Afatinib as a Potential Therapeutic Option for Patients With NSCLC With EGFR G724S

Introduction: EGFR G724S has been described to mediate resistance to first- and third-generation EGFR tyrosine kinase inhibitors (TKIs). In vitro experiments have provided compelling evidence that G724S retains sensitivity for afatinib. Nevertheless, limited data have reported the clinical efficacy of afatinib in patients with NSCLC harboring G724S mutation. Methods: We identified 52 patients with NSCLC with EGFR G724S from an inhouse database and comprehensively profiled their concurrent mutation statuses. Treatments and clinical outcomes were also collected. Results: Of 52 G724S-positive patients, 39 harbored concomitant EGFR exon 19 deletion (19del), and all 37 of the 39 patients who had available clinical data were detected with a G724S mutation after receiving EGFR TKIs. A rare variant of 19del E746_S752delinsV co-occurred with G724S the most frequently (n = 29), whereas 7 of 10 patients with concomitant EGFR exon 20 mutation were TKI treatment naive. S768I was the most common mutation in exon 20 (n = 7). One patient harbored a concomitant EGFR exon 21 mutation, and two lacked co-occurring EGFR mutations. A total of 23 patients provided valid clinical outcome data, of whom eight were treated with afatinib after the emergence of G724S, whereas 15 received non-afatinib treatment (alternative EGFR TKI, chemotherapy, or best supportive care). The disease control rate in afatinib-treated patients (n = 8) reached 100% with a median progression-free survival of 4.5 months, significantly longer than that of non–afatinib-treated (n = 15, 1.7 mo, hazard ratio [HR] = 0.32, p = 0.037) and alternative EGFR TKI-treated (n = 11, 1.8 mo, HR = 0.28, p = 0.042) patients. In the subset who had progressed on osimertinib, afatinib also yielded a superior progression-free survival (6.2 mo) than non-afatinib therapies (1.0 mo, HR = 0.04, p = 0.005) and alternative EGFR TKIs (1.8 mo, HR = 0.06, p = 0.033). Analysis of acquired mutations at afatinib progression revealed re-emergence of EGFR T790M or MET amplification as the potential mechanism of afatinib resistance. Conclusions: EGFR G724S emerges as a resistant mutation against EGFR TKI preferentially in the context of a rare variant of 19del, whereas it might mediate differential mechanisms in the context of exon 20 mutation. We also found that afatinib could be a potential therapeutic option for patients with NSCLC with G724S

Pulmonary Function Testing in Pediatric Pneumonia Patients With Wheezing Younger Than 3 Years of Age

Background. Wheezing symptoms are one of the risk factors in young pneumonia patients that often leads to asthma development. Infant pulmonary function test (iPFT) is potentially a useful tool to help identify and manage these high-risk pneumonia patients. Methods. To examine whether patients with wheezing symptoms are more likely to have poorer pulmonary function and treatment outcomes, and also to explore the clinical benefit of iPFT in young pneumonia patients, we conducted a retrospective analysis of 1005 pneumonia inpatients <3 years of age who had undergone iPFT testing in 2016 at Liuzhou Maternity and Child Healthcare Hospital in Guang-Xi, China. Results . We identified from the hospital database 505 pneumonia patients who presented with wheezing and 500 without wheezing. Univariate analysis showed that wheezing symptoms, viral infection, age <1 year, female gender, and prematurity were significantly associated with poorer iPFT results. After adjusting for confounders, patients with wheezing showed significantly poorer pulmonary function. Patients with wheezing had longer length of stay (7.9 ± 3.9 days vs 6.5 ± 2.6 days; P < .001) and lower percent with no residual clinical symptoms at discharge (58% vs 98%; P < .001) when compared with those of non-wheezing patients. In addition, 81% of patients with viral infection as compared with 43% of patients with nonviral infection presented with wheezing symptoms ( P < .001). Conclusion. Wheezing symptoms were associated with poorer iPFT measures and treatment outcomes for pneumonia inpatients <3 years of age. Patients with wheezing had poorer treatment outcomes. iPFT can be useful in assessing and monitoring young patients with high risk of developing asthma or chronic lung disease later in life

Availability of Additional Mediolateral Implant Option During Total Knee Arthroplasty Improves Femoral Component Fit Across Ethnicities

Background:. Anatomical variation may represent a challenge in achieving a close fit between a prosthesis and a patient’s osseous geometry in total knee arthroplasty (TKA). The purposes of this study were to determine whether the shape of the distal part of the femur differs among ethnicities, whether these differences affect the fit of the femoral component of a standard prosthesis, and whether the additional availability of a femoral component with a reduced mediolateral dimension for the same anteroposterior dimension improves femoral component fit across ethnicities. Methods:. Femoral dimensions were measured intraoperatively during 967 TKAs performed using the same type of prosthesis in patients of 5 different ethnicities. Aspect ratios were calculated to determine whether the shapes of the femora differed among ethnicities. The component fit (“perfect,” overhang, or underhang) when only standard prostheses were available was compared with the fit when both standard and narrow prostheses were available in all ethnic groups. This enabled us to determine whether the femoral component fit was improved by the additional availability of the narrow version. Results:. Wide variations in shape were found among ethnicities as were variations among individuals of the same ethnicity. Differences in shape among ethnicities influenced the rate of overhang. However, overhang was more frequent at the trochlear than at the condylar level across all ethnicities. The availability of both the standard and the narrow femoral components improved the rate of a perfect fit in women in 3 of the 5 ethnic groups and reduced the overhang rate in women in all 5 of the ethnic groups. In contrast, only modest improvements in femoral component fit, which were not statistically significant, were seen in men. Conclusions:. The shape of the distal part of the femur varies not only among ethnicities but also within ethnic groups, leading to a high prevalence of overhang when only standard prostheses are available. The additional availability of a femoral component with a reduced mediolateral dimension for the same anteroposterior size can reduce overhang and improve component fit across ethnicities

The Role of JAK/STAT Signaling Pathway and Its Downstream Influencing Factors in the Treatment of Atherosclerosis

Atherosclerosis is now widely considered to be a chronic inflammatory disease, with increasing evidence suggesting that lipid alone is not the main factor contributing to its development. Rather, atherosclerotic plaques contain a significant amount of inflammatory cells, characterized by the accumulation of monocytes and lymphocytes on the vessel wall. This suggests that inflammation may play a crucial role in the occurrence and progression of atherosclerosis. As research deepens, other pathological factors have also been found to influence the development of the disease. The Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway is a recently discovered target of inflammation that has gained attention in recent years. Numerous studies have provided evidence for the causal role of this pathway in atherosclerosis, and its downstream signaling factors play a significant role in this process. This brief review aims to explore the crucial role of the JAK/STAT pathway and its representative downstream signaling factors in the development of atherosclerosis. It provides a new theoretical basis for clinically affecting the development of atherosclerosis by interfering with the JAK/STAT signaling pathway

Artificial Intelligence-assisted Medical Imaging in Interventional Management of Valvular Heart Disease

The integration of medical imaging and artificial intelligence (AI) has revolutionized interventional therapy of valvular heart diseases (VHD), owing to rapid development in multimodality imaging and healthcare big data. Medical imaging techniques, such as echocardiography, cardiovascular magnetic resonance (CMR) and computed tomography (CT), play an irreplaceable role in the whole process of pre-, intra- and post-procedural intervention of VHD. Different imaging techniques have unique advantages in different stages of interventional therapy. Therefore, single imaging technique can’t fully meet the requirements of complicated clinical scenarios. More importantly, a single intraoperative image provides only limited vision of the surgical field, which could be a potential source for unsatisfactory prognosis. Besides, the non-negligible inter- and intra-observer variability limits the precise quantification of heart valve structure and function in daily clinical practice. With the help of analysis clustered and regressed by big data and exponential growth in computing power, AI broken grounds in the interventional therapy of VHD, including preoperative planning, intraoperative navigation, and postoperative follow-up. This article reviews the state-of-the-art progress and directions in the application of AI for medical imaging in the interventional therapy of VHD

Evaluation of Verteporfin as a Novel Antifibrotic Agent in a Rabbit Model of Glaucoma Filtration Surgery

Purpose: Verteporfin is a benzoporphyrin derivative which is Food and Drug Administration-approved for treatment of choroidal neovascularization in conjunction with photodynamic therapy. It has been shown to prevent fibrosis and scar formation in several organs and represents a promising novel antifibrotic agent for glaucoma surgery. The goal of this study is to determine the effect of verteporfin on wound healing after glaucoma filtration surgery. Design: Preclinical study using a rabbit model of glaucoma filtration surgery. Subjects: Eight New Zealand white rabbits underwent glaucoma filtration surgery in both eyes. Methods: Eyes were randomized into 4 study groups to receive a postoperative subconjunctival injection of 1 mg/mL verteporfin (n = 4), 0.4 mg/mL mitomycin C (MMC; n = 4), 0.4 mg/mL MMC + 1 mg/mL verteporfin (n = 4), or balanced salt solution (BSS) control (n = 4). Bleb survival, vascularity, and morphology were graded using a standard scale over a 30-day period, and intraocular pressure (IOP) was monitored. At 30 days postoperative or surgical failure, histology was performed to evaluate for inflammation, local toxicity, and scarring. Main Outcome Measures: The primary outcome measure was bleb survival. Secondary outcome measures were IOP, bleb morphology, and bleb histology. Results: Compared to BSS control blebs, verteporfin-treated blebs demonstrated a trend toward increased surgical survival (mean 9.8 vs. 7.3 days, log rank P = 0.08). Mitomycin C-treated blebs survived significantly longer than verteporfin-treated blebs (log rank P = 0.009), with all but 1 MMC-treated bleb still surviving at postoperative day 30. There were no significant differences in survival between blebs treated with combination verteporfin + MMC and MMC alone. Mitomycin C-treated blebs were less vascular than verteporfin-treated blebs (mean vascularity score 0.3 ± 0.5 for MMC vs. 1.0 ± 0.0 for verteporfin, P < 0.01). Bleb histology did not reveal any significant toxicity in verteporfin-treated eyes. There were no significant differences in inflammation or scarring across groups. Conclusions: Although verteporfin remained inferior to MMC with regard to surgical survival, there was a trend toward increased survival compared with BSS control and it had an excellent safety profile. Further studies with variations in verteporfin dosage and/or application frequency are needed to assess whether this may be a useful adjunct to glaucoma surgery. Financial Disclosure(s): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article

Comparison of the Ability of Gadobenate Dimeglumine and Gadolinium Ethoxybenzyl Dimeglumine to Display the major Features for Noninvasively Diagnosing Hepatocellular Carcinoma According to the LI-RADS 2018v

Objective To compare the ability of gadolinium ethoxybenzyl dimeglumine (Gd-EOB-DTPA) and gadobenate dimeglumine (Gd-BOPTA) to display the 3 major features recommended by the Liver Imaging Reporting and Data System (LI-RADS 2018v) for diagnosing hepatocellular carcinoma (HCC). Materials and Methods In this retrospective study, we included 98 HCC lesions that were scanned with either Gd-EOB-DTPA-MR or Gd-BOPTA-M.For each lesion, we collected multiple variables, including size and enhancement pattern in the arterial phase (AP), portal venous phase (PVP), transitional phase (TP), delayed phase (DP), and hepatobiliary phase (HBP). The lesion-to-liver contrast (LLC) was measured and calculated for each phase and then compared between the 2 contrast agents. A P value  0.750). When conducting a total evaluation of the combined data across the 5 phases, the display efficiency was excellent (AUC > 0.950). Conclusion Gd-BOPTA and Gd-EOB-DTPA are liver-specific contrast agents widely used in clinical practice. They have their own characteristics in displaying the 3 main signs of HCC. For accurate noninvasive diagnosis, the choice of agent should be made according to the specific situation

The Prevalence of Antinuclear Antibodies in the General Population of China: A Cross-Sectional Study

Background: The incidence of autoimmune diseases such as systemic lupus erythematosus, rheumatoid arthritis, and primary biliary cirrhosis has increased significantly in China. Information about the susceptibility or potential of autoimmune diseases in the general population is lacking. Objective: To explore the prevalence of antinuclear antibody (ANA) and its specificities in the general population in China. Methods: Twenty thousand nine hundred seventy sera samples were taken from the physical examination center in Baoding, China. Indirect immunofluorescence and line immunoassays were used to detect ANA and its specificities, respectively. Results: Samples from females had a higher prevalence of ANA than samples from males (χ2 = 278.55; P < 0.01). For both sexes, the prevalence of ANA positively correlated with age and there were significant differences among different age groups at 10-year intervals, except the 80 years group (P < 0.05). One thousand two hundred forty-three ANA-positive samples were further analyzed with line immunoassays. There was a significant difference among age groups and between sex groups in terms of the specific autoantibodies (P < 0.01). The autoantibodies with the top-3 positive frequencies were anti-Ro-52, anti-M2, and anti-SSA. Conclusions: There was a high prevalence of ANA positivity in the general Chinese population that seemed to be influenced by sex and age and correlated with specific autoantibodies