Lagopus mutus hyperboreus), and evaluated acquired protective immunity against challenge in birds tolerant of low-dose inoculation with Eimeria parasites. Following inoculation with two Eimeria parasites derived from Japanese rock ptarmigans (dose range of 4 × 104 to 4 × 102 for E. uekii and 1.7 × 104 to 4 × 101 for E. raichoi), oocysts were detected at 6-8 days post-inoculation (PI), and the maximum number of oocysts per gram of feces was observed 7-10 days PI and then gradually decreased. The mortality rate and reduction in weight gain of chicks increased following high-dose inoculation of oocysts with abnormal feces (soft and diarrhea). Developmental zoites were detected histopathologically in epithelial tissues and sometimes the lamina propria from the duodenum to the colon. Chicks that survived low-dose inoculation did not show clear clinical symptoms after challenge inoculation. Our results suggest that the pathological characteristics of Eimeria parasites infecting Japanese rock ptarmigans include abnormal feces and reduction in weight gain, resulting in mortality in cases of heavy infection due to high-dose inoculation. These findings provide helpful data for Japanese rock ptarmigan conservation efforts.

Acute coronary syndrome with severe coronary calcification in a patient with pseudo-pseudohypoparathyroidism.

A 40-year-old female with a history of steroid therapy for juvenile rheumatoid arthritis was brought to our hospital because of chest pain. A diagnosis of non-ST elevation myocardial infarction was made, and emergency coronary angiography revealed stenotic lesions with severe calcification in the left anterior descending artery and the right coronary artery. Percutaneous coronary intervention with rotational atherectomy followed by a drug-coated balloon was performed to the lesion in the left anterior descending artery. The patient had characteristic physical findings including short stature, a round face, and 'knuckle-dimple sign'. Whole-body computed tomography showed many ectopic calcifications, indicating Albright's hereditary osteodystrophy. Ellsworth-Howard test revealed that urinary cyclic adenosine monophosphate response was positive, thus a diagnosis of pseudo-pseudohypoparathyroidism (PPHP) was made. Here, we describe a rare case of PPHP complicated by acute coronary syndrome with severely calcified coronary arteries. Learning objective: Pseudo-pseudohypoparathyroidism (PPHP) presents with several characteristic physical findings and ectopic calcifications. Since PPHP involves coronary artery calcification as in the present case, it may be considered as a cause of coronary artery disease.

Vapor-Induced Assembly of a Platinum(II) Complex Loaded on Layered Double Hydroxide Nanoparticles.

Invited for the cover of this issue is the group of Masaki Yoshida and Masako Kato at Hokkaido University/Kwansei Gakuin University. The image depicts the changes in the assembly of PtII complexes with humidity on layered double hydroxide (LDH) nanoparticles, resulting in a drastic emission color change from green to orange. Read the full text of the article at 10.1002/chem.202301993.

Photoredox Cascade Catalyst for Efficient Hydrogen Production with Biomass Photoreforming.

Biomass photoreforming is a promising method to provide both a clean energy resource in the form of hydrogen (H2 ) and valuable chemicals as the results of water reduction and biomass oxidation. To overcome the poor contact between heterogeneous photocatalysts and biomass substrates, we fabricated a new photoredox cascade catalyst by combining a homogeneous catalyst, 2,2,6,6-tetramethylpiperidine 1-oxyl (TEMPO), and a heterogeneous dual-dye sensitized photocatalyst (DDSP) composed of two Ru(II)-polypyridine photosensitizers (RuP6 and RuCP6 ) and Pt-loaded TiO2 nanoparticles. During blue-light irradiation (λ=460±15 nm; 80 mW), the DDSP photocatalytically reduced aqueous protons to form H2 and simultaneously oxidized TEMPO• radicals to generate catalytically active TEMPO+ . It oxidized biomass substrates (water-soluble glycerol and insoluble cellulose) to regenerate TEMPO• . In the presence of N-methyl imidazole as a proton transfer mediator, the photocatalytic H2 production activities for glycerol and cellulose reforming reached 2670 and 1590 µmol H2 (gTiO2 )-1  h-1 , respectively, which were comparable to those of state-of-the-art heterogeneous photocatalysts.

Vapor-Induced Assembly of a Platinum(II) Complex Loaded on Layered Double Hydroxide Nanoparticles.

Controlled self-assembly of PtII complexes is key to the development of optical and stimuli-responsive materials, but designing and precisely controlling them is still difficult owing to weak intermolecular interactions. Herein, we report the successful water-vapor-induced assembly of an anionic PtII complex [Pt(CN)2 (ppy)]- (Hppy=2-phenylpyridine) electrostatically loaded onto cationically charged layered double hydroxide (LDH) nanoparticles consisting of Mg2+ and Al3+ ions. When the PtII complexes were densely loaded onto the LDH nanoparticles, the assembly was maintained, even in dilute aqueous media. In the case of sparse loading, the PtII complexes were loaded discretely in the dry state; however, when water vapor was adsorbed, the increased mobility of the PtII complexes led to their assembly on the LDH nanoparticles. The presence of water vapor led to a drastic change in luminescence from green to orange.

Hepatic Venous Stasis Index Reflects Hepatic Congestion and Predicts Adverse Outcomes in Patients With Heart Failure.

Background It has been reported that the hepatic vein waveforms determined by abdominal ultrasonography can assess hepatic congestion in patients with heart failure (HF). However, the parameter that quantifies hepatic vein waveforms has not been established. We suggest the hepatic venous stasis index (HVSI) as the novel indicator to evaluate hepatic congestion quantitatively. To examine the clinical significance of HVSI in patients with HF, we aimed to clarify the associations of HVSI with the parameters of cardiac function and right heart catheterization, as well as that with prognosis, in patients with HF. Methods and Results We performed abdominal ultrasonography, echocardiography, and right heart catheterization in patients with HF (n=513). The patients were divided into 3 groups based on HVSI as follows: HVSI 0 (HVSI=0, n=253), low HVSI (HVSI 0.01-0.20, n=132), and high HVSI (HVSI>0.20, n=128). We examined the associations of HVSI with parameters of cardiac function and right heart catheterization and followed up for cardiac events defined as cardiac death or worsening HF. There was a significant increase in level of B-type natriuretic peptide, inferior vena cava diameter, and mean right atrial pressure with increasing HVSI. During the follow-up period, cardiac events occurred in 87 patients. In the Kaplan-Meier analysis, cardiac event rate increased across increasing HVSI (log-rank, P=0.002). Conclusions HVSI assessed by abdominal ultrasonography reflects hepatic congestion and right-sided HF and is associated with adverse prognosis in patients with HF.

Evaluation of the host specificity of Eimeria uekii and Eimeria raichoi for Japanese rock ptarmigans by oocyst transfer to taxonomically related birds.

Eimeria spp. are protozoan parasites that are commonly found in a broad range of vertebrate hosts. These parasites generally exhibit strict host specificity, but some Eimeria spp. can infect groups of closely related species such as species within a genus or family. Compared with Eimeria spp. that infect livestock, limited information is available about such infections in wild animals including data on host specificity, virulence, and prevalence. The Japanese rock ptarmigan, Lagopus muta japonica, is an endangered bird belonging to the family Phasianidae, order Galliformes, and inhabits only alpine areas of Japan. In conservation efforts for these birds, two Eimeria spp., E. uekii and E. raichoi, were frequently detected. Here, we examined cross-transmission of the parasites to other bird species to characterize their infectivity as well as the development of experimental bird models to contribute to conservation programs by the oocyst transfer. Consequently, among the examined eight bird species (chickens, Japanese pheasants, turkeys, chukar partridges, quails, helmeted guineafowls and ducks), only turkeys (family Phasianidae, order Galliformes) could be infected with E. raichoi. However, the number of oocysts per feces was relatively low, and few parasites in the intestinal mucosa could be found by histopathological analyses. These results might indicate that E. uekii and E. raichoi are highly adapted to Japanese rock ptarmigans that inhabit the alpine zone although further studies are anticipated.