Background: The potassium voltage-gated channel subfamily Q member 1 (KCNQ1) gene has recently received much attention as a candidate susceptibility gene for type 2 diabetes mellitus, especially in Asian populations. We previously reported that Kcnq1 mutant mice exhibit reduced insulin secretion and hyperglycemia due to a decrease in pancreatic β-cell mass. Through in vivo and in vitro analyses, we ascertained that this mechanism is the result of the downregulation of the non-coding RNA ‘Kcnq1ot1,’ which is expressed in the paternal allele of the Kcnq1 gene region, causing an increase in the expression of the cell cycle inhibitor cyclin dependent kinase inhibitor 1C (Cdkn1c). It was found that decreased Kcnq1ot1 expression resulted in pancreatic β-cell failure; however, the degree of pancreatic β-cell volume reduction was not severe. Methods: We induced obesity in Kcnq1ot1 truncation mice by feeding them a high-fat diet and evaluated pancreatic β-cell mass. Results: In the present study, we reveal that CCAAT/enhancer binding protein beta (C/EBPβ), which is expressed at higher levels in pancreatic β-cells in obese individuals, further increases the expression of Cdkn1c, which is upregulated by the Kcnq1 gene mutation. We found that simultaneous Cdkn1c hypomethylation and C/EBPβ overexpression in pancreatic β-cells causes a synergistic decrease in pancreatic β-cell mass. Conclusion This finding suggests that the synergistic effect of genetic factors such as Kcnq1 gene mutations and environmental factors such as obesity and overeating, which lead to increased expression of C/EBPβ, contribute to the regulation of pancreatic β-cell mass. This study is the first to show that the Kcnq1 gene is related to pancreatic β-cell mass through genetic-environment interactions.

Objective: Almost half of all patients with cancer experience dyspnea, which can have various causes. Although systemic corticosteroids are administered to relieve symptoms, their efficacy has not been established. This systematic review aims to determine the efficacy of systemic corticosteroids for dyspnea in patients with cancer. Methods: CENTRAL, MEDLINE, EMBASE, and Ichushi-Web databases were searched for articles published from their inception to September 23, 2019, on studies of systemic corticosteroid administration for dyspnea in patients with cancer. The primary outcome measure was dyspnea intensity, as assessed by patient-reported outcomes. Secondary outcome measures were quality of life, delirium, and severe adverse events. Results: Two RCTs were included in the meta-analysis. With regard to alleviating dyspnea, the systematic corticosteroid group was associated with significantly greater dyspnea relief than the placebo group (mean difference: −0.71 [95% CI: −1.4 to −0.03]). However, a meta-analysis of quality of life and delirium could not be performed due to insufficient data. Analysis of severe adverse events showed no significant difference in their incidence between the corticosteroid and control groups (relative rate: 0.96 [95% CI: 0.19-4.93]). Conclusions: Systemic corticosteroids may be effective in treating dyspnea in patients with cancer, particularly those with lung involvement. Limiting the conditions for which corticosteroids are approved is expected to promote their appropriate use and minimize their adverse effects. However, further investigation is needed to determine the appropriate dosage, and the conditions in which corticosteroids are effective.

Background: Real-time ultrasound-guided catheterization of the internal jugular vein (IJV) is widely used for its safety and high success rate. However, it becomes difficult when the IJV’s cross-sectional area (CSA) is reduced. A reported technique applies manual pressure (with fingers) to the supraclavicular IJV to impede venous return and enlarge the distal CSA. While effective in previous studies, its clinical utility remains unclear, as those studies involved only healthy volunteers and used blind technique. Therefore, this study aimed to evaluate the efficacy of our novel ultrasound-guided compression of the proximal IJV. Methods: In this prospective observational study, 25 hospitalized patients were included. Two ultrasound machines were used: one to visualize the CSA of the distal IJV, and the other to apply and guide compression of the supraclavicular IJV, ensuring real-time confirmation of venous occlusion. Patients were asked about pain during the compression procedure. The primary outcome was the degree of dilation at the puncture site of the IJV. Results: All 25 patients (mean Sequential Organ Failure Assessment score: 5.2±3.6) completed the study. Supraclavicular IJV compression resulted in a significant increase in the CSA of the distal IJV by approximately 150%, from 0.4±0.3 cm² to 1.0±0.3 cm² (P<0.001). No patient reported any pain during the procedure. Conclusions Ultrasound-guided supraclavicular IJV compression significantly increased the CSA of the distal IJV in hospitalized patients. This method enhances vein visibility by increasing IJV volume, potentially improving the success and safety of central venous catheterization.

A 75-year-old woman was referred to our hospital with sudden onset of chest and back pain. She showed ventricular fibrillation during transportation and shock vitals on arrival at the hospital. An electrocardiogram (ECG) showed ST segment elevation in aVR, and emergency coronary angiography (CAG) was performed. CAG revealed malperfusion of the left main coronary artery (LMT) due to type A aortic dissection. Emergency percutaneous coronary intervention (PCI) was performed and coronary revascularization was achieved. Strict blood pressure management was performed in the intensive care unit. She underwent ascending aortic replacement two days after onset of the disease. Although she required long-term postoperative ventilator management, she did not develop low output syndrome (LOS). In this case, emergency PCI minimized myocardial ischemia, and LOS could have been avoided by waiting for circulation to recover and then performing surgery.

A 67-year-old man underwent endovascular aneurysmal repair for an abdominal aneurysm at another hospital about a year earlier. He presented to us with complaints of abdominal pain with an accompanying fever. Contrast-enhanced CT revealed a stent graft thrombus, with discontinuity of the aneurysmal wall, and a mass in the left retroperitoneal space, suggesting stent graft infection. The patient's fever initially subsided with antibiotic treatment, but soon recurred. Plain CT revealed an enlarged left retroperitoneal mass, which was determined to be a contained aneurysmal rupture. The stent graft was surgically removed urgently without incident and, upon examination of the removed stent graft, it was noted that there was a section of yellowish-white tissue attached to the stent graft and definitive evidence of infection was apparent. Thorough debridement of the aneurysmal wall was performed, leaving a segment of the posterior wall intact. In-situ reconstruction was carried out using a Gelsoft graft soaked in rifampicin. There was evidence of purulent pus outflow and cholecystitis during the ablation procedure of the hepatic flexure for omental filling. Post cholecystectomy, the reconstructed vascular graft was covered with omentum. A bacterium, Bacteroides thetaiotaomicron, was detected in the pus, bile, and on the stent graft removed during the surgical procedure. Subsequently, a diagnosis of hematogenous stent graft infection during the course of acute cholecystitis was made. The postoperative course of the patient was uneventful, with no recurrence of infection observed in the 3 months following surgical intervention.

Nicotine addiction is a concern worldwide. Most mechanistic investigations are on nicotine substance dependence properties based on its pharmacological effects. However, no effective therapeutic treatment has been established. Nicotine addiction is reinforced by environments or habits. We demonstrate the neurobiological basis of the behavioural aspect of nicotine addiction. We utilized the conditioned place preference to establish nicotine-associated behavioural preferences (NABP) in rats. Brain-wide neuroimaging analysis revealed that the medial prefrontal cortex (mPFC) was activated and contributed to NABP. Chemogenetic manipulation of µ-opioid receptor positive (MOR⁺) neurons in the mPFC or the excitatory outflow to the nucleus accumbens shell (NAcShell) modulated the NABP. Electrophysiological recording confirmed that the MOR⁺ neurons directly regulate the mPFC-NAcShell circuit via GABA_A receptors. Thus, the MOR⁺ neurons in the mPFC modulate the formation of behavioural aspects of nicotine addiction via direct excitatory innervation to the NAcShell, which may provide new insight for the development of effective therapeutic strategies.
Animals ; Nucleus Accumbens/drug effects* ; Prefrontal Cortex/drug effects* ; Nicotine/pharmacology* ; Receptors, Opioid, mu/metabolism* ; Male ; Rats ; Rats, Sprague-Dawley ; Tobacco Use Disorder/metabolism* ; Neurons/drug effects* ; Neural Pathways/drug effects*

Objective: To evaluate the efficacy of high-flow nasal cannula oxygen (HFNC) for dyspnea in patients with advanced disease. Methods: A literature search was conducted using MEDLINE, Cochrane Library, EMBASE, and Ichu-shi Web. Inclusion criteria were: 1) randomized controlled trials evaluating the effect of HFNC on dyspnea; 2) aged 18 years or older with advanced disease with hypoxemia; 3) control group was conventional oxygen therapy or noninvasive positive pressure ventilation. Exclusion criteria were: 1) patients in intensive care unit, 2) weaning from ventilator. Results: Six studies (4 from database searches, and 2 from hand searches) were included. In the 2 studies evaluating short-term intervention, one showed HFNC was more efficacious, and the other conventional oxygen was more efficacious. In the 2 studies evaluating long-term interventions: one showed HFNC was more efficacious, and the other showed no significant difference. In the 2 studies evaluating the intervention during exercise, one showed HFNC was more efficacious, and the other showed no significant difference. Conclusion: HFNC may be effective for dyspnea in patients with advanced disease associated with hypoxemia.

Objective: The purposes of this trial were to demonstrate the feasibility and effectiveness of the hybrid of intracavitary and interstitial brachytherapy (HBT) for locally advanced cervical cancer patients in the phase I/II prospective clinical trial. Methods: Patients with FIGO stage IB2-IVA uterine cervical cancer pretreatment width of which was ≥5 cm measured by magnetic resonance imaging were eligible for this clinical trial. The protocol therapy included 30–30.6 Gy in 15–17 fractions of whole pelvic radiotherapy concurrent with weekly CDDP, followed by 24 Gy in 4 fractions of HBT and pelvic radiotherapy with a central shield up to 50–50.4 Gy in 25–28 fractions. The primary endpoint of phase II part was 2-year pelvic progression-free survival (PPFS) rate higher than historical control of 64%. Results: Between October 2015 and October 2019, 73 patients were enrolled in the initial registration and 52 patients proceeded to the secondary registration. With the median follow-up period of 37.3 months (range, 13.9–52.9 months), the 2- PPFS was 80.7% (90% confidence interval [CI]=69.7%–88%). Because the lower range of 90% CI of 2-year PPFS was 69.7%, which was higher than the historical control ICBT data of 64%, therefore, the primary endpoint of this study was met. Conclusion The effectiveness of HBT were demonstrated by a prospective clinical study. Because the dose goal determined in the protocol was lower than 85 Gy, there is room in improvement for local control. A higher dose might have been needed for tumors with poor responses.

Objective: To evaluate the efficacy of fan therapy for the relief of dyspnea in patients with chronic progressive disease. Methods: A systematic electronic database search of all available articles published before October 23, 2019 was conducted using Ichushi-Web of the Japan Medical Abstract Society databases, CENTRAL, EMBASE, and MEDLINE. In addition, a hand-search for updates was performed using PubMed on June 30, 2020 and December 7, 2021. The inclusion criteria were: 1) any RCTs comparing the effect of fan therapy with any other intervention, and 2) patients aged ≥18 years. Exclusion criteria were: 1) duplicate references, and 2) conference presentations. Results: We identified 110 studies, of which 10 met our criteria for inclusion. Finally, five studies were used in the meta-analysis. Fan therapy significantly improved dyspnea in patients with chronic progressive disease compared to control groups with a standardized mean difference of −1.43 (95% confidence interval: −2.70 to −0.17, I2=94%, p<0.0001). Conclusion: Fan therapy was found to be effective in reducing dyspnea in chronic progressive disease.

Methods: We included 62 patients who underwent combined LLIF surgery and PPS fixation for degenerative lumbar spondylolisthesis with spinal canal stenosis. We compared the patient demographics and the accuracy of fluoroscopy-guided PPS placement between two groups: patients who remained in the lateral decubitus position for the pedicle screw fixation (single-position surgery [SPS] group) and those who were turned to the prone position (dual-position surgery [DPS] group). Results: There were 40 patients in the DPS group and 22 in the SPS group. Of the 292 PPSs, only 12 were misplaced. In other words, 280/292 screws (95.9%) were placed correctly in the pedicle’s cortical shell (grade 0). PPS insertion did not cause neurological, vascular, or visceral injuries in either group. The breach rates for the DPS and SPS groups were 4.1% (grade 1, 5 screws; grade 2, 3 screws; grade 3, 0 screw) and 4.1% (grade 1, 2 screws; grade 2, 2 screws; grade 3, 0 screw), respectively. Although there were no statistically significant differences, the downside PPS had more screw malpositioning than the upside PPS. Conclusions We found that PPS insertion with the patient in the decubitus position under fluoroscopic guidance might be as safe and reliable a technique as PPS insertion in the prone position, with a misplacement rate similar to that previously published.