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1.
Dermatol Online J ; 30(1)2024 Mar 15.
Article En | MEDLINE | ID: mdl-38762867

Osteonecrosis of the jaw is a recognized complication associated with bevacizumab. Here, we present a patient with squamous cell carcinoma of the tonsil who experienced minimal skin fibrosis following intensity-modulated radiation therapy. Subsequently, the patient developed rectal adenocarcinoma and encountered osteonecrosis of the jaw after receiving two cycles of bevacizumab. Close monitoring, accompanied by thorough examination to detect early signs of osteonecrosis of the jaw, should be considered for patients who have undergone radiation therapy in the head and neck region and are receiving bevacizumab or other medications known to be associated with osteonecrosis of the jaw.


Bevacizumab , Carcinoma, Squamous Cell , Radiotherapy, Intensity-Modulated , Tonsillar Neoplasms , Humans , Bevacizumab/adverse effects , Bevacizumab/therapeutic use , Carcinoma, Squamous Cell/radiotherapy , Carcinoma, Squamous Cell/drug therapy , Radiotherapy, Intensity-Modulated/adverse effects , Tonsillar Neoplasms/radiotherapy , Tonsillar Neoplasms/drug therapy , Male , Osteonecrosis/chemically induced , Adenocarcinoma/drug therapy , Adenocarcinoma/radiotherapy , Rectal Neoplasms/drug therapy , Rectal Neoplasms/radiotherapy , Antineoplastic Agents, Immunological/adverse effects , Middle Aged , Jaw Diseases/chemically induced
2.
Expert Rev Pharmacoecon Outcomes Res ; 24(5): 631-641, 2024 Jun.
Article En | MEDLINE | ID: mdl-38776431

OBJECTIVES: This study aims to explore the cost-effectiveness of atezolizumab plus bevacizumab against sorafenib for first-line treatment of locally advanced or metastatic hepatocellular carcinoma (HCC) in Singapore. METHODS: A partitioned survival model was developed from a healthcare system perspective, with a 10-year lifetime horizon. Clinical inputs and utilities were obtained from the IMbrave150 trial. Healthcare resource use costs were obtained from published local sources; drug costs reflected the most recent public hospital selling prices. Outcomes included life years, quality-adjusted life years (QALYs) and incremental cost-effectiveness ratios (ICERs). Deterministic and probabilistic sensitivity analyses were performed to assess the model's robustness. RESULTS: Atezolizumab plus bevacizumab offered an additional 1.42 life years and 1.09 QALYs, with an additional cost of S$111,847; the ICER was S$102,988/QALY. The World Health Organization considers interventions with ICERs <1 gross domestic product (GDP)/capita to be highly cost-effective. At a willingness-to-pay (WTP) threshold of S$114,165/QALY (Singapore's 2022 GDP/capita), atezolizumab plus bevacizumab is cost-effective compared with sorafenib. The ICER was most sensitive to variations in utilities, but all parameter variations had no significant impact on the model outcomes. CONCLUSION: At a WTP threshold of Singapore's GDP/capita, atezolizumab plus bevacizumab is cost-effective compared with sorafenib.


Antibodies, Monoclonal, Humanized , Antineoplastic Combined Chemotherapy Protocols , Bevacizumab , Carcinoma, Hepatocellular , Cost-Benefit Analysis , Liver Neoplasms , Quality-Adjusted Life Years , Sorafenib , Humans , Bevacizumab/administration & dosage , Bevacizumab/economics , Sorafenib/administration & dosage , Sorafenib/economics , Singapore , Liver Neoplasms/drug therapy , Liver Neoplasms/economics , Carcinoma, Hepatocellular/drug therapy , Carcinoma, Hepatocellular/economics , Carcinoma, Hepatocellular/pathology , Antibodies, Monoclonal, Humanized/administration & dosage , Antibodies, Monoclonal, Humanized/economics , Antineoplastic Combined Chemotherapy Protocols/economics , Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Drug Costs , Cost-Effectiveness Analysis
3.
Medicine (Baltimore) ; 103(21): e38183, 2024 May 24.
Article En | MEDLINE | ID: mdl-38788019

BACKGROUND: We aimed to compare 7 newer immunotherapies and targeted therapies for platinum-resistant relapsed ovarian cancer. METHODS: We conducted a comprehensive search of PubMed, EMBASE, and Cochrane Library electronic databases for phase III trials involving platinum-resistant recurrent ovarian cancer (PRrOC) patients treated with immunotherapy or targeted therapy in combination with chemotherapy. The quality of the included trials was assessed using the GRADE method. The primary outcome of comparison was progression-free survival, and secondary outcomes included overall survival and safety. RESULTS: This analysis included 7 randomized phase III controlled trials, encompassing 2485 PRrOC patients. Combining bevacizumab plus chemotherapy and lurbinectedin demonstrated statistically significant differences in progression-free survival compared to all other regimens of interest. However, no statistically significant differences were observed in the overall survival. Nivolumab and mirvetuximab exhibited fewer serious adverse events than the other regimens of interest. CONCLUSIONS: Our findings indicate that bevacizumab combined with chemotherapy and lurbinectedin monotherapy has significant efficacy in patients with PRrOC. For patients with PRrOC who have exhausted treatment options, nivolumab and mirvetuximab may be considered as alternatives because of their better safety profiles.


Antineoplastic Combined Chemotherapy Protocols , Bayes Theorem , Bevacizumab , Drug Resistance, Neoplasm , Neoplasm Recurrence, Local , Network Meta-Analysis , Ovarian Neoplasms , Humans , Female , Ovarian Neoplasms/drug therapy , Ovarian Neoplasms/mortality , Bevacizumab/therapeutic use , Bevacizumab/administration & dosage , Neoplasm Recurrence, Local/drug therapy , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Randomized Controlled Trials as Topic , Nivolumab/therapeutic use , Nivolumab/administration & dosage , Progression-Free Survival , Clinical Trials, Phase III as Topic , Cyclobutanes/therapeutic use , Antineoplastic Agents/therapeutic use , Immunotherapy/methods , Molecular Targeted Therapy/methods , Carbolines , Heterocyclic Compounds, 4 or More Rings
4.
ESMO Open ; 9(5): 103374, 2024 May.
Article En | MEDLINE | ID: mdl-38744100

BACKGROUND: The inflammation-based modified Glasgow Prognostic Score (mGPS) combines serum levels of C-reactive protein and albumin and was shown to predict survival in advanced cancer. We aimed to elucidate the prognostic impact of mGPS on survival as well as its predictive value when combined with gender in unselected metastatic colorectal cancer (mCRC) patients receiving first-line chemotherapy in the randomized phase III XELAVIRI trial. PATIENTS AND METHODS: In XELAVIRI, mCRC patients were treated with either fluoropyrimidine/bevacizumab followed by additional irinotecan at first progression (sequential treatment arm; Arm A) or upfront combination of fluoropyrimidine/bevacizumab/irinotecan (intensive treatment arm; Arm B). In the present post hoc analysis, survival was evaluated with respect to the assorted mGPS categories 0, 1 or 2. Interaction between mGPS and gender was analyzed. RESULTS: Out of 421 mCRC patients treated in XELAVIRI, 362 [119 women (32.9%) and 243 men (67.1%)] were assessable. For the entire study population a significant association between mGPS and overall survival (OS) was observed [mGPS = 0: median 28.9 months, 95% confidence interval (CI) 25.9-33.6 months; mGPS = 1: median 21.4 months, 95% CI 17.6-26.1 months; mGPS = 2: median 16.8 months, 95% CI 14.3-21.2 months; P < 0.00001]. Similar results were found when comparing progression-free survival between groups. The effect of mGPS on survival did not depend on the applied treatment regimen (P = 0.21). In female patients, a trend towards longer OS was observed in Arm A versus Arm B, with this effect being clearly more pronounced in the mGPS cohort 0 (41.6 versus 25.5 months; P = 0.056). By contrast, median OS was longer in male patients with an mGPS of 1-2 treated in Arm B versus Arm A (20.8 versus 17.4 months; P = 0.022). CONCLUSION: We demonstrate the role of mGPS as an independent predictor of OS regardless of the treatment regimen in mCRC patients receiving first-line treatment. mGPS may help identify gender-specific subgroups that benefit more or less from upfront intensive therapy.


Antineoplastic Combined Chemotherapy Protocols , Colorectal Neoplasms , Humans , Colorectal Neoplasms/drug therapy , Colorectal Neoplasms/pathology , Male , Female , Middle Aged , Aged , Prognosis , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/pharmacology , Inflammation/drug therapy , Inflammation/blood , Irinotecan/therapeutic use , Irinotecan/pharmacology , Adult , Capecitabine/therapeutic use , Capecitabine/pharmacology , C-Reactive Protein/analysis , C-Reactive Protein/metabolism , Oxaloacetates , Bevacizumab/therapeutic use , Bevacizumab/pharmacology , Fluorouracil/therapeutic use , Fluorouracil/pharmacology , Biomarkers, Tumor/blood , Neoplasm Metastasis
5.
BMC Ophthalmol ; 24(1): 220, 2024 May 24.
Article En | MEDLINE | ID: mdl-38790043

BACKGROUND: Retinopathy of prematurity (ROP) is a disease that affects preterm infants born younger than 30 weeks of gestation. The pathophysiology of ROP involves an initial vaso-obliterative phase followed by vaso-proliferative phase that leads to disease progression. The use of supplemental oxygen during the vaso-proliferative phase of ROP has been associated with reduced disease progression, but how this impacts the need for ROP treatment is unclear. The goal of this study was to compare the rate of laser or intravitreal bevacizumab after implementation of a new supplemental oxygen therapy protocol in preterm infants with stage 2 ROP. METHODS: This is a retrospective chart review of preterm infants diagnosed with stage 2 ROP at Riley Hospital for Children between 1/2017 and 12/2022. Patients diagnosed between 1/2017 and 6/2020 were classified as Cohort A, preprotocol implementation. Patients diagnosed from 8/2020 to 12/2022 were classified as Cohort B, postprotocol implementation. In Cohort A, oxygen saturation was kept at 91-95% through the entire hospitalization. In Cohort B, oxygen saturation was increased to 97-99% as soon as Stage 2 ROP was diagnosed. Statistical analyses were performed using chi-square and Student's T test, followed by multivariate analyses to determine the impact of the oxygen protocol on the need for ROP treatment. RESULTS: A total of 211 patients were diagnosed with stage 2 ROP between 1/2017 and 12/2022. Of those patients, 122 were before protocol implementation therapy (Cohort A), and 89 were after implementation of supplemental oxygen protocol (Cohort B). Gestational age was slightly higher in Cohort B (Cohort A 25.3 ± 1.9, Cohort B 25.8 ± 1.84, p = 0.04). There was no difference in birth weight, NEC, BPD, or survival. Cohort B had lesser need for invasive mechanical ventilation and higher days on CPAP during hospitalization. Notably, Cohort A had 67 (55%) patients treated with laser photocoagulation or intravitreal bevacizumab versus 20 (22%) patients in Cohort B (OR 0.19, 0.08-0.40). CONCLUSION: The need for laser photocoagulation or intravitreal bevacizumab was significantly decreased in high-risk patients treated with the supplemental oxygen protocol. This result supports the idea that targeted supplemental oxygen therapy to keep saturations between 97 and 99% can reduce disease progression in infants with stage 2 ROP and potentially decrease the burden of additional procedures.


Angiogenesis Inhibitors , Bevacizumab , Gestational Age , Infant, Premature , Intravitreal Injections , Retinopathy of Prematurity , Humans , Retinopathy of Prematurity/drug therapy , Retinopathy of Prematurity/therapy , Retinopathy of Prematurity/diagnosis , Bevacizumab/administration & dosage , Bevacizumab/therapeutic use , Retrospective Studies , Infant, Newborn , Angiogenesis Inhibitors/administration & dosage , Angiogenesis Inhibitors/therapeutic use , Male , Female , Laser Coagulation/methods , Oxygen Inhalation Therapy/methods , Oxygen/therapeutic use , Vascular Endothelial Growth Factor A/antagonists & inhibitors , Treatment Outcome
6.
Eur J Cancer ; 204: 114089, 2024 Jun.
Article En | MEDLINE | ID: mdl-38703618

OBJECTIVES: The development of reliable biomarkers for the prediction of immune checkpoint inhibition (ICI) response in patients with metastatic renal cell carcinoma (mRCC) and urothelial carcinoma (mUC) remains an unresolved challenge. Conventional ICI biomarkers typically focus on tumor-related factors such as PD-L1 expression. However, a comprehensive evaluation of the predictive value of serum electrolyte levels, a so far widely unexplored area, is still pending. METHODS: We conducted a post-hoc analysis of baseline sodium, potassium, chloride, magnesium and calcium levels in two independent phase 3 clinical trials: IMvigor211 for mUC comparing atezolizumab to chemotherapy, and IMmotion151 for mRCC comparing atezolizumab+bevacizumab to sunitinib. This analysis aimed to evaluate the prognostic and predictive value of these electrolyte levels in these clinical settings. A total of 1787 patients (IMvigor211 n = 901; IMmotion151 n = 886) were analyzed. RESULTS: We found a linear correlation of baseline serum sodium and chloride with prognosis across both trials, which was not found for potassium, magnesium and calcium. In multivariate analysis, the prognostic capacity of sodium was limited to patients receiving ICI as compared to the control group. Interestingly, in both studies, the chance of achieving an objective response was highest in the patient subgroup with high baseline serum sodium levels of > 140 mmol/L (IMmotion151: Complete response in 17.9% versus 2.0% in patients with mRCC with baseline sodium < 135 mmol/L). Serum sodium outperformed tumor PD-L1 expression as a predictor for immunotherapy efficacy. CONCLUSIONS: Patients exhibiting elevated serum sodium levels derive the greatest benefit from immunotherapy, suggesting that baseline serum concentration could serve as a valuable and cost-effective predictive biomarker for immunotherapy across entities.


Carcinoma, Renal Cell , Kidney Neoplasms , Sodium , Humans , Kidney Neoplasms/drug therapy , Kidney Neoplasms/blood , Kidney Neoplasms/pathology , Kidney Neoplasms/immunology , Male , Carcinoma, Renal Cell/drug therapy , Carcinoma, Renal Cell/blood , Carcinoma, Renal Cell/immunology , Carcinoma, Renal Cell/secondary , Carcinoma, Renal Cell/pathology , Female , Sodium/blood , Aged , Middle Aged , Immunotherapy/methods , Antibodies, Monoclonal, Humanized/therapeutic use , Bevacizumab/therapeutic use , Biomarkers, Tumor/blood , Immune Checkpoint Inhibitors/therapeutic use , Prognosis , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Sunitinib/therapeutic use , Carcinoma, Transitional Cell/drug therapy , Carcinoma, Transitional Cell/blood , Carcinoma, Transitional Cell/secondary , Carcinoma, Transitional Cell/immunology
7.
BMC Pediatr ; 24(1): 301, 2024 May 04.
Article En | MEDLINE | ID: mdl-38704544

BACKGROUND: We present a patient with retinopathy of prematurity (ROP) who developed worsening plus disease after complete regression of stage 3 ROP. The use of fundus fluorescein angiography (FFA) aided the visualization of occult neovascularization that caused the disease progression. CASE PRESENTATION: The patient was at high risk for ROP due to low birth weight of 690 g and gestational age of 25 weeks. After the diagnosis of stage 3 ROP in zone I without plus disease, she was treated initially with bilateral intravitreal bevacizumab (IVB) and followed by laser photocoagulation 5 weeks later. Despite the resolution of ROP stage, the plus disease worsened. Neither systemic risk factors nor skip laser areas were observed. Hence, FFA was performed and subsequently identified occult neovascularization with active leakage. Additional IVB and laser treatment in the capillary dropout area inside vascularized retina were added. The plus disease improved but mild arteriolar tortuosity persisted. CONCLUSIONS: Worsening of plus disease after completion of laser ablation and IVB with complete regression of stage 3 ROP is rare. Systemic risk factors such as continuous oxygen therapy and cardiovascular disease should be ruled out. FFA aided in identifying occult neovascularization and prompted further treatment.


Angiogenesis Inhibitors , Bevacizumab , Fluorescein Angiography , Intravitreal Injections , Laser Coagulation , Retinal Neovascularization , Retinopathy of Prematurity , Humans , Bevacizumab/therapeutic use , Bevacizumab/administration & dosage , Infant, Newborn , Angiogenesis Inhibitors/therapeutic use , Angiogenesis Inhibitors/administration & dosage , Female , Laser Coagulation/methods , Retinal Neovascularization/etiology , Retinal Neovascularization/drug therapy , Antibodies, Monoclonal, Humanized/therapeutic use , Antibodies, Monoclonal, Humanized/administration & dosage , Combined Modality Therapy
8.
JCO Precis Oncol ; 8: e2300693, 2024 May.
Article En | MEDLINE | ID: mdl-38754056

PURPOSE: To report the results of OPAL (ClinicalTrials.gov identifier: NCT03574779) cohort A, a single-arm substudy of niraparib plus dostarlimab and bevacizumab for the treatment of advanced, platinum-resistant ovarian cancer (PROC). METHODS: Participants with PROC who received 1-2 previous lines of therapy were treated with niraparib (200 or 300 mg once daily), dostarlimab (500 mg once every 3 weeks for four 21-day cycles, followed by 1,000 mg once every 6 weeks), and bevacizumab (15 mg/kg once every 3 weeks). The primary end point was investigator-assessed objective response rate (ORR) per RECIST v1.1. Safety was also assessed. Exploratory biomarker end points included evaluation of changes in the tumor molecular profile and microenvironment using baseline and on-treatment tumor samples. RESULTS: Of 41 enrolled participants (median age, 66.0 years [range, 37-83 years]), 9.8% had tumors that were BRCA-mutated, 19.5% were homologous recombination (HR)-deficient, and 17.1% were HR repair (HRR)-mutated. As of the cutoff date, all participants discontinued treatment. The ORR was 17.1% (80% CI, 9.8 to 27.0), including one complete response (2.4%); the disease control rate was 73.2% (80% CI, 62.3 to 82.2). Two participants withdrew before first postbaseline scan because of adverse events (AEs). Grade ≥3 treatment-emergent AEs were reported in 92.7% of participants, with the most common being hypertension (26.8%). Response was not correlated with BRCA, HRR, HR deficiency (HRD), or PD-L1 status. Changes suggesting immune activation were observed in on-treatment samples after triplet therapy. CONCLUSION: Results demonstrated modest activity of niraparib, dostarlimab, and bevacizumab in participants with PROC, many of whom had prognostic factors for poor treatment response. Most participants with response were bevacizumab-naïve. No association was found with HRD, BRCA, or PD-L1 status. AEs were consistent with previous monotherapy reports, except that hypertension was reported more frequently.


Antineoplastic Combined Chemotherapy Protocols , Bevacizumab , Drug Resistance, Neoplasm , Indazoles , Ovarian Neoplasms , Piperidines , Humans , Female , Middle Aged , Ovarian Neoplasms/drug therapy , Aged , Bevacizumab/therapeutic use , Adult , Indazoles/therapeutic use , Aged, 80 and over , Piperidines/therapeutic use , Piperidines/adverse effects , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Antibodies, Monoclonal, Humanized/therapeutic use , Cohort Studies
11.
Int Ophthalmol ; 44(1): 225, 2024 May 15.
Article En | MEDLINE | ID: mdl-38748185

PURPOSE: To evaluate the importance of the status of posterior vitreous in eyes with endophthalmitis following intravitreal anti-vascular endothelial growth factor (anti-VEGF). METHODS: The absence or existence of posterior vitreous detachment (PVD) was elicited in 23 eyes of 23 patients with injection related endophthalmitis, during pars plana vitrectomy (PPV) and compared with 24 control eyes of 24 patients who received intravitreal anti-VEGF without any complication. RESULTS: Thirtten (54.2%) out of 24 patients in the control group had full PVD, whereas only 2 (9.5%) out of 23 eyes in endophthalmitis group (p < 0.001) had full PVD. In all eyes without PVD, posterior vitreous was inducted to be detached at least from optic nerve and macular area without any iatrogenic tear. CONCLUSION: The absence of PVD is a factor that increases the risk of endophthalmitis after intravitreal injections. Uncomplicated separation of the posterior vitreous from the retina in PPV contributes to better prognosis.


Angiogenesis Inhibitors , Endophthalmitis , Intravitreal Injections , Vascular Endothelial Growth Factor A , Vitrectomy , Vitreous Detachment , Humans , Endophthalmitis/etiology , Endophthalmitis/diagnosis , Endophthalmitis/epidemiology , Intravitreal Injections/adverse effects , Male , Female , Angiogenesis Inhibitors/administration & dosage , Angiogenesis Inhibitors/adverse effects , Risk Factors , Vascular Endothelial Growth Factor A/antagonists & inhibitors , Aged , Middle Aged , Vitrectomy/adverse effects , Vitrectomy/methods , Vitreous Body , Ranibizumab/administration & dosage , Ranibizumab/adverse effects , Bevacizumab/administration & dosage , Bevacizumab/adverse effects , Aged, 80 and over
12.
Am J Manag Care ; 30(2 Suppl): S31-S35, 2024 May.
Article En | MEDLINE | ID: mdl-38701364

Numerous advances in the standard of care for metastatic colorectal cancer (mCRC), including the approval of several new treatments indicated for treatment in the third line or later (3L+), have been made, yet data and appropriate guidance on the optimal sequencing and treatment strategies for these lines of therapy are lacking. Four treatments-regorafenib, trifluridine/tipiracil alone or with bevacizumab, and fruquintinib-are FDA-approved and recommended by the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for the treatment of mCRC in the 3L+. When considering sequencing of treatment options for patients in the 3L+, the goal of treatment is to improve survival, but also maintain quality of life, a goal that requires consideration of relative efficacy and cumulative toxicity such as persistent myelosuppression.


Antineoplastic Combined Chemotherapy Protocols , Colorectal Neoplasms , Thymine , Trifluridine , Humans , Colorectal Neoplasms/drug therapy , Colorectal Neoplasms/pathology , Colorectal Neoplasms/genetics , Trifluridine/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Bevacizumab/therapeutic use , Bevacizumab/administration & dosage , Pyridines/therapeutic use , Phenylurea Compounds/therapeutic use , Pyrrolidines/therapeutic use , Drug Combinations , Neoplasm Metastasis , Quality of Life
13.
Int Ophthalmol ; 44(1): 216, 2024 May 05.
Article En | MEDLINE | ID: mdl-38705908

PURPOSE: To evaluate clinical features, treatment protocol, outcomes, and complications that developed in this case series of 24 patients who had consecutive sterile endophthalmitis after intravitreal bevacizumab (IVB) injection. METHODS: In this retrospective case series, IVB was repackaged in individual aliquots from the three batches that were used on the same day. IVB was injected into 26 eyes of 26 patients due to diabetic macular edema, age-related macular degeneration, and branch retinal vein occlusion. All patients had intraocular inflammation. Patients were divided into two groups severe and moderate inflammation according to the intraocular inflammation. The medical records of all patients were reviewed. At each follow-up visit, the complete ophthalmologic examination was performed, including best corrected visual acuity (BCVA), intraocular pressure, biomicroscopy, and posterior fundus examination. RESULTS: Twenty-four of 26 patients were included in the study. Two patients were excluded from this study since they didn't come to follow-up visits. The mean BCVA was 1.00 ± 0.52 Log MAR units before IVB. At the final visit, the BCVA was 1.04 ± 0.47 Log MAR units. These differences were not significant (p = 0.58). Of the 24 eyes, 16 eyes had severe, and 8 eyes had moderate intraocular inflammation. Eleven eyes in the severe inflammation group underwent pars plana vitrectomy due to intense vitreous opacity. Smear, culture results, and polymerase chain reaction results were negative. CONCLUSION: Sterile endophthalmitis may occur after IVB injection. Differential diagnosis of sterile endophthalmitis from infective endophthalmitis is crucial to adjust the appropriate treatment and prevent long-term complications due to unnecessary treatment.


Angiogenesis Inhibitors , Bevacizumab , Endophthalmitis , Intravitreal Injections , Visual Acuity , Humans , Bevacizumab/administration & dosage , Bevacizumab/adverse effects , Endophthalmitis/diagnosis , Endophthalmitis/etiology , Retrospective Studies , Male , Female , Angiogenesis Inhibitors/administration & dosage , Angiogenesis Inhibitors/adverse effects , Aged , Middle Aged , Aged, 80 and over , Vascular Endothelial Growth Factor A/antagonists & inhibitors , Macular Edema/drug therapy , Macular Edema/diagnosis , Macular Edema/etiology , Retinal Vein Occlusion/diagnosis , Retinal Vein Occlusion/drug therapy , Retinal Vein Occlusion/complications , Follow-Up Studies , Diabetic Retinopathy/diagnosis , Diabetic Retinopathy/drug therapy
14.
J Dev Orig Health Dis ; 15: e10, 2024 May 10.
Article En | MEDLINE | ID: mdl-38724487

Premature infants have a risk of neurodevelopmental deficits. Little is known, however, about how retinopathy of prematurity (ROP) affects visual motor integration (VMI), which is necessary for both fine motor skills and further school abilities. Due to the systemic escape of bevacizumab in the treatment of ROP, concerns regarding the long-term neurodevelopmental effect of the drug have arisen. The aim is to evaluate VMI and motor development long-term outcomes after intravitreal bevacizumab (IVB) injection and laser treatment for ROP. Two groups of premature children were included: Bevacizumab group - 16 premature children who received IVB treatment and laser group - 23 premature children who underwent laser photocoagulation treatment in this single center cross-sectional study. At 2-6 years of age, VMI (Beery-Buktenica Developmental Test), motor development (Peabody Developmental Motor Scales-2), visual acuity, and refractive status were assessed. The incidence of abnormal visual function was significantly higher in bevacizumab group than in laser group (p = 0.022). The incidence of abnormal VMI skill was significantly higher in bevacizumab group than in laser group (p = 0.024). Incidences of abnormal gross, fine, and total motor skills were significantly higher in bevacizumab group compared to laser group (p < 0.05). Premature children who received bevacizumab for ROP demonstrated significantly lower VMI and motor development features than those with laser treatment at preschool age. Although our results suggest the relevance of bevacizumab injection in impaired VMI and motor development outcomes, general level of sickness rather than treatment might be the cause of delayed motor development.


Bevacizumab , Child Development , Retinopathy of Prematurity , Humans , Retinopathy of Prematurity/therapy , Retinopathy of Prematurity/physiopathology , Retinopathy of Prematurity/surgery , Male , Female , Bevacizumab/administration & dosage , Bevacizumab/therapeutic use , Child, Preschool , Cross-Sectional Studies , Child , Child Development/drug effects , Child Development/physiology , Infant, Newborn , Infant, Premature , Angiogenesis Inhibitors/administration & dosage , Angiogenesis Inhibitors/therapeutic use , Motor Skills/physiology , Intravitreal Injections
16.
Article En | MEDLINE | ID: mdl-38701802

A 17-year-old Appaloosa mare was referred for evaluation of presumed refractory keratitis of the left eye. Gross examination revealed ocular discomfort and corneal neovascularization with a nasal focal opacification affecting approximately 40% of the corneal surface. On ophthalmic examination, extensive subepithelial to mid-stromal vascular branching accompanied by a homogeneous white, dense opacification, which affected up to 80% of the total corneal thickness, were apparent. Signs of concurrent uveitis were absent. Deep-stromal lamellar keratectomy with a conjunctival pedicle graft was performed under general anesthesia. Histopathology confirmed a poorly differentiated corneal stromal invasive squamous cell carcinoma (SI-SCC) with neoplastic cell extension to the surgical margins. Postoperatively, 4 topical mitomycin C 0.04% chemotherapy cycles combined with oral firocoxib therapy were initiated. Seven months after surgery, regrowth of the SI-SCC was clinically suspected. A total volume of 1 ml bevacizumab 2.5% was administered in the standing sedated horse via 3 mid-stromal corneal injections. Four weeks later, intrastromal bevacizumab injections (ISBIs) were repeated, however, this time the solution was injected directly into the main corneal vessel branches.Seven weeks after the second ISBIs, the left eye was comfortable and significant remission of corneal vascularization and opacity was recognized. No recurrence has been noted for a follow-up period of more than 53 months.Equine SI-SCC usually has a very poor prognosis for globe maintenance. To the authors' knowledge this is the first report of well-tolerated intrastromal antivascular endothelial growth factor adjunctive therapy with bevazicumab 2.5% and SI-SCC resolution after a multimodal treatment approach.


Bevacizumab , Carcinoma, Squamous Cell , Eye Neoplasms , Horse Diseases , Horses , Animals , Bevacizumab/therapeutic use , Bevacizumab/administration & dosage , Horse Diseases/drug therapy , Female , Carcinoma, Squamous Cell/veterinary , Carcinoma, Squamous Cell/drug therapy , Carcinoma, Squamous Cell/pathology , Carcinoma, Squamous Cell/surgery , Eye Neoplasms/veterinary , Eye Neoplasms/drug therapy , Eye Neoplasms/pathology , Eye Neoplasms/surgery , Angiogenesis Inhibitors/therapeutic use , Angiogenesis Inhibitors/administration & dosage , Corneal Stroma/drug effects , Corneal Stroma/pathology
17.
Ophthalmic Res ; 67(1): 282-291, 2024.
Article En | MEDLINE | ID: mdl-38621369

INTRODUCTION: The purpose of this study was to investigate long-term outcomes of intravitreal injections (IVI) of antivascular endothelial growth factor (VEGF) in neovascular age-related macular degeneration (nAMD) with type 3 macular neovascularization (MNV). METHODS: This retrospective study included 19 eyes of 17 patients with nAMD and type 3 MNV treated with anti-VEGF IVI with a loading dose and a PRN regimen. Best corrected visual acuity (BCVA), central macular thickness (CMT), presence of macular intraretinal fluid (IRF) and subretinal fluid (SRF), flow area (FA), subfoveal choroidal thickness (CT), and macular atrophy (MA) were assessed at baseline (T0) and during follow-up (T1, post-loading phase; T2, 1 year; T3, 2 years; T4 >2 years). The correlations between MA at the last follow-up and standard deviation (SD) values of CMT and CT during follow-up were assessed. The influence of the number of injections on the change in MA over time was also analyzed. MA differences at T4 were assessed for pseudodrusen presence. RESULTS: BCVA improved significantly during follow-up (p = 0.013) particularly increasing from baseline to post-loading phase and then did not modify significantly thereafter. CMT significantly reduced from T0 to T1 and remained stable during follow-up (p = <0.001). MNV flow area showed a trend toward an increase in the post-loading phase that was not statistically significant (p = 0.082) and CT decreased significantly during follow-up (p < 0.001). MA changed significantly during follow-up (p < 0.001) with a significant increase from T0 to T3 and from T0 to T4 (p < 0.010). A Cochran-Armitage test for trend showed a significant reduction (p = 0.001) of macular IRF and SRF during follow-up. MA at T4 showed a significant positive correlation with SD (standard deviation) values of CMT (p = 0.040) and CT (p = 0.020). Indeed, the number of injections did not influence the change over time of MA (p = 0.709). MA at T4 was not statistically significantly different between patients with pseudodrusen at baseline (p = 0.497). CONCLUSIONS: Intravitreal anti-VEGF injections with PRN regimen in MNV type 3 showed functional and anatomical benefits. Variations of retinal thickness and choroidal thickness during treatment were related to MA modification over time.


Angiogenesis Inhibitors , Fluorescein Angiography , Intravitreal Injections , Ranibizumab , Tomography, Optical Coherence , Vascular Endothelial Growth Factor A , Visual Acuity , Humans , Retrospective Studies , Male , Female , Angiogenesis Inhibitors/administration & dosage , Aged , Vascular Endothelial Growth Factor A/antagonists & inhibitors , Tomography, Optical Coherence/methods , Follow-Up Studies , Aged, 80 and over , Ranibizumab/administration & dosage , Fluorescein Angiography/methods , Macula Lutea/pathology , Bevacizumab/administration & dosage , Treatment Outcome , Wet Macular Degeneration/drug therapy , Wet Macular Degeneration/diagnosis , Wet Macular Degeneration/physiopathology , Fundus Oculi , Time Factors , Middle Aged
18.
Eur J Pharm Biopharm ; 199: 114308, 2024 Jun.
Article En | MEDLINE | ID: mdl-38688439

We have previously developed an in vitro instrument, termed subcutaneous injection site simulator (SCISSOR), that can be used to monitor release properties of an active pharmaceutical ingredient (API) and formulation components of a medicine designed for SC injection. Initial studies to validate the SCISSOR instrument applications used a simple hyaluronic acid (HA) hydrogel to monitor early release events. We now report a type of cross-linked HA that can, when combined with HA, provide a hydrogel (HA-XR) with optical clarity and rheological properties that remain stable for at least 6 days. Incorporation of 0.05-0.1 mg/mL of collagens isolated from human fibroblasts (Col F), bovine type I collagen (Col I), chicken collagen type II (Col II), or chondroitin sulphate (CS) produced HA or HA-XR hydrogel formats with optical clarity and rheological properties comparable to HA or HA-XR alone. HA + Col F hydrogel had a much greater effect on release rates of 70 kDa compared to 4 kDa dextran, while Col F incorporated into the HA-XR hydrogel accentuated differences in release rates of prandial and basal forms of insulin as well as decreased the release rate of denosumab. A hydrogel format of HA + Col I was used to examine the complex events for bevacizumab release under conditions where a target ligand (vascular endothelial growth factor) can interact with extracellular matrix (ECM). Together, these data have demonstrated the feasibility of using a cross-linked HA format to examine API release over multiple days and incorporation of specific ECM elements to prepare more biomimetic hydrogels that allow for tractable examination of their potential impact of API release.


Hyaluronic Acid , Hydrogels , Injections, Subcutaneous , Hyaluronic Acid/chemistry , Hydrogels/chemistry , Humans , Animals , Drug Interactions/physiology , Cattle , Rheology , Chondroitin Sulfates/chemistry , Chondroitin Sulfates/administration & dosage , Insulin/administration & dosage , Insulin/chemistry , Bevacizumab/administration & dosage , Bevacizumab/chemistry , Collagen/chemistry
20.
Neurosurg Rev ; 47(1): 137, 2024 Apr 02.
Article En | MEDLINE | ID: mdl-38564039

Despite 2-staged stereotactic radiosurgery (2-SSRS) has been reported to provide patients with improved survival and limited toxicity, 2-SSRS for brainstem metastases (BSM) larger than 2 cm3 remains challenging. We tried to find out the effectiveness and safety of 2-SSRS plus bevacizumab therapy for BSMs over 2 cm3 and prognostic factors that related to the tumor local control. Patients that received 2-SSRS plus bevacizumab therapy from four gamma knife center were retrospectively studied from Jan 2014 to December 2023. Patients' domestic characteristics and the tumor features were evaluated before and after the treatment. Cox regression model was used to find out prognostic factors for tumor local control. 53 patients with 63 lesions received the therapy. The median peri-tumor edema volume greatly reduced at the end of therapy (P < 0.01), the median tumor volume dramatically reduced (P < 0.01) and patients' KPS score improved significantly (P < 0.05) 3 months after the therapy. Patients' median OS was 12.8 months. The tumor local control rate at 3, 6, and 12 months was 98.4%, 93.4%, and 85.2%. The incidence side effects were mainly oral and nasal hemorrhage (5.7%, 3/53), and radiation necrosis (13.2%, 7/53). Patients with primary lung adenocarcinoma, therapeutic dose over 12 Gy at second-stage SRS, primary peri-tumor edema volume less than 2.3 cm³, primary tumor volume less than 3.7 cm³ would enjoy longer tumor local control. These results suggested that 2-SSRS plus bevacizumab therapy was effective and safe for BSMs over 2 cm3. However, it is important for patients with BSM to receive early diagnosis and treatment to achieve good tumor local control.


Brain Stem , Neoplasms , Humans , Bevacizumab/therapeutic use , Retrospective Studies , Edema
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