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Neovascular age-related macular degeneration (nvAMD) is the leading cause of severe vision loss in the elderly in the developed world. While the introduction of therapies targeting vascular endothelial growth factor (VEGF) has provided the first opportunity to significantly improve vision in patients with nvAMD, many patients respond inadequately to current anti-VEGF therapies. It was recently demonstrated that expression of a second angiogenic mediator, angiopoietin-like 4 (ANGPTL4), synergizes with VEGF to promote choroidal neovascularization (CNV) in mice and correlates with reduced response to anti-VEGF therapy in patients with nvAMD. Here, we report that expression of ANGPTL4 in patients with nvAMD increases following treatment with anti-VEGF therapy and that this increase is dependent on accumulation of hypoxia-inducible factor (HIF)-1α in response to inhibition of VEGF/KDR signaling in the retinal pigment epithelium (RPE). We therefore explored HIF-1 inhibition with 32-134D, a recently developed pharmacologic HIF-inhibitor, for the treatment of nvAMD. 32-134D prevented the expression of both VEGF and ANGPTL4 and was at least as effective as aflibercept in treating CNV in mice. Moreover, by preventing the increase in HIF-1α accumulation in the RPE in response to anti-VEGF therapy, combining 32-134D with aflibercept was more effective than either drug alone for the treatment of CNV. Collectively, these results help explain why many patients with nvAMD respond inadequately to anti-VEGF therapy and suggest that the HIF inhibitor 32-134D will be an effective drug-alone or in combination with current anti-VEGF therapies-for the treatment of patients with this blinding disease.

PurposeTo evaluate 2-year efficacy, durability, and safety of the bispecific antibody faricimab, which inhibits both angiopoietin-2 and VEGF-A.DesignTENAYA (ClinicalTrials.gov identifier, NCT03823287) and LUCERNE (ClinicalTrials.gov identifier, NCT03823300) were identically designed, randomized, double-masked, active comparator-controlled phase 3 noninferiority trials.ParticipantsTreatment-naive patients with neovascular age-related macular degeneration (nAMD) 50 years of age or older.MethodsPatients were randomized (1:1) to intravitreal faricimab 6.0 mg up to every 16 weeks (Q16W) or aflibercept 2.0 mg every 8 weeks (Q8W). Faricimab fixed dosing based on protocol-defined disease activity at weeks 20 and 24 up to week 60, followed up to week 108 by a treat-and-extend personalized treatment interval regimen.Main outcome measuresEfficacy analyses included change in best-corrected visual acuity (BCVA) from baseline at 2 years (averaged over weeks 104, 108, and 112) and proportion of patients receiving Q16W, every 12 weeks (Q12W), and Q8W dosing at week 112 in the intention-to-treat population. Safety analyses included ocular adverse events (AEs) in the study eye through study end at week 112.ResultsOf 1326 patients treated across TENAYA/LUCERNE, 1113 (83.9%) completed treatment (n = 555 faricimab; n = 558 aflibercept). The BCVA change from baseline at 2 years was comparable between faricimab and aflibercept groups in TENAYA (adjusted mean change, +3.7 letters [95% confidence interval (CI), +2.1 to +5.4] and +3.3 letters [95% CI, +1.7 to +4.9], respectively; mean difference, +0.4 letters [95% CI, -1.9 to +2.8]) and LUCERNE (adjusted mean change, +5.0 letters [95% CI, +3.4 to +6.6] and +5.2 letters [95% CI, +3.6 to +6.8], respectively; mean difference, -0.2 letters [95% CI, -2.4 to +2.1]). At week 112 in TENAYA and LUCERNE, 59.0% and 66.9%, respectively, achieved Q16W faricimab dosing, increasing from year 1, and 74.1% and 81.2%, achieved Q12W or longer dosing. Ocular AEs in the study eye were comparable between faricimab and aflibercept groups in TENAYA (55.0% and 56.5% of patients, respectively) and LUCERNE (52.9% and 47.5% of patients, respectively) through week 112.ConclusionsTreat-and-extend faricimab treatment based on nAMD disease activity maintained vision gains through year 2, with most patients achieving extended dosing intervals.Financial disclosure(s)Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Objective: This systematic review aimed to summarise the most common drugs with antiangiogenic effects associated with MRONJ, the diseases that patients can present and discuss the appropriate course of treatment. Materials and Methods: PubMed, Web of Science, Scopus and Embase were screened for case reports up to February 2024. Two independent reviewers selected the articles in a two‐step selection, screening 1.327 articles. The final sample was composed of 32 articles. Results: Most of the patients were male with a mean age of 58 years. Although the majority of patients had cancer, 20% were treated with drugs with antiangiogenic effects for other diseases. The lesions occurred mainly in the posterior mandible, with dental extraction associated in more than half of the cases. Antibiotic treatment was employed in most cases with amoxicillin and clavulanic acid, usually associated with 0.12% chlorhexidine or a 0.2% oral rinse. Bevacizumab was the medication most associated with the lesions (40%). Conclusion: The dental community needs to be aware of the new drugs that can cause MRONJ through antiangiogenic effects, given that new medications are being reported every day. [ABSTRACT FROM AUTHOR]

Background: Glioblastoma multiforme (GBM) is the most common malignant brain tumor in adults. Typically treated with initial surgical resection, and chemoradiotherapy, despite current treatments, patients typically survive only 12–14 months, necessitating new therapeutic approaches. Our meta-analysis evaluates combining antiangiogenic medications with chemoradiotherapy versus using chemoradiotherapy alone in treating newly diagnosed GBM. Methods: A comprehensive literature search was conducted using PubMed/MEDLINE, Scopus, Cochrane and the Web of Science databases. The search aimed to identify studies reporting overall survival (OS), progression-free survival (PFS), and hazard ratio (HR) with corresponding confidence intervals (CIs) in patients with newly diagnosed GBM. We employed random-effect meta-analysis. Results: Twelve randomized clinical trials (RCTs) involved 3,309 patients included in the study. The findings showed that angiogenesis inhibitors significantly prolonged PFS [HR 0.85, 95% CI (0.73, 0.99), p-value = 0.04], while there was no significant difference on OS [HR 1.014, 95%CI (0.89, 1.15), p-value = 0.84]. Bevacizumab (BEV) exhibited the highest [HR 0.67, 95% CI (0.56, 0.79), p-value < 0.0001] and thalidomide exhibited the lowest [HR 1.46, 95% CI (1.004, 2.1), p-value = 0.048] improvements of PFS. Meta-regression revealed that age, white race, study sample size, infection, vascular disease complications, KPS > 60, biopsy, gross and subtotal resection can significantly influenced the PFS, while only the year of publication affected OS. Conclusions: The current study showed that improve the PFS with no significant effect on OS. Our findings may provide some evidence for decision-making regarding the utilization of angiogenesis inhibitors for the treatment of adult patients with newly diagnosed GBM. [ABSTRACT FROM AUTHOR]

Interest in biological therapy for cancer has surged due to its precise targeting of cancer cells and minimized impact on surrounding healthy tissues. This review discusses various biological cancer therapies, highlighting advanced alternatives over conventional chemotherapy alone. It explores DNA and RNA-based vaccines, T-cell modifications, adoptive cell transfer, CAR T cell therapy, angiogenesis inhibitors, and the combination of immunotherapy with chemotherapy, offering a holistic view of the potential in cancer treatment. Additionally, it discusses the role of nanotechnology in increasing the efficacy of cancer-targeting drugs, as well as cytokine and immunoconjugate therapies for bolstering immune system effectiveness against neoplastic cells. The potential of gene potential for precise targeting of cancer-linked genes and the application of oncolytic viruses against virus-associated cancers are also discussed. The review identifies significant advancements in the targeted treatment of cancer by biological methods. It acknowledges the challenges, including drug resistance and the need for high specificity in certain therapies, while also highlighting the effectiveness of cancer vaccines, modified T-cells, and oncolytic viruses. Biological therapies are a promising frontier in cancer treatment, offering the potential for more personalized and effective therapeutic strategies. Despite existing challenges, ongoing research and clinical trials are fundamental for overcoming current limitations and enhancing the efficacy of biological therapies in cancer care. [ABSTRACT FROM AUTHOR]

Objective: To assess the efficacy and safety of anlotinib combined with immune checkpoint inhibitors (ICIs) in patients with advanced non-small-cell lung cancer (NSCLC). Methods: Clinical data on patients with advanced NSCLC were collected from June 2019 to October 2022 at Hebei General Hospital, China. The efficacy and safety of anlotinib combined with ICIs and platinum-containing chemotherapy were retrospectively analyzed. The primary endpoint was progression-free survival (PFS). The secondary endpoint was the disease control rate (DCR) and overall survival (OS). Survival curves were created using the Kaplan–Meier method. The efficacy and adverse reactions were evaluated according to the RECIST 1.1 and CTCAE 5.0 standards. Results: A total of 54 patients were enrolled in this study after propensity score matching (PSM), including 27 men and 17 women, with a median age of 59. A total of 26 patients received anlotinib + ICIs + platinum-containing chemotherapy (AIC), 15 patients received anlotinib + platinum-containing chemotherapy (AC), and 13 patients received ICIs + platinum-containing chemotherapy (IC). The PFS of the AIC group was 7.76 months (95% CI: 3.71–NC). The DCR was 65.38%. The OS endpoint had not been reached, The AIC combination regimen group had a significantly longer PFS than the IC group (mPFS, 7.76 vs. 2.33 months, p=0.012, HR=0.23, 95% CI: 0.06–0.8). There was no significant difference in the DCR between the two groups (65.38% vs. 53.85%, p=0.326). There was a statistically significant difference in PFS between the AC group and the IC group (mPFS, 9.2 vs. 2.33 months, p=0.02, HR=0.14, 95% CI: 0.03–0.65). There was no significant difference in the DCR between the two groups (40% vs. 53.85%, p=0.445). The common adverse reactions of the combination of anti-angiogenic agents, ICIs, and platinum-containing chemotherapy were anemia (34.62%), allergic reactions (19.23%), thrombocytopenia (11.54%), gastrointestinal reactions (15.38%), and hepatobiliary disorders (11.54%). Most of them were manageable. Conclusions: Anlotinib combined with immune checkpoint inhibitors and platinum-containing chemotherapy regimens offers a good survival benefit for patients with advanced non-small-cell lung cancer who fail to respond to standard therapy. When both efficacy and safety are considered, a combination of anti-angiogenic agents, ICIs, and platinum-containing chemotherapy can be used as a choice for the treatment of advanced NSCLC. [ABSTRACT FROM AUTHOR]

Anas Alamoudi,1 Ahmed N Alnabihi,2,3 Ali Saleh Alsudais,2,3 Naif Almufarriji,1 Waleed T Batais,2,3 Abdulaziz Khalid Aldahlawi,2,3 Abdullah Altalhi,4 Hassan A Al-Dhibi,5 Adel G Alakeely6 1Department of Ophthalmology, Jeddah Eye Hospital, Jeddah, Saudi Arabia; 2College of Medicine, King Saud Bin Abdulaziz University for Health Sciences, Jeddah, Saudi Arabia; 3King Abdullah International Medical Research Center, Jeddah, Saudi Arabia; 4Division of Vitreoretinal Surgery, King Khaled Eye Specialist Hospital, Riyadh, Saudi Arabia; 5Division of Vitreoretinal Surgery and Uveitis, King Khaled Eye Specialist Hospital, Riyadh, Saudi Arabia; 6Magrabi Hospitals and Centers, Riyadh, Saudi ArabiaCorrespondence: Anas Alamoudi, Department of Ophthalmology, Jeddah Eye Hospital, Jeddah, Saudi Arabia, Email anasalamoudi99@gmail.comAim: This systematic review and meta-analysis aimed to evaluate the safety and efficacy of combined laser and anti-VEGF therapy for (retinopathy of prematurity ROP), focusing on both structural and functional outcomes.Methods: A comprehensive search was conducted in multiple databases to identify randomized controlled trials (RCTs) that investigated combination therapy for ROP. The PRISMA guidelines were followed. Data were extracted and analyzed using risk ratios and 95% confidence intervals (CIs). The Cochrane Risk of Bias tool was used to assess the risk of bias.Results: Three RCTs involving a total of 162 premature infants were included in the meta-analysis. Combination therapy of anti-VEGF and laser photocoagulation was compared with other interventions. The pooled analysis of favorable structural outcomes did not show a statistically significant difference between combination therapy with anti-VEGFs and laser therapy compared to the interventions in the control groups (P=0.25). The incidence of adverse events was comparable between the combination therapy group and other intervention groups.Conclusion: This systematic review and meta-analysis suggest that risk ratio of combination therapy with anti-VEGF and laser for ROP is associated with favorable outcomes, albeit insignificant. The safety profile of combination therapy appears to be similar to other interventions. However, due to the limited number of included studies, further research is needed.Keywords: neonatal retinal disease, angiogenesis inhibitors, retinal photocoagulation, premature infant eye health

Abstract Interest in biological therapy for cancer has surged due to its precise targeting of cancer cells and minimized impact on surrounding healthy tissues. This review discusses various biological cancer therapies, highlighting advanced alternatives over conventional chemotherapy alone. It explores DNA and RNA-based vaccines, T-cell modifications, adoptive cell transfer, CAR T cell therapy, angiogenesis inhibitors, and the combination of immunotherapy with chemotherapy, offering a holistic view of the potential in cancer treatment. Additionally, it discusses the role of nanotechnology in increasing the efficacy of cancer-targeting drugs, as well as cytokine and immunoconjugate therapies for bolstering immune system effectiveness against neoplastic cells. The potential of gene potential for precise targeting of cancer-linked genes and the application of oncolytic viruses against virus-associated cancers are also discussed. The review identifies significant advancements in the targeted treatment of cancer by biological methods. It acknowledges the challenges, including drug resistance and the need for high specificity in certain therapies, while also highlighting the effectiveness of cancer vaccines, modified T-cells, and oncolytic viruses. Biological therapies are a promising frontier in cancer treatment, offering the potential for more personalized and effective therapeutic strategies. Despite existing challenges, ongoing research and clinical trials are fundamental for overcoming current limitations and enhancing the efficacy of biological therapies in cancer care.

Opinion statementThe treatment landscape of renal cell carcinoma (RCC) has evolved significantly over the past three decades. Active surveillance and tumor ablation are alternatives to extirpative therapy in appropriately selected patients. Stereotactic body radiation therapy (SBRT) is an emerging noninvasive alternative to treat primary RCC tumors. The advent of immune checkpoint inhibitors (ICIs) has greatly improved the overall survival of advanced RCC, and now the ICI-based doublet (dual ICI-ICI doublet; or ICI in combination with a vascular endothelial growth factor tyrosine kinase inhibitor, ICI-TKI doublet) has become the standard frontline therapy. Based on unprecedented outcomes in the metastatic with ICIs, they are also being explored in the neoadjuvant and adjuvant setting for patients with high-risk disease. Adjuvant pembrolizumab has proven efficacy to reduce the risk of RCC recurrence after nephrectomy. Historically considered a radioresistant tumor, SBRT occupies an expanding role to treat RCC with oligometastasis or oligoprogression in combination with systemic therapy. Furthermore, SBRT is being investigated in combination with ICI-doublet in the advanced disease setting. Lastly, given the treatment paradigm is shifting to adopt ICIs at earlier disease course, the prospective studies guiding treatment sequencing in the post-ICI setting is maturing. The effort is ongoing in search of predictive biomarkers to guide optimal treatment option in RCC.

Background: Metastatic colorectal cancer (mCRC) constitutes a significant health burden globally, accompanied by elevated mortality rates. This study aimed to assess the cost-effectiveness of regorafenib, an orally administered multi-kinase inhibitor, compared to the combination of Cetuximab and Irinotecan (CetIri) as third-line therapy for mCRC in Iran.Method: A model-based cost-utility analysis was conducted employing a semi-Markov model for a hypothetical cohort of 1,000 patients, integrating time-dependent transition probabilities. From the perspective of the Iranian healthcare payer, the analysis included direct medical costs, such as therapy, monitoring, and adverse effect-related expenses, sourced from national databases in Iran. A yearly discount rate of 5% was applied to both costs and outcomes. Data analysis utilized Microsoft Excel, R version 4.1.3, and TreeAge Pro Healthcare version 2022 software, with the significance threshold set at 0.05.Results: The base-case analysis revealed that regorafenib offers a cost saving of $12,154 and an incremental gain of 0.1 quality-adjusted life years per patient over a 19-month horizon compared with the CetIri regimen. Probabilistic sensitivity analysis showed a greater than 99% probability of regorafenib being cost-effective.Conclusion: Consistent with existing evidence, the findings advocate regorafenib as a cost-effective alternative to CetIri for third-line treatment of mCRC in Iran, considering the specific healthcare system context. Given the foundational assumptions, caution is advised when extrapolating these results to other regions.

Pediatric - type low - grade glioma (pLGG) is the most common central nervous system tumor in children, and most pLGG exhibits non -invasive clinical behavior with a good prognosis. Total surgical resection is an important prognostic factor, and patients can achieve long-term survival after total tumor resection. However, tumors in deep location such as brain stem and optic pathway cannot be completely removed by surgery. Chemotherapy is the first choice of adjuvant treatment when the clinical symptoms of pLGG worsen or imaging progress. In recent years, in addition to traditional chemotherapy, the development and application of targeted therapy drugs have also made great progress. This article reviews the research progress and challenges of chemotherapy and targeted therapy of pLGG, in order to provide guidance for clinical practice.

Copyright of Arquivos Brasileiros de Oftalmologia is the property of Arquivos Brasileiros de Oftalmologia and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background: Metastatic colorectal cancer (mCRC) constitutes a significant health burden globally, accompanied by elevated mortality rates. This study aimed to assess the cost-effectiveness of regorafenib, an orally administered multi-kinase inhibitor, compared to the combination of Cetuximab and Irinotecan (CetIri) as third-line therapy for mCRC in Iran. Method: A model-based cost-utility analysis was conducted employing a semi- Markov model for a hypothetical cohort of 1,000 patients, integrating time-dependent transition probabilities. From the perspective of the Iranian healthcare payer, the analysis included direct medical costs, such as therapy, monitoring, and adverse effectrelated expenses, sourced from national databases in Iran. A yearly discount rate of 5% was applied to both costs and outcomes. Data analysis utilized Microsoft Excel, R version 4.1.3, and TreeAge Pro Healthcare version 2022 software, with the significance threshold set at 0.05. Results: The base-case analysis revealed that regorafenib offers a cost saving of $12,154 and an incremental gain of 0.1 quality-adjusted life years per patient over a 19-month horizon compared with the CetIri regimen. Probabilistic sensitivity analysis showed a greater than 99% probability of regorafenib being cost-effective. Conclusion: Consistent with existing evidence, the findings advocate regorafenib as a cost-effective alternative to CetIri for third-line treatment of mCRC in Iran, considering the specific healthcare system context. Given the foundational assumptions, caution is advised when extrapolating these results to other regions. [ABSTRACT FROM AUTHOR]

• Angiogenic biomarkers are important tools for the early prediction and diagnosis of preeclampsia. • Data from intervention trials do not support using angiogenic biomarkers for monitoring progressing of preeclampsia or deciding the timing of delivery. • There is insufficient evidence to recommend angiogenic biomarkers as an alternative to Doppler for surveillance and timing of delivery in fetal growth restriction. • Angiogenic biomarkers may have help differentiate between hypertension in chronic kidney disease from superimposed preeclampsia in pregnant women. Monitoring and timing of delivery in preterm preeclampsia and fetal growth restriction is one of the biggest challenges in Obstetrics. Finding the optimal time of delivery of these fetuses usually involves a trade-off between the severity of the disease and prematurity. So far, most clinical guidelines recommend the use of a combination between clinical, laboratory and ultrasound markers to guide the time of delivery. Angiogenic biomarkers, especially placental growth factor (PlGF) and soluble fms-like tyrosine kinase-1 (sFlt-1), have gained significant attention in recent years for their potential role in the prediction and diagnosis of placenta-related disorders including preeclampsia and fetal growth restriction. Another potential clinical application of the angiogenic biomarkers is for the differential diagnosis of patients with chronic kidney disease, as this condition shares similar clinical features with preeclampsia. Consequently, angiogenic biomarkers have been advocated as tools for monitoring and deciding the optimal time of the delivery of fetuses affected by placental dysfunction. In this clinical opinion, we critically review the available literature on PlGF and sFlt-1 for the surveillance and time of the delivery in fetuses affected by preterm preeclampsia and fetal growth restriction. Moreover, we explore the use of angiogenic biomarkers for the differentiation between chronic kidney disease and superimposed preeclampsia. [ABSTRACT FROM AUTHOR]

Proteinuria is a common adverse event arising from treatment with bevacizumab, requiring diagnostic testing via 24-h urine collection. However, this method is cumbersome. We assessed urine screenings in gynecologic cancer patients from February 2021 to May 2022. Along with a simple urine dipstick (UD), the urine microalbumin, total protein, and creatinine were measured and calculated as the urine albumin to creatinine ratio (UACR) and the urine protein to creatinine ratio (UPCR), which were further adjusted through the Modification of Diet in Renal Disease and Chronic Kidney Disease Epidemiology Collaboration equations to be estimated and correlated with 24-h urine total protein content. The incremental cost-effectiveness ratio was used for cost analysis. There were 129 urine samples from 36 patients. The sensitivity and specificity for the UACR were 0.56 and 0.97, and for the UPCR, 0.71 and 0.88, respectively. The 24-h TP correlated strongly with the UACR (r = 0.75; p < 0.001) and UPCR (r = 0.79; p < 0.001) and fair for the simple UD (r = 0.35; p < 0.001). The UPCR saves one unnecessary 24-h urine test for less than a dollar compared to a simple UD. The results indicate that using the UPCR could enhance diagnostic accuracy, lower costs, and reduce unnecessary 24-h urine sampling. [ABSTRACT FROM AUTHOR]

Copyright of Arquivos Brasileiros de Oftalmologia is the property of Arquivos Brasileiros de Oftalmologia and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Médicas UIS is the property of Universidad Industrial de Santander and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

PurposeAntiangiogenic therapies are known to cause high radiographic response rates due to reduction in vascular permeability resulting in a lower degree of contrast extravasation. In this study, we investigate the prognostic ability for model-derived parameters describing enhancing tumor volumetric dynamics to predict survival in recurrent glioblastoma treated with antiangiogenic therapy.Experimental designN = 276 patients in two phase II trials were used as training data, including bevacizumab ± irinotecan (NCT00345163) and cabozantinib (NCT00704288), and N = 74 patients in the bevacizumab arm of a phase III trial (NCT02511405) were used for validation. Enhancing volumes were estimated using T1 subtraction maps, and a biexponential model was used to estimate regrowth (g) and regression (d) rates, time to tumor regrowth (TTG), and the depth of response (DpR). Response characteristics were compared to diffusion MR phenotypes previously shown to predict survival.ResultsOptimized thresholds occurred at g = 0.07 months-1 (phase II: HR = 0.2579, P = 5 × 10-20; phase III: HR = 0.2197, P = 5 × 10-5); d = 0.11 months-1 (HR = 0.3365, P < 0.0001; HR = 0.3675, P = 0.0113); TTG = 3.8 months (HR = 0.2702, P = 6 × 10-17; HR = 0.2061, P = 2 × 10-5); and DpR = 11.3% (HR = 0.6326, P = 0.0028; HR = 0.4785, P = 0.0206). Multivariable Cox regression controlling for age and baseline tumor volume confirmed these factors as significant predictors of survival. Patients with a favorable pretreatment diffusion MRI phenotype had a significantly longer TTG and slower regrowth.ConclusionsRecurrent glioblastoma patients with a large, durable radiographic response to antiangiogenic agents have significantly longer survival. This information is useful for interpreting activity of antiangiogenic agents in recurrent glioblastoma.

PURPOSE: The purpose of this study was to determine the impact of prophylactic ranibizumab (PR) injections given every 3 months in eyes with intermediate nonexudative age-related macular degeneration (AMD) on drusen volume, macular layer thicknesses, and progression of geographic atrophy (GA) area over 24 months in the PREVENT trial. METHODS: This post hoc analysis of the prospective PREVENT trial compared eyes with intermediate AMD randomized to PR versus sham injections to determine rates of conversion to neovascular AMD over 24 months. Drusen area and volume, macular thickness and volume, and retinal layer thicknesses were measured on spectral-domain optical coherence tomography images and analyzed. Masked grading of GA area and subretinal drusenoid deposits (SDDs) using fundus autofluorescence images was performed. RESULTS: There were no statistical differences in drusen area and volumes between groups, and similar reductions in central subfield thickness, mean cube thickness, cube volume, and retinal sublayer thickness from baseline to 24 months (P = 0.018 to < 0.001), with no statistical differences between groups in any of these anatomic parameters. These findings were not impacted by the presence or absence of SDD. Among the 9 eyes with GA in this study, mean GA growth rate from baseline to 24 months was 1.34 +/- 0.79 mm2/year after PR and 1.95 +/- 1.73 mm2/year in sham-treated eyes (P = 0.49), and similarly showed no statistical difference with square root transformation (P = 0.61). CONCLUSIONS: Prophylactic ranibizumab given every 3 months did not appear to affect drusen volume, macular thinning, or GA progression in eyes with intermediate AMD. TRANSLATIONAL RELEVANCE: This work investigates the impact of PR on progressive retinal degeneration in a clinical trial.

ObjectiveThis study aims to evaluate the hemorrhage risk in solid tumor patients receiving angiogenesis inhibitors (AGIs), immune checkpoint inhibitors (ICIs), and their combination using the FDA Adverse Event Reporting System (FAERS) database.MethodsData from Q1 2011 to Q4 2023 were extracted from the FAERS database for solid tumor patients treated with AGIs, ICIs, or their combination. A disproportionality analysis was conducted by calculating the reporting odds ratio (ROR) and corresponding 95% confidence interval (CI), as well as the Proportional Reporting Ratio (PRR), to identify potential safety signals. To assess whether the hemorrhage risk is higher with combination therapy compared to monotherapy, additive and multiplicative models were employed to evaluate the interactions between combination and single-agent treatments.ResultsThe combination of AGIs and ICIs significantly increased the risk of hemorrhagic adverse events, particularly tumor and pulmonary hemorrhage. Hemorrhagic events were common in females (50.97%) and older patients (aged 64+), frequently occurring within the first 30 days of treatment (38.11%). Gingival hemorrhage (ROR 3, PRR 418.9) and tumor hemorrhage (ROR 9.65, PRR 1893.36) were most common in the AGI group, while tumor hemorrhage (ROR 9.49, PRR 1350.78) and pulmonary hemorrhage (ROR 2.6, PRR 98.97) were prominent in the ICI group. In the combination group, esophageal variceal hemorrhage (ROR 40.72, PRR 2344.72) and tumor hemorrhage (ROR 19.31, PRR 1056.63) exhibited significantly increased risks Additive and multiplicative models indicated that the excess risk (RDAB = 0.01025, P

PurposeEganelisib (IPI-549) is a first-in-class, orally administered, highly selective PI3Kγ inhibitor with antitumor activity alone and in combination with programmed cell death protein 1/ligand 1 (PD-1/PD-L1) inhibitors in preclinical studies. This phase 1/1b first-in-human, MAcrophage Reprogramming in Immuno-Oncology-1 (NCT02637531) study evaluated the safety and tolerability of once-daily eganelisib as monotherapy and in combination with nivolumab in patients with solid tumors.Patients and methodsDose-escalation cohorts received eganelisib 10-60 mg as monotherapy (n = 39) and 20-40 mg when combined with nivolumab (n = 180). Primary endpoints included incidence of dose-limiting toxicities (DLT) and adverse events (AE).ResultsThe most common treatment-related grade ≥3 toxicities with monotherapy were increased alanine aminotransferase (ALT; 18%), aspartate aminotransferase (AST; 18%), and alkaline phosphatase (5%). No DLTs occurred in the first 28 days; however, toxicities meeting DLT criteria (mostly grade 3 reversible hepatic enzyme elevations) occurred with eganelisib 60 mg in later treatment cycles. In combination, the most common treatment-related grade ≥3 toxicities were increased AST (13%) and increased ALT and rash (10%). Treatment-related serious AEs occurred in 5% of monotherapy patients (grade 4 bilirubin and hepatic enzyme increases in one patient each) and 13% in combination (pyrexia, rash, cytokine release syndrome, and infusion-related reaction in ≥2 patients each). Antitumor activity was observed in combination, including patients who had progressed on PD-1/PD-L1 inhibitors.ConclusionsOn the basis of the observed safety profile, eganelisib doses of 30 and 40 mg once daily in combination with PD-1/PD-L1 inhibitors were chosen for phase 2 study.

Durable objective response rate (ORR) remains a meaningful endpoint in recurrent cancer; however, the target ORR for single-arm recurrent glioblastoma trials has not been based on historic information or tied to patient outcomes. The current study reviewed 68 treatment arms comprising 4793 patients in past trials in recurrent glioblastoma in order to judiciously define target ORRs for use in recurrent glioblastoma trials. ORR was estimated at 6.1% [95% CI 4.23; 8.76%] for cytotoxic chemothera + pies (ORR = 7.59% for lomustine, 7.57% for temozolomide, 0.64% for irinotecan, and 5.32% for other agents), 3.37% for biologic agents, 7.97% for (select) immunotherapies, and 26.8% for anti-angiogenic agents. ORRs were significantly correlated with median overall survival (mOS) across chemotherapy (R2= 0.4078, P < .0001), biologics (R2= 0.4003, P = .0003), and immunotherapy trials (R2= 0.8994, P < .0001), but not anti-angiogenic agents (R2= 0, P = .8937). Pooling data from chemotherapy, biologics, and immunotherapy trials, a meta-analysis indicated a strong correlation between ORR and mOS (R2= 0.3900, P < .0001; mOS [weeks] = 1.4xORR + 24.8). Assuming an ineffective cytotoxic (control) therapy has ORR = 7.6%, the average ORR for lomustine and temozolomide trials, a sample size of ≥40 patients with target ORR>25% is needed to demonstrate statistical significance compared to control with a high level of confidence (P < .01) and adequate power (>80%). Given this historic data and potential biases in patient selection, we recommend that well-controlled, single-arm phase II studies in recurrent glioblastoma should have a target ORR >25% (which translates to a median OS of approximately 15 months) and a sample size of ≥40 patients, in order to convincingly demonstrate antitumor activity. Crucially, this response needs to have sufficient durability, which was not addressed in the current study.

Angiogenesis is an essential process in normal development and in adult physiology, but can be disrupted in numerous diseases. The concept of targeting angiogenesis for treating diseases was proposed more than 50 years ago, and the first two drugs targeting vascular endothelial growth factor (VEGF), bevacizumab and pegaptanib, were approved in 2004 for the treatment of cancer and neovascular ophthalmic diseases, respectively. Since then, nearly 20 years of clinical experience with anti-angiogenic drugs (AADs) have demonstrated the importance of this therapeutic modality for these disorders. However, there is a need to improve clinical outcomes by enhancing therapeutic efficacy, overcoming drug resistance, defining surrogate markers, combining with other drugs and developing the next generation of therapeutics. In this Review, we examine emerging new targets, the development of new drugs and challenging issues such as the mode of action of AADs and elucidating mechanisms underlying clinical benefits; we also discuss possible future directions of the field.

PurposeTo evaluate efficacy, durability, and safety of faricimab in Japanese patients with diabetic macular edema (DME).Study designSubgroup analysis of 2 global, multicenter, randomized, double-masked, active-comparator-controlled, phase 3 trials (YOSEMITE, NCT03622580; RHINE, NCT03622593).MethodsPatients with DME were randomized 1:1:1 to intravitreal faricimab 6.0 mg every 8 weeks (Q8W), faricimab 6.0 mg per personalized treatment interval (PTI), or aflibercept 2.0 mg Q8W through week 100. Primary endpoint was best-corrected visual acuity (BCVA) change from baseline at 1 year, averaged over weeks 48, 52, and 56. This is the first time 1-year outcomes between Japanese patients (only enrolled into YOSEMITE) and the pooled YOSEMITE/RHINE cohort (N = 1891) have been compared.ResultsThe YOSEMITE Japan subgroup included 60 patients randomized to faricimab Q8W (n = 21), faricimab PTI (n = 19), or aflibercept Q8W (n = 20). Consistent with global results, the adjusted mean (95.04% confidence interval) BCVA change at 1 year in the Japan subgroup was comparable with faricimab Q8W (+11.1 [7.6-14.6] letters), faricimab PTI (+8.1 [4.4-11.7] letters), and aflibercept Q8W (+6.9 [3.3-10.5] letters). At week 52, 13 (72%) patients in the faricimab PTI arm achieved ≥ Q12W dosing, including 7 (39%) patients receiving Q16W dosing. Anatomic improvements with faricimab were generally consistent between the Japan subgroup and pooled YOSEMITE/RHINE cohort. Faricimab was well tolerated; no new or unexpected safety signals were identified.ConclusionConsistent with global results, faricimab up to Q16W offered durable vision gains and improved anatomic and disease-specific outcomes among Japanese patients with DME.

Background: Ovarian cancer (OC) is a gynecological malignancy with a high mortality rate worldwide. The unfavorable prognosis of OC is mainly attributed to the recurrent propensity. Recently, mortality from OC has exhibited a downward trend. These favorable patterns are likely to be driven by advancements in novel therapeutic regimens. However, there is a lack of visualize analysis of the application of these new drugs on women with recurrent OC (ROC). Therefore, we aimed to provide a bibliometric analysis of the evolving paradigms in the ROC treatment. Methods: Documents on ROC treatment were systematically collected from the MEDLINE database and Web of Science Core Collection (WOSCC). The retrieved documents were exported in the plain text file format, and files were named and saved to the paths specified by the Java application. Microsoft Excel (version 2010), Citespace (6.2.R4) and VOSviewer (1.6.19) were used for data analysis, and included the following: 1) annual publication trend; 2) contributions of countries, institutions and authors; 3) co-citation of journals and references; and 4) cooccurrence of keywords. Results: A total of 914 documents published in the MEDLINE and 9,980 ones in WOSCC were retrieved. There has been an upward trend in the productivity of publications on ROC treatment on by years. The United States was the leading contributor in this field, and the University of Texas System stood out as the most productive institution. Giovanni Scambia and Maurie Markman were the research leaders in the field of ROC treatment. The journal Gynecologic Oncology had the highest citation frequency. The reference entitled with "Niraparib Maintenance Therapy in Platinum-Sensitive, Recurrent Ovarian Cancer" got highest centrality of 0.14 in the co-citation network. Keyword analysis revealed that the focus of current ROC treatment was on platinum-based anticancer drugs, paclitaxel, angiogenesis inhibitors (AIs), immune checkpoint inhibitors (ICIs) and poly (ADP-ribose) polymerase inhibitors (PARPis). Conclusion: Scholars from a multitude of countries have been instrumental in the advancement of ROC treatment. The research hotspots and trend in the field of predominantly originated from leading international journals and specialized periodicals focused on gynecologic oncology. Maintenance therapy using AIs or (and) PARPis has emerged as a significant complement to platinum-based chemotherapy for patients with ROC. [ABSTRACT FROM AUTHOR]

A number of conditions and factors can cause the transformation of normal cells in the body into malignant tissue by changing the normal functions of a wide range of regulatory, apoptotic, and signal transduction pathways. Despite the current deficiency in fully understanding the mechanism of cancer action accurately and clearly, numerous genes and proteins that are causally involved in the initiation, progression, and metastasis of cancer have been identified. But due to the lack of space and the abundance of details on this complex topic, we have emphasized here more recent advances in our understanding of the principles implied tumor cell transformation, development, invasion, angiogenesis, and metastasis. Inhibition of angiogenesis is a significant strategy for the treatment of various solid tumors, that essentially depend on cutting or at least limiting the supply of blood to micro-regions of tumors, leading to pan-hypoxia and pan-necrosis inside solid tumor tissues. Researchers have continued to enhance the efficiency of anti-angiogenic drugs over the past two decades, to identify their potential in the drug interaction, and to discover reasonable interpretations for possible resistance to treatment. In this review, we have discussed an overview of cancer history and recent methods use in cancer therapy, focusing on anti-angiogenic inhibitors targeting angiogenesis formation. Further, this review has explained the molecular mechanism of action of these anti-angiogenic inhibitors in various tumor types and their limitations use. In addition, we described the synergistic mechanisms of immunotherapy and anti-angiogenic therapy and summarizes current clinical trials of these combinations. Many phase III trials found that combining immunotherapy and anti-angiogenic therapy improved survival. Therefore, targeting the source supply of cancer cells to grow and spread with new anti-angiogenic agents in combination with different conventional therapy is a novel method to reduce cancer progression. The aim of this paper is to overview the varying concepts of cancer focusing on mechanisms involved in tumor angiogenesis and provide an overview of the recent trends in anti-angiogenic strategies for cancer therapy. [ABSTRACT FROM AUTHOR]

Simple Summary: Given the wide usage of Bevacizumab in current oncological practice, it is very important to compare the "real-world" results to those obtained in controlled clinical trials. This study aims to describe the clinical experience of using Bevacizumab in a large cohort of cancer patients in "non-controlled real-world" conditions regarding effectiveness, safety, and cost of therapy. For this purpose, we conducted an open, observational, retrospective study involving all patients treated for solid malignant tumors in the Bucharest Institute of Oncology with "Prof. Dr. Al. Trestioreanu" with Bevacizumab-based systemic therapy, between 2017 and 2021. Bevacizumab re-mains a high-cost therapy, but it can add to clinical benefits (like overall survival, progression-free survival, and response rate) when used in conjunction with standard chemotherapy. Similar results as those presented in various controlled trials are observable even on unselected cohorts of patients in the uncontrolled conditions of "real-world" oncological practice. Overall, it is estimated that more than 3,500,000 patients have received Bevacizumab as part of systemic oncologic treatment. Bevacizumab and its biosimilars are currently marketed in over 130 countries. Given the wide usage of Bevacizumab in current oncological practice, it is very important to compare the "real-world" results to those obtained in controlled clinical trials. This study aims to describe the clinical experience of using Bevacizumab in a large cohort of cancer patients in "non-controlled real-world" conditions with regard to effectiveness, safety, and cost of therapy. Methods: For this purpose, we conducted an open, observational, retrospective study involving all patients treated for solid malignant tumors in the Bucharest Institute of Oncology with "Prof. Dr. Al. Trestioreanu" with Bevacizumab-based systemic therapy, between 2017 and 2021. Results: The study consisted of 657 treatment episodes in 625 patients (F/B = 1.62/1, with a median age of 57.6 years) which were treated for malignant tumors (majority colorectal, non-small cell lung, ovarian, and breast cancer). First-line treatment was administered in 229 patients, and the rest received Bevacizumab as second or subsequent lines of treatment. The overall response rate to Bevacizumab-based therapies was around 60–65% across all indication except for subsequent treatment lines in colorectal and ovarian cancers, where lower values were recorded (27.1%, and 31.5% respectively). Median PFS for the entire cohort was 8.2 months (95% CI 6.8–9.6), and the median OS was 13.2 months (95% CI 11.5–14.9). Usual bevacizumab-related toxicities were observed, including bleeding, hypertension, wound-healing complications, gastrointestinal perforation, other types of fistulas, septic complications, and thromboembolic events. Although the clinical benefits are undeniable, the addition of Bevacizumab to standard chemotherapy increased the overall treatment cost by 213%. Conclusions: Bevacizumab remains a high-cost therapy, but it can add to clinical benefits (like overall survival, progression-free survival, and response rate) when used in conjunction with standard chemotherapy. Similar results as those presented in various controlled trials are observable even on unselected cohorts of patients in the uncontrolled conditions of "real-world" oncological practice. Off-label usage is encountered in clinical practice, and this aspect should be monitored given the potential adverse effects of the therapy. [ABSTRACT FROM AUTHOR]

Angiogenesis is a key process in the development and progression of hepatocellular carcinoma （HCC） and can provide essential material conditions for the proliferation, invasion, and metastasis of HCC cells. Inhibition of angiogenesis has become a research hotspot in the field of HCC therapy. Traditional Chinese medicine has become a potential drug for HCC therapy due to its characteristics of multiple targets and pathways, enhancing efficacy and reducing toxicity, improving tumor prognosis, and prolonging survival time. Modern studies have confirmed that traditional Chinese medicine can inhibit tumor angiogenesis by inhibiting the expression of angiogenic factors, upregulating the levels of anti-angiogenic factors, inhibiting endothelial cell proliferation, reducing the microvascular density of HCC tissue, and regulating related signaling pathways, and therefore, traditional Chinese medicine has unique advantages in the treatment of HCC. By summarizing related articles in China and globally in recent years, this article analyzes the mechanism of action of traditional Chinese medicine on inhibiting HCC angiogenesis, in order to provide certain theoretical basis and reference for the optimization of HCC treatment strategies in clinical practice. [ABSTRACT FROM AUTHOR]

Purpose: Nivolumab and regorafenib are second-line therapies for patients with advanced hepatocellular carcinoma (HCC). We aimed to compare the effectiveness of nivolumab and regorafenib. Materials and Methods: We retrospectively reviewed patients with HCC treated with nivolumab or regorafenib after sorafenib failure. Progression-free survival (PFS) and overall survival (OS) were analyzed. An inverse probability of treatment weighting using the propensity score (PS) was performed to reduce treatment selection bias. Results: Among the 189 patients recruited, 137 and 52 patients received regorafenib and nivolumab after sorafenib failure, respectively. Nivolumab users showed higher Child-Pugh B patients (42.3% vs. 24.1%) and shorter median sorafenib maintenance (2.2 months vs. 3.5 months) compared to regorafenib users. Nivolumab users showed shorter median OS (4.2 months vs. 7.4 months, p=0.045) than regorafenib users and similar median PFS (1.8 months vs. 2.7 months, p=0.070). However, the median overall and PFS did not differ between the two treatment groups after the 1:1 PS matching (log-rank p=0.810 and 0.810, respectively) and after the stabilized inverse probability of treatment weighting (log-rank p=0.445 and 0.878, respectively). In addition, covariate-adjusted Cox regression analyses showed that overall and PFS did not significantly differ between nivolumab and regorafenib users after 1:1 PS matching and stabilized inverse probability of treatment weighting (all p>0.05). Conclusion: Clinical outcomes of patients treated with nivolumab and regorafenib after sorafenib treatment failure did not differ significantly. [ABSTRACT FROM AUTHOR]

Unfortunately, ovarian cancer is still diagnosed most often only in an advanced stage and is also the most lethal gynecological cancer. Another problem is the fact that treated patients have a high risk of disease recurrence. Moreover, ovarian cancer is very diverse in terms of molecular, histological features and mutations. Many patients may also develop platinum resistance, resulting in poor response to subsequent lines of treatment. To improve the prognosis of patients with ovarian cancer, it is expected to make better existing and implement new, promising treatment methods. Targeted therapies seem very promising. Currently, bevacizumab - a VEGF inhibitor and therapy with olaparib - a polyADP-ribose polymerase inhibitor are approved. Other methods worth considering in the future include: folate receptor a, immune checkpoints or other immunotherapy methods. To improve the treatment of ovarian cancer, it is also important to ameliorate the determination of molecular features to describe and understand which group of patients will benefit most from a given treatment method. This is important because a larger group of patients treated for ovarian cancer can have a greater chance of surviving longer without recurrence. [ABSTRACT FROM AUTHOR]

Magnetic resonance (MR) relaxometry is a quantitative imaging method that measures tissue relaxation properties. This review discusses the state of the art of clinical proton MR relaxometry for glial brain tumors. Current MR relaxometry technology also includes MR fingerprinting and synthetic MRI, which solve the inefficiencies and challenges of earlier techniques. Despite mixed results regarding its capability for brain tumor differential diagnosis, there is growing evidence that MR relaxometry can differentiate between gliomas and metastases and between glioma grades. Studies of the peritumoral zones have demonstrated their heterogeneity and possible directions of tumor infiltration. In addition, relaxometry offers T2* mapping that can define areas of tissue hypoxia not discriminated by perfusion assessment. Studies of tumor therapy response have demonstrated an association between survival and progression terms and dynamics of native and contrast-enhanced tumor relaxometric profiles. In conclusion, MR relaxometry is a promising technique for glial tumor diagnosis, particularly in association with neuropathological studies and other imaging techniques. [ABSTRACT FROM AUTHOR]

ObjectiveTo assess the efficacy and safety of anlotinib combined with immune checkpoint inhibitors (ICIs) in patients with advanced non-small-cell lung cancer (NSCLC).MethodsClinical data on patients with advanced NSCLC were collected from June 2019 to October 2022 at Hebei General Hospital, China. The efficacy and safety of anlotinib combined with ICIs and platinum-containing chemotherapy were retrospectively analyzed. The primary endpoint was progression-free survival (PFS). The secondary endpoint was the disease control rate (DCR) and overall survival (OS). Survival curves were created using the Kaplan–Meier method. The efficacy and adverse reactions were evaluated according to the RECIST 1.1 and CTCAE 5.0 standards.ResultsA total of 54 patients were enrolled in this study after propensity score matching (PSM), including 27 men and 17 women, with a median age of 59. A total of 26 patients received anlotinib + ICIs + platinum-containing chemotherapy (AIC), 15 patients received anlotinib + platinum-containing chemotherapy (AC), and 13 patients received ICIs + platinum-containing chemotherapy (IC). The PFS of the AIC group was 7.76 months (95% CI: 3.71–NC). The DCR was 65.38%. The OS endpoint had not been reached, The AIC combination regimen group had a significantly longer PFS than the IC group (mPFS, 7.76 vs. 2.33 months, p=0.012, HR=0.23, 95% CI: 0.06–0.8). There was no significant difference in the DCR between the two groups (65.38% vs. 53.85%, p=0.326). There was a statistically significant difference in PFS between the AC group and the IC group (mPFS, 9.2 vs. 2.33 months, p=0.02, HR=0.14, 95% CI: 0.03–0.65). There was no significant difference in the DCR between the two groups (40% vs. 53.85%, p=0.445). The common adverse reactions of the combination of anti-angiogenic agents, ICIs, and platinum-containing chemotherapy were anemia (34.62%), allergic reactions (19.23%), thrombocytopenia (11.54%), gastrointestinal reactions (15.38%), and hepatobiliary disorders (11.54%). Most of them were manageable.ConclusionsAnlotinib combined with immune checkpoint inhibitors and platinum-containing chemotherapy regimens offers a good survival benefit for patients with advanced non-small-cell lung cancer who fail to respond to standard therapy. When both efficacy and safety are considered, a combination of anti-angiogenic agents, ICIs, and platinum-containing chemotherapy can be used as a choice for the treatment of advanced NSCLC.

PurposeTo evaluate refractive and structural outcomes for patients treated for retinopathy of prematurity (ROP) with the anti-vascular endothelial growth factor (anti-VEGF) agent ranibizumab and "delayed laser," defined as any laser photocoagulation treatment administered at least 2 weeks and

Diabetes mellitus (DM) is a major public health problem, with approximately one third having signs of diabetic retinopathy (DR). In such patients, cataracts develop at an earlier age and 2–5 times more frequently. The incidence of macular edema (ME) after phacoemulsification of cataracts (FEC) in patients with diabetes has been shown to increase by 1.80 times and, in the presence of DR by 6.23. The critical period for retinal deterioration is 2 months after FEC, which requires an active therapy and monitoring. For patients with pre-existing diabetic macular edema (DME), If the cataract does not affect daily activities of patients with a pre-existing DME and the optical clarity is adequate, it is preferable to postpone surgical treatment in order to maximize retinal stabilization on OCT at two consecutive visits with a month’s interval between. In the case of severe impairment of lens transparency, FEC with an intravitreal injection of anti-VEGF 28 days or steroids 1 month before surgery under strict monitoring of the retinal condition using OCT is recommended. If macular changes are absent and there is a risk of developing DME, the use of nonsteroid anti-inflammatory drugs is necessary. Prophylactic intravitreal therapy is unacceptable in the absence of MO.

Antiangiogenic drugs are widely used in ophthalmology. They act by inhibiting the vascular endothelial growth factor, reducing the formation of neovessels and their use can cause side effects, such as increased intraocular pressure (IOP), which can lead to the development of glaucoma and irreversible loss of vision. This ocular hypertension can be temporary or require intervention, such as medication or surgery. The aim of this study is to determine whether intravitreal injection of antiangiogenics causes an increase in IOP. A literature search was carried out in the PubMed, Google Scholar and Science Direct databases. After applying the criteria, 9 relevant articles were selected for the literature review. The increase in IOP after anti-VEGF injections is associated with risk factors such as frequency and total number of injections, pre-existing glaucoma and type of retinal disease treated. Although there is variability between studies, it is suggested that repeated injections can destabilize ocular pressure, especially in phakic patients. In addition, the need for monitoring among patients at higher risk was highlighted. Such injections are safe, but increased intraocular pressure has been observed in patients. It is therefore essential to monitor IOP, as this increase can lead to serious complications such as glaucomatous optic neuropathy and irreversible loss of vision. [ABSTRACT FROM AUTHOR]

With the continuous emergence of biotherapy drugs in recent years, great progress has been made in the systemic therapy for advanced liver cancer. Immune checkpoint inhibitors combined with anti-angiogenic targeted drugs has become the first-line regimen recommended for the treatment of advanced liver cancer and has achieved clear oncology benefits and survival benefits. The regimens for immunotherapy combined with local treatment continue to emerge and have clearly improved objective response rate, and targeted and immune therapeutic regimens combined with sequential surgical treatment are reshaping the treatment pattern of advanced liver cancer and have finally improved radical surgical resection rate and long-term survival rate. Such changes in treatment guided by immunotherapy with or without targeted therapy have brought great challenges and thus require meticulous thoughts. With exploration of immune and targeted therapies combined with sequential surgical regimen as an example, there is a series of new problems and challenges before they are widely applied in routine diagnosis and treatment, including the selection of drug combination regimens, the evaluation of therapeutic efficacy, the treatment of toxic and side effects, surgical standards and timing, postoperative adjuvant treatment regimens, the validation of long-term survival benefits, and the selection of second-line treatment regimens for primary and secondary drug resistance. This article puts forward some suggestions and thoughts for several key aspects. [ABSTRACT FROM AUTHOR]

PURPOSE: Low-dose and very low-dose intravitreal bevacizumab (IVB) have been reported to be successful in short-term treatment of type 1 retinopathy of prematurity (ROP), down to an initial dose of 0.004 mg. We now report 12-month outcomes for these infants. DESIGN: Masked, multicenter, dose de-escalation study. PARTICIPANTS: One hundred twenty prematurely born infants with type 1 ROP. METHODS: A cohort of 120 infants with type 1 ROP in at least 1 eye from 2 sequential dose de-escalation studies of low-dose IVB (0.25 mg, 0.125 mg, 0.063 mg, and 0.031 mg) or very low-dose IVB (0.016 mg, 0.008 mg, 0.004 mg, and 0.002 mg) to the study eye; the fellow eye (if also type 1) received 1 dose level higher of IVB. After primary success or failure at 4 weeks, clinical management was at investigator discretion, including all additional treatment. MAIN OUTCOME MEASURES: Reactivation of severe ROP by 6 months corrected age, additional treatments, retinal and other ocular structural outcomes, and refractive error at 12 months corrected age. RESULTS: Sixty-two of 113 study eyes (55%) and 55 of 98 fellow eyes (56%) received additional treatment. Of the study eyes, 31 (27%) received additional ROP treatment, and 31 (27%) received prophylactic laser therapy for persistent avascular retina. No trend toward a higher risk of additional ROP treatment related to initial IVB doses was found. However, time to reactivation among study eyes was shorter in eyes that received very low-dose IVB (mean, 76.4 days) than in those that received low-dose IVB (mean, 85.7 days). At 12 months, poor retinal outcomes and anterior segment abnormalities both were uncommon (3% and 5%, respectively), optic atrophy was noted in 10%, median refraction was mildly myopic (-0.31 diopter), and strabismus was present in 29% of infants. CONCLUSIONS: Retinal structural outcomes were very good after low- and very low-dose IVB as initial treatment for type 1 ROP, although many eyes received additional treatment. The rate of reactivation of severe ROP was not associated with dose; however, a post hoc data-driven analysis suggested that reactivation was sooner with very low doses.

PURPOSE: To describe predominantly persistent intraretinal fluid (PP-IRF) and its association with visual acuity (VA) and retinal anatomic findings at long-term follow-up in eyes treated with pro re nata (PRN) ranibizumab or bevacizumab for neovascular age-related macular degeneration. DESIGN: Cohort within a randomized clinical trial. PARTICIPANTS: Participants in the Comparison of Age-related Macular Degeneration Treatments Trials (CATT) assigned to PRN treatment. METHODS: The presence of intraretinal fluid (IRF) on OCT scans was assessed at baseline and monthly follow-up visits by Duke OCT Reading Center. Predominantly persistent intraretinal fluid through week 12, year 1, and year 2 was defined as the presence of IRF at the baseline and in ≥ 80% of follow-up visits. Among eyes with baseline IRF, the mean VA scores (letters) and changes from the baseline were compared between eyes with and those without PP-IRF. Adjusted mean VA scores and changes from the baseline were also calculated using the linear regression analysis to account for baseline patient features identified as predictors of VA in previous CATT studies. Furthermore, outcomes were adjusted for concomitant predominantly persistent subretinal fluid. MAIN OUTCOME MEASURES: Predominantly persistent intraretinal fluid through week 12, year 1, and year 2; VA score and VA change; and scar development at year 2. RESULTS: Among 363 eyes with baseline IRF, 108 (29.8%) had PP-IRF through year 1 and 95 (26.1%) had PP-IRF through year 2. When eyes with PP-IRF through year 1 were compared with those without PP-IRF, the mean 1-year VA score was 62.4 and 68.5, respectively (P = 0.002), and was 65.0 and 67.4, respectively (P = 0.13), after adjustment. Predominantly persistent intraretinal fluid through year 2 was associated with worse adjusted 1-year mean VA scores (64.8 vs. 69.2; P = 0.006) and change (4.3 vs. 8.1; P = 0.01) as well as worse adjusted 2-year mean VA scores (63.0 vs. 68.3; P = 0.004) and changes (2.4 vs. 7.1; P = 0.009). Predominantly persistent intraretinal fluid through year 2 was associated with a higher 2-year risk of scar development (adjusted hazard ratio = 1.49; P = 0.03). CONCLUSIONS: Approximately one quarter of eyes had PP-IRF through year 2. Predominantly persistent intraretinal fluid through year 1 was associated with worse long-term VA, but the relationship disappeared after adjustment for baseline predictors of VA. Predominantly persistent intraretinal fluid through year 2 was independently associated with worse long-term VA and scar development.