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1.
Post-intensive care syndrome follow-up system after hospital discharge: a narrative review.
Nakanishi, N, Liu, K, Hatakeyama, J, Kawauchi, A, Yoshida, M, Sumita, H, Miyamoto, K, Nakamura, K
Journal of intensive care. 2024;(1):2
Abstract
BACKGROUND Post-intensive care syndrome (PICS) is the long-lasting impairment of physical functions, cognitive functions, and mental health after intensive care. Although a long-term follow-up is essential for the successful management of PICS, few reviews have summarized evidence for the efficacy and management of the PICS follow-up system. MAIN TEXT The PICS follow-up system includes a PICS follow-up clinic, home visitations, telephone or mail follow-ups, and telemedicine. The first PICS follow-up clinic was established in the U.K. in 1993 and its use spread thereafter. There are currently no consistent findings on the efficacy of PICS follow-up clinics. Under recent evidence and recommendations, attendance at a PICS follow-up clinic needs to start within three months after hospital discharge. A multidisciplinary team approach is important for the treatment of PICS from various aspects of impairments, including the nutritional status. We classified face-to-face and telephone-based assessments for a PICS follow-up from recent recommendations. Recent findings on medications, rehabilitation, and nutrition for the treatment of PICS were summarized. CONCLUSIONS This narrative review aimed to summarize the PICS follow-up system after hospital discharge and provide a comprehensive approach for the prevention and treatment of PICS.
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2.
Denosumab-induced hypocalcemia in patients with solid tumors and renal dysfunction: a multicenter, retrospective, observational study.
Nakamura, K, Kaya, M, Yanagisawa, Y, Yamamoto, K, Takayashiki, N, Ukita, H, Nagura, M, Sugiue, K, Kitajima, M, Hirano, K, et al
BMC cancer. 2024;(1):218
Abstract
BACKGROUND Bone metastases are frequently observed in advanced cancer, and bone modifying agents are used to prevent or treat skeletal-related events. Zoledronic acid is contraindicated in patients with severe renal impairment (Ccr < 30 mL/min), but it is not completely known whether denosumab can be used in them. We aimed to determine the association between renal function and hypocalcemia development during denosumab treatment. METHODS We included patients with solid cancer and bone metastases who started denosumab treatment between April 2017 and March 2019. They were classified into four groups based on creatinine clearance (Ccr; mL/min): normal (Ccr ≥ 80), mild (50 ≤ Ccr ˂80), moderate (30 ≤ Ccr ˂50), and severe (Ccr ˂30). Hypocalcemia was evaluated using the Common Terminology Criteria for Adverse Events (v5.0) based on the albumin-adjusted serum calcium levels; its incidence (stratified by renal function) and risk factors were investigated using a Chi-square test and logistic regression analysis. RESULTS Of 524 patients (age: 69 ± 11 years; 303 men), 153 had a normal renal function and 222, 117, and 32 had mild, moderate, and severe renal dysfunction. The albumin-adjusted serum calcium level was higher than the measured (total) calcium level in most patients. The incidence of grade ≥ 1 hypocalcemia was 32.0% in the normal group and 37.4%, 29.9%, and 62.5% in the mild, moderate, and severe renal dysfunction groups, respectively. It was, therefore, higher in the severe renal dysfunction groups than in the normal group (P = 0.002). The incidence of grade ≥ 3 hypocalcemia did not differ significantly among the groups. Pre-treatment low serum calcium levels and severe renal dysfunction were risk factors for hypocalcemia. CONCLUSIONS Evaluating denosumab-induced hypocalcemia required albumin adjustment, and its incidence was high among patients with severe renal dysfunction. Reduced serum calcium levels and severely impaired renal function were associated with an elevated hypocalcemia risk.
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3.
Enteral nutrition practice in the prone position in patients with coronavirus disease 2019: An international one-day point prevalence analysis.
Kitayama, M, Unoki, T, Liu, K, Nakamura, K
Clinical nutrition ESPEN. 2024;:257-263
Abstract
BACKGROUND & AIMS Enteral nutrition (EN) in the prone position for severe respiratory failure is considered possible with care. However, the extent to which it is feasible, especially its association with the length of intensive care unit (ICU) stay, is unclear. Therefore, we investigated the relationship between the duration of prone position therapy and adequacy of EN delivery and explored factors associated with this relationship in an observational study of critically ill patients with coronavirus disease 2019 (COVID-19) who were actively treated in the prone position. METHODS This study was a secondary analysis of a worldwide one-day prevalence study in the COVID-19 era. We investigated the care and nutritional therapy provided to critically ill patients with COVID-19 admitted to ICU, along with ICU-related information. We targeted patients who received only tube feeding and analyzed the relationship between the duration of prone position, length of ICU stays, and nutrition delivery via EN. In addition, a multivariate analysis was performed to examine factors affecting the achievement of EN delivery of 20 kcal/kg/day or more in patients who were placed in the prone position for at least 6 h. RESULTS A total of 399 patients who received only EN, excluding parenteral nutrition and oral intake, were included, of whom 58 % received EN energy delivery of ≥20 kcal/kg/day; this rate increased with the length of ICU stay, regardless of the duration of prone position. In a multivariate analysis of 121 patients who were in the prone position for at least 6 h, the presence of dedicated dietitians in the ICU (OR = 6.91, 95 % CI = 1.98 to 24.1, p < 0.01) was associated with a higher energy delivery. Conversely, the use of muscle relaxants (OR = 0.32, 95 % CI = 0.11 to 0.98, p = 0.04) and presence of nutrition protocols (OR = 0.24, 95 % CI = 0.07 to 0.77, p = 0.02) was associated with a lower energy delivery. CONCLUSIONS Patients with COVID-19 received adequate nutrition by EN even during prone position. Target EN delivery would be achieved with the introduction of prone position.
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4.
Review on stabilization/solidification methods and mechanism of heavy metals based on OPC-based binders.
Chen, L, Nakamura, K, Hama, T
Journal of environmental management. 2023;:117362
Abstract
Stabilization/solidification (S/S) with ordinary portland cement (OPC)-based binders is a suitable method to remediate heavy metal (HM)-contaminated soil and reuse resources of industrial wastes. In industrial wastes, alkaline wastes such as red mud (RM), soda residue (SR), pulverized fly ash (PFA), and alkalinity granulated blast furnace slag (GGBS) can immobilize HM ions (Pb2+, Zn2+, Cd2+, Cr3+, and Cu2+) by precipitation. However, some HM ions (such as AsO43-) would redissolve within the strong alkali environment. In this case, PFA, GGBS, metakaolin (MK), and incinerated sewage sludge ash (ISSA) which have low pH, can be used to immobilize HM ions or added to the OPC-based binders to adjust the pH in the soil products. Moreover, the calcium silicate hydrate (CSH), calcium aluminum silicate hydrate (CASH), ettringite (AFt), and calcium monosulfoalumiante hydrates (AFm) generated during the pozzolanic reaction can also immobilize HM ions by adsorption on the surface, ion exchange, and encapsulation. SR and GGBS can be used to immobilize the HMs (such as CrO42- and AsO43-), which are mainly affected by AFt and AFm. For those not affected by AFt and AFm but related to immobilization by precipitating (such as Mn2+), other wastes except SR and GGBS are suitable for treating contaminated soil. Nevertheless, the formation of AFt is also instrumental for soil product strength. There are several factors affecting soil product strength. In the future, the influence of different hydration products on the S/S effects, competitive adsorption of HM ions, effects on long-term HM stabilization, and novel materials are worth being explored by researchers.
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Ketogenic effects of medium chain triglycerides containing formula and its correlation to breath acetone in healthy volunteers: a randomized, double-blinded, placebo-controlled, single dose-response study.
Nakamura, K, Hagihara, K, Nagai, N, Egashira, R, Takeuchi, M, Nakano, M, Saito, H, Moriguchi, M, Tonari, S, Fujii, H, et al
Frontiers in nutrition. 2023;:1224740
Abstract
The efficacy of low-carbohydrate, high-fat diets, such as ketogenic diets, for cancer patients is of research interest. We previously demonstrated the efficacy of the ketogenic diet in a case study in which medium-chain triglycerides (MCTs) or MCT-containing formula (ketogenic formula) was used as a supplement to increase blood ketone bodies. However, little is known about the amounts needed to induce ketogenic effects and about the usefulness of monitoring of breath acetone. To investigate the pharmacokinetics of MCTs and their metabolites, blood ketone bodies and breath acetone, 24 healthy subjects received one of four single oral doses of the ketogenic formula (equivalent to 0, 10, 20, and 30 g of MCTs) under fasting conditions. Total blood ketone bodies, β-hydroxybutyrate, octanoic acid, and decanoic acid were increased in a dose-dependent manner. The ketogenic effect was considered to depend on octanoic and decanoic acids, because a positive correlation was observed between them. A strong positive correlation was also observed between total serum ketone bodies and breath acetone at each time points. Therefore, monitoring breath acetone levels seems a less invasive method to predict blood concentrations of ketone bodies during ketogenic diet therapy. Clinical trial registration:https://rctportal.niph.go.jp/en/detail?trial_id=UMIN000032634, UMIN-CTR UMIN000032634.
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Registry for Evaluating Healthy Life Expectancy and Long-Term Outcomes after Catheter Ablation of Atrial Fibrillation in the Very Elderly (REHEALTH AF) study: rationale and design of a prospective, multicentre, observational, comparative study.
Okumura, Y, Nagashima, K, Watanabe, R, Yokoyama, K, Kato, T, Fukaya, H, Hayashi, H, Nakahara, S, Shimizu, W, Iwasaki, YK, et al
BMJ open. 2023;(2):e068894
Abstract
INTRODUCTION Data are lacking on the extent to which patients with non-valvular atrial fibrillation (AF) who are aged ≥80 years benefit from ablation treatment. The question pertains especially to patients' postablation quality of life (QoL) and long-term clinical outcomes. METHODS AND ANALYSIS We are initiating a prospective, registry-based, multicentre observational study that will include patients aged ≥80 years with non-valvular AF who choose to undergo treatment by catheter ablation and, for comparison, such patients who do not choose to undergo ablation (either according to their physician's advice or their own preference). Study subjects are to be enrolled from 52 participant hospitals and three clinics located throughout Japan from 1 June 2022 to 31 December 2023, and each will be followed up for 1 year. The planned sample size is 660, comprising 220 ablation group patients and 440 non-ablation group patients. The primary endpoint will be the composite incidence of stroke/transient ischaemic attack (TIA) or systemic embolism (SE), another cardiovascular event, major bleeding and/or death from any cause. Other clinical events such as postablation AF recurrence, a fall or bone fracture will be recorded. We will collect standard clinical background information plus each patient's Clinical Frailty Scale score, AF-related symptoms, QoL (Five-Level Version of EQ-5D) scores, Mini-Mental State Examination (optional) score and laboratory test results, including measures of nutritional status, on entry into the study and 1 year later, and serial changes in symptoms and QoL will also be secondary endpoints. Propensity score matching will be performed to account for covariates that could affect study results. ETHICS AND DISSEMINATION The study conforms to the Declaration of Helsinki and the Ethical Guidelines for Clinical Studies issued by the Ministry of Health, Labour and Welfare, Japan. Results of the study will be published in one or more peer-reviewed journals. TRIAL REGISTRATION NUMBER UMIN000047023.
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Dissociation process of polyalanine aggregates by free electron laser irradiation.
Okumura, H, Itoh, SG, Zen, H, Nakamura, K
PloS one. 2023;(9):e0291093
Abstract
Polyalanine (polyA) disease-causative proteins with an expansion of alanine repeats can be aggregated. Although curative treatments for polyA diseases have not been explored, the dissociation of polyA aggregates likely reduces the cytotoxicity of polyA. Mid-infrared free electron laser (FEL) successfully dissociated multiple aggregates. However, whether the FEL dissociates polyA aggregates like other aggregates has not been tested. Here, we show that FEL at 6.1 μm experimentally weakened the extent of aggregation of a peptide with 13 alanine repeats (13A), and the irradiated 13A exerted lesser cytotoxicity to neuron-like cells than non-irradiated 13A. Then, we applied molecular dynamics (MD) simulation to follow the dissociation process by FEL. We successfully observed how the intermolecular β-sheet of polyA aggregates was dissociated and separated into monomers with helix structures upon FEL irradiation. After the dissociation by FEL, water molecules inhibited the reformation of polyA aggregates. We recently verified the same dissociation process using FEL-treated amyloid-β aggregates. Thus, a common mechanism underlies the dissociation of different protein aggregates that cause different diseases, polyA disease and Alzheimer's disease. However, MD simulation indicated that polyA aggregates are less easily dissociated than amyloid-β aggregates and require longer laser irradiation due to hydrophobic alanine repeats.
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8.
Association between Cardiovascular Disease and Liver Disease, from a Clinically Pragmatic Perspective as a Cardiologist.
Nakashima, M, Nakamura, K, Nishihara, T, Ichikawa, K, Nakayama, R, Takaya, Y, Toh, N, Akagi, S, Miyoshi, T, Akagi, T, et al
Nutrients. 2023;(3)
Abstract
Cardiovascular diseases and liver diseases are closely related. Non-alcoholic fatty liver disease has the same risk factors as those for atherosclerotic cardiovascular disease and may also be a risk factor for atherosclerotic cardiovascular disease on its own. Heart failure causes liver fibrosis, and liver fibrosis results in worsened cardiac preload and congestion. Although some previous reports regard the association between cardiovascular diseases and liver disease, the management strategy for liver disease in patients with cardiovascular diseases is not still established. This review summarized the association between cardiovascular diseases and liver disease. In patients with non-alcoholic fatty liver disease, the degree of liver fibrosis progresses with worsening cardiovascular prognosis. In patients with heart failure, liver fibrosis could be a prognostic marker. Liver stiffness assessed with shear wave elastography, the fibrosis-4 index, and non-alcoholic fatty liver disease fibrosis score is associated with both liver fibrosis in patients with liver diseases and worse prognosis in patients with heart failure. With the current population ageing, the importance of management for cardiovascular diseases and liver disease has been increasing. However, whether management and interventions for liver disease improve the prognosis of cardiovascular diseases has not been fully understood. Future investigations are needed.
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Explorative Clustering of the Nitrogen Balance Trajectory in Critically Ill Patients: A Preliminary post hoc Analysis of a Single-Center Prospective Observational Study.
Nakamura, K, Ogura, K, Nakano, H, Ikechi, D, Mochizuki, M, Takahashi, Y, Goto, T
Annals of nutrition & metabolism. 2023;(5):460-468
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Abstract
BACKGROUND The nitrogen balance estimates a protein net difference. However, since it has a number of limitations, it is important to consider the trajectory of the nitrogen balance in the clinical course of critically ill patients. OBJECTIVES We herein exploratively classified the nitrogen balance trajectory using a machine learning method. METHOD This is a post hoc analysis of a single-center prospective study for the patients admitted to our Emergency and Critical Center ICU. The nitrogen balance was evaluated with 24-h urine collection from ICU days 1-10 with 9 points. K-means clustering was performed to classify the nitrogen balance trajectory. We also evaluated factors associated with uncovered clusters. RESULTS Seventy-six eligible patients were included in the present study. After clustering, the nitrogen balance trajectory was classified into 4 classes. Class 1 was trajected as a negative balance over 10 days (24 patients). Class 2 had a positive conversion on day 3 or 4 (8 patients). Class 3 had a positive conversion on day 8 or 9 (28 patients). Class 4 initially had a positive balance and then converted to a negative balance (16 patients). Sepsis complication and steroid use were associated with negative nitrogen balance trajectory. Class 2 was associated with lower length of hospital stay and femoral muscle volume loss, however, frequently had frailty and sarcopenia on admission. Active nutrition therapy intention was not correlated with positive trajectory. CONCLUSIONS The nitrogen balance trajectory in critically ill patients may be classified into 4 classes for clinical practice. Among patients emergently admitted to the ICU, the positive conversion of the nitrogen balance might be delayed over 10 days.
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Risk factor analysis for cisplatin-induced nephrotoxicity with the short hydration method in diabetic patients.
Saito, Y, Kobayashi, M, Tamaki, S, Nakamura, K, Hirate, D, Takahashi, K, Takekuma, Y, Sakakibara-Konishi, J, Shimizu, Y, Kinoshita, I, et al
Scientific reports. 2023;(1):17126
Abstract
The occurrence of cisplatin (CDDP)-induced nephrotoxicity (CIN) has decreased with advancements in supportive care. In contrast, we reported that baseline diabetes mellitus (DM) complications significantly worsen CIN. This study aimed to determine further risk factors associated with CIN development in DM patients. Patients with thoracic cancer requiring DM pharmacotherapy, who received CDDP (≥ 60 mg/m2)-containing regimens using the short hydration method (n = 140), were enrolled in this retrospective multicenter observational study. The primary endpoint of the present study was the elucidation of risk factors (patient factors, DM medication influence, and treatment-related factors) associated with CIN development in patients with DM. Cisplatin-induced nephrotoxicity occurred in 22.1% of patients with DM. The median worst variation of serum creatinine levels and creatinine clearance (worst level - baseline level) was 0.16 mg/dL (range: - 0.12-1.41 mg/dL) and - 15.9 mL/min (- 85.5-24.3 mL/min), respectively. Multivariate logistic regression analyses identified female sex as the singular risk factor for CIN development in the DM population (adjusted odds ratio; 2.87, 95% confidence interval; 1.08-7.67, P = 0.04). Diabetes mellitus medication and treatment-related factors did not affect CIN development. In conclusion, our study revealed that female sex is significantly associated with CIN development in patients with DM and thoracic cancer.