Abrupt visual loss during anti-vascular endothelial growth factor treatment for type 3 neovascularization

AIM: To investigate the incidence of abrupt visual loss and its associated factors, during anti-vascular endothelial growth factor (VEGF) treatment for type 3 neovascularization. METHODS: This retrospective study included 137 eyes that were newly diagnosed with type 3 neovascularization. All eyes were treated with anti-VEGF therapy. Abrupt visual loss was defined as loss of 5 or more lines in best-corrected visual acuity (BCVA) in comparison to the previous visit. The incidence and timing of abrupt visual loss as well as the factors associated with it, were determined. In addition, the BCVA at the final follow-up was compared between the eyes with and those without abrupt visual loss. RESULTS: The mean follow-up period was 42.4±18.9mo after diagnosis, and abrupt visual loss was noted in 22 eyes (16.1%) at a mean of 19.6±13.9mo. Abrupt visual loss was found to be associated with subretinal hemorrhage in 11 eyes (50.0%), development of or increase in the height of pigment epithelial detachment with fluid in 8 eyes (36.4%), and tears in the retinal pigment epithelium in 3 eyes (13.6%). The logarithm of minimum angle of resolution (logMAR) mean BCVA at the final follow-up was 2.07±0.67 (Snellen equivalents: 20/2349) and 1.00±0.55 (20/200) in eyes with and without abrupt visual loss, respectively. BCVA was significantly worse in the eyes with abrupt visual loss (P<0.001). CONCLUSION: Abrupt visual loss is noted in 16.1% of patients with type 3 neovascularization and is associated with poor visual outcome. Additional studies are needed to determine how abrupt visual loss can be prevented.     

Multimorbidity and healthcare utilization among early survivors of pediatric cancer

Early survivors of pediatric cancer are at increased risk of experiencing chronic conditions; however, little is known about the morbidity burden in this population. In this observational cohort study of commercially insured pediatric cancer survivors in the United States (2009–2014), we find that 22.5% of survivors had one chronic condition, and 36.3% had multiple. Compared with survivors without chronic conditions, the presence of multiple conditions significantly increased the odds of an emergency department visit by 70% (odds ratios [OR], 1.7; 95% confidence interval [CI], 1.4–2.1) and of a hospitalization almost four‐fold (OR, 3.8; 95% CI], 2.5–5.5). Findings are important for informing pediatric survivorship care plans in the years following completion of therapy.     

Higher executive abilities following a blood transfusion in children and young adults with sickle cell disease

Individuals with sickle cell disease (SCD) experience cognitive deficits; however, it remains unclear whether medical treatments for SCD improve cognition. Given that executive abilities are typically impaired in individuals with SCD, they were the focus of the current study. Our primary hypothesis was that executive abilities would be higher acutely soon after a blood transfusion in children and young adults with SCD. We used tests from the NIH Toolbox to assess executive abilities in 27 participants with SCD receiving chronic transfusion in comparison to 34 participants with SCD receiving hydroxyurea (HU) and 41 non‐SCD demographically matched controls, all of whom were tested at two time points. Participants in the transfusion group completed cognitive testing within 3 days after a transfusion (soon after transfusion) and then within 3 days before their next transfusion (long after transfusion) over an interval of 3‐7 weeks. We found that executive abilities were significantly poorer for the transfusion and HU groups than for the control group. In support of our primary hypothesis, executive abilities for the transfusion group were significantly better soon after a transfusion compared to long after a transfusion, χ²(1) = 17.8, P < .0001. Our results demonstrate that executive abilities were higher acutely following a blood transfusion. These findings have implications for daily functioning, medical decision making, and academic achievement in children and young adults with SCD.     

PI3K inhibitors in trastuzumab-resistant HER2-positive breast cancer cells with PI3K pathway alterations

The activation of the PI3K signaling pathway resulting from genetic alterations induces carcinogenesis and resistance to anticancer therapies. Breast cancer is a major malignancy that is associated with dysregulation of the PI3K signaling pathway. PIK3CA mutations and PTEN loss occur in every subtype of breast cancer. PI3K inhibitors are being evaluated in breast cancer after the success of an alpha isoform-specific PI3K inhibitor in estrogen receptor (ER)-positive/HER2-negative metastatic breast cancer. Some preclinical data indicate the potential for PI3K/mTOR targeting in combination with trastuzumab for HER2-positive breast cancer with or without expression of the estrogen receptor. However, the role of this therapy in HER2-positive breast cancer with PIK3CA mutations and/or PTEN loss remains unclear. We examined three HER2-positive, ER-negative breast cancer cell lines to determine the efficacy of a novel alpha isoform-specific PI3K inhibitor in combination with trastuzumab. The results indicated that this combination was effective in PIK3CA-mutant or PTEN-deficient breast cancer cells by inducing apoptosis and inhibiting the expression of downstream proteins. PTEN loss by siRNA modulation in parental HER2-positive cancer cells with PI3K signaling pathway alterations could not confer resistance to alpelisib or GDC-0077 plus trastuzumab. We selected the CK-MB-1 cell line without alterations in the PI3K pathway to demonstrate that PI3K inhibitors plus trastuzumab represented a biomarker-specific treatment. In vivo effects of alpelisib plus trastuzumab were tested and confirmed in a mouse model, showing the combination strategy offered the best opportunity to achieve tumor volume reduction. With known safety profiles, this cytotoxic chemotherapy-free regimen warrants further attention as a biomarker-driven strategy for treating HER2-positive breast cancer.     

The Butterfly Fragment in Wedge‐Shaped Femoral Shaft Fracture: Comparison of Two Different Surgical Methods

ObjectiveOur study compared the results of wedge‐shaped femoral shaft fracture following intramedullary (IM) nailing with or without fixation of the third fragment.MethodsWe retrospectively reviewed patients presenting with femoral shaft fracture with AO/OTA type 32‐B from 2011 to 2016. Patients were divided into two groups: closed reduction without touching the third fragment and open reduction with fixation of the third fragment. The fragment ratio, fragment length, nail size, dynamization or not, mRUST scores, union rate, and union time were compared between the two groups. Risk factors of non‐union were also investigated, including sex, age, fracture pattern, fracture location, dynamization, nail size, fragment ratio, fragment size, and postoperative fragment displacement.ResultsA total of 80 patients met inclusion criteria, 20 patients with wedge‐shaped shaft femoral fracture were managed with IM nailing and open reduction with fixation of the third fragment. Sixty patients were treated with IM nail without touching the third fragment. The union rate for the fixation and non‐fixation groups were 60.0% and 81.7%, respectively. The mean union time for the fixation group was 19 months vs 14 months for the non‐fixation group. Multi‐regression analysis showed larger nail size (odds ratio: 2.26) and fixation of the third fragment (odds ratio: 0.18) influenced fracture healing.ConclusionsFixation of the third fragment in wedge‐shaped shaft femoral fracture results in a longer union time and lower union rate. In the management of femoral fracture with a third fragment, a larger nail size is recommended and fixation should be performed in a closed manner. Fixation of the fragment may achieve better fracture reduction. However, disruption of the vasculature and surrounding structures may further result in nonunion of the fracture site.     

Associations of Emergency Department Visits for Asthma with Precipitation and Temperature on Thunderstorm Days: A Time-Series Analysis of Data from Louisiana,USA, 2010–2012

Background: Studies of thunderstorm asthma to understand risk factors using high-resolution climate data and asthma outcomes on a large scale are scarce. Moreover, thunderstorm asthma is not well studied in the United States.Objectives: We examined whether climate parameters involved in thunderstorms are associated with emergency department (ED) visits for acute asthma attacks in the United States.Methods: We analyzed 63,789 asthma-related, daily ED visits for all age groups, and thunderstorm-associated climate data in Louisiana during 2010 through 2012. We performed time-series analyses using quasi-Poisson regression models with natural cubic splines of date, parish, holiday, day of week, season, daily maximum concentrations of ozone (O3) and fine particulate matter [PM ≤2.5μm in aerodynamic diameter (PM2.5)], and daily mean pressure, precipitation, and temperature. Because of a significant interaction effect between temperature and lightning days on asthma-related visits, we performed stratified analyses by days with/without lightning or thunderstorm (defined by any lightning and precipitation).Results: On thunderstorm days, higher asthma-related ED visits were associated with higher daily mean precipitation [relative risk (RR)=1.145 per 1g/m2/s (95% CI: 1.009, 1.300)] and lower daily mean temperature [RR=1.011 per 1°C change (1.000–1.021)] without carry-over effect to the next non-thunderstorm day. These higher risks were found mainly among children and adults <65 years of age. We observed similar results on lightning days. However, we did not find similar associations for non-thunderstorm or non-lightning days. Daily maximum O3 and PM2.5 levels were not significantly associated with asthma ED visits on thunderstorm days.Discussion: Higher precipitation and lower temperature on thunderstorm days appear to contribute to asthma attacks among people with asthma, suggesting they should consider taking precautions during thunderstorms. EDs should consider preparing for a potential increase of asthma-related visits and ensuring sufficient stock of emergency medication and supplies for forecasted severe thunderstorm days. https://doi.org/10.1289/{"type":"entrez-protein","attrs":{"text":"EHP10440","term_id":"372009825","term_text":"EHP10440"}}EHP10440     

Role of phloretin as a sensitizer to TRAIL-induced apoptosis in colon cancer

Phloretin is one of the apple polyphenols with anticancer activities. Since tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) serves important roles in inducing apoptosis, the present study examined the effect of phloretin on TRAIL-induced apoptosis in colon cancer cells. Treatment with both phloretin and TRAIL markedly suppressed the survival of cancer cells from several colon cancer cell lines compared with that of cells treated with either TRAIL or phloretin. Additionally, decreased numbers of colonies were observed following addition of phloretin and TRAIL. Furthermore, TRAIL- and phloretin-treated HT-29-Luc cells exhibited decreased luciferase activity. Increased apoptosis was observed in phloretin- and TRAIL-treated HT-29-Luc colon cancer cells, accompanying elevated levels of cleaved poly(ADP-ribose) polymerase, and caspase-3, −8 and −9. The expression levels of MCL1 apoptosis regulator BCL2 family member (Mcl-1) were decreased following addition of phloretin in colon cancer cells. In addition, overexpression of Mcl-1 in phloretin- and TRAIL-treated HT-29-Luc cells resulted in increased cell survival. Treatment of HT-29-Luc cells with a combination of cycloheximide (CHX) and phloretin led to a more prominent decrease in Mcl-1 expression compared with that in cells treated with CHX alone, while Mcl-1 expression was recovered by treatment with MG132. Binding of ubiquitin with Mcl-1 was verified using immunoprecipitation. Intraperitoneal injection of both TRAIL and phloretin into tumor xenografts was associated with a decreased tumor volume compared with that following injection with either TRAIL or phloretin. Overall, the present results suggest a synergistic effect of phloretin on TRAIL-induced apoptosis in colon cancer cells.     

Factors associated with long-term smoking relapse in those who succeeded in smoking cessation using regional smoking cessation programs

It is known that approximately 10% of successful quitters relapse annually. This study aimed to investigate the factors related to long-term smoking relapse in individuals who succeeded in maintaining smoking cessation for 6 months after attending a regional smoking cessation program.This study enrolled 943 individuals registered for the regional smoking cessation program at the Busan Smoking Cessation Center in 2018–2019 who maintained smoking cessation for 6 months. A survey was conducted using a smartphone link or through phone calls, and the data for 305 participants who finally completed the survey were analyzed. The questionnaire addressed individual, inter-individual, organizational, and community-level factors related to smoking relapse. Multivariate logistic regression analysis was performed to evaluate the factors associated with smoking relapse by period. The Cox proportional hazard regression model was used for the factors associated with smoking relapse for the entire period.The smoking relapse rate at the time of the survey was 25.4%. In the analysis of smoking relapse by period, relapse was associated with the belief that smoking relieves stress, the number of single-person households, and poor subjective health status. In the analysis of smoking relapse during the entire period, we observed a significant association with the belief that smoking relieves stress (hazard ratio [HR]: 2.65, 95% confidence interval [CI]: 1.52–4.61), single-person households (HR: 1.95, 95% CI: 1.16–3.26), and high levels of emotional stress (HR: 1.72, 95% CI: 1.04–2.85).Long-term follow-up is necessary to prevent smoking relapse in single-person households, individuals who believe that smoking relieves stress, and those experiencing high levels of subjective emotional stress. Interventional therapies for stress relief and awareness improvement in smokers need to be developed.