Utilization and Issues Related to Discharge Medication Summaries from Hospital Pharmacies to Community Pharmacies.

In 2020, the Japan Community Healthcare Organization (JCHO) Hoshigaoka Medical Center started providing information to community pharmacies about patients admitted to the acute care ward using discharge medication summaries (the summaries). We conducted an online self-recording survey of 149 pharmacies belonging to the Hirakata City Pharmacists Association to clarify the usability of the summaries, any related issues, and to further discuss future collaboration between hospitals and pharmacies. 46 pharmacies have received the summaries in the past, of which 44 pharmacies answered that they have utilized the summaries with patient instruction and prescription queries of doctors. However, two pharmacies responded they did not utilize the summaries, and the reasons were (a) the information was not timely and (b) patients whom the discharge medical summary was sent for did not come to the pharmacy. There were some requests regarding the summaries such as, "I would like to know what kind of information hospital pharmacists want from community pharmacists." Preference for sharing information other than the summaries (e.g., online tools) with hospital pharmacists was related to whether the pharmacy was providing home pharmaceutical visit services. The survey revealed that, in addition to the usability of the summaries, there are also events that prevent them from being utilized. Some of the challenges include the timing of sending the summaries, the accurate identification of the family pharmacy and the communication of follow-up after discharge from hospital. Collaborating with pharmacies providing home pharmaceutical visit services would be beneficial in creating new system of bidirectional information sharing.

Isolation of stage-specific spermatogenic cells by dynamic histone incorporation and removal in spermatogenesis.

Due to the lack of an efficient in vitro spermatogenesis system, studies on mammalian spermatogenesis require the isolation of specific germ cell populations for further analyses. BSA gradient and elutriation have been used for several decades to purify testicular germ cells; more recently, flow cytometric cell sorting has become popular. Although each method has its advantages and disadvantages and is used depending on the purpose of the experiment, reliance on flow cytometric cell sorting is expected to be more prevalent because fewer cells can be managed. However, the currently used flow cytometric cell sorting method for testicular germ cells relies on karyotypic differences via DNA staining. Thus, it remains challenging to separate post-meiotic haploid cells (spermatids) according to their differentiation stage despite significant variations in morphology and chromatin state. In this study, we developed a method for finely separating testicular germ cells using VC mice carrying fluorescently tagged histones. This method enables the separation of spermatogonia, spermatocytes, and spermatids based on the intensity of histone fluorescence and cell size. Combined with a DNA staining dye, this method separates spermatids after elongation according to each spermiogenic stage. Although the necessity for a specific transgenic mouse line is less versatile, this method is expected to be helpful for the isolation of testicular germ cell populations because it is highly reproducible and independent of complex cell sorter settings and staining conditions.

Estimability study on the age of toddlers' gait development based on gait parameters.

In the first few years of toddlers' locomotion, various gait parameters improve gradually and dynamically with gait development. Therefore, in this study, we hypothesized that the age of gait development, or the level of gait development with age as its indicator, can be estimated from several gait parameters related to gait development, and investigated its estimability. In total, 97 healthy toddlers aged about 1-3 years participated in the study. All five selected gait parameters showed a moderate or higher correlation with age, but the duration with a large change and the strength of the association with gait development varied for each gait parameter. Multiple regression analysis was performed using age as the objective variable and five selected gait parameters as explanatory variables, and an estimation model (R2 = 0.683, adjusted R2 = 0.665) was created. The estimation model was verified using a test dataset separate from the training dataset (R2 = 0.82, p < 0.001). It was suggested that the age of gait development could be estimated from gait alone. Gait analysis based on empirical observations may reduce the need for skilled observers and their potential variability.

Appetite loss and associated factors at 1 year after intensive care unit elder survivors in a secondary analysis of the SMAP-HoPe study.

Appetite loss, a common but serious issue in older patients, is an independent risk factor for sarcopenia, which is associated with high mortality. However, few studies have explored the phenomenon of appetite loss after discharge from the intensive care unit (ICU). Therefore, we aimed to describe the prevalence of appetite loss and relationship between appetite loss and depression in patients living at home 12 months after intensive care. This study involved secondary analysis of data obtained from a published ambidirectional study examining post-intensive care syndrome 12 months after discharge (SMAP-HoPe study) conducted in 12 ICUs in Japan. We included patients aged > 65 years. The Short Nutritional Assessment Questionnaire and Hospital Anxiety Depression Scale were used for the analysis. Descriptive statistics and a multilevel generalized linear model were used to clarify the relationship between appetite loss and depression. Data from 468 patients were analyzed. The prevalence of appetite loss was 25.4% (95% confidence interval [CI], 21.5-29.4). High severity of depression was associated with a high probability of appetite loss (odds ratio, 1.2; 95%CI, 1.14-1.28; p = 0.00). Poor appetite is common 12 months after intensive care and is associated with the severity of depression.

Solubilization of Mouse Sperm Chromatin for Sequencing Analyses Using a Chaperon Protein.

Sperm chromatin compaction is physiologically essential for sperm to acquire the fertility. However, this unique structure composed of protamines makes us unable to solubilize the chromatin due to its resistance to sonication and enzymes usually used for chromatin fragmentation in somatic cells. Even when intense enzymatic treatment is applied, it appears to solubilize only certain portions of sperm chromatin presumably because of the heterogeneous properties. To overcome this issue, we previously developed a method to treat the sperm with recombinant nucleoplasmin, a protamine remover in fertilized embryos, followed by sonication. The nucleoplasmin treatment dramatically increased the efficiency of sperm chromatin solubilization, while a relatively large amount of recombinant nucleoplasmin was required. Here, we describe an improvement of nucleoplasmin method with a less amount of recombinant protein and a shorter reaction time.

Reoccurrence of takotsubo cardiomyopathy induced by osimertinib: A case report.

A patient with lung cancer was administrated osimertinib. She developed symptomatic heart failure due to Takotsubo cardiomyopathy (TC). As her condition improved after discontinuing osimertinib, TC was thought to be caused by osimertinib. Reoccurrence of TC was seen after readministrating half dose of osimertinib.

Employment status and its associated factors for patients 12 months after intensive care: Secondary analysis of the SMAP-HoPe study.

BACKGROUND: Returning to work is a serious issue that affects patients who are discharged from the intensive care unit (ICU). This study aimed to clarify the employment status and the perceived household financial status of ICU patients 12 months following ICU discharge. Additionally, we evaluated whether there exists an association between depressive symptoms and subsequent unemployment status. METHODS: This study was a subgroup analysis of the published Survey of Multicenter Assessment with Postal questionnaire for Post-Intensive Care Syndrome for Home Living Patients (the SMAP-HoPe study) in Japan. Eligible patients were those who were employed before ICU admission, stayed in the ICU for at least three nights between October 2019 and July 2020, and lived at home for 12 months after discharge. We assessed the employment status, subjective cognitive functions, household financial status, Hospital Anxiety and Depression Scale, and EuroQOL-5 dimensions of physical function at 12 months following intensive care. RESULTS: This study included 328 patients, with a median age of 64 (interquartile range [IQR], 52-72) years. Of these, 79 (24%) were unemployed 12 months after ICU discharge. The number of patients who reported worsened financial status was significantly higher in the unemployed group (p<0.01) than in the employed group. Multivariable analysis showed that higher age (odds ratio [OR], 1.06; 95% confidence interval [CI], 1.03-1.08]) and greater severity of depressive symptoms (OR, 1.13 [95% CI, 1.05-1.23]) were independent factors for unemployment status at 12 months after ICU discharge. CONCLUSIONS: We found that 24.1% of our patients who had been employed prior to ICU admission were subsequently unemployed following ICU discharge and that depressive symptoms were associated with unemployment status. The government and the local municipalities should provide medical and financial support to such patients. Additionally, community and workplace support for such patients are warranted.

Effect of wearing diapers on toddler's gait.

Gait maturation in infants develops gradually through several phases. However, external factors such as childrearing practices, especially the wearing of diapers, may affect an infant's motor development. This study investigated the influence of different bulk stresses on the gait of toddlers wearing a disposable diaper. Twenty-six healthy toddlers (age: 19.2 ± 0.9 months) participated in this study. We measured the joint kinematics (pelvis angle and hip-joint angle) and spatiotemporal parameters (step length and step width) of the toddlers' gait under four dress conditions (wearing Type A_WET, Type A_DRY, and Type B_WET diapers and naked). Type B_WET had a higher bulk stress than Type A_WET, and Type A_DRY had lower stress than Type A _ WET. Our results indicate that the walk of toddlers when wearing a diaper differs from that when naked. This difference is due to the effect of the bulk of the diaper on the lower limb. A high bulk stress has a greater influence than that of a low bulk stress on joint dynamics and step width. Therefore, our findings suggest that wearing diapers with high bulk stress may inhibit the natural gait patterns of toddlers.

Low-Refractive-Index Deep-Ultraviolet Transparent Poly(fluoroalkyl-co-methylsilsesquioxane) Resins Synthesized by Cosolvent-Free Hydrolytic Polycondensation of Organotrimethoxysilanes.

Cosolvent-free (solventless) hydrolytic polycondensation of fluoroalkyltrimethoxysilanes of linear fluoroalkyl groups of the form R = CnF2n+1C2H4 (n = 1, 4, and 8) and methyltrimethoxysilane followed by thermal curing yielded dense polymeric silsesquioxane (SQ) resins with low refractive indices and deep-ultraviolet transparency with an ultraviolet absorption edge at ∼210 nm. The refractive index at 589 nm was adjustable at ∼1.35-1.39, and the lowest value was ∼1.354 for the stiff resin and ∼1.347 for the soft resin of poly(R-co-Me-SQ) prepared at n = 8. The refractive indices of these resins were consistent with the linear combinations of molar refractivities of constituent functional groups, and there were no free-volume anomalies.

Prevalence of and risk factors for post-intensive care syndrome: Multicenter study of patients living at home after treatment in 12 Japanese intensive care units, SMAP-HoPe study.

Few studies have examined the epidemiology of post-intensive care syndrome in Japan. This study investigated the mental health and quality of life of patients living at home in Japan after intensive care unit (ICU) discharge. Additionally, we examined whether unplanned admission to the ICU was associated with more severe post-traumatic stress disorder (PTSD), anxiety, and depressive symptoms. An ambidirectional cohort study was conducted at 12 ICUs in Japan. Patients who stayed in the ICU for > 3 nights and were living at home for 1 year afterward were included. One year after ICU discharge, we retrospectively screened patients and performed a mail survey on a monthly basis, including the Impact of Event Scale-Revised (IER-S), the Hospital Anxiety Depression Scale (HADS), and the EuroQOL-5 Dimension (EQ-5D-L) questionnaires. Patients' characteristics, delirium and coma status, drugs used, and ICU and hospital length of stay were assessed from medical records. Descriptive statistics and multilevel linear regression modeling were used to examine our hypothesis. Among 7,030 discharged patients, 854 patients were surveyed by mail. Of these, 778 patients responded (response rate = 91.1%). The data from 754 patients were analyzed. The median IES-R score was 3 (interquartile range [IQR] = 1‒9), and the prevalence of suspected PTSD was 6.0%. The median HADS anxiety score was 4.00 (IQR = 1.17‒6.00), and the prevalence of anxiety was 16.6%. The median HADS depression score was 5 (IQR = 2‒8), and the prevalence of depression was 28.1%. EQ-5D-L scores were lower in our participants than in the sex- and age-matched Japanese population. Unplanned admission was an independent risk factor for more severe PTSD, anxiety, and depressive symptoms. Approximately one-third of patients in the general ICU population experienced mental health issues one year after ICU discharge. Unplanned admission was an independent predictor for more severe PTSD symptoms.

Practical guidance for echocardiography for cancer therapeutics-related cardiac dysfunction.

The prognosis of patients with cancer has improved due to an early diagnosis of cancer and advances in cancer treatment. There are emerging reports on cardiotoxicity in cancer treatment and on cardiovascular disease in cancer patients, from which cardiovascular disease has been recognized as a common cause of death among cancer survivors. This situation has led to the need for a medical system in which oncologists and cardiologists work together to treat patients. With the growing importance of onco-cardiology, the role of echocardiography in cancer care is rapidly expanding, but at present, the practice of echocardiography in clinical settings varies from institution to institution, and is empirical with no established systematic guidance. In view of these circumstances, we thought that brief guidance for clinical application was necessary and have therefore developed this guidance, although evidence in this field is still insufficient.

4'-[methyl-11C]-thiothymidine as a proliferation imaging tracer for detection of colorectal cancer: comparison with 18F-FDG.

OBJECTIVE: The novel radiotracer, 4'-[methyl-11C]-thiothymidine (11C-4DST), was developed based on the DNA incorporation method as a cell proliferation marker. This study investigated the feasibility of 11C-4DST positron emission tomography/computed tomography (PET/CT) for detection of colorectal cancer, as compared with 2-deoxy-2-18F-fluoro-D-glucose (18F-FDG) PET/CT, and to correlate the two radiotracers with proliferative activity. METHODS: A total of 18 patients with newly diagnosed colorectal cancer underwent both 11C-4DST and 18F-FDG PET/CT. Tumor lesions were identified as areas of focally increased uptake, exceeding that of adjacent normal tissue. For semiquantitative analysis, the maximal standardized uptake value (SUVmax) was calculated. Proliferative activity as quantified by the Ki-67 index was estimated in tumor specimens. RESULTS: In all 18 patients, colorectal cancers were detected by both 11C-4DST and 18F-FDG PET/CT. The median (± SD) SUVmax for 11C-4DST (6.02 ± 2.55) was significantly lower than that for 18F-FDG (13.91 ± 7.62) (P < 0.001). 11C-4DST SUVmax and 18F-FDG SUVmax showed a significant correlation (r = 0.69, P = 0.002). 11C-4DST SUVmax and Ki-67 index were weakly correlated (r = 0.50, P = 0.04). 18F-FDG SUVmax and Ki-67 index were not significantly correlated (r = 0.44, P = 0.06). CONCLUSIONS: Despite a significantly lower uptake of 11C-4DST than that of 18F-FDG, detection of colorectal cancer was also feasible with 11C-4DST PET/CT. 11C-4DST PET/CT might have a role in the noninvasive assessment of proliferation in colorectal cancer.

[CLINICAL STUDY OF THE PROSTATE CANCERS WITH A SERUM PROSTATE SPECIFIC ANTIGEN LEVEL OF MORE THAN 100 ng/ml AT THE FIRST DIAGNOSIS].

In patients with prostate cancer high serum prostate specific antigen (PSA) at diagnosis was generally regarded as a strong impression of advanced disease with distant metastasis and poor prognosis. (Objective) We reported a retrospective study of prognostic factor and Overall survival (OS) in patients with prostate specific antigen (PSA) level of greater than 100 ng/ml (PSA≥100 ng/ml). (Subjects and methods) Between January 2002 and December 2015, 60 patients were diagnosed prostate cancer with PSA≥100 ng/ml and performed hormonal monotherapy at Kanazawa Medical University hospital. We evaluated initial PSA level, Gleason score, Gleason Grading Group, clinical stage, site of metastasis, PSA nadir level, Time to PSA nadir (TTN), serum Hemoglobin (Hb) level, serum C-Reactive Protein (CRP) level, serum Lactate Dehydrogenase (LDH) level, serum Alkaline Phosphatase (ALP) level, clinical passage and survival time. (Results) The median age of the patients was 73 years old (54-90) and the initial PSA levels ranged from 100 ng/ml to 15,823 ng/ml (median 390).Prognostic factors of overall survival were site of metastasis, Gleason score, Gleason Grading Group, PSA nadir level, TTN, serum CRP level, serum LDH level and serum ALP level at the diagnosis. In multivariate analysis serum LDH level remained an independent predictor of OS.

Re-evaluating the Localization of Sperm-Retained Histones Revealed the Modification-Dependent Accumulation in Specific Genome Regions.

The question of whether retained histones in the sperm genome localize to gene-coding regions or gene deserts has been debated for years. Previous contradictory observations are likely caused by the non-uniform sensitivity of sperm chromatin to micrococcal nuclease (MNase) digestion. Sperm chromatin has a highly condensed but heterogeneous structure and is composed of 90%∼99% protamines and 1%∼10% histones. In this study, we utilized nucleoplasmin (NPM) to improve the solubility of sperm chromatin by removing protamines in vitro. NPM treatment efficiently solubilized histones while maintaining quality and quantity. Chromatin immunoprecipitation sequencing (ChIP-seq) analyses using NPM-treated sperm demonstrated the predominant localization of H4 to distal intergenic regions, whereas modified histones exhibited a modification-dependent preferential enrichment in specific genomic elements, such as H3K4me3 at CpG-rich promoters and H3K9me3 in satellite repeats, respectively, implying the existence of machinery protecting modified histones from eviction.

TH2A is phosphorylated at meiotic centromere by Haspin.

Histone phosphorylation is sometimes associated with mitosis and meiosis. We have recently identified a phosphorylation of the 127th threonine on TH2A (pTH2A), a germ cell-specific H2A variant, in condensed spermatids and mitotic early preimplantation embryos of mice. Here, we further report the existence of pTH2A at the centromeres in metaphase I spermatocytes and oocytes. Moreover, we identified Haspin, a known kinase for the 3rd threonine on H3, is responsible for pTH2A in vivo. In contrast to the severe meiotic defect in oocytes treated with a Haspin inhibitor, pTH2A-deficient mice, in which the 127th threonine was replaced by alanine, maintained the fertility and exhibited no obvious defect in both oocytes and spermatogenesis. Interestingly, pTH2A was significantly decreased in aged oocytes, suggesting that its accumulation is regulated by centromeric cohesins. Collectively, our study proposes a new set of kinase-histone pair at meiotic centromere, which is highly coordinated during meiosis.

Significance of sequential cardiac rehabilitation program through inter-hospital cooperation between acute care and rehabilitation hospitals in elderly patients after cardiac surgery in Japan.

This study is to evaluate the impact of cooperation between acute care hospital and rehabilitation hospital on physical function, exercise tolerance, activities of daily living (ADL), health-related quality of life (HR-QOL), and psychological function in heart disease patients undergoing cardiac rehabilitation. Among patients undergoing concurrent medical treatment and cardiac rehabilitation starting early in acute care hospitalization, we selected 30 patients who required continued cardiac rehabilitation in rehabilitation hospitals as subjects. At the time of admission and discharge from the rehabilitation hospital, we measured and compared physical function [grip strength, knee extension strength, and the short physical performance battery (SPPB)], ADL ability using the Functional Independence Measure (FIM), exercise tolerance [six-minute walking distance (6MD)], and psychological functions such as the MOS 36-Item Short-Form Health Survey (SF-36). The average age of the subjects was 76.8 years and 60% were women. In 70% of cases, musculoskeletal causes were the reasons for continued cardiac rehabilitation in a rehabilitation hospital. In evaluations before and after hospitalization, significant improvements were observed in knee extension strength and the results of the SPPB (p < 0.01), FIM, and 6MD (p < 0.01). In SF-36, significant improvements were observed in physical function, role functioning, vitality, and emotional functioning (p < 0.05, p < 0.01). With intensive cardiac rehabilitation in rehabilitation hospitals, physical function, ADL, exercise tolerance, and HR-QOL improved significantly. As the severity and prevalence of heart disease are expected to increase in association with multiple disabilities and aging, the importance of cooperation between acute care hospitals and rehabilitation hospitals will increase; therefore, cardiac rehabilitation should be the basis for such cooperation.

Patient-reported postoperative pain, body image, and cosmetic satisfaction after transumbilical laparoendoscopic single-site adrenalectomy.

INTRODUCTION: Laparoendoscopic single-site surgery is a recently innovated urologic surgical procedure. Transumbilical laparoendoscopic single-site adrenalectomy (LESS-A) is technically safe and feasible in patients with benign adrenal tumors. To improve patient counseling and informed consent, we evaluated patient-reported postoperative pain, body image, and cosmetic satisfaction after transumbilical LESS-A. METHODS: We reviewed 24 patients who underwent transumbilical LESS-A and assessed their operative and esthetic outcomes and incisional pain. Incisional pain was evaluated using a 10-point visual analog scale, and the body image and cosmetic satisfaction were measured using a questionnaire that included a body image scale (range, 5-20 points) and a cosmetic scale (range, 3-24 points). RESULTS: Pure LESS-A was performed on 10 patients using a multichannel port; an additional 5-mm trocar was used in two obese patients. Supplementary to the single-incision approach, one or two 3-mm ports were used in 12 patients. The mean operative time was 203 min; the mean blood loss was 41 mL. The mean pain visual analog scale scores on postoperative days 1, 3, and 7 were 3.5, 2.2 (P = 0.012), and 1.5 points (P = 0.018), respectively. The mean body image scale and cosmetic scale scores indicating wound satisfaction 1 month after the surgery were 20 and 22 points, respectively. Although one patient had liver injury during surgery, the postoperative course during the 3-month follow-up was uneventful. CONCLUSION: Transumbilical LESS-A confers less postoperative pain and better cosmetic satisfaction than conventional laparoscopic adrenalectomy. Therefore, this procedure could potentially become a standard treatment option for benign adrenal tumors.

Right ventricular relative wall thickness as a predictor of outcomes and of right ventricular reverse remodeling for patients with pulmonary hypertension.

Mid-term right ventricular (RV) reverse remodeling after treatment in patients with pulmonary hypertension (PH) is associated with long-term outcome as well as baseline RV remodeling. However, baseline factors influencing mid-term RV reverse remodeling after treatment and its prognostic capability remain unclear. We studied 54 PH patients. Mid-term RV remodeling was assessed in terms of the RV area, which was traced planimetrically at the end-systole (RVESA). RV reverse remodeling was defined as a relative decrease in the RVESA of at least 15% at 10.2 ± 9.4 months after treatment. Long-term follow-up was 5 years. Adverse events occurred in ten patients (19%) and mid-term RV reverse remodeling after treatment was observed in 37 (69%). Patients with mid-term RV reverse remodeling had more favorable long-term outcomes than those without (log-rank: p = 0.01). Multivariate logistic regression analysis showed that RV relative wall thickness (RV-RWT), as calculated as RV free-wall thickness/RV basal linear dimension at end-diastole, was an independent predictor of mid-term RV reverse remodeling (OR 1.334; 95% CI, 1.039-1.713; p = 0.03). Moreover, patients with RV-RWT ≥0.21 showed better long-term outcomes than did those without (log-rank p = 0.03), while those with RV-RWT ≥0.21 and mid-term RV reverse remodeling had the best long-term outcomes. Patients with RV-RWT <0.21 and without mid-term RV reverse remodeling, on the other hand, had worse long-term outcomes than other sub-groups. In conclusions, RV-RWT could predict mid-term RV reverse remodeling after treatment in PH patients, and was associated with long-term outcomes. Our finding may have clinical implications for better management of PH patients.

Poly(n-alkylsilsesquioxane) liquids prepared by cosolvent-free hydrolytic polycondensation of n-alkyltrialkoxysilanes: effects of liquid-liquid phase separation during aging and alkyl chain length on structure and viscosity.

The effect of the alkyl chain length and alkoxy groups on the viscosity and related properties of polysilsesquioxanes (PSQs) prepared by cosolvent-free hydrolytic polycondensation from n-alkyltrialkoxysilane-water binary systems via aging was investigated. n-Alkyltrialkoxysilanes with ethyl, n-propyl, and n-butyl groups gave PSQ liquids, whereas those with methyl groups yielded gels. The viscosity of the PSQ liquids remained stable over a month at room temperature despite the presence of many SiOH groups, and decreased with an increase in the alkyl chain length. The aging step was crucial for obtaining PSQ liquids with low viscosities, and both n-alkyltrimethoxysilane and n-alkyltriethoxysilane with the same alkyl group produced PSQ liquids with comparable viscosities. However, during aging, liquid-liquid phase separation occurred only in the solutions derived from alkyltrimethoxysilanes. These observations confirmed that liquid-liquid phase separation is not essential for the preparation of PSQ liquids. The temperature dependence of the viscosity indicated that the PSQ liquids are fragile.