Tumor hypoxia and reoxygenation: the yin and yang for radiotherapy.

Tumor hypoxia, a common feature occurring in nearly all human solid tumors is a major contributing factor for failures of anticancer therapies. Because ionizing radiation depends heavily on the presence of molecular oxygen to produce cytotoxic effect, the negative impact of tumor hypoxia had long been recognized. In this review, we will highlight some of the past attempts to overcome tumor hypoxia including hypoxic radiosensitizers and hypoxia-selective cytotoxin. Although they were (still are) a very clever idea, they lacked clinical efficacy largely because of ‘reoxygenation’ phenomenon occurring in the conventional low dose hyperfractionation radiotherapy prevented proper activation of these compounds. Recent meta-analysis and imaging studies do however indicate that there may be a significant clinical benefit in lowering the locoregional failures by using these compounds. Latest technological advancement in radiotherapy has allowed to deliver high doses of radiation conformally to the tumor volume. Although this technology has brought superb clinical responses for many types of cancer, recent modeling studies have predicted that tumor hypoxia is even more serious because ‘reoxygenation’ is low thereby leaving a large portion of hypoxic tumor cells behind. Wouldn’t it be then reasonable to combine hypoxic radiosensitizers and/or hypoxia-selective cytotoxin with the latest radiotherapy? We will provide some preclinical and clinical evidence to support this idea hoping to revamp an enthusiasm for hypoxic radiosensitizers or hypoxia-selective cytotoxins as an adjunct therapy for radiotherapy. © 2016. The Korean Society for Radiation Oncology.11Yscopu

Cardiovascular safety of evogliptin dual and triple therapy in patients with type 2 diabetes: a nationwide cohort study

Objective: To investigate the risk of cardiovascular events associated with commonly used dual and triple therapies of evogliptin, a recently introduced dipeptidyl peptidase-4 inhibitor (DPP4i), for managing type 2 diabetes in routine clinical practice. Design: A retrospective cohort study. Setting: Korean Health Insurance Review and Assessment database. Participants: Patients who initiated metformin-based dual therapy and metformin+sulfonylurea-based triple therapy in South Korea from 2014 to 2018. Interventions: Initiation of combination therapy with evogliptin. Primary and secondary outcome measures: Hazards of cardiovascular events, a composite endpoint of myocardial infarction, heart failure and cerebrovascular events, and its individual components. Cox proportional hazards model with propensity score-based inverse probability of treatment weighting were used to estimate HRs and 95% CIs. Results: From the dual and triple therapy cohorts, 5830 metformin+evogliptin users and 2198 metformin+sulfonylurea+evogliptin users were identified, respectively. Metformin+evogliptin users, as compared with metformin+non-DPP4i, had a 29% reduced risk of cardiovascular events (HR 0.71, 95% CI 0.62 to 0.82); HRs for individual outcomes were cerebrovascular events (0.71, 95% CI 0.53 to 0.95), heart failure (0.70, 95% CI 0.59 to 0.82), myocardial infarction (0.89, 95% CI 0.60 to 1.31). Metformin+sulfonylurea+evogliptin users, compared with metformin+sulfonylurea+non-DPP4i, had a 24% reduced risk of cardiovascular events (0.76, 95% CI 0.59 to 0.97); HRs for individual outcomes were myocardial infarction (0.57, 95% CI 0.27 to 1.19), heart failure (0.74, 95% CI 0.55 to 1.01), cerebrovascular events (0.96, 95% CI 0.61 to 1.51). Conclusions: These findings suggest that dual or triple therapies of evogliptin for the management of type 2 diabetes in routine clinical practice present no cardiovascular harms, but could alternatively offer cardiovascular benefits in this patient population

Robot-assisted distal gastrectomy for gastric cancer in a situs inversus totalis patient

A 47-year-old man was referred to Seoul National University Bundang Hospital with an ulcerative lesion in the midbody of the stomach. Computed tomography revealed that he was a situs inversus totalis (SIT) patient. Robot-assisted distal gastrectomy with D1+β lymph node dissection and Billroth II anastomosis were performed. With the aid of robotic surgery, the surgeon didn't need to change his position and could perform the surgery without any confusion resulting from the patient's reversed anatomy. The operation took 300 minutes, with no intraoperative complications. The postoperative course was uneventful, and the patient was discharged on postoperative day 8. The final pathologic report was pT3N3a by American Joint Committee on Cancer 7th tumor-node-metastasis staging. We successfully performed robot-assisted distal gastrectomy for gastric cancer in a SIT patient. We believe that this is the first case of robotic surgery reported in a SIT patient with gastric cancer

25th annual computational neuroscience meeting: CNS-2016

The same neuron may play different functional roles in the neural circuits to which it belongs. For example, neurons in the Tritonia pedal ganglia may participate in variable phases of the swim motor rhythms [1]. While such neuronal functional variability is likely to play a major role the delivery of the functionality of neural systems, it is difficult to study it in most nervous systems. We work on the pyloric rhythm network of the crustacean stomatogastric ganglion (STG) [2]. Typically network models of the STG treat neurons of the same functional type as a single model neuron (e.g. PD neurons), assuming the same conductance parameters for these neurons and implying their synchronous firing [3, 4]. However, simultaneous recording of PD neurons shows differences between the timings of spikes of these neurons. This may indicate functional variability of these neurons. Here we modelled separately the two PD neurons of the STG in a multi-neuron model of the pyloric network. Our neuron models comply with known correlations between conductance parameters of ionic currents. Our results reproduce the experimental finding of increasing spike time distance between spikes originating from the two model PD neurons during their synchronised burst phase. The PD neuron with the larger calcium conductance generates its spikes before the other PD neuron. Larger potassium conductance values in the follower neuron imply longer delays between spikes, see Fig. 17.Neuromodulators change the conductance parameters of neurons and maintain the ratios of these parameters [5]. Our results show that such changes may shift the individual contribution of two PD neurons to the PD-phase of the pyloric rhythm altering their functionality within this rhythm. Our work paves the way towards an accessible experimental and computational framework for the analysis of the mechanisms and impact of functional variability of neurons within the neural circuits to which they belong

Hypoxia inducible factor-1 (HIF-1) in myeloid cells of the pre-metastatic niche suppresses tumor metastasis

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Preoperative Cytologic Diagnosis of Warthin-like Variant of Papillary Thyroid Carcinoma

Background Warthin-like variant of papillary thyroid carcinoma (WLV-PTC) is a relatively rare variant of papillary thyroid carcinoma with favorable prognosis. However, preoperative diagnosis using fine-needle aspiration (FNA) specimens is challenging especially with lymphocytic thyroiditis characterized by Hürthle cells and lymphocytic background. To determine a helpful cytological differential point, we compared WLV-PTC FNA findings with conventional papillary thyroid carcinoma with lymphocytic thyroiditis (PTC-LT) and conventional papillary thyroid carcinoma without lymphocytic thyroiditis (PTC) regarding infiltrating inflammatory cells and their distribution. Preoperative diagnosis or potential for WLV-PTC will be helpful for surgeons to decide the scope of operation. Methods Of the 8,179 patients treated for papillary thyroid carcinoma between January 2007 and December 2012, 16 patients (0.2%) were pathologically confirmed as WLV-PTC and four cases were available for cytologic review. For comparison, we randomly selected six PTC-LT cases and five PTC cases during the same period. The number of intratumoral and background lymphocytes, histiocytes, neutrophils, and the presence of giant cells were evaluated and compared using conventional smear and ThinPrep preparations. Results WLV-PTC showed extensive lymphocytic smear with incorporation of thyroid follicular tumor cell clusters and frequent histiocytes. WLV-PTC was associated with higher intratumoral and background lymphocytes and histiocytes compared with PTC-LT or PTC. The difference was more distinct in liquid-based cytology. Conclusions The lymphocytic smear pattern and the number of inflammatory cells of WLV-PTC are different from those of PTC-LT or PTC and will be helpful for the differential diagnosis of WLV-PTC in preoperative FNA

Anterior skull base reconstruction using nasoseptal flap: cadaveric feasibility study and clinical implication [SevEN-001]

Abstract Background Pedicled nasoseptal flap (PNSF) has significantly improved the surgical outcomes of endoscopic endonasal approach (EEAs) by reducing cerebrospinal fluid (CSF) leakage. The purpose of this study is to assess the feasibility of using a PNSF for anterior skull base (ASB) reconstruction and to describe a method to compensate for a short flap based on our results. Methods In this cadaveric study, ASB dissection without sphenoidotomy was performed using 10 formalin-fixed and 5 fresh adult cadaver specimens, and the sufficiency of the PNSF to cover the ASB was assessed. After the sphenoidotomy, the length by which the PNSF fell short in providing coverage at the posterior wall of the frontal sinus (CPFS), and the extent of the anterior coverage from the limbus (CL) of the sphenoid bone was measured. Results Without sphenoidotomy, the mean length of the remaining PNSF after the coverage of the posterior wall of the frontal sinus was 0.67 cm. After sphenoidotomy, the PNSF fell short by a mean length of 2.10 cm, in providing CPFS. The CL was 1.86 cm. Based on these findings, defects resulting from an endoscopic resection of ASB tumors were reconstructed using PNSF without total sphenoidotomy in 3 patients. There were no postoperative CSF leaks or complications. Conclusions The use of PNSF for ASB reconstruction may be insufficient to cover the entire ASB defect after removal of large lesions which need total sphenoidotomy. When possible, by leaving some portion of the anterior sphenoid wall for supporting the PNSF, successful ASB reconstruction could be achieved in endoscopic resection of ASB tumors. Additional methods might be needed in some cases of large ASB lesions wherein the anterior sphenoid wall should be removed totally and the ASB defect is too large

Characteristics of Korean Children and Adolescents Who Die by Suicide Based on Teachers’ Reports

We analyzed the clinical characteristics and suicide-related factors of students who died by suicide in Korea in 2016–2020, based on teachers’ reports. Using data on total suicide deaths (N = 654, mean age = 16.0, 52.6% boys) collected by the Ministry of Education of Korea, we investigated the demographic and clinical characteristics and suicide-related factors of suicide deaths in students aged 9–18 years. Considering gender, more boys (52.6%, N = 344) died by suicide than girls (47.4%, N = 310). About 425 (65.0%) of the suicides were among high school students. The most common suicide method was jumping from a high place (70.6%, N = 454), followed by hanging (25.7%, N = 165). Additionally, 9.4% (N = 48) of the students who died by suicide had a history of attempted suicide, 13.4% (N = 73) had attempted self-harm, and 12.8% (N = 48) were acquainted with someone who had died by suicide. Teachers observed 20.6% (N = 120) of the suicide warning signs at school. Girls tended to have higher rates of attempted suicide, emotional problems, and psychiatric disorders than boys. This study was conducted with the largest sample of Korean suicide students observed at school. Effective suicide-related mental health training for teachers could contribute to suicide prevention in students