Effect of Foot Position on Ankle Muscle Activity During Wobble Board Training in Individuals With Chronic Ankle Instability.

OBJECTIVE: The purpose of this study was to compare the effects of foot positioning on muscle activities of the peroneus longus (PL), medial gastrocnemius (MG), and tibialis anterior (TA)/PL ratio in individuals with chronic ankle instabilities (CAI) during wobble board training. METHODS: Thirty individuals with CAI were included, and statistical significance of PL and MG muscle activities was determined using 1-way repeated measures analysis of variance alongside TA/PL activity ratio at the university research laboratory. The participants performed the wobble board training in 3 different foot positions: medial from the centerline of the wobble board (WBT-M), middle from the centerline of the wobble board, and lateral from the centerline of the wobble board (WBT-L). Peroneus longus, MG, and TA muscle activities were measured using surface electromyography. RESULTS: Peroneus longus activity was significantly higher in the WBT-L position than in the other 2 positions, and it was significantly higher in the middle from the centerline of the wobble board than in the WBT-M position. Medial gastrocnemius activity was significantly greater in the WBT-L position than in the other 2 positions. Tibialis anterior/PL ratio was higher in the WBT-M position than in the other 2 positions. CONCLUSION: The findings of this study showed that WBT-L increased PL muscle activity by >70% of the maximal voluntary isometric contraction without increasing TA/PL ratio in individuals with CAI.

Scalable production of siRNA-encapsulated extracellular vesicles for the inhibition of KRAS-mutant cancer using acoustic shock waves.

Extracellular vesicles (EVs) have emerged as a potential delivery vehicle for nucleic-acid-based therapeutics, but challenges related to their large-scale production and cargo-loading efficiency have limited their therapeutic potential. To address these issues, we developed a novel "shock wave extracellular vesicles engineering technology" (SWEET) as a non-genetic, scalable manufacturing strategy that uses shock waves (SWs) to encapsulate siRNAs in EVs. Here, we describe the use of the SWEET platform to load large quantities of KRASG12C-targeting siRNA into small bovine-milk-derived EVs (sBMEVs), with high efficiency. The siRNA-loaded sBMEVs effectively silenced oncogenic KRASG12C expression in cancer cells; they inhibited tumour growth when administered intravenously in a non-small cell lung cancer xenograft mouse model. Our study demonstrates the potential for the SWEET platform to serve as a novel method that allows large-scale production of cargo-loaded EVs for use in a wide range of therapeutic applications.

Regional Burden of Enlarged Perivascular Spaces and Cognition and Neuropsychiatric Symptoms in Drug-Naive Patients With Parkinson Disease.

BACKGROUND AND OBJECTIVES: Although the potential role of enlarged perivascular spaces (EPVSs) in Parkinson disease (PD) is increasingly recognized, whether EPVSs located in different anatomical regions exert differential effects on clinical manifestation remains uncertain. We investigated the regional EPVS burden and its association with cognition and neuropsychiatric symptoms (NPSs) in newly diagnosed PD population. METHODS: In this retrospective, cross-sectional study, EPVS in the temporal lobe (T-EPVS), centrum semiovale (CS-EPVS), and basal ganglia (BG-EPVS) were visually rated in drug-naive patients with PD who underwent magnetic resonance imaging, dopamine transporter (DAT) scans, neuropsychological assessments, and Neuropsychiatric Inventory Questionnaire at baseline. Cognitive performance, NPS burden, vascular risk factors, small vessel disease (SVD) imaging markers, and DAT availability were compared across groups dichotomized by their regional EPVS burden (cutoff for high-degree vs low-degree: >10 for T-EPVS/BG-EPVS and >20 for CS-EPVS). RESULTS: A total of 480 patients with PD (123 without cognitive impairment, 291 with mild cognitive impairment, and 66 with dementia) were included. The proportion of high-degree T-EPVS (p for trend <0.001) and BG-EPVS (p for trend = 0.001) exhibited an increasing trend across the cognitive spectrum, corresponding to worsening cognition. Compared with the low-degree group, the high-degree BG-EPVS group showed higher SVD burden (moderate-to-severe white matter hyperintensity [14.8% vs 40.5%, p < 0.001], lacune [10.3% vs 30.7%, p < 0.001], and cerebral microbleeds [8.1% vs 22.2%, p < 0.001]), greater atrophy in cortical gray matter (40.73% ± 1.09% vs 39.96% ± 1.20% of intracranial volume, p < 0.001), and lower cognitive performance (in language [-0.22 ± 1.18 vs -0.53 ± 1.29, p = 0.013], and visual memory domains [-0.24 ± 0.97 vs -0.61 ± 0.96, p = 0.009]). The high-degree T-EPVS group presented with greater NPS burden in decreased motivation (0.61 ± 1.78 vs 1.35 ± 2.36, p = 0.007), affective dysregulation (0.88 ± 2.13 vs 2.36 ± 3.53, p < 0.001), and impulse dyscontrol (0.43 ± 1.67 vs 1.74 ± 4.29, p < 0.001), compared with the low-degree T-EPVS group. Meanwhile, the burden of CS-EPVS did not reveal any differences in cognition or NPS. DISCUSSION: BG-EPVS and T-EPVS seem to exert differential effects on cognition and NPS in patients with PD. Investigating the EPVS profile in distinct anatomical regions may be useful in disentangling the heterogeneity within PD.

Transcanal endoscopic ear surgery for glomus tympanicum removal: A case series on the necessity of preoperative embolization.

BACKGROUND: Transcanal endoscopic ear surgery (TEES) has become popular in recent years in the treatment of glomus tympanicum tumors (GTT). The most significant risk for TEES is bleeding. In some cases, preoperative vascular embolization is performed to mitigate bleeding during TEES. However, guidelines regarding the necessity and efficacy of preoperative vascular embolization have not been established yet. CASE PRESENTATION: This report aimed to assess the necessity and usefulness of preoperative vascular embolization in TEES for GTT by comparing the surgical findings of TEES without preoperative vascular embolization (Case 1) and TEES with preoperative vascular embolization (Case 2). Compared to Case 1, Case 2 included less bleeding and a more convenient procedure. However, no significant difference was observed. CONCLUSIONS: For GTT confined to the middle ear cavity (Glasscock-Jackson Grade II or less), when performed by a proficient otolaryngologist, TEES alone is sufficient without preoperative vascular embolization.

Plant-expressed Zika virus envelope protein elicited protective immunity against the Zika virus in immunocompetent mice.

Zika virus infection causes multiple clinical issues, including Guillain-Barré syndrome and neonatal malformation. Vaccination is considered as the only strategy for the prevention of ZIKV-induced clinical issues. This study developed a plant-based recombinant vaccine that transiently expressed the ZIKV envelope protein (ZikaEnv:aghFc) in Nicotiana benthamiana and evaluated the protective immunity afforded by it in immunocompetent mice. ZikaEnv:aghFc induced both humoral and cellular immunity at a low dose (1-5 µg). This immune-inducing potential was enhanced further when adjuvanted CIA09A. In addition, antigen-specific antibodies and neutralizing antibodies were vertically transferred from immunized females to their progeny and afforded both protective immunity to ZIKV and cross-protection to Dengue virus infection. These results suggest that our plant-based ZIKV vaccine provides a safe and efficient protective strategy with a competitive edge.

Dosimetric comparison between RapidArc and HyperArc in hippocampal-sparing whole-brain radiotherapy with a simultaneous integrated boost.

The HyperArc technique is known for generating high-quality radiosurgical treatment plans for intracranial lesions or hippocampal-sparing whole-brain radiotherapy (WBRT). However, there is no reported feasibility of using the HyperArc technique in hippocampal-sparing WBRT with a simultaneous integrated boost (SIB). This study aimed to compare dosimetric parameters of 2 commercially-available volumetric-modulated arc radiotherapy techniques, HyperArc and RapidArc, when using hippocampal-sparing WBRT with a SIB to treat brain metastases. Treatment plans using HyperArc and RapidArc techniques were generated retrospectively for 19 previously treated patients (1 to 3 brain metastases). The planning target volumes for the whole brain (excluding the hippocampal avoidance region; PTVWB) and metastases (PTVmet) were prescribed 25 and 45 Gy, respectively, in 10 fractions. Each plan included homogeneous and inhomogeneous delivery to the PTVmet. Dosimetric parameters for the target (conformity index [CI], homogeneity index [HI], target coverage [D95%]), and nontarget organs at risk were compared for the HyperArc and RapidArc plans. For homogeneous delivery, dosimetric parameters, including mean CI, HI, and target coverage in PTVWB and PTVmet, were superior for HyperArc than RapidArc plans (all p < 0.01). The PTVWB and PTVmet target coverage for HyperArc plans was significantly greater than for RapidArc plans (96.17% vs 93.38%, p < 0.01; 94.02% vs 92.21%, p < 0.01, respectively). HyperArc plans had significantly lower mean hippocampal Dmax and Dmin values than RapidArc plans (Dmax: 15.53 Gy vs, 16.71 Gy, p < 0.01; Dmin: 8.33 Gy vs 8.93 Gy, p < 0.01, respectively). Similarly, inhomogeneous delivery of hyperArc produced a superior target and lower hippocampal dosimetric parameters than RapidArc, except for the HI of PTVmet (all p < 0.01). HyperArc generated superior conformity and target coverage with lower hippocampal doses than RapidArc. HyperArc could be an attractive technique for hippocampal-sparing WBRT with an SIB.

A scoping review of the different types of exercise programs proposed for the improvement of postural balance in adolescents with idiopathic scoliosis.

BACKGROUND: Adolescent idiopathic scoliosis (AIS), which is the most common type of scoliosis, is a progressive disease that occurs in children aged 10-16 years. Abnormal curvature in AIS provokes spinal asymmetry of the upper body alignment and might deteriorate postural balancing and control ability. OBJECTIVE: To evaluate the effect of exercise interventions on balance and postural stability in patients with adolescent idiopathic scoliosis. METHODS: Embase, Scopus, Pubmed (Medline) and Web of Science databases were searched using the terms idiopathic scoliosis, physiotherapy, and balance. The articles selected were published in English in peer-reviewed journals from 2012 to July 2022. RESULTS: Ten studies met the inclusion criteria. The PEDro scale values ranged from 2 to 6 (mean, 3.6), indicating a low level of scientific rigor. In the sample studies, spinal stabilization exercises were most often trialed (n= 3), followed by Schroth's exercise (n= 2), stretching and self-elongation exercise (n= 2), the exercise protocol of Blount and Moe, physiotherapeutic scoliosis-specific exercise, and proprioceptive neuromuscular facilitation exercise (all n= 1). CONCLUSIONS: Physical therapists will be able to apply hippotherapy, Schroth exercise, physiotherapy scoliosis-specific exercise, trunk stabilization, proprioceptive neuromuscular facilitation exercise, spinal stabilization exercise, core stabilization exercise, and body awareness therapy to manage balance impairments in patients with adolescent idiopathic scoliosis, and further studies are needed to provide stronger evidence.

Effects of Particulate Matter Exposure on the Eustachian Tube and Middle Ear Mucosa of Rats.

OBJECTIVES: Particulate matter (PM) is a risk factor for various diseases. Recent studies have established an association between otitis media (OM) and PM exposure. To confirm this relationship, we developed a novel exposure model designed to control the concentration of PM, and we observed the effects of PM exposure on the Eustachian tube (ET) and middle ear mucosa of rats. METHODS: Forty healthy, 10-week-old, male Sprague-Dawley rats were divided into 3-day, 7-day, 14-day exposure, and control groups (each, n=10). The rats were exposed to incense smoke as the PM source for 3 hours per day. After exposure, bilateral ETs and mastoid bullae were harvested, and histopathological findings were compared using microscopy and transmission electron microscopy (TEM). The expression levels of interleukin (IL)-1ß, IL-6, tumor necrosis factor-α, and vascular endothelial growth factor (VEGF) in the middle ear mucosa of each group were compared using real-time reverse transcription polymerase chain reaction (RT-PCR). RESULTS: In the ET mucosa of the exposure group, the goblet cell count significantly increased after PM exposure (P=0.032). In the middle ear mucosa, subepithelial space thickening, increased angio-capillary tissue, and inflammatory cell infiltration were observed. Moreover, the thickness of the middle ear mucosa in the exposure groups increased compared to the control group (P<0.01). The TEM findings showed PM particles on the surface of the ET and middle ear mucosa, and RT-PCR revealed that messenger RNA (mRNA) expression of IL-1ß significantly increased in the 3-day and 7-day exposure groups compared to the control group (P=0.035). VEGF expression significantly increased in the 7-day exposure group compared to the control and 3-day exposure groups (P<0.01). CONCLUSION: The ET and middle ear mucosa of rats showed histopathologic changes after acute exposure to PM that directly reached the ET and middle ear mucosa. Therefore, acute exposure to PM may play a role in the development of OM.

EGT022, an RGD-containing recombinant disintegrin, inhibits the VEGF-induced angiogenic process by targeting integrin ß3 in endothelial cells.

OBJECTIVES: EGT022, an RGD-containing recombinant disintegrin from human ADAM metallopeptidase domain 15 (ADAM15), has been reported to stimulate vascular maturation of retinal blood vessels with promotion of pericyte coverage through binding to integrin αIIbß3. Previous studies have reported that angiogenesis can be inhibited by several RGD motif-containing disintegrins; however, the effect of EGT022 on Vascular endothelial growth factor (VEGF)-induced angiogenesis has not yet been determined. This study was conducted in order to evaluate the anti-angiogenic function of EGT022 in VEGF-induced endothelial cells. METHODS: A proliferation and migration assay was performed using human umbilical vein endothelial cells (HUVEC) cells stimulated with VEGF to determine whether the angiogenic process was suppressed by EGT022. An in vitro trans-well assay and Mile's permeability assay were performed to determine the effect of EGT022 on permeability. Western blot was performed in order to further determine whether EGT022 can inhibit phosphorylation of VEGF receptor-2 (VEGFR2) and Phospholipase C gamma1 (PLC-γ1). An integrin binding assay and luciferase assay were performed for identification of the integrin target of EGT022. RESULTS: Angiogenesis including proliferation, migration, tube formation, and permeability was significantly inhibited by EGT022 in HUVEC cells. Our findings also demonstrated that EGT022 binds directly to integrin αvß3, induces dephosphorylation of integrin ß3, and inhibits phosphorylation of VEGFR2. In addition, phosphorylation of PLC-γ1 and activation of Nuclear Factor of Activated T-cell (NFAT), a downstream pathway of VEGF, are inhibited by EGT022 in HUVEC cells. CONCLUSION: These results clearly demonstrate the anti-angiogenic role played by EGT022 as a potent antagonist of integrin ß3 in endothelial cells.

Comparison of the Effects of Isometric Horizontal Abduction on Shoulder Muscle Activity During Wall Push-Up Plus and Wall Slide in Individuals With Scapular Winging.

CONTEXT: Wall push-up plus (WPP) and wall slide (WS) are commonly prescribed in early rehabilitation to increase serratus anterior (SA) muscle activity. For individuals with scapular winging (SW), synergistic muscles such as upper trapezius (UT) and pectoralis major (PM) may compensate for weak SA during scapular movement. However, no studies have applied isometric horizontal abduction (IHA) during WS in individuals with SW nor have compared it with WPP with IHA. OBJECTIVES: This study compared the effects of IHA on shoulder muscle activity during WPP and WS exercises in individuals with SW. DESIGN: Cross-sectional study; 2-way repeated-measures analysis of variance was used to assess the statistical significance of observed differences in SA, UT, PM, lower trapezius (LT), and infraspinatus (IS) muscle activities. SETTING: Research laboratory. PATIENTS: We recruited 30 individuals with SW comprising 20 men and 10 women. INTERVENTIONS: The individuals performed WPP and WS exercises with and without IHA using Thera-Band. MAIN OUTCOME MEASURES: Surface electromyography was used to measure muscle activity of the SA, UT, PM, LT, and IS during the isometric phase of WPP and WS. Maximal voluntary isometric contractions were recorded to normalize electromyographic data. RESULTS: There was no significant interaction between IHA application and exercise type for any of the shoulder muscles. IHA application increased SA (P = .008), UT (P = .001), LT (P = .009), and IS (P = .000) activities and decreased PM (P = .001) activity compared with those without IHA. WS exercises elicited higher PM (P = .017) and LT (P = .011) activities than WPP. CONCLUSION: WPP and WS with IHA may be effective in increasing the muscle activities of shoulder stabilizers and preventing overactivation of PM activity. WPP may be recommended for individuals with overactivated PM, whereas WS may be used to increase LT activity.

Recombinant proteins of spike protein of SARS-CoV-2 with the Omicron receptor-binding domain induce production of highly Omicron-specific neutralizing antibodies.

Various vaccines have been developed to fight severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus responsible for the coronavirus disease 2019 pandemic. However, new variants of SARS-CoV-2 undermine the effort to fight SARS-CoV-2. Here, we produced S proteins harboring the receptor-binding domain (RBD) of the Omicron variant in plants. Plant-produced S proteins together with adjuvant CIA09A triggered strong immune responses in mice. Antibodies in serum inhibited interaction of recombinant human angiotensin-converting enzyme 2 with RBD of the Omicron variant, but not RBD of other variants. These results suggest that antibodies induced by RBD of the Omicron variant are highly specific for the Omicron RBD, but not for that of other variants.

Machine-Learning-Based Clinical Biomarker Using Cell-Free DNA for Hepatocellular Carcinoma (HCC).

(1) Background: Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related death worldwide. Although various serum enzymes have been utilized for the diagnosis and prognosis of HCC, the currently available biomarkers lack the sensitivity needed to detect HCC at early stages and accurately predict treatment responses. (2) Methods: We utilized our highly sensitive cell-free DNA (cfDNA) detection system, in combination with a machine learning algorithm, to provide a platform for improved diagnosis and prognosis of HCC. (3) Results: cfDNA, specifically alpha-fetoprotein (AFP) expression in captured cfDNA, demonstrated the highest accuracy for diagnosing malignancies among the serum/plasma biomarkers used in this study, including AFP, aspartate aminotransferase, alanine aminotransferase, albumin, alkaline phosphatase, and bilirubin. The diagnostic/prognostic capability of cfDNA was further improved by establishing a cfDNA score (cfDHCC), which integrated the total plasma cfDNA levels and cfAFP-DNA expression into a single score using machine learning algorithms. (4) Conclusion: The cfDHCC score demonstrated significantly improved accuracy in determining the pathological features of HCC and predicting patients' survival outcomes compared to the other biomarkers. The results presented herein reveal that our cfDNA capture/analysis platform is a promising approach to effectively utilize cfDNA as a biomarker for the diagnosis and prognosis of HCC.

DDR-coin: An Efficient Probabilistic Distributed Trigger Counting Algorithm.

A distributed trigger counting (DTC) problem is to detect w triggers in the distributed system consisting of n nodes. DTC algorithms can be used for monitoring systems using sensors to detect a significant global change. When designing an efficient DTC algorithm, the following goals should be considered; minimizing the whole number of exchanged messages used for counting triggers and even distribution of communication loads among nodes. In this paper, we present an efficient DTC algorithm, DDR-coin (Deterministic Detection of Randomly generated coins). The message complexity-the total number of exchanged messages-of DDR-coin is O(nlogn(w/n)) in average. MaxRcvLoad-the maximum number of received messages to detect w triggers in each node-is O(logn(w/n)) on average. DDR-coin is not an exact algorithm; even though w triggers are received by the n nodes, it can fail to raise an alarm with a negligible probability. However, DDR-coin is more efficient than exact DTC algorithms on average and the gap between those is increased for larger n. We implemented the prototype of the proposed scheme using NetLogo 6.1.1. We confirmed that experimental results are close to our mathematical analysis. Compared with the previous schemes-TreeFill, CoinRand, and RingRand- DDR-coin shows smaller message complexity and MaxRcvLoad.

Prognostic impact of CD8 and programmed death-ligand 1 expression in patients with resectable non-small cell lung cancer.

BACKGROUND: The prognostic impact of the expression of CD8 and programmed death-ligand 1 (PD-L1) has not been established in patients with resectable non-small cell lung cancer (NSCLC). METHODS: Surgical tissue specimens were obtained from 136 patients with NSCLC who underwent surgical resection. The expression levels of CD8 and PD-L1 were assessed using tissue microarrays and immunohistochemistry. RESULTS: The CD8-positive group showed significant increases in overall survival (OS) (median, not reached [NR] vs. 28.452 months) and relapse-free survival (RFS) (median, NR vs. 14.916 months) compared with the CD8-negative group. In contrast to CD8, the PD-L1-negative group demonstrated significant increases in OS (median, NR vs. 29.405 months) and RFS (median, 63.573 vs. 17.577 months) compared with the PD-L1-positive group. Two prognostic groups were stratified according to CD8/PD-L1 expression: group 1 (CD8-positive/PD-L1-negative) vs. group 2 (CD8/PD-L1: positive/positive, negative/negative, negative/positive). Group 1 had better OS (median, NR vs. 29.405 months) and RFS (median, NR vs. 17.577 months) than group 2. Multivariate analysis indicated that group 1 constituted an independent favourable prognostic factor for OS (hazard ratio [HR], 0.329, p = 0.001) and RFS (HR, 0.293; p < 0.001). CONCLUSIONS: Positive CD8 and negative PD-L1 expression together may be favourable prognostic markers in resectable NSCLC.

Prognostic impact of pretreatment albumin to globulin ratio in patients with diffuse large B-cell lymphoma treated with R-CHOP.

OBJECTIVE: We evaluated the clinical implications of the albumin to globulin ratio (AGR) in patients with diffuse large B-cell lymphoma (DLBCL) treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone (R-CHOP). METHODS: Data of 232 patients with DLBCL treated with first-line R-CHOP from 2004 to 2017 were reviewed retrospectively. Patients with AGR values ≥1.22 and <1.22 were assigned to the high and low AGR groups, respectively. Treatment response, treatment-related toxicity, and survival were compared according to the AGR. RESULTS: The complete response rate was significantly lower in the low AGR group than in the high AGR group (59.1% vs. 81.3%; p < 0.001). Treatment-related mortality was also more frequent in the low AGR group than in the high AGR group (14.0% vs. 4.3%; p = 0.009). The low AGR group (median overall survival [OS] = 26.87 months; 95% confidence interval [CI] = 4.19-49.55) showed a significant decrease in OS compared to the high AGR group (median OS = 148.83 months; 95% CI = 76.26-221.41; p < 0.001). Progression-free survival (PFS) also decreased significantly in the low AGR group (median PFS = 14.29 months; 95% CI = 2.58-26.01) compared to the high AGR group (median PFS = 148.83 months; 95% CI = 76.21-221.45; p < 0.001). In a multivariate analysis, low AGR was an independent poor prognostic factor for OS and PFS. CONCLUSIONS: Pretreatment AGR was useful for predicting treatment response, treatment-related toxicity, and prognosis in patients with DLBCL treated with R-CHOP. Further large prospective studies will be necessary to validate our findings.

Differential Diagnosis of Sinonasal Lymphoma and Squamous Cell Carcinoma on CT, MRI, and PET/CT.

Objective The purpose of this study was to analyze computed tomography (CT) and magnetic resonance (MR) images and to evaluate the maximum standardized uptake value (SUV max) of positron emission tomography (PET)/CT parameters between sinonasal non-Hodgkin's lymphoma (NHL) and squamous cell carcinoma (SCC), knowing the imaging features that distinguish sinonasal NHL from SCC. Study Design Case series with chart review. Setting University tertiary care facility. Subjects and Methods We analyzed the features on CT, MR imaging, and PET/CT of 78 patients diagnosed with sinonasal NHL or SCC histopathologically. The CT (n = 34), MRI (n = 25), and PET/CT (n = 33) images of 39 patients with sinonasal NHL and the CT (n = 38), MR (n = 28), and PET/CT (n = 31) images of 39 patients with SCC were evaluated. The sinonasal NHL was diagnosed as natural killer/T-cell lymphoma (n = 28) and diffuse large B-cell lymphoma (n = 11). Results Patients with sinonasal NHL had a larger tumor volume and higher tumor homogeneity than patients with SCC on T2-weighted and postcontrast MR images. Most of the sinonasal NHL and SCC showed a high degree of enhancement. The apparent diffusion coefficient (ADC) values and adjacent bone destruction were significantly lower in sinonasal NHL than in SCC. However, cervical lymphadenopathy, Waldeyer's ring involvement, and PET/CT SUV max showed no significant differences between sinonasal NHL and SCC. Conclusion CT and MR images of sinonasal masses showing a bulky lesion, marked homogeneity, and low ADC values without adjacent bone destruction are more suggestive of sinonasal NHL than SCC.

Prognostic significance of phosphoinositide 3-kinase p110α and p110ß isoforms in non-small cell lung cancer.

The proteins p110α and p110ß are isoforms of the catalytic subunit of class I phosphoinositide 3-kinases (PI3Ks). Class I PI3Ks are involved in the regulation of cell survival, growth, proliferation, and migration, and their aberrant activation contributes to the oncogenesis of various human cancers. In this study, we assessed expression of p110α and p110ß in non-small cell lung cancer (NSCLC) and their association with clinicopathological factors and patient survival. Seventy-six NSCLC cases were analyzed by immunohistochemical staining for p110α and p110ß. Of the 76 tumors, 18 (23.7%) and 43 (56.6%) were classified in the high p110α and p110ß expression groups, respectively. Expression of p110α was higher in smokers compared with non-smokers (P = 0.042). No other clinicopathological factors showed significant association with p110α or p110ß expression. In univariate and multivariate survival analyses, high p110ß expression was associated with worse overall survival (OS) in stage I NSCLCs (P < 0.001), whereas the high p110α expression group had shorter OS in stage II to IV NSCLCs (P = 0.005). Our results suggest that p110α and p110ß play different roles depending on tumor stage, and that both p110α and p110ß have potential as independent prognostic biomarkers of NSCLC.

Multicenter Retrospective Analysis of Clinical Characteristics, Treatment Patterns, and Outcomes in Very Elderly Patients with Diffuse Large B-Cell Lymphoma: The Korean Cancer Study Group LY16-01.

PURPOSE: The treatment strategy for elderly patients older than 80 years with diffuse large B-cell lymphoma (DLBCL) has not been established because of poor treatment tolerability and lack of data. MATERIALS AND METHODS: This multicenter retrospective study was conducted to investigate clinical characteristics, treatment patterns and outcomes of patients older than 80 years who were diagnosed with DLBCL at 19 institutions in Korea between 2005 and 2016. RESULTS: A total of 194 patients were identified (median age, 83.3 years). Of these, 114 patients had an age-adjusted International Prognostic Index (aaIPI) score of 2-3 and 48 had a Charlson index score of 4 or more. R-CHOP was given in 124 cases, R-CVP in 13 cases, other chemotherapy in 17 cases, radiation alone in nine cases, and surgery alone in two cases. Twenty-nine patients did not undergo any treatment. The median number of chemotherapy cycles was three. Only 37 patients completed the planned treatment cycles. The overall response rate from 105 evaluable patientswas 90.5% (complete response, 41.9%). Twentynine patients died due to treatment-related toxicities (TRT). Thirteen patients died due to TRT after the first cycle. Median overall survival was 14.0 months. The main causes of death were disease progression (30.8%) and TRT (27.1%). In multivariate analysis, overall survival was affected by aaIPI, hypoalbuminemia, elevated creatinine, and treatment. CONCLUSION: Age itself should not be a contraindication to treatment. However, since elderly patients show higher rates of TRT due to infection, careful monitoring and dose modification of chemotherapeutic agents is needed.

Feasibility and safety of nerve stimulator attachment to energy-based devices: A porcine model study.

BACKGROUND: Recently, several energy-based devices (EBDs) have been developed and applied in the context of thyroid surgery. EBDs can reduce operation time, blood loss, and postoperative pain. Compared to conventional electrocautery, EBDs operate at a relatively lower temperature and produce minimal lateral tissue damage. Yet, during device operation, the tip of the EBD is hot enough to cause thermal nerve damage, increasing the need for surgeons to be cautious about EBD application. To increase the safety of EBDs, we attached nerve stimulators to the tips of two EBDs and compared them to conventional monopolar nerve stimulation using a porcine model. METHODS: Three piglets (30-40 kg) underwent total thyroidectomy after orotracheal intubation with a nerve integrity monitor (NIM) electromyography (EMG) endotracheal tube. Nerve stimulators were attached to two EBDs (Harmonic Focus®+ and LigaSure™). After dissection and identification of six recurrent laryngeal nerves in the three piglets, both of the EBDs with attached nerve stimulators and a conventional monopolar nerve stimulator were applied near the nerve and EMG parameters were recorded using the NIM 3.0 system. The stimulus intensity was varied from 5 mA to 1 mA and the maximum distance and amplitude at which nerve detection was achieved were measured. RESULTS: There were no statistically significant differences between the maximum distance or mean amplitude obtained from nerve stimulators attached to EBDs and those obtained from the conventional nerve stimulator. Additionally, there were no adverse EMG events related to the use of nerve stimulators attached to EBDs. CONCLUSIONS: Attachment of a nerve stimulator to an EBD for nerve detection during thyroidectomy was as safe and effective as attachment of a conventional nerve stimulator. Use of a nerve stimulator attachment may reduce the likelihood of EBD-associated nerve damage during thyroid surgery.