Although the addition of bevacizumab to platinum-based combination chemotherapy has been recommended as a standard regimen for patients with advanced or recurrent cervical cancer, there is no clear evidence regarding the effectiveness of bevacizumab monotherapy as salvage chemotherapy. This study prospectively examined the efficacy and safety of switching from platinum-based chemotherapy combined with bevacizumab to single maintenance therapy in patients with advanced or recurrent cervical cancer. Patients were first treated with standard combination chemotherapy. However, if chemotherapy was discontinued because of an adverse event, bevacizumab monotherapy was continued for patients who agreed to participate in this study and provided written informed consent. The study protocol was approved by the Independent Review Board of Tohoku University School of Medicine (reception number 2017-1-540). A total of 15 patients (median age of 55 years, range 33-69 years) participated in this study. The median number of cycles of bevacizumab single maintenance administration was 8, and the main reasons for discontinuation were disease progression and adverse events. Bevacizumab single maintenance therapy had a disease control rate of 53.3% (CR 40%, PR 6.7%, SD 6.7%). The most frequent grade 3/4 clinical adverse events were proteinuria (5/15) and hypertension (4/15). No treatment-related deaths occurred. Bevacizumab single maintenance therapy was effective as salvage chemotherapy in patients with advanced or recurrent cervical cancer, and the safety profile was generally consistent with those reported in previous studies of bevacizumab monotherapy.

Management of nausea is an important dimension of palliative care. The first choice for treating nausea is antiemetics, but their efficacy is inadequate. Acupressure intervention for nausea in cancer patients has been studied as a non-pharmacological therapy, and appears to have had some effect. However, such a therapy has not been well reviewed in patients with terminal cancer. The purpose of this study was to clarify the feasibility of acupressure intervention and examine its safety and preliminary efficacy. We recruited cancer patients that fulfilled the eligibility criteria and were admitted to the palliative care unit, from August 2018 to February 2019, in Tohoku University Hospital, Japan. We conducted a longitudinal assessment of acupressure intervention in a single arm. We identified the patient’s research accomplishments and evaluated possible fainting due to the vagal reflex and symptom severity. Descriptive statistics were used to calculate the completion rate for the feasibility and Wilcoxon signed-rank tests to compare the average of continuous variables for the safety and efficacy. Twelve patients participated in this study and completed the procedure. Their average age was 70 years (SD = 9.3), and the most common primary cancer sites were the rectum and pancreas. The blood pressure and pulse rate did not drop sharply. Four patients exhibited decreased nausea but there was no statistically significant difference (P = 0.5). We suggested that acupressure has high feasibility and safety, as an intervention for patients with terminal cancer. However, no significant differences were observed regarding its effect on nausea.

The exact incidence of acute kidney injury (AKI) during chemotherapy for acute lymphoblastic leukemia (ALL)/lymphoblastic lymphoma (LBL) is unknown. Furthermore, childhood cancer survivors are at risk of AKI-chronic kidney disease transition. Thus, early diagnosis of AKI is crucial. This study aimed to elucidate the incidence of AKI in patients undergoing chemotherapy for pediatric ALL/LBL and to compare the usefulness of serum cystatin C (CysC)- and creatinine (Cr)-based estimated glomerular filtration rate (eGFR) as diagnostic measures. Data of 16 patients with ALL/LBL treated with a total of 75 courses of chemotherapy were retrospectively analyzed. CysC- and Cr-based eGFR were measured before and three times per week during therapy. To calculate the eGFR, an equation for Japanese children was used. AKI was diagnosed when eGFR dropped by ≥ 25% from the highest eGFR value obtained during the latest 2 weeks since the start of chemotherapy. AKI was graded based on the pediatric Risk, Injury, Failure, Loss, End Stage Renal Disease scale. All patients developed AKI during chemotherapy; however, more than 90% of the cases were mild and eventually recovered. No significant differences were found in the incidence of AKI between CysC- and Cr-based eGFR (p = 0.104). The median time to AKI diagnosis was significantly shorter in the CysC-based eGFR than in the Cr-based eGFR (8 vs. 17 days, p < 0.001). In this study, all patients with pediatric ALL/LBL could develop mild AKI during treatment. CysC-based eGFR is a more effective measure than Cr-based eGFR for the early diagnosis of AKI.

Ulcerative colitis is chronic immune-mediated disorder that affects primarily colonic mucosa. The metabolic syndrome has increasing global prevalence with a significant impact on biology of chronic diseases, such as ulcerative colitis. Today it is known that the metabolic syndrome attenuates severity of ulcerative colitis. Still, there is no evidence that different stages of metabolic syndrome alter the course of the ulcerative colitis. The aim of this study was to dissect out how progression of the metabolic syndrome impacted the biology of ulcerative colitis and severity of clinical presentation. Seventy-two patients (41 men and 31 women, 22-81 years old) were enrolled in this observational cross-sectional study. Concentrations of pro- and anti-inflammatory cytokines in serum and feces samples were measured and phenotype of colon infiltrating cells was analyzed. Patients in the terminal phase of the metabolic syndrome have clinically and pathohistologically more severe form of ulcerative colitis, which is followed by decreased concentrations of systemic galectin-1, increased values of systemic pro-inflammatory mediators and increased influx of lymphocytes in affected colon tissue. Our data suggest that reduced concentrations of galectin-1 and predomination of the pro-inflammatory mediators in patients with terminal stage of the metabolic syndrome enhance local chronic inflammatory response and subsequent tissue damage, and together point on important role of galectin-1 in immune response in ulcerative colitis patients with the metabolic syndrome.

The semi-sitting position is well known to neurosurgeons. However, there are few reports of microvascular decompression surgery for glossopharyngeal neuralgia performed using the semi-sitting position. The semi-sitting position is not widely adopted in Japan, but it is considered to be a very useful neurosurgical position. Microvascular decompression surgery for glossopharyngeal neuralgia is a relatively rare procedure, and the semi-sitting position is very effective, considering the possibility of intraoperative cardiac arrest and postoperative complications of lower cranial nerve palsy. This report describes two cases of glossopharyngeal neuralgia operated in the semi-sitting position. Microvascular decompression was performed on both patients, and postoperative pain controls were good and no complications were observed. We show that the use of the semi-sitting position to perform microvascular decompression for glossopharyngeal neuralgia provides an excellent surgical view of the brainstem.

Circular RNAs (circRNAs) feature prominently in regulating tumor progression. The study aims to investigate the role and mechanism of circ_0046264 in osteosarcoma. In this study, dysregulated circRNAs in osteosarcoma tissues and adjacent tissues were screened out by analyzing circRNA microarray (GSE140256). The expressions of circ_0046264 in 58 osteosarcoma tissues and 4 osteosarcoma cell lines were detected by quantitative real-time polymerase chain reaction. Subsequently, the relationship of circ_0046264 expression level and clinical features were analyzed. Ethyldeoxyuridine assay and Transwell assay were employed to detect cell viability, migration and invasion. Dual-luciferase reporter assay was adopted to confirm the targeting relationships between circ_0046264 and microRNA-940 (miR-940), as well as miR-940 and secreted frizzled related protein 1 (SFRP1). SFRP1 expression was determined by western blot. Here, we demonstrated that circ_0046264 was greatly down-regulated in osteosarcoma and was inversely related to tumor size and Ki67 expression. Functional assays validated that circ_0046264 could restrain the proliferation, migration and invasion. Mechanistically, circ_0046264 could adsorb miR-940 and indirectly modulate SFRP1 expression. Furthermore, the transfection of miR-940 mimics or SFRP1 small interfering RNA could reverse the impact of circ_0046264 overexpression on the growth, migration and invasion of osteosarcoma cells. Taken together, circ_0046264 is a tumor suppressor to inhibit the osteosarcoma progression via modulating the miR-940 / SFRP1 axis.

Differentiating neutrophils based on the count of nuclear lobulation is useful for diagnosing various hematological disorders, including megaloblastic anemia, myelodysplastic syndrome, and sepsis. It has been reported that one-fifth of sepsis-infected patients worldwide died between 1990 and 2017. Notably, fewer nuclear-lobed and stab-formed neutrophils develop in the peripheral blood during sepsis. This abnormality can serve as an early diagnostic criterion. However, testing this feature is a complex and time-consuming task that is rife with human error. For this reason, we apply deep learning to automatically differentiate neutrophil and nuclear lobulation counts and report the world’s first small-scale pilot. Blood films are prepared using venous peripheral blood taken from four healthy volunteers and are stained with May–Grünwald Giemsa stain. Six-hundred 360 × 363-pixel images of neutrophils having five different nuclear lobulations are automatically captured by Cellavision DM-96, an automatic digital microscope camera. Images are input to an original architecture with five convolutional layers built on a deep learning neural-network platform by Sony, Neural Network Console. The deep learning system distinguishes the four groups (i.e., band-formed, two-, three-, and four- and five- segmented) of neutrophils with up to 99% accuracy, suggesting that neutrophils can be automatically differentiated based on their count of segmented nuclei using deep learning.

The multikinase inhibitor, regorafenib, is known to exert its antitumor effects by targeting several kinases, inhibiting interstitial intracellular signaling and suppressing tumor cell proliferation. Regorafenib causes gastrointestinal perforation and gastrointestinal fistula as adverse events, and discontinuation is recommended if these adverse events occur during administration. However, there are no prescribed standards for re-administration after discontinuation and for administration in patients with a history of gastrointestinal perforation. Herein, we report a case of gastrointestinal perforation in a patient, with a history of gastrointestinal microperforation, undergoing bevacizumab therapy, within a few days of starting regorafenib; this had a significant effect on the prognosis. The site of gastrointestinal perforation was consistent with previously reported sites around the tumor and at the anastomotic site. Based on a review of literature and our experience with the case presented here, we recommend that administration of regorafenib to patients with a history of gastrointestinal perforation should be avoided to the extent possible. Moreover, in case of prior administration of a drug reported to cause gastrointestinal perforation, such as an anti-VEGFR drug, the risk of gastrointestinal perforation should be considered during the administration of regorafenib. In the event of complaints, such as abdominal pain, gastrointestinal perforation should be considered as a differential diagnosis and appropriate tests and treatments should be initiated at an early stage.

Saliva is used as a diagnosis and monitoring tool for various diseases because it can maintain the balance of the oral ecosystem and reflect the physiological and pathological state of the body. Because women suffer more fatigue than men because of physiological, psychological, and social factors, individual management strategies are needed to evaluate mental health and oral diseases. Therefore, this study examined the oral health risk level from seven saliva factors using a saliva multi-test system for adult women to confirm the possibility of screening for sleep disorders. The saliva of 83 adult female participants was surveyed along with a self-reported questionnaire consisting of seven subjective oral health symptoms and three questions about sleep disorders. Seven saliva factors were evaluated using the saliva multi-test system (SiLL-Ha ST-4910) to assess the oral health risk levels. In the tooth health risk groups, the acidity was high, while the buffering capacity was low (p < 0.001). The periodontal health risk groups showed significant differences in acidity, occult blood, leukocytes, proteins, and ammonia (p < 0.05). The oral malodor risk group had higher levels of cariogenic bacteria, occult blood, leukocytes, and ammonia (p < 0.05). In groups with ‘irregular sleep times’ and ‘insomnia’, the acidity was high, and the buffering capacity was low (p < 0.001). This study confirmed the relevance of saliva factors and sleep disorder. Therefore, an evaluation using saliva was confirmed for oral health risk assessments and as an early screening tool for sleep disorders.

Heart failure is a common cardiovascular disease, which has been regarded as one of the highest health care costs with high morbidity and mortality in the western countries. Long noncoding RNAs have been widely reported to regulate the initiation or progression of cardiovascular diseases. However, the specific role of SOX2 overlapping transcript (SOX2-OT) in ischemic heart failure remains uncharacterized. The present study aimed to explore the function and mechanism of SOX2-OT in ischemic heart failure. The starBase website was used to predict potential miRNAs or target mRNAs. Western blot assay was implemented to test collagen protein levels. Functional assays were conducted to evaluate the effects of SOX2-OT on H9c2 cell viability and apoptosis. RNA pull down and luciferase reporter assays were used to confirm the combination between miR-215-5p and SOX2-OT. We found out that SOX2-OT level was increased by oxygen glucose deprivation/reoxygenation treatment in H9c2 cells. Silencing of SOX2-OT ameliorated cell injury by promoting cell viability, inhibiting cell apoptosis and reducing productions of collagens. Mechanistically, miR-215-5p was confirmed to bind with SOX2-OT after prediction and screening. In addition, we discovered that miR-215-5p negatively regulated zinc finger E-box binding homeobox 2 (ZEB2) protein level by directly binding with ZEB2 3′ untranslated region. Finally, we verified that SOX2-OT aggravated cell injury by targeting ZEB2 in H9c2 cells. In conclusion, SOX2-OT aggravated heart failure in vivo and promoted H9c2 cell injury via the miR-215-5p/ZEB2 axis in vitro, implying a novel insight into heart failure treatment.

Prognosis of patients with hepatocellular carcinoma remains poor because of progression of hepatocellular carcinoma and high recurrence rates. Cyclin D2 (CCND2) plays a vital role in regulating the cell cycle; indeed, aberrant methylation of CCND2 is involved in the development of hepatocellular carcinoma. Therefore, we aimed to investigate levels of CCND2 methylation in patients with hepatitis B virus (HBV)-associated hepatocellular carcinoma and to evaluate its prognostic significance after hepatectomy. In total, 257 subjects were enrolled (166 hepatocellular carcinoma patients undergoing surgical resection, 61 chronic hepatitis B (CHB) patients, and 30 healthy controls). CCND2 methylation in peripheral blood mononuclear cells was measured quantitatively using MethyLight. We found that CCND2 methylation levels in patients with HBV-associated hepatocellular carcinoma were significantly higher than in CHB patients (P < 0.001) or healthy controls (P < 0.001). Within the hepatocellular carcinoma group, CCND2 methylation levels were higher in patients with portal vein invasion, early tumor recurrence, TNM III/IV stage, and tumor size ≥ 5 cm (P < 0.05). Furthermore, higher levels of CCND2 methylation were associated with worse overall survival and disease-free survival (P = 0.005 and P < 0.001, respectively). Multivariate analysis identified CCND2 methylation as an independent prognostic factor for early tumor recurrence (P = 0.021), overall survival (P = 0.022), and disease-free survival (P < 0.001) in hepatocellular carcinoma patients after resection. In conclusion, hypermethylation of CCND2 may have clinical utility for predicting a high risk of poor prognosis and early tumor recurrence in patients with HBV-associated hepatocellular carcinoma after hepatectomy.