Head and neck squamous cell carcinomas (HNSCC) are common human malignancies with poor clinical outcomes. The 5-year survival rates for patients with advanced stage HNSCC have not changed appreciably in the past few decades, underscoring a dire need for improved therapeutic options. Recent studies have elucidated a key signaling axis, the EGFR-STAT3-Bcl-XL signaling axis, that is aberrantly activated in a majority of HNSCC and contributes to the proliferation and survival of malignant cells. Considerable effort is being placed on developing highly specific inhibitors of different components of this pathway. This review highlights the progress that is being made towards achieving potent inhibition of the EGFR-STAT3-Bcl-XL signaling axis in HNSCC and the promising therapeutic strategies that are currently under development for this disease.
Animals ; Antibodies, Monoclonal ; pharmacology ; Antineoplastic Agents ; pharmacology ; Apoptosis ; Biphenyl Compounds ; pharmacology ; Cell Proliferation ; Head and Neck Neoplasms ; metabolism ; pathology ; Humans ; Nitrophenols ; pharmacology ; Piperazines ; pharmacology ; Receptor, Epidermal Growth Factor ; antagonists & inhibitors ; STAT3 Transcription Factor ; antagonists & inhibitors ; metabolism ; Signal Transduction ; drug effects ; Sulfonamides ; pharmacology ; bcl-X Protein ; antagonists & inhibitors ; metabolism

The purpose of this study was to examine the effect of regular exercise training on insulin sensitivity in adults with type 2 diabetes mellitus (T2DM) using the pooled data available from randomised controlled trials. In addition, we sought to determine whether short-term periods of physical inactivity diminish the exercise-induced improvement in insulin sensitivity. Eligible trials included exercise interventions that involved ≥3 exercise sessions, and reported a dynamic measurement of insulin sensitivity. There was a significant pooled effect size (ES) for the effect of exercise on insulin sensitivity (ES, –0.588; 95% confidence interval [CI], –0.816 to –0.359; P<0.001). Of the 14 studies included for meta-analyses, nine studies reported the time of data collection from the last exercise bout. There was a significant improvement in insulin sensitivity in favour of exercise versus control between 48 and 72 hours after exercise (ES, –0.702; 95% CI, –1.392 to –0.012; P=0.046); and this persisted when insulin sensitivity was measured more than 72 hours after the last exercise session (ES, –0.890; 95% CI, –1.675 to –0.105; P=0.026). Regular exercise has a significant benefit on insulin sensitivity in adults with T2DM and this may persist beyond 72 hours after the last exercise session.
Adult ; Data Collection ; Diabetes Mellitus, Type 2* ; Glucose Tolerance Test ; Humans ; Insulin Resistance* ; Insulin* ; Resistance Training

Purpose: Visual impairment from retinal re-detachment could be debilitating. The aim of this review is to evaluate the role of 360° laser retinopexy on success rate of rhegmatogenous retinal detachment (RRD) repair by a meta-analysis study. Methods: The PubMed, Scopus, and the Cochrane Library databases were searched comprehensively from the date of database inception to January 2021, evaluating the role of 360° laser retinopexy in visual and anatomical success rate of RRD repair. This review was conducted based on the preferred reporting items for systematic review and meta-analysis (PRISMA) protocols. Results: Among 202 articles screened for eligibility, six studies were found to be eligible for inclusion in our final analysis. Our meta-analysis demonstrates that prophylactic treatment with circumferential laser photocoagulation has no significant effect on the initial rate of retinal re-detachment or final best-corrected visual acuity following pars plana vitrectomy repair of RRD. Subgroup analysis of studies (n = 3) with 23-gauge pars plana vitrectomy, however, favors attachment rate in patients undergoing 360° prophylactic laser treatment. Conclusions Three hundred and sixty degree laser retinopexy appears to have favorable outcomes in patients undergoing 23-gauge retinal detachment repair. This protective effect, however, is not apparent with inclusion of 20-gauge vitrectomy studies.

Purpose: Visual impairment from retinal re-detachment could be debilitating. The aim of this review is to evaluate the role of 360° laser retinopexy on success rate of rhegmatogenous retinal detachment (RRD) repair by a meta-analysis study. Methods: The PubMed, Scopus, and the Cochrane Library databases were searched comprehensively from the date of database inception to January 2021, evaluating the role of 360° laser retinopexy in visual and anatomical success rate of RRD repair. This review was conducted based on the preferred reporting items for systematic review and meta-analysis (PRISMA) protocols. Results: Among 202 articles screened for eligibility, six studies were found to be eligible for inclusion in our final analysis. Our meta-analysis demonstrates that prophylactic treatment with circumferential laser photocoagulation has no significant effect on the initial rate of retinal re-detachment or final best-corrected visual acuity following pars plana vitrectomy repair of RRD. Subgroup analysis of studies (n = 3) with 23-gauge pars plana vitrectomy, however, favors attachment rate in patients undergoing 360° prophylactic laser treatment. Conclusions Three hundred and sixty degree laser retinopexy appears to have favorable outcomes in patients undergoing 23-gauge retinal detachment repair. This protective effect, however, is not apparent with inclusion of 20-gauge vitrectomy studies.

Purpose: Central retinal artery occlusion (CRAO) is a vision-threatening condition with a potentially poor visual prognosis. Many different treatment modalities are suggested but controversy remains regarding effectiveness of these treatments. The purpose of this study is to perform a systematic review and meta-analysis in addition to analyzing retrospective data at our own tertiary care center regarding effectiveness of hyperbaric oxygen therapy (HBOT) in treatment of CRAO. Methods: The PubMed, Scopus, and the Cochrane Library are searched from the date of database inception to September 2021 to conduct a review based on the PRISMA (preferred reporting items for systematic review and meta-analysis), evaluating the role of HBOT in visual recovery of CRAO patients. In addition, a retrospective chart review of patients clinically diagnosed with CRAO at our university-based hospital (University of Texas Health, San Antonio, TX, USA) from year 2011 to 2021 was conducted. Results: After a review of 376 articles, three articles met the inclusion criteria for meta-analysis, where a total of 207 patients received HBOT versus 89 patients that did not receive any form of oxygen therapy. Analysis of these results demonstrate that HBOT in CRAO patients does not enhance the final visual outcome (p = 0.83). Similar conclusion was also drawn from retrospective analysis of 48 patients (15 HBOT versus 33 controls) at our tertiary care center, where no visual benefit was observed in the HBOT group. Conclusions HBOT does not appear to improve final visual outcome and concerns remain regarding adverse reactions such as barotrauma and generalized seizures. Large, randomized studies are required for further understanding of the role of HBOT in treatment of CRAO.

Preoperative traditional software planning (TSP) is a method used to assist surgeons with implant selection and glenoid guide-pin insertion in shoulder arthroplasty. Mixed-Reality (MR) is a new technology that uses digital holograms of the preoperative plan and guide-pin trajectory projected into the operative field. The purpose of this study was to compare TSP to MR in a simulated surgical environment involving insertion of guide-pins into models of severely deformed glenoids. Methods: Eight surgeons inserted guide-pins into eight randomized three-dimensional-printed severely eroded glenoid models in a simulated surgical environment using either TSP or MR. In total, 128 glenoid models were used and statistically compared. The outcomes compared between techniques included procedural time, difference in guide-pin start point, difference in version and inclination, and surgeon confidence via a confidence rating scale. Results: When comparing traditional preoperative software planning to MR visualization as techniques to assist surgeons in glenoid guide pin insertion, there were no statistically significant differences in terms of mean procedure time (P=0.634), glenoid start-point (TSP = 2.2 ± 0.2 mm , MR = 2.1 ± 0.1 mm; P=0.760), guide-pin orientation (P=0.586), or confidence rating score (P=0.850). Conclusions: The results demonstrate that there were no significant differences between traditional preoperative software planning and MR visualization for guide-pin placement into models of eroded glenoids. A perceived benefit of MR is the real-time intraoperative visibility of the surgical plan and the patient’s anatomy; however, this did not translate into decreased procedural time or improved guide-pin position. Level of evidence: Basic Science Study; Biomechanics

Recently, lyso-globotriaosylsphingosine (lyso-Gb3) was found to be elevated in plasma of treatment naive male patients and some female patients with Fabry Disease (FD). This study tested whether lyso-Gb3 could be analyzed in dried blood spots (DBS) from filter cards and whether concentrations are elevated in newborn infants with FD. Lyso-Gb3 concentrations were analyzed in DBS following extraction using a novel HPLC-mass spectrometry (MS)/MS method. Lyso-Gb3 levels in DBS were above the lower limit of quantitation (0.28 ng/mL) in 5/17 newborn FD infants (16 males; range: 1.02-8.81 ng/mL), but in none of the newborn controls, in all 13 patients (4 males) with classic FD (range: 2.06-54.1 ng/mL), in 125/159 Taiwanese individuals with symptomatic or asymptomatic FD who carry the late onset alpha-galactosidase A (GLA) mutation c.936+919G>A (IVS4+919G>A) (3.75+/-0.69 ng/mL; range: 0.418-3.97 ng/mL) and in 20/29 healthy controls (0.77+/-0.24 ng/mL; range: 0.507-1.4 ng/mL). The HPLC-MS/MS method for analysis of lyso-Gb3 is robust and yields reproducible results in DBS in patients with FD. However, concentrations of lyso-Gb3 were below the limit of quantitation in most newborn infants with FD rendering this approach not suitable for newborn screening. In addition, most females with the late onset mutation have undetectable lyso-Gb3 concentrations.
Adolescent ; Adult ; Blood Chemical Analysis/*methods ; Child ; Chromatography, High Pressure Liquid ; *Dried Blood Spot Testing ; Fabry Disease/blood/diagnosis ; Female ; Glycolipids/*blood ; Humans ; Infant, Newborn ; Male ; Sphingolipids/*blood ; Tandem Mass Spectrometry ; Young Adult

Antineoplastic Agents ; therapeutic use ; Antineoplastic Protocols ; standards ; Carcinoma, Non-Small-Cell Lung ; drug therapy ; Guidelines as Topic ; Humans ; Lung Neoplasms ; drug therapy ; Neoplasm Staging ; Societies, Medical ; United States

BACKGROUND AND PURPOSE: Epilepsy is a chronic neurological disease that represents a tremendous burden on both patients and society in general. Studies have addressed how demographic variables, socioeconomic variables, and psychological comorbidity are related to the quality of life (QOL) of people with epilepsy (PWE). However, there has been less focus on how these factors may differ between patients who exhibit varying degrees of seizure control. This study utilized data from the Managing Epilepsy Well (MEW) Network of the Centers for Disease Control and Prevention with the aim of elucidating differences in demographic variables, depression, and QOL between adult PWE. METHODS: Demographic variables, depression, and QOL were compared between PWE who experience clinically relevant differences in seizure occurrence. RESULTS: Gender, ethnicity, race, education, income, and relationship status did not differ significantly between the seizure-frequency categories (p>0.05). People with worse seizure control were significantly younger (p=0.039), more depressed (as assessed using the Patient Health Questionnaire) (p=0.036), and had lower QOL (as determined using the 10-item Quality of Life in Epilepsy for Adults scale) (p < 0.001). CONCLUSIONS: The present results underscore the importance of early screening, detection, and treatment of depression, since these factors relate to both seizure occurrence and QOL in PWE.
Adult ; Centers for Disease Control and Prevention (U.S.) ; Comorbidity ; Continental Population Groups ; Depression ; Education ; Epilepsy* ; Humans ; Mass Screening ; Quality of Life ; Seizures* ; Self Care