Control Rate Research Articles

Managing vitreoretinal complications in uveal melanoma: Surgical treatment and practical considerations.

In the past few decades, the primary management for uveal melanoma has evolved from enucleation to eye-preservingtreatments. However, despite achieving ahigh rate of local tumour control, complications following eye-preservingtreatments still occur and are partly responsible for functional loss and secondary enucleation. A literature review by a broad international panel. We summarised the current literature on utilizing vitreoretinal (VR) surgery for managing the complications of uveal melanoma. We also provided insights from the authors' personal experience and practical recommendations for clinical care. With the advancement of VR instruments and surgical techniques and the combination of VR and ocular oncology knowledge ("Onco-VR"), it is now possible to manage or even prevent complications such as vitreous haemorrhage, retinal detachment, and toxic tumour syndrome.

Real-world outcomes of FOLFOXIRI plus bevacizumab in patients with metastatic colorectal cancer: the JSCCR-TRIPON study.

FOLFOXIRI plus bevacizumab is a standard first-line chemotherapy for patients with metastatic colorectal cancer (mCRC). However, due to the severe toxicities, this regimen is not widely used. There is limited data on the real-world efficacy and safety. We conducted a retrospective analysis of clinical data from mCRC patients who received FOLFOXIRI plus bevacizumab as first-line chemotherapy at 31 institutions. The initial dose was standardized according to the TRIBE regimen. Induction therapy was defined as a combination of oxaliplatin, irinotecan, and fluorouracil. Out of 104 patients who met the criteria, the median age was 58years (range, 16-72). 81% of patients had an eastern cooperative oncology group performance status (PS) of 0. An initial dose reduction was observed in 63% of patients. The median number of preplanned induction therapy cycles was 12 (range, 4-12). The completion of scheduled induction therapy cycles was observed in 45% of patients, with treatment-related toxicities being the main reason for discontinuation (63%). The median progression-free survival and overall survival were 12.8months (95% CI, 10.6-15.0) and 27.9months (95% CI 21.6-34.2), respectively. The objective response rate and disease control rate were 63.7% and 98.9%, respectively. The R0 resection rate was 21.2%. The main grade 3 or higher toxicities were neutropenia (51%), febrile neutropenia (10%), and nausea/vomiting (5%). No treatment-related deaths were observed. In a real-world clinical setting, FOLFOXIRI plus bevacizumab demonstrated efficacy and safety comparable to previous clinical trials.

Potential of Nutritional Markers as Predictors After Immunotherapy in Advanced Head and Neck Squamous Cell Carcinoma.

Immune checkpoint inhibitors (ICIs) are the standard treatment for advanced head and neck squamous cell carcinoma (HNSCC). Programmed death-ligand 1 (PD-L1) is clinically assessed before initiating ICIs; however, there are no established biomarkers for predicting the response to immunotherapy. In this study, inflammatory and nutritional parameters were examined to determine the therapeutic outcomes of ICIs for HNSCC. Sixty-five patients with metastatic or recurrent HNSCC who received programmed death-1 (PD-1) blockade were enrolled. Inflammatory and nutritional indices were correlated with patient outcomes, including the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), systemic immune-inflammation index (SII), and prognostic nutritional index (PNI). Patients aged <70 years were significantly associated with a high NLR, whereas those with a performance status of 2 or 3 were closely related to a high NLR, high SII, and low PNI. Although all patients achieved an objective response rate of 24.6% and a disease control rate of 36.9%, the NLR, PLR, SII, and PNI values were not significantly different between responders and non-responders. Univariate analysis showed that the NLR, PLR, SII, and PNI were significant predictors of progression-free survival (PFS) and overall survival (OS). Multivariate analysis identified PNI as an independent predictor of PFS and OS. PNI, as a nutritional marker, was identified as a significant predictor of outcomes following PD-1 blockade administration in patients with advanced HNSCC, compared to inflammatory markers, such as NLR, PLR, and SII.

Role of Hematological Markers in Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma Treated With Pembrolizumab.

The predictive role of hematological markers in patients with recurrent or metastatic squamous cell carcinoma of the head and neck (R/M SCCHN) treated with pembrolizumab remains unclear. We conducted a multicenter retrospective cohort study to investigate the predictive impact of the pre-treatment hematological markers neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), CRP-albumin-lymphocyte (CALLY) index, and the modified Glasgow prognostic score (mGPS) on overall survival (OS) and progression-free survival (PFS) in patients with R/M SCCHN treated with pembrolizumab. From December 2019 to February 2022, 119 and 28 patients were treated with pembrolizumab alone and pembrolizumab plus chemotherapy, respectively. The optimal cut-off point of dichotomized hematological markers was calculated using the area under the receiver operating characteristic curve. Hazard ratios (HRs) and 95% confidence intervals (95%CIs) were estimated using Cox proportional hazard models with adjustment for potential confounders. In the pembrolizumab monotherapy group, patients with higher NLR, PLR, and mGPS and a lower CALLY index showed significantly shorter OS after adjustment for potential confounders. In addition, all hematological markers examined in this study tended to be associated with clinical response, such as overall response rate or disease control rate (DCR); in particular, a lower CALLY index and higher mGPS were significantly associated with poor DCR. In the pembrolizumab with chemotherapy group, these hematological markers had a similar association with OS but not with clinical response. Pre-treatment NLR, PLR, CALLY index, and mGPS might be predictive markers of survival in patients with R/M SCCHN treated with pembrolizumab.

Efficacy and safety of pralsetinib in patients with RET fusion positive non–small cell lung cancer: An observational real world study

BackgroundPralsetinib, a selective RET targeted tyrosine kinase inhibitor (TKI), has been approved for treating locally advanced or metastatic RET fusion-positive NSCLC in adults who have previously received platinum-based chemotherapy in China. MethodsIn this retrospective analysis conducted at Hunan Cancer Hospital in China, we examined 36 patients with advanced NSCLC with RET fusion, who were treated with pralsetinib between January 2021 and December 2023. The study focused on assessing the efficacy (Progression-free survival (PFS) and overall survival (OS)) and safety profile of pralsetinib in these patients. Statistical analyses were conducted using SPSS version 20.0, with a significance level set at p < 0.05. ResultsThe results revealed that pralsetinib exhibited significant activity in this patient cohort. Kaplan-Meier survival analysis indicated a median PFS of 10.7 months and a median OS of 21.2 months. The overall response rate(ORR) and disease control rate (DCR) was 55.6 % and 72.2 %, respectively. Pralsetinib was generally well tolerated, with most adverse events being mild to moderate (grades 1–2). The most common serious adverse events (≥grade 3) observed were lymphopenia (13.9 %), hypertension (11.1 %), leukopenia (8.3 %), neutropenia (8.3 %), and creatine kinase elevation (8.3 %). ConclusionPralsetinib demonstrated promising activity in patients with advanced NSCLC harboring RET fusion with a favorable safety profile.

Prevalence, awareness, treatment, and control rates of hypertension in the general population of Australia: a systematic review and meta-analysis.

A recent call-to-action highlighted that Australia is lagging behind high-income countries regarding hypertension control rates. We performed a systematic literature search of reports on prevalence, awareness, treatment and control rates since 2010. We also undertook an individual participant data meta-analysis of six population-based studies in the general population from 1980 to 2018 to understand the size of the problem and trajectories over time. The aggregated data showed that after 2010, hypertension prevalence was 31% ]95% confidence interval (CI) 27-34%], and awareness, treatment, and control rates among people with hypertension were 56% (41-71%), 54% (46-62%) and 34% (22-47%), respectively. Since 1980, these figures have shown slight improvement. However, we noted a low availability of quality nationwide randomized databases for Australia. We require critical action to improve the prevention, detection and treatment of hypertension, and highlight the need for large-scale investment in tracking population health in order to produce vital health statistics for the nation.

Stereotactic radiosurgery for brain metastases from human epidermal receptor 2 positive breast Cancer: an international, multi-center study.

To report patient outcomes and local tumor control rates in a cohort of patients with biopsy-proven HER-2 positive breast cancer treated with stereotactic radiosurgery (SRS) for brain metastases (BM). This international, retrospective, multicenter study, included 195 female patients with 1706 SRS-treated BM. Radiologic and clinical outcomes after SRS were determined and prognostic factors identified. At SRS, median patient age was 55 years [interquartile range (IQR) 47.6-62.0], and 156 (80%) patients had KPS ≥ 80. The median tumor volume was 0.1 cm3 (IQR 0.1-0.5) and the median prescription dose was 16Gy (IQR 16-18). Local tumor control (LTC) rate was 98%, 94%, 93%, 90%, and 88% at six-, 12-, 24-, 36- and 60-months post-SRS, respectively. On multivariate analysis, tumor volume (p = < 0.001) and concurrent pertuzumab (p = 0.02) improved LTC. Overall survival (OS) rates at six-, 12-, 24-, 36-, 48-, and 60-months were 90%, 69%, 46%, 27%, 22%, and 18%, respectively. Concurrent pertuzumab improved OS (p = 0.032). In this patient subgroup, GPA scores ≥ 2.5 (p = 0.038 and p = 0.003) and rare primary tumor histologies (p = 0.01) were associated with increased and decreased OS, respectively. Asymptomatic adverse radiation events (ARE) occurred in 27 (14.0%) and symptomatic ARE in five (2.6%) patients. Invasive lobular carcinoma primary (p = 0.042) and concurrent pertuzumab (p < 0.001) conferred an increased risk for overall but not for symptomatic ARE. SRS affords effective LTC for selected patients with BM from HER-2 positive breast cancer. Concurrent pertuzumab improved LTC and OS but at the same time increased the risk for overall, but not symptomatic, ARE.

Nickel-Copper Bimetallic Oxide Nanoparticles Prepared by Simple Coprecipitation Method as High Performance Electrode Materials for Asymmetric Supercapacitors.

Supercapacitors with transition bimetallic oxides as pseudocapacitive materials have been of wide concern for their excellent energy storage performance. In this work, a simple coprecipitation method was used to synthesize the precursor, followed by calcination to prepare Ni-Cu bimetallic oxide materials. The structure, morphology and properties of the materials prepared by different precipitating agents and different calcination temperatures of NCO-H2C2O4 precursor were investigated. The optimum precipitant was determined to be H2C2O4, and Ni-Cu nanoparticles with regular lamellar microstructure were obtained at the calcination temperature of 400 °C. The nanostructure and morphology provide a large active channel for the rapid diffusion of electrolyte ions, and the specific capacitance of NCO-H2C2O4-400 electrode material can reach 740.31 F/g Cs at 1 A/g. The investigation of charge storage mechanism shows that the contribution rate of capacitance and diffusion control is about 37.9% and 67.2%, respectively. The electrochemical test results of the asymmetric supercapacitors (ASC) constructed with NCO-H2C2O4-400 and activated carbon show that the specific capacitance, energy density, and power density of the capacitor are 52.66 F/g, 16.45 Wh/kg, and 759.51 W/kg, respectively. Even after 5000 charge/discharge cycles at 5 A/g, it can still keep 90.57% of its initial capacity. This work not only provides competitive electrode materials for energy storage devices but also provides a feasible strategy for producing complex transition metal oxide materials with high capacitance performance.

Cryoablation and post-progression immune checkpoint inhibition in metastatic melanoma: a phase II trial

Image-guided percutaneous cryoablation is an established minimally invasive oncologic treatment. We hypothesized that cryoablation may modify the immune microenvironment through direct modulation of the tumor, thereby generating an anti-tumor response in tumors refractory to immune checkpoint inhibition (ICI). In this non-randomized phase II single-center study (NCT03290677), subjects with unresectable melanoma progressing on ICI underwent cryoablation of an enlarging metastasis, and ICI was continued for a minimum of two additional cycles. The primary endpoints were safety, feasibility and tumor response in non-ablated lesions. From May 2018 through July 2020, 17 patients were treated on study. The study met its primary endpoints with the combination strategy found to be safe and feasible with an objective response rate of 23.5% and disease control rate of 41% (4 partial response, 3 stable disease). Our data support further study of this synergistic therapeutic approach.

The Impact of Pembrolizumab as a Salvage Therapy Based on HER2 Expression in Advanced Gastric Cancer.

Immune checkpoint inhibitors (ICIs) are used as salvage treatments for advanced gastric cancer (AGC) regardless of HER2 status. This study assessed the efficacy of ICIs based on HER2 expression in AGC patients who received pembrolizumab as salvage monotherapy at Samsung Medical Center from November 2017 to March 2023. HER2 status was determined via immunohistochemistry, and tumor response and survival outcomes were compared accordingly. Among the 113 patients analyzed, with a median age of 61 years and 64.6% being male, 12 patients (10.6%) were HER2-positive, and 101 patients (89.4%) were HER2-negative. Of 92 evaluable patients, none had a complete response. However, 50% of HER2-positive patients had a partial response, compared to 4.9% of HER2-negative patients (p < 0.001). The disease control rate was 70% in HER2-positive and 37.8% in HER2-negative patients (p = 0.086). Median progression-free survival was 5.53 months for HER2-positive patients versus 1.81 months for HER2-negative patients (p = 0.037). Pembrolizumab as a salvage chemotherapy for the treatment of AGC demonstrated superior effectiveness in HER2-positive patients compared with HER2-negative patients.

Salvage stereotactic ablative body radiotherapy after thermal ablation of primary kidney cancer.

To evaluate the effectiveness and safety of salvage stereotactic ablative body radiotherapy (SABR) for recurrent renal cell carcinoma (RCC) after thermal ablation (TA). This study was a multi-institutional retrospective analysis of patients with recurrent RCC following TA who received SABR between 2016 and 2020. The primary study outcome was freedom from local failure, evaluated radiographically based on Response Evaluation Criteria in Solid Tumours (RECIST) v1.1. Distant failure, cancer-specific survival (CSS), overall survival (OS), treatment-related toxicity and renal function changes following SABR were the secondary outcomes. The Kaplan-Meier method was used to estimate freedom from local and distant failure, CSS and OS. Seventeen patients with 18 biopsy-confirmed RCCs were included, with a median (interquartile range [IQR]) age at time of SABR of 75.2 (72.6-68.7) years, a median (IQR) tumour size of 3.5 (1.9-4.1) cm and follow-up (reverse Kaplan-Meier method) of 3.36 (95% confidence interval [CI] 1.6-4.1) years. Six of the 17 patients had a solitary kidney. Five patients had failed repeat TA prior to SABR. The median (IQR) time from TA procedure to SABR was 3.03 (1.5-5.1) years. No patient experienced local progression, with a local control rate of 100%. Four patients, two with baseline metastatic disease, experienced distant progression. The distant progression-free survival, CSS and OS at 3 years were 72.1% (95% CI 51.9%-100%), 92.3% (95% CI 78.9%-100%) and 82.1% (95% CI 62.1%-100%), respectively. The median (IQR) glomerular filtration rate before SABR was 58 (40-71) mL/min, and at last follow-up, it was 48 (33-57) mL/min. No patient experienced grade 3+ toxicity or went on to develop end-stage renal disease. The results showed that SABR appears to be an effective and safe salvage strategy in patients with recurrent RCC following TA.

A single institution retrospective study of efficacy and complications perspective of Gamma Knife Radiosurgery for benign skull base meningioma: A 12-year follow-up

Background and Objectives: Gamma knife radiosurgery (GKRS) has established its role as an effective treatment modality for inaccessible, recurrent, and residual benign skull base meningioma. Therefore, it is necessary to study the outcome in the long term. The current retrospective study aims to analyze and report the clinical and radiological outcomes after long-term follow-up of GKRS for skull base meningiomas &gt;= 12 years. Patients and methods: The present study was conducted on 106 consecutive patients harboring benign skull base meningiomas treated by GKRS at our IMC center between 2005 and 2012 and was followed till the end of 2023. Results: After a median follow-up of 13 years (3.6-18 years), a tumor control rate was reported in 88.7% of patients (n 94/106). Recurrences and tumor progression occurred in 11.3% (n 12/106) at a median follow-up period of 5.4 years (3–10.3 years). The 3, 5-, 10-, 12-and 15-year actuarial tumor control rate was 100%, 95.3%, 89.7%, 88.7%, and 78.1% respectively. Conclusions: The current retrospective study provides a long-term 12-year follow-up and comprises one of the longest follow-up studies of GKRS-treated benign skull base meningiomas. The current series documents a persistent long-term high local tumor control and an acceptable low incidence of neurological deficits. Benign skull base meningioma volume variant at the time of GKRS is a statistically significance predictor factor for tumor control at long-term outcomes.

Camrelizumab plus apatinib in patients with advanced or recurrent endometrial cancer after failure of at least one prior systemic therapy (CAP 04): a single-arm phase II trial

BackgroundThe combination of anti-programmed death 1 (PD-1) inhibitors and tyrosine kinase inhibitors is an effective treatment strategy in endometrial cancer. We aimed to explore the efficacy and safety of camrelizumab plus apatinib as an alternative therapeutic option in patients with previously treated endometrial cancer.MethodsThis single-arm Simon’s two-stage phase II trial was conducted at the Fudan University Shanghai Cancer Center. Patients with advanced or recurrent endometrial cancer who had failed at least one prior systemic therapy were screened for potential participation. Eligible patients were treated with intravenous camrelizumab (200 mg d1 q2w) and oral apatinib (250 mg qd) every 4 weeks. The primary end point was the objective response rate (ORR) per RECIST v1.1 in the intention-to-treat principle.ResultsBetween January 20, 2020, and October 14, 2022, 36 patients (29 with microsatellite stability/mismatch repair proficient [MSS/pMMR] tumors; two with microsatellite instability-high/mismatch repair deficient [MSI-H/dMMR] tumors) were enrolled and treated. The confirmed ORR was 44.4% (95% CI: 27.9, 61.9) and the disease control rate was 91.7% (95% CI: 77.5, 98.2). The median duration of response was 9.3 (95% CI: 4.3, not reached) months, the median progression-free survival was 6.2 (95% CI: 5.3, 11.1) months, and the median overall survival was 21.0 (95% CI: 13.4, not reached) months during a median follow-up of 14.2 (interquartile range: 10.3, 27.6) months. Treatment-related adverse events of grade 3 or 4 occurred in 20 (55.6%) patients, with the most common being increased γ-glutamyl transferase (27.8%), alanine aminotransferase (16.7%) and aspartate aminotransferase (13.9%), and hypertension (11.1%). No treatment-related death occurred.ConclusionsCamrelizumab plus apatinib showed promising antitumor activity with manageable toxicity in patients with advanced or recurrent endometrial cancer who had failed at least one prior systemic therapy. The findings of this study support further investigation of camrelizumab plus apatinib as an alternative therapeutic option, especially for patients with MSS/pMMR tumors.Trial registrationThis trial was retrospectively registered with ChiCTR.org.cn, number ChiCTR2000031932.

Overexpression of CCL-20 and CXCL-8 genes enhances tumor escape and resistance to cemiplimab, a programmed cell death protein-1 (PD-1) inhibitor, in patients with locally advanced and metastatic cutaneous squamous cell carcinoma

ABSTRACT Cemiplimab has demonstrated relevant clinical activity in cutaneous squamous cell carcinoma (cSCC) but mechanisms of primary and acquired resistance to immunotherapy are still unknown. We collected clinical data from locally advanced and/or metastatic cSSC patients treated with cemiplimab in two Italian University centers. In addition, gene expression analysis by using Nanostring Technologies platform to evaluate 770 cancer- and immune-related genes on 20 tumor tissue samples (9 responders and 11 non-responders to cemiplimab) was performed. We enrolled 81 patients with a median age of 82 years. After 16.4 months of median follow-up, 12- and 24-months PFS were 53% and 42%, respectively; while 12- and 24-months OS were 71% and 61%, respectively. Treatment was well tolerated. Overall response rate (ORR) was 58%, with a disease control rate (DCR) of 77.8%. The difference between genes expressed in responder versus non-responder patient samples was substantial, particularly for genes involved in immune system regulation. Cemiplimab-resistant tumors were associated with over-expression of CCL-20 and CXCL-8. Cemiplimab confirmed efficacy and safety data in real-life cSCC patients. Overexpression of CCL-20 and CXCL-8 could represent biomarkers of lack of response to immunotherapy.

Efficacy and safety of hepatic arterial infusion chemotherapy combined with donafenib in the treatment of unresectable hepatocellular carcinoma.

This study aimed at ascertaining the efficacy and safety of hepatic arterial infusion chemotherapy (HAIC) combined with donafenib versus HAIC alone in the treatment of unresectable hepatocellular carcinoma (HCC). Seventy HCC patients were enrolled for our study, and they were randomized by simple randomization using computer-generated random numbers into two groups: control group and observation group. Regular follow-up reviews were conducted to assess the efficacy of treatments. The levels of apoptotic factors, the levels of hepatic fibrosis indices, the levels of serum tumor vascular factors and tumor markers, and the occurrence of adverse reactions in the two groups were recorded and compared. Disease control rate, objective response rate, and progression-free survival (PFS) of patients in the observation group were higher in contrast to the control group. After 12 weeks of treatment, lower mRNA expression of c-mesenchymal-epithelial transition factor, telomerase, and Fas Ligand and higher mRNA expression of Fas and Caspase-3 were observed in HCC tissues of the observation group versus the control group (p<0.05); lower detection values of serum laminin, hyaluronic acid, collage type IV, vascular endothelial growth factor receptor 2, and alpha-fetal protein (AFP) were noted in HCC patients of the observation group in comparison to the control group (p<0.05); there was no difference in the incidence of adverse reactions between the two groups. Donafenib combined with HAIC in the treatment of unresectable HCC patients can notably reduce serum AFP levels, improve hepatic fibrosis, enhance short-term efficacy, prolong PFS, and have a favorable safety profile.

Effect and safety of ripretinib in the treatment of advanced gastrointestinal stromal tumor: A systematic review and meta-analysis.

Imatinib (IMA) has received approval as the primary treatment for gastrointestinal stromal tumors (GIST). Nonetheless, approximately half of the patients with advanced GIST show disease advancement following IMA treatment. Presently, the efficacy of secondary and tertiary medications in addressing various GIST secondary mutations is somewhat restricted. Consequently, there is a significant medical demand for the creation of kinase inhibitors that extensively block secondary drug-resistant mutations in advanced GIST. Ripretinib (RPT) is a new, switch-control tyrosine kinase inhibitors that can suppress different mutations of KIT and PDGFRA via a dual mechanism of action. To investigate the literature on RPT to assess an effective, safe, and successful treatment strategy against advanced GIST. The present systematic review and meta-analysis was performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. PubMed, Embase, Cochrane, Web of Science and ClinicalTrials.gov databases were screened from January 1, 2003 to May 1, 2024. A total of 4 studies were included, with a total of 507 patients enrolled. The objective response rate (ORR) of the RPT-treated advanced GIST was 17% (95%CI: 0.11-0.27), while the disease control rate (DCR) was 66% (95%CI: 0.59-0.73). The overall occurrence of adverse events with varying degrees was 97% (95%CI: 0.93-1), whereas that of grade ≥ 3 adverse reactions was 42% (95%CI: 0.28-0.63). The sensitivity analysis revealed that omitting some studies did not yield statistically notable variances in the aggregate data regarding the ORR, DCR, and the occurrence of adverse events of grade 3 or higher. The publication bias was absent because no significant asymmetry was observed in Begg's funnel plot in all studies. RPT has favorable efficacy profiles in GIST patients, but the adverse reactions are obvious, and patient management needs to be strengthened to achieve better safety and tolerability.

Characterizing apparent treatment resistant hypertension in the United States: insights from the All of Us Research Program.

Hypertension (HTN) remains a significant public health concern and the primary modifiable risk factor for cardiovascular disease, which is the leading cause of death in the United States. We applied our validated HTN computable phenotypes within the All of Us Research Program to uncover prevalence and characteristics of HTN and apparent treatment-resistant hypertension (aTRH) in United States. Within the All of Us Researcher Workbench, we built a retrospective cohort (January 1, 2008-July 1, 2023), identifying all adults with available age data, at least one blood pressure (BP) measurement, prescribed at least one antihypertensive medication, and with at least one SNOMED "Essential hypertension" diagnosis code. We identified 99 461 participants with HTN who met the eligibility criteria. Following the application of our computable phenotypes, an overall population of 81 462 were further categorized to aTRH (14.4%), stable-controlled HTN (SCH) (39.5%), and Other HTN (46.1%). Compared to participants with SCH, participants with aTRH were older, more likely to be of Black or African American race, had higher levels of social deprivation, and a heightened prevalence of comorbidities such as hyperlipidemia and diabetes. Heart failure, chronic kidney disease, and diabetes were the comorbidities most strongly associated with aTRH. β-blockers were the most prescribed antihypertensive medication. At index date, the overall BP control rate was 62%. All of Us provides a unique opportunity to characterize HTN in the United States. Consistent findings from this study with our prior research highlight the interoperability of our computable phenotypes.

Stereotactic radio-neurosurgery for jugular foramen schwannomas

BackgroundStereotactic radiosurgery (SRS) represents a minimally invasive and valuable alternative for jugular foramen schwannomas (JFS), both as upfront and/or adjuvant treatment (in hybrid approaches).MethodsWe conducted a retrospective review of our cases treated at the Lausanne University Hospital (CHUV) from June 2010 to October 2023. Eleven patients underwent SRS, among whom three had prior surgery, two in our center in the frame of a planned combined approach and one in another center. Two patients received "volume-staged" SRS. The mean age at SRS was 60 years (median 68; range 29–83). Cranial nerve (CN) symptoms were present in six patients, while five were asymptomatic. The mean tumor volume at SRS was 2.1 cc (median 1.2; range 0.068–7.3 cc), with a 12 Gy marginal dose prescribed in all cases.ResultsThe mean follow-up period was 3.9 years (median 2, range 1–7). Cranial nerve function improved after SRS in six patients, while five remained stable. At the last follow-up, all tumors showed a decrease in volume, except for one patient, who underwent surgery at 18 months after SRS, for volumetric increase at 6 and 12 months, with further XII−th CN palsy and medulla oblongata compression. Although tumor decreased at 18 months, such patient needed microsurgical resection for symptom persistence and was further controlled. The mean tumor volume at 1 year post-SRS was 1.6 cc (median 0.55; range 0.028–7.77 cc), at 2 years was 1.31 cc (median 0.76; range 0.19–5), and at 3 years was 1.32 cc (median 0.59; range 0.23–4.8). No adverse radiation events were observed.ConclusionsStereotactic radiosurgery is considered a safe and effective treatment for jugular foramen schwannomas, ensuring high rates of tumor control in all patients over the long term. The cranial nerve function improved after SRS in the 6 patients who had deficits and the other 5 patients who had no deficits remained asymptomatic. For larger tumors, combined/hybrid approaches can be a valuable alternative, to obtain tumor control and to preserve neurological function.

Runoff Control Performance of Three Typical Low-Impact Development Facilities: A Case Study of a Community in Beijing

The development of sponge cities advocates for sustainable urban rainwater management, effectively alleviating urban flood disasters, reducing non-point-source pollution, and promoting the recycling of rainwater resources. Low-Impact Development (LID) serves as a key strategy in this context, providing essential support for urban rainwater control and pollution reduction. To investigate the runoff control effects of LID measures and to reveal the relationship between facility runoff control performance and installation scale, this study focuses on a sponge community in Beijing. A SWMM model was constructed to analyze the rainwater flood control and pollutant load reduction effects of different LID facilities, including bio-retention cells, green roofs, and permeable pavements. Using evaluation indicators such as surface runoff, node overflow, and pollutant control rates, this study examined how facility performance varies with installation scale under different rainfall conditions. The combination scheme of LID equipment optimal configuration is designed by using multiple criteria decision analysis (MCDA) and cost–benefit theory. The results indicate significant differences in performance among the various LID facilities across different rainfall scenarios. Specifically, the optimal installation proportion for runoff and overflow control of permeable pavements were found to be between 30% and 70%. Green roofs demonstrate superior performance in handling extreme rainfall events, while bio-retention cells exhibit significant effectiveness in controlling Total Suspended Solids (TSSs). Through comprehensive performance evaluation, this study identified the optimal combination scale under a 3-year rainfall recurrence interval as 30% permeable pavements, 20% green roof, and 60% bio-retention cells. This combination effectively leverages the strengths of each facility, ensuring system stability and efficiency while also demonstrating optimal management efficiency in cost–benefit analyses. The findings of this research provide valuable insights for future urban water management and infrastructure development.

Tislelizumab plus cetuximab and irinotecan in refractory microsatellite stable and RAS wild-type metastatic colorectal cancer: a single-arm phase 2 study

Immunotherapy confers little to no benefit in the treatment of microsatellite stable (MSS) metastatic colorectal cancer (mCRC). Mechanistic insights suggested that epidermal growth factor receptor (EGFR) antibody plus irinotecan might augment the tumor immune response in mCRC. Therefore, we conducted a proof-of-concept, single-arm, phase 2 study (ChiCTR identifier: ChiCTR2000035642) of a combination treatment regimen including tislelizumab (anti-PD-1), cetuximab (anti-EGFR) and irinotecan in 33 patients with MSS and RAS wild-type (WT) mCRC who were previously treated with ≥2 lines of therapy. The primary endpoint was met, with a confirmed objective response rate of 33%. As secondary endpoints, the disease control rate was 79%, and the median progression-free survival and overall survival were 7.3 and 17.4 months respectively. Among the 33 patients, 32 (97.0%) had treatment-related adverse events (AEs). Three (9.1%) reported grade ≥ 3 AEs, including rash (n = 1), neutropenia (n = 2). The post-hoc evaluation of dynamic circulating tumor DNA using next generation sequencing and the analysis of peripheral immune proteomics landscape using Olink revealed that lower variant allele frequency (VAF) at baseline, greater reduction in VAF on treatment, and a hot peripheral macroenvironment were associated with the treatment response independently. Our study showed the antitumor activity of tislelizumab, cetuximab, and irinotecan combination with a tolerable safety profile in previously treated MSS and RAS WT mCRC.