Toward personalized skin cancer care: multiple skin cancer development in five cohorts.

Importance: Many patients will develop more than one skin cancer, however most research to date has examined only case status. Objective: Describe the frequency and timing of the treatment of multiple skin cancers in individual patients over time. Design: Longitudinal claims and electronic health record-based cohort study. Setting: Vanderbilt University Medical Center database called the Synthetic Derivative, VA, Medicare, Optum Clinformatics® Data Mart Database, IBM Marketscan. Participants: All patients with a Current Procedural Terminology code for the surgical management of a skin cancer in each of five cohorts. Exposures: None. Main Outcomes and Measures: The number of CPT codes for skin cancer treatment in each individual occurring on the same day as an ICD code for skin cancer over time. Results: Our cohort included 5,508,374 patients and 13,102,123 total skin cancers treated. Conclusions and Relevance: Nearly half of patients treated for skin cancer were treated for more than one skin cancer. Patients who have not developed a second skin cancer by 2 years after the first are unlikely to develop multiple skin cancers within the following 5 years. Better data formatting will allow for improved granularity in identifying individuals at high risk for multiple skin cancers and those unlikely to benefit from continued annual surveillance. Resource planning should take into account not just the number of skin cancer cases, but the individual burden of disease.

Neoadjuvant chemotherapy-induced remodeling of human hormonal receptor-positive breast cancer revealed by single-cell RNA sequencing.

Hormone receptor-positive breast cancer (HR+ BC) is known to be relatively insensitive to chemotherapy, and since chemotherapy has remained the major neoadjuvant therapy for HR+ BC, the undetermined mechanism of chemoresistance and how chemotherapy reshapes the immune microenvironment need to be explored by high-throughput technology. By using single-cell RNA sequencing and multiplexed immunofluorescence staining analysis of HR+ BC samples (paired pre- and post-neoadjuvant chemotherapy (NAC)), the levels of previously unrecognized immune cell subsets, including CD8+ T cells with pronounced expression of T-cell development (LMNA) and cytotoxicity (FGFBP2) markers, CD4+ T cells characterized by proliferation marker (ATP1B3) expression and macrophages characterized by CD52 expression, were found to be increased post-NAC, which were predictive of chemosensitivity and their antitumor function was also validated with in vitro experiments. In terms of immune checkpoint expression of CD8+ T cells, we found their changes were inconsistent post-NAC, that LAG3, VSIR were decreased, and PDCD1, HAVCR2, CTLA4, KLRC1 and BTLA were increased. In addition, we have identified novel genomic and transcriptional patterns of chemoresistant cancer cells, both innate and acquired, and have confirmed their prognostic value with TCGA cohorts. By shedding light on the ecosystem of HR+ BC reshaped by chemotherapy, our results uncover valuable candidates for predicting chemosensitivity and overcoming chemoresistance in HR+ BC.

Registered trials on novel therapies for myasthenia gravis: a cross-sectional study on ClinicalTrials.gov.

Novel biologics in MG therapy research is on the rise. This research aimed to investigate the characteristics of registered trials on novel therapies for myasthenia gravis on ClinicalTrials.gov. This cross-sectional study used a descriptive approach to assess the features of the included trials on ClinicalTrials.gov. We found 62 registered trials from 2007 to 2023 on ClinicalTrials.gov. The results showed a yearly rise in the number of registered trials (r = 0.76, p < 0.001). Following 2017, more industry-sponsored trials were conducted (91.5% [43] vs. 60% [9], p = 0.009), fewer results were released (10.6% [5] vs. 60% [9], p = 0.001), and more trials entered phase 3 (67.4% [31] vs. 20% [2], p = 0.001). The most researched novel medications were neonatal Fc receptor inhibitors (51.2% [21]), complement inhibitors (39.0% [16]), and B cell depletors (14.6% [6]). According to the website's data, the neonatal Fc receptor inhibitors and complement inhibitors were effective in treating myasthenia gravis patients in three trials (NCT03315130, NCT03669588, and NCT00727194). This study provides valuable insights into the profile of registered trials on novel therapies for myasthenia gravis. More clinical studies are needed in the future to prove the value of its application.

CD24hiCD27+ Bregs within Metastatic Lymph Nodes Promote Multidrug Resistance in Breast Cancer.

PURPOSE: Axillary lymph nodes (LN) are the primary and dominant metastatic sites in breast cancer. However, the interaction between tumor cells and immune cells within metastatic LNs (mLN) remains poorly understood. In our study, we explored the effect of CD24hiCD27+ regulatory B cells (Breg) within mLNs on orchestrating drug resistance of breast cancer cells. EXPERIMENTAL DESIGN: We collected mLN samples from patients with breast cancer who had received standard neoadjuvant therapy (NAT) and analyzed the spatial features of CD24hiCD27+ Bregs through multicolor immunofluorescence staining. The effect of CD24hiCD27+ Bregs on drug resistance of breast cancer cells was evaluated via in vitro experiments. A mouse model with mLNs was used to evaluate the strategies with blocking the interactions between Bregs and breast cancer for improving tumor regression within mLNs. RESULTS: In patients with breast cancer who had received NAT, there is a close spatial correlation between activated CD24hiCD27+ Bregs and residual tumor cells within mLNs. Mechanistically, CD24hiCD27+ Bregs greatly enhance the acquisition of multidrug resistance and stem-like features of breast cancer cells by secreting IL6 and TNFα. More importantly, breast cancer cells further promote the activation of CD24hiCD27+ Bregs via CD40L-dependent and PD-L1-dependent proximal signals, forming a positive feedback pattern. PD-L1 blockade significantly attenuates the drug resistance of breast cancer cells induced by CD24hiCD27+ Bregs, and addition of anti-PD-L1 antibody to chemotherapy improves tumor cell remission in mLNs. CONCLUSIONS: Our study reveals the pivotal role of CD24hiCD27+ Bregs in promoting drug resistance by interacting with breast cancer cells in mLNs, providing novel evidence for an improved strategy of chemoimmunotherapy combination for patients with breast cancer with mLNs.

Clinical outcomes for femoral tunneled-cuffed hemodialysis catheters with different tip positions: A single-center retrospective study.

BACKGROUND: Tunneled-cuffed catheter (TCC) reaching the mid-atrium has been demonstrated to be associated with improved catheter survival. However, whether similar conclusions can be made for femoral TCC reaching the inferior vena cava (IVC) remains unknown. METHODS: Data from 47 patients with end-stage renal disease receiving right femoral TCC were retrospectively collected and analyzed. The primary patency, catheter dysfunction, and TCC-associated infection rate were compared between patients with TCC tip at the IVC and those with TCC tip at non-IVC. RESULTS: TCC tips were located at the IVC in 26 patients and non-IVC in 21 patients. The technical success rates for both groups were 100%. The primary patency of the former group were significantly higher than those of the latter group at 3 months (92.3% vs 61.9%, p = 0.011), 6 months (80.8% vs 52.4%, p = 0.017), and 12 months (50.0% vs 28.5%, p = 0.024) follow-up, respectively. Kaplan-Meier curve analysis demonstrated significantly different catheter dysfunction-free survival between the two groups (log-rank p = 0.017). The overall TCC-associated infection rate was similar between the two groups (7.7% vs 9.5%, p = 0.82). CONCLUSION: Femoral TCC with tips at IVC was associated with higher primary patency, lower catheter dysfunction but similar TCC-associated infection rate as compared with those at non-IVC.

COVID-19 and healthcare system in China: challenges and progression for a sustainable future.

With the ongoing COVID-19 outbreak, healthcare systems across the world have been pushed to the brink. The approach of traditional healthcare systems to disaster preparedness and prevention has demonstrated intrinsic problems, such as failure to detect early the spread of the virus, public hospitals being overwhelmed, a dire shortage of personal protective equipment, and exhaustion of healthcare workers. Consequently, this situation resulted in manpower and resource costs, leading to the widespread and exponential rise of infected cases at the early stage of the epidemic. To limit the spread of infection, the Chinese government adopted innovative, specialized, and advanced systems, including empowered Fangcang and Internet hospitals, as well as high technologies such as 5G, big data analysis, cloud computing, and artificial intelligence. The efficient use of these new forces helped China win its fight against the virus. As the rampant spread of the virus continues outside China, these new forces need to be integrated into the global healthcare system to combat the disease. Global healthcare system integrated with new forces is essential not only for COVID-19 but also for unknown infections in the future.

Analysis of Ornidazole Injection in Clinical Use at Post-marketing Stage by Centralized Hospital Monitoring System.

This study aims to analyze the clinical use of ornidazole injection at the post-marketing stage by centralized hospital monitoring system method, and investigate its widespread use in patients, in order to regulate and guide the rational drug use, improve the drug specificity and provide a basis for drug therapy. The study adopts a prospective, multi-center, large sample size, centralized hospital monitoring system. We selected five leading hospitals in Hubei province, and observed the inpatients who received the ornidazole injection from July 1, 2015 to October 31, 2015. The basic information of patients was recorded, as well as the drug use and adverse events. The statistical analysis was performed based on these data. A total of 4396 individuals were enrolled in this study, most of them were middle-aged female patients and the ornidazole injection was mainly used as prophylactic prior to surgery to prevent the infections, and surgical treatment of anaerobic infections, abdominal infections and pelvic infections. The irrational drug use existed mainly in the prescribing and administration process, including unreasonable dosing frequency, rapid intravenous drip speed and extended duration of drug use. Eleven cases of adverse reactions were collected during the monitoring, incidence rate of adverse reactions was 2.5‰; adverse drug reactions occurred within 30 min. The study results fully reflected the usage of ornidazole injection in the real world. Based on the study, we calculated the adverse reaction incidence of ornidazole and identified the risk factors which may affect the safety of ornidazole injection. Study results strongly recommend that the manufacturers should publish standards for inpatient use and doctors should prescribe with caution accordingly.

Clinical application analysis of andrographolide total ester sulfonate injection, a traditional Chinese medicine licensed in China.

Andrographolide total ester sulfonate (ATES) injection is one of the products of traditional Chinese medicine (TCM) currently used against viral infection in China. ATES injection was approved for manufacturing and marketing in January 2002. It is indicated for acute respiratory infections, tonsillitis, chronic obstructive pulmonary disease, influenza, foot and mouth disease, bronchiolitis, herpangina, mumps, infectious mononucleosis and psychosis. However, its usage also carries risk. We investigated the use of ATES at the Wuhan Union Hospital from January 2014 to December 2014 and evaluated its real-world clinical application using the hospital centralized monitoring method. A total of 848 cases were enrolled in this study. In these cases, it was mainly used for postoperative anti-inflammation and treating upper respiratory infection, pneumonia and bronchitis. Among them, 39.86% were contraindicated. Irregular medication of adults and children accounted for 1.91% and 23.38%, respectively. Improper choice of solvent accounted for 3.18%. The choice of intravenous drip versus aerosol inhalation was reasonable. A case of adverse events (AEs) was observed in the monitoring period, and the incidence of adverse drug reaction (ADR) of ATES injection was 0.12%. ATES injection in our hospital is relatively safe with a low incidence of adverse reactions. The study assesses the clinical usage and adverse reactions of ATES injection, and provides suggestions for rational use in clinical practice.

Clinical Application Analysis of Andrographolide Total Ester Sulfonate Injection, a Traditional Chinese Medicine Licensed in China / 华中科技大学学报（医学）（英德文版）

Andrographolide total ester sulfonate (ATES) injection is one of the products of traditional Chinese medicine (TCM) currently used against viral infection in China.ATES injection was approved for manufacturing and marketing in January 2002.It is indicated for acute respiratory infections,tonsillitis,chronic obstructive pulmonary disease,influenza,foot and mouth disease,bronchiolitis,herpangina,mumps,infectious mononucleosis and psychosis.However,its usage also carries risk.We investigated the use of ATES at the Wuhan Union Hospital from January 2014 to December 2014 and evaluated its real-word clinical application using the hospital centralized monitoring method.A total of 848 cases were enrolled in this study.In these cases,it was mainly used for postoperative anti-inflammation and treating upper respiratory infection,pneumonia and bronchitis.Among them,39.86％ were contraindicated.Irregular medication of adults and children accounted for 1.91％ and 23.38％,respectively.Improper choice of solvent accounted for 3.18％.The choice of intravenous drip versus aerosol inhalation was reasonable.A case of adverse events (AEs) was observed in the monitoring period,and the incidence of adverse drug reaction (ADR) of ATES injection was 0.12％.ATES injection in our hospital is relatively safe with a low incidence of adverse reactions.The study assesses the clinical usage and adverse reactions of ATES injection,and provides suggestions for rational use in clinical practice.

[Analysis of 47 Cases of Adverse Events of Ozonic Therapeutic Instrument].

With retrospective case study, this paper classified, summerized and evaluated 47 reports induced by ozonic therapeutic instrument. The results showed:25 cases of adverse events were clearly related to the use of instruments;the cases mainly reported by equipment use enterprises; the delay treatment by instrument failure was the most common adverse event performances;adverse events might be relevant to the risk factors of product quality, technical operation, patient specificity and instrument disinfection. Monitoring should be strengthened in order to reduce the ozonic therapeutic instrument adverse events and maintenance of public safety.

[Analysis of 177 Cases of Adverse Events of CSF Flow Control Shunts Based on Spontaneous Response System].

Objective: Monitoring and analyzing CSF flow control shunts adverse event reports by SRS provide a reference for the safe and reasonable use. Methods: Retrospective analysis of 177 CSF flow control shunts adverse event reports, to proceed data mining analysis and early warning. Results: 170 cases of adverse events in 177 cases may be related to the use of CSF flow control shunts. Ventricular dilatation and infection were the most common adverse event performances, according for 21.2% and 19.4% respectively. Adverse events might be relevant to the risk factors of product quality, surgical operation, patient pathological conditions.. Conclusion: Monitoring should be strengthened in order to reduce the CSF flow control shunts adverse events and maintain public safety.