Simple hepatic cysts are typically saccular, thin-walled masses with fluid-filled epithelial lined cavities. They arise from aberrant bile duct cells that develop during embryonic development. With the development of diagnostic modalities such as ultrasonography (US), CT, and MRI, simple hepatic cysts are frequently detected in clinical examinations. US is the most useful and noninvasive tool for diagnosis of simple hepatic cysts and can usually differentiate simple hepatic cysts from abscesses, hemangiomas, and malignancies. Cysts with irregular walls, septations, calcifications, or daughter cysts on US should be evaluated with enhanced CT or MRI, to differentiate simple hepatic cysts from cystic neoplasms or hydatid cysts. Growth and compression of hepatic cysts cause abdominal discomfort, pain, distension, and dietary symptoms such as nausea, vomiting, a feeling of fullness, and early satiety. Complications of simple hepatic cysts include infection, spontaneous hemorrhage, rupture, and external compression of biliary tree or major vessels. Asymptomatic simple hepatic cysts do not require treatment. Treatment for symptomatic simple hepatic cysts includes percutaneous aspiration, aspiration followed by sclerotherapy, and surgery. The American College of Gastroenterology clinical guidelines recommend laparoscopic fenestration because of its high success rate and low invasiveness. Percutaneous procedures for treatment of simple hepatic cysts are particularly effective for immediate palliation of patient symptoms; however, they are not generally recommended because of the high rate of recurrence. Management of simple hepatic cysts requires correct differentiation from neoplasms and infections, and selection of a reliable treatment.

Molecular aspects of living systems are important because it is the most basic aspects of life as exemplified in biochemistry and structural biology. Since molecules move due to interactive forces between atoms, physics plays an important role to understand the dynamic phenomena of living systems. Here we review our multiscale approaches for computationally treating different levels of molecular motions: vibrational dynamics of molecules, conformational change of biomolecules, and cellular dynamics using statistical-mechanics-based models.

Depressive symptoms are prevalent in cancer patients and are one of the most distressing symptoms in this population. Although mental health professionals such as psychiatrists and psychologists are now engaged in cancer care, the management of depressive symptoms in cancer patients needs further improvement. Peer support interventions (PSIs) in cancer care have attracted substantial attention and have several advantages over support by medical professionals, potentially improving depressive symptoms in cancer patients. However, there may be some potential risks. Several strategies using PSIs have been developed to improve depressive symptoms and have been evaluated in randomized controlled trials. The strategies include education on stress management skills, promoting emotional support, counseling on specific topics that are difficult to discuss with others, helping patients navigate the use of resources, and promoting health-related behaviors to decrease depressive symptoms. In this paper, we present recent findings on PSIs in cancer, focusing on randomized controlled trials.

Adjuvant chemotherapy is administered to cancer patients after curative resection but is unnecessary when patients without micro-metastatic lesions undergo a perfectly curative surgical procedure. Patients who need adjuvant chemotherapy are those with micro-metastases outside the resection area that are not detectable by imaging, despite curative resection at primary sites. If biomarkers that reflect metastatic potential could be developed, personalized adjuvant chemotherapy could be provided in clinical settings. Actinin-4 (ACTN4, gene name ACTN4) is an actin-bundling protein identified in 1998 as a novel molecule involved in cancer invasion and metastasis. Overexpression of actinin-4 protein in cancer cells leads to an invasive phenotype, and patients with gene amplification of ACTN4 have a worse prognosis than patients with a normal copy number for cancers of the pancreas, lung, and salivary glands, among others. This review summarizes the biological roles of actinin-4 in cancer invasion and metastasis and examines the potential usefulness of actinin-4 as a biomarker for evaluation of metastatic ability.

In Japan, deaths in bathtubs or bathtub deaths are frequently investigated as unnatural deaths. About 19,000 bathtub deaths occur annually in Japan. This pattern of death has become a social issue in forensic pathology and emergency medicine and public health. It is assumed that the death of an adult by drowning in a bathtub cannot be avoided due to disturbance of consciousness. The PubMed database was used for literature search using the retrieval words, "bathing "OR" bathtub "AND" submersion "OR" drowning "OR" death "OR" cardiopulmonary arrest". From the epidemiological characteristics and pathophysiological findings of bath mortality in Japan, three etiologies of impaired consciousness have been proposed: acute ischemic heart failure, heatstroke, and blood pressure fluctuation. Moreover, other causes such as epilepsy and alcohol or drug intake cannot be ignored as potential risks for death in a bathtub. It is also important to note the possibility of suicide and, although extremely rare, homicide in a bathtub. Despite research, the exact causal relationship between bathtub bathing and death remains unclear. Further, the cause of death by postmortem investigation is not always easily determined. Hence, it is desirable to carry out a field survey of causes of death, including bathing conditions, and, wherever possible, a complete autopsy survey. An exclusion of critical cases such as crime-related death, suicide, drug poisoning, and carbon monoxide poisoning is optimal. Of the many hypotheses about the causes of bathtub mortality, the most consistent hypothesis will be medically inferred from the death history, case findings, and test results.

Background: Miscarriage occurs in 10-15% of pregnancies and recurrent pregnancy loss (RPL) occurs in 1% of couples hoping for a child. Various risk factors, such as thrombophilia, uterine malformation, and embryonic chromosomal aberration cause RPL. We hypothesized that antithrombotic therapy for RPL patients with thrombophilia would reduce miscarriage due to thrombophilia, which would reduce the total miscarriages and result in a relative increase in miscarriage due to embryonic chromosomal aberrations. In this study, we investigated the incidence of chromosomal aberrations in products of conception in RPL patients with and without antithrombotic therapy. Methods: We performed a single-center, retrospective review of cases diagnosed as miscarriage with embryo chromosome analysis between July 1, 2000, and May 31, 2019. Rates of chromosomal aberration were compared between RPL patients with and without thrombophilia or antithrombotic therapy. Results: One hundred and-ninety RPL cases were analyzed. The average age was 37.4 ± 4.3 years, and the average number of previous pregnancy losses was 2.2 ± 1.1. The overall chromosomal aberration rate was 67.4% (128/190). There was no difference in the chromosomal aberration rate between the factors for RPL, with or without thrombophilia, and antithrombotic therapy. Only advancing maternal age had significant correlation to increased embryo chromosomal aberration rates. Conclusions: With or without antithrombotic therapy, miscarriage was caused by embryonic chromosome abnormalities at a certain rate. Antithrombotic therapy in RPL patients with thrombophilia may reduce abortions due to thrombophilia, which may also normalize the rate of embryonic chromosome aberrations in the subsequent miscarriages.

Background: Children who survive traffic accidents, and their parents, may develop post-traumatic stress disorder (PTSD) or related symptoms (depression or anxiety), which can hinder the children's development and the parents' ability to provide effective care. In Japan, the PTSD incidence rate after traffic accidents and its related factors remain unclarified. Methods: The participants were 79 children and 104 parents. The children were aged 3-18 years when injured. From August through December 2015, participants completed a self-reported questionnaire survey that comprised the 15-item Post-traumatic Stress Symptoms for Children and the Japanese version of the Impact of Event Scale-Revised. The children's Injury Severity Score (ISS) was also obtained from their medical records. Correlation analysis, analysis of variance, and multiple regression analysis were conducted. Results: Among the children and parents, 10.1% and 22.1%, respectively, were deemed to be at high risk of PTSD. Their stress scores were significantly positively correlated with each other and negatively correlated with the children's age at the time of the accident. Parents who witnessed their children's accidents and those whose children were hospitalized were more stressed. Neither the children's nor the parents' risk for PTSD was associated with ISS or the amount of time since the accident. Conclusions: A system that simultaneously works with children and parents to support both parties' psychological recovery is required. To ensure psychological care post-injury, it is necessary to evaluate PTSD risk, regardless of injury severity. Implementing preventive and early interventions can prove more valuable than awaiting natural recovery.

Background: Although rikkunshito was reported to be effective for treatment-resistant nonerosive gastroesophageal reflux disease (NERD), it is unclear which Rome IV subgroups of NERD patients benefit fromrikkunshito. This study investigated the efficacy of rikkunshito in patients with functional heartburn. Methods: Ten patients with functional heartburn who experienced symptoms of dyspepsia were enrolled and received rikkunshito for 8 weeks. The Frequency Scale for Symptoms of GERD (FSSG), the Japanese translation of the Quality of Life in Reflux and Dyspepsia (QOLRAD-J) questionnaire, and the Hospital Anxiety and Depression Scale (HADS) before, and 4 and 8 weeks after, administration were evaluated. Overall treatment efficacy (OTE) was evaluated at 8 weeks after administration. Results: One patient voluntarily withdrew from treatment at 4 weeks. Total FSSG score was significantly (P = 0.039) lower 8 weeks after treatment or at discontinuation (13.2 ± 8.0) than before treatment (18.3 ± 10.7). Although QOLRAD-J score was higher 8 weeks after treatment or at discontinuation than before treatment, the difference was not significant different. HADS score was not significantly lower 8 weeks after treatment or at discontinuation, as compared with before treatment. However, total FSSG and HADS anxiety scores were positively correlated (correlation coefficient: 0.684, P = 0.027). Conclusions: The findings from this first study of the efficacy of rikkunshito for functional heartburn suggest that it might be effective in such patients.

Background: PIK3CA is associated with tumor progression, and the prevalence of PIK3CA mutation is high in breast cancer. Liquid biopsy offers convenient, noninvasive, and real-time insight into genetic alteration. In this study, we used liquid biopsy to detect PIK3CA mutations in patients with breast cancer. Methods: We recruited patients with histologically confirmed breast cancer and distant metastases between April 2020 and September 2020. Circulating DNA was extracted from plasma (ctDNA) and exosomes (exoDNA). PIK3CA mutations (exons 9 and 20) were analyzed by droplet digital PCR. Results: Of the 52 patients recruited, 16 had PIK3CA mutations in tumor tissue or blood: 9 had exon 9 mutations (E542K and E545K) and 8 had exon 20 mutations (H1047 L and H1047R). In 8 (15%) of the 52 patients, PIK3CA mutations were detected by liquid biopsies using ctDNA in 5 (9%), exoDNA in 6 (11%), and both ctDNA and exoDNA in 3 (6%). Of the 8 patients with PIK3CA mutations detected by liquid biopsies, 3 had no PIK3CA mutations in the primary tumors. Conclusions: PIK3CA mutations can be detected by liquid biopsy even in patients with no PIK3CA mutations in their primary tumors; thus, combination analysis using tissue and liquid biopsies can provide clinically useful information for patients with breast cancer.

Background: The number of patients on peritoneal dialysis (PD) in our hospital has increased during the past 5 years, but the number discontinuing PD has also increased. The purpose of this study was to identify the risk factors for PD discontinuation by analyzing the association between technical survival period (defined as the duration of PD) and various clinical factors. Methods: We retrospectively investigated 87 patients who were started on PD at our hospital and attended regularly from April 2015 to March 2020, and we analyzed the association between technical survival period and various clinical factors. We also looked for associations between technical survival period and hospitalizations for heart failure, peritonitis, and exit-site infections among patients undergoing PD. Results: The patients using renin-angiotensin-aldosterone system inhibitors (RASi) (P = 0.0218), those with left ventricular ejection fraction (LVEF) > 50% (P = 0.0194) when they started PD, and those with estimated glomerular filtration rate (eGFR) ≥ 6 (mL/min/1.73 m²) (P = 0.0013) at the initiation of PD showed significantly longer technical survival period, and those who were hospitalized for heart failure had significantly shorter period (P = 0.0008). Conclusion: Treatment of RASi, LVEF > 50% and eGFR ≥ 6 mL/ min/1.73 m² when the initiation of PD and better volume control to prevent ultrafiltration failure and heart failure may improve technical survival period in patients undergoing PD.

Background: This study evaluated clinical outcomes of elderly adults with coronal shear fractures (CSFs) of the distal humerus treated by open reduction and internal fixation (ORIF). Methods: Between April 2002 and March 2019, data from eight elderly patients (76.3 ± 5.1 years) with CSFs of the distal humerus were analyzed retrospectively. Postoperative complications, range of motion of the elbow joint, and functional elbow scoring (Mayo Elbow Performance Score; MEPS) were assessed. Results: The mean follow-up duration was 23.6 ± 13.9 months. CSFs were treated by a buried implantable headless screw or Kirshner wires or bioresorbable screw with/without lateral locking plates. There were no superficial or deep infections or elbow joint instability. Seven patients obtained fracture healing, but one patient exhibited nonunion. Osteochondritis dissecans was present in one patient. Three patients had a step-off deformity (>2 mm) of the articular surface. Two patients exhibited collapse of the fractured articular surface. A patient with severe comminution of both the capitellum and trochlea exhibited collapse of the entire articular surface, with osteonecrosis of the capitellum and trochlea. Mean range of motion of the elbow was 116.3±12.7° of flexion and -28.8±14.1° of extension. The mean MEPS was 78.8±10.2 points, representing patients scored as excellent (n=1), good (n=3), and fair (n=4). Conclusions: ORIF yielded satisfactory outcomes for elderly adults with noncomminuted CSFs of the distal humerus. However, treatment of comminuted articular fracture fragment and complex posterior fracture remains challenging.

Background: The emergence of molecular targeted therapies (MTTs) has altered the treatment landscape for hormone receptor-positive (HR+), human epidermal growth factor 2-negative (HER2−) metastatic breast cancer (MBC). The objective of this study was to describe treatment patterns, clinical outcomes, and safety profiles for patients with HR+/HER2− MBC treated with palbociclib, abemaciclib, or everolimus in clinical practice. Methods: Forty-five patients with HR+/HER2− MBC were enrolled; 40 received MTT as the third line or later and 5 received MTT as the first/second line. The results were compared with those of clinical trials. Results: Median overall progression-free survival (PFS) was 5.3 months (95% confidence interval [CI] 2.8-8.4), and PFS was similar for patients receiving first/second line (5.5 months, 95% CI 1.8-) and third line or later (5.1 months, 95% CI 2.8-9.4) treatments. Eleven patients continued with the same regimen for >1 year; treatment is ongoing for 15 patients. In 23 patients (51%), everolimus was administered before cyclin-dependent kinase (CDK) 4/6 inhibitors. The most frequent grade 3 or worse adverse event (AE) with CDK4/6 inhibitors was neutropenia, whereas grade 3 or worse AEs with everolimus were Pneumocystis pneumonia, sepsis, and stomatitis. Conclusions: MTT was mostly used in third or later lines, and PFS was similar for patients receiving first/second line and third or later line treatments. However, this study included heavily treated patients and a small number of cases. Treatment options should consider maximal patient benefit, as indicated by the results of clinical trials.

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a novel, highly pathogenic coronavirus that has spread rapidly worldwide and caused an international public health emergency. Patients with hematological cancers are regarded as a high-risk group for coronavirus disease 2019 (COVID-19). However, few reports have investigated factors that might account for the differential severity of COVID-19 disease in these patients. Methods: Gene expression of SARS-CoV-2 entry-promoting factors and entry-restricting factors and the associated effects on myeloid malignancies were evaluated. Gene expression levels of 11 SARS-CoV-2 entry-promoting factors and 4 SARS-CoV-2 entry-restricting factors were analyzed in patients with myelodysplastic syndromes (MDS), chronic myeloid leukemia (CML), and acute myeloid leukemia and its subtypes. Results: Expression levels of promoting and restricting factors were most affected in MDS. Specifically, 4 of the 11 analyzed SARS-CoV-2 entry-promoting factors were significantly increased (TMPRSS4, CD209, CLEC4G, and CTSB), and 2 of the 4 analyzed SARS-CoV-2 entry-restricting factors were significantly decreased (IFITM1 and IFITM2) in MDS. Patients with CML also exhibited a pattern of significant changes in SARS-CoV-2 entry-promoting and entry-restricting factors. Five of the 11 analyzed SARS-CoV-2 entry-promoting factors were significantly increased (ACE2, TMPRSS2, TMPRSS4, ANPEP, CD209), and 1 of the 4 analyzed SARS-CoV-2 entry-restricting factors was significantly decreased (LY6E) in CML. Conclusions: The present and past results highlight the importance of investigating SARS-CoV-2 entry-promoting factors and entry-restricting factors, because of their crucial role in determining the differential severity of COVID-19 disease.

Background: Postprandial syndrome is characterized by hunger, weakness, and anxiety neurosis after meals. Although abnormal glucagon response is a suggested mechanism, inaccuracies in conventional glucagon measurement methods have prevented precise analysis. Recently, a more reliable dual-antibody sandwich enzyme-linked immunosorbent assay for glucagon was developed. Methods: We conducted a 75-g oral glucose tolerance test (OGTT) extending to 4 hours in 14 patients with idiopathic postprandial syndrome. In addition to blood glucose and insulin, glucagon concentration was measured with the novel method and analyzed retrospectively. Results: Median (lower quartile, upper quartile) age and body-mass index were 40 years (30, 49) and 24.9 (23.1, 26.2), respectively. The OGTT revealed that one patient had a diabetic pattern, and two were glucose intolerant. Fasting insulin was 7.6 μU/mL (6.8, 8.8) and reached 73.7 μU/mL (54.3, 82.6) at 30 min. Insulin remained elevated until 180 min. Fasting glucagon was 21.1 pg/mL (16.1, 33.8), reached a nadir of 6.9 (3.5, 10.3) at 60 min, one-third the baseline level, and remained suppressed until 180 min. We observed two types of glucagon dynamics: a lower fasting glucagon with further suppression and a normal or higher fasting glucagon with a subsequent large decrease. Conclusions: These data suggest that glucagon suppression is greater in patients with idiopathic postprandial syndrome than in previously studied healthy subjects. The present data will contribute to our understanding and future research of this syndrome.

Background: Knees with severe varus osteoarthritis can develop medial structure contracture. However, there is no report on the relationship between severity of varus deformity and contracture of the medial structure. We aimed to determine the threshold angle that could be corrected in proportion to the width of medial osteophyte removal and to examine correction differences between angles larger and smaller than the threshold angle in total knee arthroplasty. Methods: This study included 27 varus osteoarthritic knees scheduled for total knee arthroplasty (TKA). A navigation system was used to measure hip-knee-ankle angle (HKA) in all knees at maximum extension and 30˚ and 60˚ flexion, before and after osteophyte removal and with and without external 10 N-m valgus torque loads. Subsequently, resected osteophyte widths were measured. Mean correction angle per 1 mm of osteophyte removal was calculated, and the threshold angle was calculated with the receiver operating characteristic curve. HKA differences were compared against deformities larger and smaller than the threshold angle. Results: Mean osteophyte width was 7.1±2.20 mm. Osteophyte removal produced a mean 3.1° correction, which equaled a 0.4° correction per 1 mm of osteophyte width removal. The varus deformity threshold angle was 9.5°. However, when comparing groups with angles larger and smaller than the threshold angle, there was no significant difference in HKA difference between each step and flexion angle. Conclusions: The threshold angle for expected correction with medial osteophyte removal was 9.5˚. However, because there were no differences in correction between those with angles larger or smaller than this, medial structure contracture seemed to be unrelated to the severity of deformity.

Background: Adult-onset Still's disease (AOSD) is a systemic autoinflammatory disorder accompanied by skin eruption. However, typical skin eruptions, such as evanescent, salmon-pink erythema, are not specific to AOSD and dermatologists often face difficulty in diagnosing AOSD. In this study, we examined serum IL-18 levels as well as IL-6, ferritin and C-reactive protein in 6 Japanese patients with AOSD. Methods: Serum levels of IL-6 and IL-18 were evaluated in the acute phase and at the time of remission. Serum levels of IL-6 were analyzed using a commercial chemiluminescent enzyme immunoassay (CLEIA; SRL, Tokyo, Japan). Serum IL-18 levels were measured using a commercial ELISA kit (Medical & Biological Laboratories Co., LTD. Nagoya, Japan). Result: In active AOSD, serum ferritin levels and CRP levels were above normal range in 6 patients. In remission, serum ferritin levels of 3 patients were slightly above the normal range, while CRP serum levels of 6 patients were all normalized. Serum IL-18 levels were markedly elevated in 5 cases during the acute phase. In remission, serum IL-18 levels remained at higher values than the normal range in 5 cases. Serum IL-6 levels were also highly elevated in 5 patients in active AOSD and became normalized in remission except in case 2. Conclusion: High levels of serum IL-18 will be a clue to the diagnosis of AOSD. CRP is also useful biomarker for monitoring disease activity compared with IL-6 and IL-18.

Amyloid light-chain (AL) cardiac amyloidosis can cause restrictive cardiomyopathy, which has a poor prognosis. Although electrocardiography (ECG) is useful for its diagnosis and management, there are few reports on the long-term follow-up of electrocardiographic changes in affected patients. The present patient was a 62-year-old woman who visited our hospital for assessment of palpitations and lower leg edema. A chest radiograph showed cardiac enlargement, and ECG revealed sinus rhythm, first-degree atrioventricular block, low QRS voltage in the limb leads and a pseudo-myocardial infarction pattern in the precordial leads. Echocardiography revealed left ventricular hypertrophy with systolic and diastolic dysfunction. Immunoelectrophoresis demonstrated M-protein (IgGλ), and bone marrow biopsy suggested IgGλ-type plasmacytoma. Myocardial biopsy findings were compatible with cardiac amyloidosis. On the basis of these findings, we diagnosed AL cardiac amyloidosis. Melphalan-prednisolone (MP) therapy was started in conjunction with treatment for non-sustained ventricular tachycardia and congestive heart failure. Two years and 4 months later, the sinus rhythm converted to atrial tachycardia. At a follow-up examination at 4 years and 8 months, right branch block appeared. After that, intraventricular conduction worsened, and the low voltage in the limb leads was not observed. Seven years after diagnosis, she was hospitalized for treatment of pneumonia and heart failure with tachycardia. On the seventh day of hospitalization, heart rhythm changed to atrial stand-still with escaped ventricular rhythm and she died of cardiac arrest. These ECG changes are valuable information regarding the pathophysiological changes that occur in AL cardiac amyloidosis.