Treatment Interval Research Articles

Dynamic Projection of Medication Nonpersistence and Nonadherence Among Patients With Early Breast Cancer.

Oral endocrine treatments have been shown to be effective when carefully adhered to. However, in patients with early breast cancer, adherence challenges are notable, with 17% experiencing nonpersistence and 41% nonadherence at least once. To model the persistence of and adherence to oral anticancer treatment of a patient with localized breast cancer. This cohort study was conducted using anonymous reimbursement data belonging to French female patients with breast cancer, extracted from the French Health Insurance database from January 2013 to December 2018. Data analysis was conducted from January 2021 to May 2022. The main outcome was the detection of episodes of nonpersistence and nonadherence 6 months before they happened. Adherence was defined as the ratio between the time covered by a drug purchase and the time between 2 purchases; patients were considered nonadherent if the ratio of their next 3 purchases was less than 80%. Disparities in persistence and adherence based on criteria such as age, treatment type, and income were identified. A total of 229 695 female patients (median [IQR] age, 63 [52-72] years) with localized breast cancer were included. A deep learning model based on a gated-recurrent unit architecture was used to detect episodes of nonpersistence or nonadherence. This model demonstrated an area under the receiving operating curve of 0.71 for persistence and 0.73 for adherence. Analyzing the Shapley Additive Explanations values also gave insights into the contribution of the different features over the model's decision. Patients older than 70 years, with past nonadherence, taking more than 1 treatment in the previous 3 months, and with low income had greater risk of episodes of nonpersistence. Age and past nonadherence, including regularity of past adherence, were also important features in the nonadherence model. This cohort study found associations of patient age and past adherence with nonpersistence or nonadherence. It also suggested that regular intervals in treatment purchases enhanced adherence, in contrast to irregular purchasing patterns. This research offers valuable tools for improving persistence of and adherence to oral anticancer treatment among patients with early breast cancer.

Spontaneous and Treatment-Related Changes of Serum Calcitonin in Medullary Thyroid Cancer: Long-Term Experience in a Patient With Multiple Endocrine Neoplasia Type 2B.

Medullary thyroid carcinoma (MTC) in MEN2B syndrome is associated with germline RET mutation. Patients harboring de novo mutations are usually diagnosed at more advanced disease stages. We present a young woman with Met918Th mutation diagnosed with stage IV MTC at age 10 years. The disease progressed despite total thyroidectomy and multiple surgical interventions for cervical lymph node recurrences, leading to distant metastases in the fifth year after the initial diagnosis. Subsequently, she underwent five different types of tyrosine kinase inhibitor (TKI) treatments. The 17-year disease course was divided into periods defined by four surgical interventions and sequential treatment intervals with four multikinase (sunitinib, vandetanib, cabozantinib, and lenvatinib) and one RET-selective TKI (selpercatinib). Tumor growth for different phases of spontaneous development and drug treatment intervals was characterized by changes in serial log-transformed calcitonin measurements (n = 114). Three operations (one for calcitonin-producing adrenal pheochromocytoma) were associated with drops in calcitonin levels. All of the nonselective TKIs were stopped due to adverse effects. As reflected by the negative calcitonin doubling rate, the best treatment response was observed with selpercatinib, which was associated with an initial large drop followed by a decreasing calcitonin trajectory over 514 days without any major side effects. This case of MEN2B medullary thyroid cancer with long-term survival presents how the effectiveness of different treatment modalities can be estimated using log-transformed calcitonin levels. Furthermore, our experience supports the view that serial calcitonin measurements may be more sensitive than radiological follow-up in advanced MTC. Our patient also represents a new case of rarely reported calcitonin-producing pheochromocytomas.

Dose escalation of biologic treatment in patients with moderate-to-severe psoriasis in Japan.

Patients receiving interleukin (IL)-inhibiting biologics for moderate-to-severe psoriasis (PsO) may be treated with escalated doses to optimize outcomes. This study evaluated escalation prevalence in a Japanese claims analysis of patients with PsO diagnosis preceding IL-inhibiting biologic treatment and ≥1 post-induction maintenance claim (index date) with sufficient data availability from January 2014 to May 2022. Patients with non-persistence were excluded. Expected daily dose (EDD) was calculated as the recommended maintenance dose divided by the treatment interval. Dose escalation was defined as ≥2 claims showing a ≥20% increase in the observed average daily dose (ADD) over the EDD (with sensitivities requiring ≥1 claim and ≥30%). Significant differences were tested using multivariable regressions. The study included 982 unique patients treated with brodalumab (BRO; n = 104), guselkumab (GUS; n = 207), ixekizumab (IXE; n = 159), risankizumab (RIS; n = 135), secukinumab (SEC; n = 215) and ustekinumab (UST; n = 196). Within 12 months, dose escalation was observed for all IL-inhibiting biologics other than GUS and RIS: 44.4% for UST, 37.2% for IXE, 3.4% for SEC and 1.4% for BRO. In multivariable-adjusted analyses, odds of dose escalation were significantly lower for all products relative to UST. In sensitivities, escalation was observed for all products except RIS.

Closing the Sex-Based Differences in Stroke Care: Insights from a Large Telestroke Network on Treatment and Postacute Management.

The evolution of ischemic stroke is different accordin'g to sex and is one of the main causes of death in women. Previous studies have shown that women are less likely to receive acute treatment, and stroke center type is an important predictor of door-to-needle times. We investigated whether women are attended in a similar way to men in the telestroke network with specialized stroke physicians. A prospective registry of ischemic strokes recorded in the centralized Andalusian telestroke network was analyzed, focusing on sex differences. Demographic data, clinical characteristics, neuroimaging data, treatment intervals, follow-up visits, and clinical outcomes were collected. A total of 3009 suspected stroke patients were attended to in the telestroke network from 2019 to 2023, of which 42.74% were women. Women were older (p < 0.001) and less independent upon arrival (p = 0.006) than men. There was no difference in the treatment received or in the treatment time intervals between the groups. Importantly, there was no difference in modified Rankin scale scores at 3 months between sexes. At 3 months post-stroke follow-up, women had fewer imaging tests (p = 0.018) and fewer outpatient visits (p < 0.001) than men. No significant difference between men and women has been found in the acute treatment of stroke in a large telestroke network. However, the same is not true for the follow-up and management of patients after the acute phase. This fact supports that strict adherence to protocols and specialization of care lead to equal care that avoids sex differences in stroke treatment and functional outcomes.

Prognostic relevance of circulating lymphoma cells at diagnosis in newly diagnosed follicular lymphoma patients.

Follicular lymphoma (FL) is the most common indolent B-cell non-Hodgkin lymphoma. Circulating lymphoma (CL) cells can be seen at diagnosis in some FL patients, however, previous studies evaluating this have shown mixed results. Therefore, we sought to evaluate the impact of CL at diagnosis on outcomes in patients with newly diagnosed FL using data from a single center. Patients were divided into CL+ and CL- based on immunophenotyping via peripheral blood (PB) flow cytometry. CL was defined as detectable clonally restricted B-cells that matched the actual or expected B-cell immunophenotype of FL. The primary endpoint was progression-free survival (PFS) after first-line treatment and secondary endpoints included overall response rate (ORR), overall survival (OS), diagnosis to treatment interval (DTI), progression of disease within 2years of diagnosis (POD24), and cumulative incidence of transformation between the two groups. Among the 541 patients with FL, 204 had PB flow cytometry performed at diagnosis, and after excluding patients not meeting the eligibility criteria, 147 cases remained with 24 (16%) CL+ at diagnosis. Patients in the CL+ group were younger (53 vs. 58years, p=0.02), had more extranodal involvement (83% vs. 44%, p<0.01), follicular lymphoma international prognostic index 3-5 (55% vs. 31%, p=0.01), and a higher proportion received first-line immunochemotherapy (75% vs. 43%, p=0.01) compared to the CL-group. The median PFS was not significantly different between CL+ (6.27years, 95% CI=3.61-NR) and CL- (6.61years, 95% CI=5.10-9.82) cohorts regardless of the first-line treatment or level of absolute PB CL cells. There was no significant difference in ORR, median OS, DTI, POD24, and cumulative incidence of transformation between the two groups. In our study, we found that the presence of CL cells at diagnosis in FL in the contemporary era did not impact outcomes and survival.

Real-world data on efficacy/safety and economic impact of nivolumab administered every 2 and 4weeks among Japanese patients.

A new treatment interval for nivolumab administration at 480mg every 4weeks, in addition to 240mg every 2weeks, was approved in Japan in 2020. Using model-based evaluation, it was speculated that the effects or safety of nivolumab do not differ between the two treatment intervals; however, real-world data on nivolumab efficacy, safety, and economic impact are lacking. Accordingly, we aimed to examine the effects of nivolumab treatment intervals (2weeks vs. 4weeks) in terms of efficacy, safety, and economic impact in Japanese patients with cancer. We retrospectively analyzed 126 patients treated with nivolumab. The patients were divided into two groups depending on whether they received nivolumab at 240mg every 2weeks (2-week group) or 480mg every 4weeks (4-week group). Efficacy results found no significant difference between the 4- and 2-week groups considering median overall survival (p=0.70) and median progression-free survival (p=0.57). The incidence of any grade and≥grade 3 immune-related adverse events did not differ between the 4-week and 2-week groups (any grade, p=0.13;≥grade 3, p=0.36). Excluding drug costs, the 4-week group had significantly lower medical costs than the 2-week group (2-week vs. 4-week: mean, 94,659 JPY [679.0 USD] vs. 58,737 JPY [421.3 USD]; p<0.05). Collectively, our findings suggest that nivolumab 480mg every 4weeks may be more effective than nivolumab 240mg every 2weeks in terms of economic impact.

E054 Rituximab dose minimisation in rheumatoid arthritis, a retrospective outcome analysis

Abstract Background/Aims Rituximab was originally developed as a non-Hodgkin lymphoma treatment and rheumatology adopted the same dosing for rheumatoid arthritis(RA); two 1000mg doses two weeks apart for each maintenance cycle. UHSussex utilises self-referral for maintenance rituximab dosing once disease control lessens. Evidence demonstrates patients treated with lower dose rituximab still enjoy good disease control with less immunosuppression, reduced hospital attendance and reduction in drug expenditure. Following one two-dose cycle, stable RA patients were prescribed a single 1000mg dose from 2020 onwards. A retrospective outcome analysis was completed in August 2022; however, results were highly impacted by Covid-19 and a repeat analysis was required. Aim: to assess impact of a single 1000mg dose rituximab regime on patient sustained outcomes, dose intervals, Disease Activity Scores (DAS) and drug expenditure. Methods The pharmacy database was used to identify RA patients receiving rituximab from March 2020 to August 2023. Patients received at least one standard two-dose cycle before switching to a single infusion. Patients were excluded if lost to follow up (under care of rheumatology for less than a year following dose switching) or considered clinically unstable. Patient letters and departmental records were accessed for disease scores and treatment intervals. Results Table1: Results from the two analysis periods From the original cohort (31/59)53% remained on single dosing. Switch back tended to occur within 18 months of switching. DAS scores were not collected reliably and were omitted. Conclusion Covid-19 impacted services and attitudes during the initial study period. Many patients stopped treatment, particularly rituximab, due to the prolonged duration of effect, excluding them from analysis. The dose-interval increase during the first analysis was considered a result of the pandemic. Patients and clinicians delayed infusions; minimising immunosuppression due to perceived increased risk of Covid-19. The continued interval increase in the second analysis may identify a patient cohort in deep remission eligible for therapy review. The study highlights poor practice in collecting and recording DAS scores and appropriate patient-clinician interaction opportunities. 53% of patients remained on single infusions in August 2023 resulting in resource savings, reduced hospital attendance, immunosuppression and significant cost savings demonstrating the rationale for this option. Disclosure S. Butler: Honoraria; Abbvie, Janssen. H. Smith: Honoraria; Novartis, Abbvie.

Understanding breast cancer patient pathways and their impact on survival in Mexico

BackgroundUnderstanding patient pathways from discovery of breast symptoms to treatment start can aid in identifying ways to improve access to timely cancer care. This study aimed to describe the patient pathways experienced by uninsured women from detection to treatment initiation for breast cancer in Mexico City and estimate the potential impact of earlier treatment on patient survival. MethodsWe used process mining, a data analytics technique, to create maps of the patient pathways. We then compared the waiting times and pathways between patients who initially consulted a private service versus those who sought care at a public health service. Finally, we conducted scenario modelling to estimate the impact of early diagnosis and treatment on patient survival. ResultsOur study revealed a common pathway followed by breast cancer patients treated at the two largest public cancer centres in Mexico City. However, patients who initially sought care in private clinics experienced shorter mean wait times for their first medical consultation (66 vs 88 days), and diagnostic confirmation of cancer (57 vs 71 days) compared to those who initially utilized public clinics. Our scenario modelling indicated that improving early diagnosis to achieve at least 60% of patients starting treatment at early stages could increase mean patient survival by up to two years. ConclusionOur study highlights the potential of process mining to inform healthcare policy for improvement of breast cancer care in Mexico. Also, our findings indicate that reducing diagnostic and treatment intervals for breast cancer patients could result in substantially better patient outcomes. Policy summaryThis study revealed significant differences in time intervals along the pathways of women with breast cancer according to the type of health service first consulted by the patients: whether public primary care clinics or private doctors. Policies directed to reduce these inequities in access to timely cancer care are desperately needed to reduce socioeconomic disparities in breast cancer survival.

Extended interval dosing with ocrelizumab in multiple sclerosis

Background: This study investigates clinical and biomarker differences between standard interval dosing (SID) and extended interval dosing (EID) of ocrelizumab therapy in multiple sclerosis (MS). Methods: This is a prospective, double-arm, open-label, multi-center study in Denmark. Participants diagnosed with MS on ocrelizumab therapy >12 months were included (n = 184). Clinical, radiological, and blood-based biomarker outcomes were evaluated. MRI disease activity, relapses, worsening of neurostatus, and No Evidence of Disease Activity-3 (NEDA-3) were used as a combined endpoint. Results: Out of 184 participants, 107 participants received EID (58.2%), whereas 77 participants received SID (41.8%). The average extension was 9 weeks with a maximum of 78 weeks. When comparing EID to SID, we found higher levels of B-cells, lower serum concentrations of ocrelizumab, and similar levels of age-adjusted NFL and GFAP in the two groups. No difference in NEDA-3 between EID and SID was demonstrated (hazard ratio: 1.174, p = 0.69). Higher levels of NFL were identified in participants with disease activity. Body mass index correlated with levels of ocrelizumab and B-cells. Conclusion: Extending one treatment interval of ocrelizumab on average 9 weeks and up to 78 weeks did not result in clinical, radiological, or biomarker evidence of worsening compared with SID.

Weekly Pulsed Dye Laser Treatments for Port-Wine Birthmarks in Infants

Early treatment of port-wine birthmark (PWB) can be life-altering and is often associated with improved outcomes and quality of life. There is growing evidence that shorter treatment intervals may play a role in more rapid PWB clearance; however, the optimal treatment interval has not been established. To describe the outcomes of once-weekly pulsed dye laser (PDL) treatments for PWB in infants. This case series analyzed the medical records of patients with PWB who received once-weekly PDL treatments between January 1, 2022, and December 31, 2023, at the Laser & Skin Surgery Center of New York. These patients were younger than 6 months. Before-and-after treatment photographs were independently assessed and graded 2 months after initiation of treatment. Once-weekly PDL treatments. The primary outcome was the percentage improvement of PWB, which was graded using the following scale: 0% (no improvement), 1% to 25% (mild improvement), 26% to 50% (moderate improvement), 51% to 75% (marked improvement), 76% to 95% (near-total clearance), and 96% to 100% (total clearance). Of the 10 patients (6 males [60%]; median [range] age at first treatment, 4 [<1 to 20] weeks) included, 7 (70%) had experienced either near-total clearance (76%-95%) or total clearance (96%-100%) of their PWB with once-weekly PDL treatments after 2 months. The other 3 patients all saw marked improvement (51%-75%) and subsequently went on to achieve near-total clearance with additional treatments. The median (range) duration of treatment and number of treatments to achieve near-total or total clearance in all patients were 2 (0.2-5.1) months and 8 (2-20) treatments, respectively. No adverse events were noted. This case series found that once-weekly PDL treatments for PWB in the first few months of life was associated with near-total or total clearance of PWB with no reported adverse events, suggesting improved outcomes can be achieved with shorter overall treatment duration. Further investigation into this novel decreased treatment interval of 1 week is warranted.

Factors Associated with Success of Switching to Faricimab for Neovascular Age-Related Macular Degeneration Refractory to Intravitreal Aflibercept.

We investigated the factors associated with the success of switching to faricimab for type 1 macular neovascularization (MNV) refractory to intravitreal aflibercept (IVA). This retrospective cohort study included patients with type 1 MNV who were switched to faricimab because they were refractory to IVA at two centers. The primary endpoint was a more than two-week extension of the treatment interval after 6 months. In addition, factors related to the success or failure of extension and visual and anatomical outcomes were assessed. The analysis included 43 eyes from 43 patients. Extended dosing intervals of >2 weeks were identified in 14 eyes (32.6%). A short dosing interval before switching, absence of polypoidal lesions, and thin central choroidal thickness before switching were identified as factors involved in successful extension. For patients with refractory type 1 MNV, switching to faricimab is a safe and potential option to extend existing dosing intervals.

Resurfacing of atrophic facial acne scars with a multimodality CO2 and 1570 nm laser system.

Scarring is one of the most prevalent long-term complications of acne vulgaris and has cosmetic, psychological, and social burdens. Contemporary management programs integrate multiple modalities to best address the multiple factors underlying their development and persistence. This work assessed the impact of sequential multimodal laser therapy on acne scar geometrics and texture. Adult patients (n = 16) with Fitzpatrick skin type II-IV and presenting with facial acne scars, underwent three combination ablative (CO2), and nonablative (1570 nm) laser treatment sessions at two-month intervals. Treatment was delivered using a ProScan Hybrid applicator, with each regimen including illumination with both ablative and a nonablative lasers applied in a grid mode sequence. Scar microtopography was assessed at baseline and 6 months after the last treatment session. At baseline, all patients had both box and rolling scars, while only three had icepick scars. Six months following treatment, mean scar volume improved from 5.7 ± 5.2 mm3 at baseline to 3.1 ± 3.0 mm3 and mean affected area improved from 165.6 ± 134.0 mm2 94.0 ± 80.1 mm2, translating to 47.0 ± 7.9% and 43.2 ± 8.6% reductions from baseline, respectively. Patients were highly satisfied with treatment outcomes, and no serious adverse reactions were documented during the course of treatment or follow-up. Multimodal CO2 and 1570-nm laser treatment improved the surface profilometry of patients with atrophic facial acne scars. Customization of both treatment intervals and laser settings to cosmetic regions, scar profiles and skin phototypes may further enhance treatment outcomes and expand its applicability to additional skin deformities.

Anti-VEGF Treatment for Secondary Neovascularization in Pseudoxanthoma Elasticum - Age of Onset, Treatment Frequency, and Visual Outcome

PurposeTo assess the onset, treatment frequency, and visual outcome of anti-vascular endothelial growth factor (anti-VEGF) treatment due to secondary choroidal neovascularization (CNV) in patients with pseudoxanthoma elasticum (PXE). DesignRetrospective cohort study MethodsOne-hundred six eyes of 53 patients with PXE were analyzed. The assessment of CNV activity relied on hemorrhage visible on funduscopy and intra- / subretinal fluid on optical coherence tomography (OCT), individually defining a shortening or extension of treatment interval. Best-corrected visual acuity (BCVA) at baseline, age at anti-VEGF therapy initiation, and BCVA-drop events at exudation onset (worsening of BCVA of 2 or more lines) were documented. Further, we assessed the number of injections during the first year and the total number of injections, the time to treatment initiation of the fellow eye, and BCVA over time. ResultsDuring a median observation period of 77 months (IQR 49; 126) patients received a median number of 28.0 anti VEGF-injections (IQR 9.8; 43.5). Eight patients received no injection (median age at baseline 38.1 years), 11 patients underwent anti-VEGF treatment in one eye (median age 47.2 years) and 34 patients in both eyes (median age 51.8 years). The median age at the first anti-VEGF treatment was 52.80 years (IQR 47.2 – 57.6). Applying Cox regression models, the median 'survival' time of fellow eye until treatment initiation was 16.8 months. In the group of bilateral treated patients, the median time difference was 9.6 months (IQR 2.1 – 32.4, range 0 – 122) The median number of injections was 5.5 per eye in the first year of treatment (IQR 3 – 7) and was associated with the total number of injections in the observation period (2.33, CI 1.22 – 3.44, p<0.001). A better BCVA at the last follow-up visit was associated with a better baseline BCVA (p<0.001, R2=0.318) and with the absence of a BCVA drop at the onset of exudation (p=0.035, R2=0.339). ConclusionsThe results of this study indicate that anti-VEGF treatment is required for most PXE patients at a relatively young age. Once treatment in one eye is initiated, the time to fellow eye treatment is relatively short. A BCVA drop before treatment initiation is a risk factor for worse visual outcomes, suggesting that treatment is prudent before exudation affects the central retina. Given the young age of onset and intensive treatment needs, patients with PXE might particularly benefit from longer-acting anti-VEGF therapeutics.

IMPLEMENTATION OF RELIABILITY CENTERED MAINTENANCE (RCM) II IN PACKAGING INDUSTRY PRODUCTION MACHINERY MAINTENANCE ACTIVITIES

Along with the increasing need for productivity and the use of high technology in the form of production machines and factories, the need for maintenance functions is also increasing. At PT. Weiss Tech, a packaging machine manufacturer, has problems mainly related to wire cut machine malfunctions which cause interruptions and delays in the production process and reduce machine performance. In overcoming these problems in this study, the Reliability Centered Maintenance (RCM) II method from Failure Modes and Effect Analyze (FMEA) was used. RCM II is one of the methods used to determine which components are due for repairs, while FMEA is defined as a method for identifying the root cause of engine failure. From the results of calculations using FMEA and RCM II, the results of the maintenance interval for the Electromotor component (electric motor) with a maintenance interval of 20 hours, for the Lower and upper nozzle components (upper and lower nozzles) with a maintenance interval of 181 hours, and for the Roller component (drive roller) ) with a treatment interval of 177 hours

First-Year Real-Life Experience with Intravitreal Faricimab for Refractory Neovascular Age-Related Macular Degeneration.

Background: To evaluate the outcomes of intravitreal faricimab (IVF) for refractory neovascular age-related macular degeneration (nAMD) and investigate the impact of baseline optical coherence tomography, biomarkers for total IVF injections are needed. Methods: A retrospective analysis of 33 eyes of patients who completed one year (52 W) of treatment with IVF. The eyes received four IVF injections (6 mg/0.05 mL) as the upload phase. Thereafter, the treatment interval was extended to 8 or 12 weeks if disease activity was not recorded. The outcome measures included best-corrected visual acuity (BCVA), central macular thickness (CMT), subfoveal choroidal thickness (SFCT), and retinal fluid distribution. Results: A total of 33 eyes were included. CMT decreased significantly at 52 W (p < 0.01). BCVA and SFCT did not change significantly at 52 W (p > 0.05). The number of eyes with subretinal fluid decreased significantly at 52 W (p < 0.01). Complete fluid resolution was achieved in 20 eyes (60%). The total number of injections was significantly negatively correlated with the presence of hyperreflective dots at baseline (HRDs, p < 0.01) and SFCT at baseline (p < 0.01). Conclusions: IVF led to a significant reduction in CMT with stabilization of BCVA. The total number of injections was lower in eyes with HRDs and increased SFCT at baseline. This might provide clues regarding response to IVF for future studies.

Immuno-Haematological Indices Stabilizing Attributes of Co-Enzyme Q10 Supplementation in Thioacetamide Poisoned Wistar Rats

Coenzyme Q10 (CoQ10 or Co_Q10) as a known endogenous compound has been linked to some therapeutic functions, thus, the need for further exploration in more dysfunctional biological scenarios. This present study, thus, evaluated the stabilizing attributes of Co-enzyme Q10 supplementation in thioacetamide (TAA) altered immuno-haematological system in Wistar rats. One hundred and twenty (120) male Wistar rats weighing 250 and 280g were used for the study and were randomly separated into four sub-groups of 30 rats per treatment interval of week 3, 6, 9 and 12. In the individual weeks, the rats were further grouped into six different groups of five rats each. The groups included Group 1-control and received 1ml of normal saline (intraperitoneally―ip), Group 2 received only 200 mg/kg TAA (ip) twice weekly, Group 3 received 5mg/kg Co_Q10, daily per oral (po), Group 4 received 10mg/kg Co_Q10 daily (po), Group 5 received 200 mg/kg TAA (ip) twice weekly and 5mg/kg Co_Q10 (po) daily and Group 6 received 200 mg/kg TAA (ip) twice weekly and 10mg/kg Co_Q10 (po) daily. After weeks 3, 6, 9 and 12 of treatments, blood samples were collected and instantly transferred into well labeled blood sample bottles with anticoagulant. After appropriate laboratory and statistical analyses, the quantitative results were obtained. The result showed that following TAA toxicity, the levels of white blood cells (WBC) were significantly (P&lt;0.05) reduced; meanwhile, those of macrophage and tissue necrotic factor alpha (TNFα) were remarkably (P&lt;0.05) increased. However, upon the supplementations with Co-Q10 in the respective weeks (3, 6, 9 and 12) of treatment, all the aforementioned deranged values of WBC, macrophages and TNFα were significantly (P&lt;0.05) stabilized/normalized (i.e. brought to similar range of the normal untreated rats). Therefore, Co-Q10 supplementation may be of beneficial therapeutic value in particular haematological dysfunctional scenarios.

Adjuvant re-irradiation vs. no early re-irradiation of resected recurrent glioblastoma: pooled comparative cohort analysis from two tertiary centers

BackgroundThe optimal management strategy for recurrent glioblastoma (rGBM) remains uncertain, and the impact of re-irradiation (Re-RT) on overall survival (OS) is still a matter of debate. This study included patients who achieved gross total resection (GTR) after a second surgery after recurrence, following the GlioCave criteria.MethodsInclusion criteria include being 18 years or older, having histologically confirmed locally recurrent IDHwt or IDH unknown GBM, achieving MRI-proven GTR after the second surgery, having a Karnofsky performance status of at least 60% after the second surgery, having a minimum interval of 6 months between the first radiotherapy and the second surgery, and a maximum of 8 weeks from second surgery to the start of Re-RT.ResultsA total of 44 patients have met the inclusion criteria. The median OS after the second surgery was 14 months. All patients underwent standard treatment after initial diagnosis, including maximum safe resection, adjuvant radiochemotherapy and adjuvant chemotherapy. Re-RT did not significantly impact OS. However, MGMT promoter methylation status and a longer interval (> 12 months) between treatments were associated with better OS. Multivariate analysis revealed the MGMT status as the only significant predictor of OS.ConclusionFactors such as MGMT promoter methylation status and treatment interval play crucial roles in determining patient outcomes after second surgery. Personalized treatment strategies should consider these factors to optimize the management of rGBM. Prospective research is needed to define the value of re-RT after second surgery and to inform decision making in this situation.

Evaluation of two-dimensional total bone uptake (2D-TBU) and bone scan index (BSI) extracted from active bone metastatic burden on the bone scintigraphy in patients with radium-223 treatment.

Radium-223 is a first alpha-emitting radionuclide treatment for metastatic castration-resistant prostate cancer (mCRPC) patients with bone metastases. Although the spread-based bone scan index (BSI) and novel index of the intensity-based two-dimensional total bone uptake (2D-TBU) from bone scintigraphy may provide useful input in radium-223 treatment, they have not been evaluated in detail yet. This study aimed to fill this gap by evaluating BSI and 2D-TBU in patients treated with radium-223. Twenty-seven Japanese patients with mCRPC treated with radium-223 were retrospectively analyzed. The patients were evaluated via blood tests and bone scans at baseline and 3 cycles intervals of treatment. BSI and 2D-TBU were analyzed via VSBONE BSI in terms of correlations, response to radium-223 treatment, association with treatment completion, and the Kaplan-Meier survival analysis was performed. Nineteen patients (70.4%) completed six cycles of radium-223 treatment, whereas eight patients (29.6%) did not complete the treatment regimen. A significant difference in baseline BSI and 2D-TBU was observed between these groups of patients. Both BSI and 2D-TBU were highly correlated (r = 0.96, p < 0.001). Univariate analysis showed an association between radium-223 completion in median BSI and 2D-TBU values (p = 0.015) and completion percentage differences (91.7% vs. 45.5%; p = 0.027). The Kaplan-Meier product limit estimator showed that the median overall survival was 25.2 months (95% CI 14.0-33.6 months) in the completion group and 7.5 months (95% CI 3.3-14.2 months) in the without completion group (p < 0.001). The overall survival based on median cutoff levels showed a significant difference in 2D-TBU (p = 0.007), but not in BSI (p = 0.15). The 2D-TBU may offer advantages over BSI in classifying patients towards radium-223 treatment based on the degree of progression of bone metastases. This study supports the importance of preliminary assessment of bone metastasis status using BSI and 2D-TBU extracted from VSBONE BSI for radium-223 treatment decisions.

Real-World Experience with Brolucizumab Compared to Aflibercept in Treatment-Naïve and Therapy-Refractory Patients with Diabetic Macular Edema.

Background: To report on the outcome of intravitreal brolucizumab compared to aflibercept in patients with diabetic macular edema (DME). Methods: Prospective, observational, study in 35 eyes of 24 patients with a loading dose of five injections of 6 mg brolucizumab every 6 weeks (q6w, treatment-naïve eyes) or a minimum of two injections of brolucizumab q6w after the switch (recalcitrant DME eyes), followed by a treat and extend (T&E) regimen. The results were compared with 40 eyes of 31 DME patients who were treated with aflibercept. The data were obtained from the Berlin Macula Registry. The primary outcome measure was the change in best-corrected visual acuity (BCVA) at week 36. Secondary outcome measures were the change in central retinal thickness (CRT) and the treatment intervals until week 36. Results: BCVA increased significantly in treatment-naïve DME eyes treated with either brolucizumab (+0.12 logMAR, +6.4 letters, p = 0.03) or aflibercept (+0.19 logMAR, +9.5 letters, p = 0.001). In recalcitrant DME eyes, BCVA also increased significantly after switching to brolucizumab (+0.1 logMAR, +5 letters, p = 0.006) or aflibercept (+0.11 logMAR, +5.5 letters, p = 0.02). All treatment-naïve and recalcitrant DME eyes had a significant decrease in CRT after treatment with brolucizumab (p = 0.001 and p < 0.001) or aflibercept (p = 0.0002 and p = 0.03). At week 36, the mean treatment interval for brolucizumab was 11.3 weeks, while for aflibercept, it was 6.5 weeks for treatment-naïve eyes and 9.3 weeks vs. 5.3 weeks for pretreated eyes. Conclusions: In routine clinical practice, patients with treatment-naïve and recalcitrant DME showed a favorable response to brolucizumab and aflibercept therapy, with a reduced injection frequency after brolucizumab treatment.

Quantifying Fluid and Function in Suboptimal Responders Switched From an Anti-vascular Endothelial Growth Factor (VEGF) to Faricimab.

Background Anti-vascular endothelial growth factor (VEGF) injections have been successful in reducing vision loss from neovascular age-related macular degeneration, a leading cause of blindness. Due to the high treatment burden and suboptimal responses, switching to bi-specific faricimab treatment may lead to improved outcomes. Methods This retrospective chart review evaluated if suboptimal responders to anti-VEGF injections had better outcomes when switched to faricimab. Suboptimal responders were defined as patients with a history of >3 months of injections and the presence of fluid after ≥3 injections. The primary endpoints were best-corrected visual acuity, treatment interval, and fluid levels. Visual acuity measurements and optical coherence tomography were performed before each injection. The total fluid area (TFA) was measured using MATLAB 2023a (MathWorks, Natick, MA, USA). Results Nineteen eyes were included in the analysis. After three faricimab injections, average letters increased from 54.5 to 59.0 (SD: 15.3; p<0.05), and the injection interval was extended from 7.6 to 9.3 weeks (SD: 3.9; p<0.01) after four injections. Patients also experienced anatomical retinal changes, with a reduction in the TFA to 47.3% (p<0.005) after the second injection and a reduction in pigment epithelial detachment height to 82.3% (p<0.005) after one injection. The central subfield thickness was significantly reduced after the second injection (90.6% (SD: 17.6%)p<0.05). Conclusion Switching to faricimab after a suboptimal anti-VEGF response results in improvements in visual acuity, reduced treatment burden, and reduced fluid levels.