Treatment Dose Research Articles

Danicopan (Voydeya)

Canada’s Drug Agency (CDA-AMC) recommends that Voydeya be reimbursed by public drug plans as an add-on to ravulizumab or eculizumab for the treatment of adult patients with paroxysmal nocturnal hemoglobinuria (PNH) who have residual hemolytic anemia due to extravascular hemolysis (EVH) if certain conditions are met. Voydeya should only be covered to treat adult patients with a diagnosis of PNH, who have met the public drug plan reimbursement criteria for initiating complement 5 inhibitor (C5i) treatments (ravulizumab or eculizumab) before receiving C5i treatment, and who have been on a stable dose of C5i treatment for 6 months or more, in addition, patients should also have persistent anemia caused by EVH, and an absolute reticulocyte count of 120 × 109/L or greater. Voydeya should only be reimbursed if prescribed by a hematologist with experience managing PNH. The cost of Voydeya should be negotiated so that Voydeya plus a C5i as a regimen does not exceed the drug program cost of treatment with pegcetacoplan for the treatment of adult patients with PNH who have residual hemolytic anemia due to EVH.

Olaparib-associated toxicity in cancer patients: a systematic review and meta-analysis.

To investigate the characteristics of olaparib-associated adverse events (AEs) in cancer patients. Databases were searched for phase II and III randomized controlled trials (RCTs) involving olaparib treatment up to March 2024. A systematic assessment was performed. Twenty-seven RCTs involving 9542 patients were included. This meta-analysis indicates that olaparib could significantly increase the risk of developing any all-grade (RR, 1.08; 95% CI, 1.03-1.13; p = 0.001) and high-grade (RR, 1.45; 95% CI, 1.19-1.77; p = 0.0003) AEs in cancer patients. Olaparib could increase the risk of dose reduction (RR, 3.00; 95% CI, 1.59-5.70; p = 0.0007) and treatment discontinuation (RR, 2.00; 95% CI, 1.28-3.14; p = 0.002). Hematologic toxicities and gastrointestinal toxicities commonly occur in patients receiving olaparib. Anemia, nausea, and fatigue were the most frequent AEs, with olaparib increasing the risk of both all-grade and high-grade occurrences of these events. Patients with longer treatment durations tend to have a higher risk of anemia. Patients with urinary system tumors tend to have a higher risk of nausea, while those with breast cancer tend to have a higher risk of fatigue. Olaparib maintenance therapy may be associated with a higher risk of fatigue. Olaparib could increase other AEs such as diarrhea, vomiting, decreased appetite, dyspepsia, dysgeusia, dizziness, headache, back pain, urinary tract infection, dyspnea, and cough. Olaparib-containing therapy could increase the occurrence of specific AEs in patients with cancer. Clinicians should be aware of these risks and conduct regular monitoring.

The Effects of Proton and Photon Radiation Therapy on the Development of Pediatric Dermatitis

Although radiation therapy is the leading option for effective cancer treatment, a prevalent side effect associated with it is dermatitis. Despite some available literature on this topic, there remain many gaps that need to be addressed. The goal of this study is to determine the incidence of radiation-induced dermatitis (RID) among children receiving proton and photon therapies; a retrospective chart review, at a single institution, was conducted on oncology patients who underwent proton or photon therapy radiation between 2018 and 2023. Significant differences were found between the Radiation Therapy Oncology Group (RTOG) score and the total radiation dose (p = 0.04). The median total dose of radiation received by those with an RTOG score of l was 5040.0 mGy and increased to 7600 mGy for those with a score of 3. A significant association was found between those who received chemotherapy and dermatitis (p = 0.04). No significance was found between the incidence of dermatitis in photon and proton therapy (p = 1.00). The study showed that multiple factors, including total radiation dose and chemotherapy, can affect RID. These relationships can be used to determine the modality, dose, and additional treatment options best suited to treat cancer patients in the pediatric population.

Treatment of atopic dermatitis with abrocitinib in real practice in Spain: efficacy and safety results from a 24-week multicenter study.

Abrocitinib, a selective JAK 1 inhibitor, was recently approved in Europe. Despite its approval, real-world data on its efficacy and safety in treating moderate-to-severe atopic dermatitis (AD) remains limited. This study aimed to evaluate the short-term effectiveness and safety of abrocitinib in a real-life setting for patients with moderate-to-severe AD. We conducted a retrospective multicenter study involving adult patients with moderate-to-severe AD who started abrocitinib treatment between May 1, 2023, and September 30, 2023, in 15 Spanish hospitals. Treatment doses were 100 or 200 mg daily, based on clinical assessment. Data collection included patient demographics, AD history, comorbidities, previous treatments, and disease severity indicators such as SCORing atopic dermatitis (SCORAD), Eczema Area and Severity Index (EASI), body surface area, and Peak Pruritus NRS scores at baseline, 4, 12, and 24 weeks. Quality of life was measured using the Dermatology Life Quality Index (DLQI), and safety was assessed by monitoring adverse reactions and various biochemical parameters. The cohort comprised 76 patients with an average age of 33.93 years; 57.89% were male. Before abrocitinib, 36.84% were naïve to advanced therapies. The baseline mean scores were SCORAD 47.04, EASI 21.79, and DLQI 15.01. At Week 24, there were significant improvements: EASI was reduced to 2.81, and 70.58% of the patients achieved EASI 75. However, 18.42% discontinued treatment mainly due to inefficacy or adverse effects. The safety profile was favorable, with 22.37% reporting mild adverse events (AEs) and one serious case of cutaneous lymphoma. This first Spanish series assessing abrocitinib in real-world conditions reveals a significant improvement in AD symptoms and quality of life in a range of severity and prior treatment failures. Abrocitinib was well-tolerated, with few serious AEs, highlighting its potential as an effective treatment option for AD.

Camizestrant, a next-generation oral SERD, versus fulvestrant in post-menopausal women with oestrogen receptor-positive, HER2-negative advanced breast cancer (SERENA-2): a multi-dose, open-label, randomised, phase 2 trial

Resistance to endocrine therapies in hormone receptor-positive breast cancer is challenging. We aimed to assess the next-generation oral selective oestrogen receptor degrader (SERD) and complete oestrogen receptor antagonist, camizestrant, versus the first-approved SERD, fulvestrant, in post-menopausal women with oestrogen receptor-positive, HER2-negative, advanced breast cancer. SERENA-2 is an open-label, randomised, phase 2 trial that is being conducted at 74 study centres across Asia, Europe, the Middle East, and North America. Female patients aged 18 years or older who were post-menopausal with histologically or cytologically confirmed metastastic or locoregional oestrogen receptor-positive, HER2-negative breast cancer, an Eastern Cooperative Oncology Group or WHO performance status of 0 or 1, and disease recurrence or progression on at least one line of endocrine therapy, and no more than one previous endocrine therapy in the advanced setting. Patients were initially randomly assigned (1:1:1:1) to receive oral camizestrant once daily at 75 mg, 150 mg, or 300 mg (until the 300 mg group was closed), or fulvestrant intramuscularly at 500 mg (per label). Randomisation was managed through an interactive web-based system and stratified by previous treatment with CDK4/6 inhibitors and presence of liver and/or lung metastases. The primary objective was to determine clinical efficacy of camizestrant versus fulvestrant at each dose level using the primary endpoint of investigator-assessed progression-free survival, per Response Evaluation Criteria in Solid Tumours (version 1.1), assessed by intention to treat in all randomly assigned patients (full analysis set). No formal statistical comparison for the efficacy analysis of the camizestrant 300 mg dose versus fulvestrant was to be performed. Safety analyses included all randomly assigned patients who received at least one dose of study treatment. This study is registered with ClinicalTrials.gov, NCT04214288, and is ongoing. Between May 11, 2020, and Aug 10, 2021, 240 patients were randomly assigned to receive camizestrant 75 mg (n=74), 150 mg (n=73), 300 mg (n=20), or fulvestrant (n=73), and were included in the full analysis set. All patients received at least one dose of study drug. Median follow-up was 16·6 months (IQR 12·9-19·4) for the camizestrant 75 mg group, 16·3 months (12·9-18·3) for the camizestrant 150 mg group, and 14·7 months (12·7-20·1) for the fulvestrant 500 mg group. Median progression-free survival was 7·2 months (90% CI 3·7-10·9) with camizestrant 75 mg, 7·7 months (5·5-12·9) with camizestrant 150 mg, and 3·7 months (2·0-6·0) with fulvestrant. The hazard ratio for camizestrant 75 mg versus fulvestrant was 0·59 (90% CI 0·42-0·82; p=0·017), and the hazard ratio for camizestrant 150 mg versus fulvestrant was 0·64 (0·46-0·89; p=0·0090). Treatment-related adverse events occurred in 39 (53%) of 74 patients in the camizestrant 75 mg group, 49 (67%) of 73 patients in the camizestrant 150 mg group, 14 (70%) of 20 patients in the camizestrant 300 mg group, and 13 (18%) of 73 patients in the fulvestrant group. No single grade 3 or worse treatment-emergent adverse event occurred in more than two (3%) patients in any group. Serious treatment-emergent adverse events occurred in six (8%) patients in the camizestrant 75 mg group, seven (10%) patients in the camizestrant 150 mg group, two (10%) patients in the camizestrant 300 mg group, and four (5%) patients in the fulvestrant group. No treatment-related deaths occurred. Camizestrant at 75 and 150 mg showed a significant benefit in progression-free survival versus fulvestrant. These results support further development of camizestrant for the treatment of oestrogen receptor-positive, HER2-negative breast cancer. AstraZeneca.

P50 Systemic lupus erythematous presenting as Kikuchi-Fujimoto disease complicated with haemophagocytic lymphohistiocytosis: a case report and review of the literature

Abstract Introduction Kikuchi-Fujimoto disease (KFD) or histiocytic necrotising lymphadenitis is a rare, self-limiting inflammatory condition that can be associated with autoimmune connective tissue disorders (CTD) especially systemic lupus erythematosus (SLE). The aetiopathogenesis remains unclear but it is thought to be triggered by an infection in individuals with autoimmune predisposition leading to T-cells mediated apoptosis and inflammatory cascade. This condition most commonly affects children and young adults of Asian descent with a slight female preponderance although it can affect any age and ethnic groups. Cervical lymphadenopathy and fever are the salient manifestations, and it can be fatal if complicated with haemophagocytic lymphohistiocytosis (HLH). Case description A 16 year old girl presented with a 2-month history of persistent fever, progressive bilateral cervical lymphadenopathy, generalised maculopapular rash, angioedema-like facial swelling, oral ulcers and B symptoms. Laboratory investigations revealed pancytopaenia, profound acute phase response and abnormalities consistent with HLH with an HScore of 200 points. A thorough infectious workup was unrevealing apart from serological evidence of past Epstein-Barr virus (EBV) infection. ANA, anti-Sm, anti-RNP and anti-B2GP1 IgG were positive. An ultrasound of her neck showed bilateral multilevel cervical lymphadenopathy and the excision biopsy of her lymph node confirmed features of histiocytic necrotising lymphadenitis and ruled out lymphoma. Notably, there were scattered EBV-positive blasts and the special staining for mycobacteria was negative. A CT scan has also demonstrated bilateral axillary and abdominal lymphadenopathy with no hepatosplenomegaly. There was thrombosis in her right internal jugular vein with no intracranial or cardiac extension of the thrombus. The patient was admitted to ITU for close monitoring due to concerns about possible airway compromise but she did not require any respiratory support. She received intravenous (IV) methylprednisolone pulses for three consecutive days, mycophenolate mofetil, hydroxychloroquine and treatment dose of enoxaparin with good response and did not require IV immunoglobulins (IVIG) and/or interleukin-1 receptor antagonists. However, she subsequently developed an abscess in her neck which was complicated by Staphylococcus aureus bacteraemia and underwent an emergency incision and drainage of the abscess. She recovered well with IV antibiotics and was followed up in the CTD clinic with continuous psychological support from the rheumatology clinical nurse specialists. Discussion KFD most commonly presents with acute to subacute tender cervical lymphadenopathy and fevers which can be associated with other systemic features such as arthralgia, various cutaneous manifestations with great histologic heterogeneity, and neurological manifestations including aseptic meningitis, meningoencephalitis, acute cerebellar syndrome and optic neuritis. Generalised lymphadenopathy has been reported in 22% of cases but hepato- and/or splenomegaly is uncommon (3-5% of cases). Various infectious agents including the EBV have been implicated as the potential trigger of this condition but the evidence remains inconclusive. Our patient’s lymph node biopsy has demonstrated EBV-positive blasts with serological evidence of past EBV infection but a causal relationship between these findings and KFD cannot be established with certainty. It remains a diagnostic challenge to differentiate KFD from the other more sinister pathologies such as lymphoma, various infectious lymphadenitis and autoimmune conditions such as sarcoidosis and Kawasaki disease. Therefore, early excisional biopsy of the affected lymph nodes is essential for establishing the correct diagnosis and may obviate the need for inappropriate treatments. Both KFD and SLE share a complex clinicopathological relationship as SLE may precede, occur concurrently as in this case or develop later following the diagnosis of KFD. Moreover, lupus lymphadenitis can mimic KFD clinically and these two entities can only be distinguished histologically by the demonstration of haematoxylin bodies in lupus lymphadenitis. Our patient developed thrombosis in her right internal jugular vein which was thought to be secondary to the compressive effect from her cervical lymphadenopathy rather than due the antiphospholipid syndrome as her repeat antiphospholipid screen was negative. Key learning points • Clinicians should be aware of this rare clinical entity to make an early diagnosis and avoid unnecessary investigations. Differentiating KFD from the other sinister conditions such as lymphoma remains a diagnostic challenge therefore an early excisional biopsy of the affected lymph nodes would avoid delayed diagnosis and obviate the need for potentially risky treatments. Patients with KFD should be carefully screened and monitored for SLE as it can precede, occur in conjunction with or follow the diagnosis of SLE. Most cases of KFD resolve within 1-6 months although recurrence has been reported in 3-4% and the mortality rate is estimated to be 2.1%. It is crucial to follow up these patients given the increased risk of recurrence which can continue for many years. Despite having a good response to treatments, our patient suffered from significant alopecia and post-inflammatory hyperpigmentation in her skin which has had a great impact on her self-esteem and mental well-being. We would like to highlight in this case the biopsychosocial ramifications of this condition and demonstrate the importance of a multidisciplinary approach in the management of young people with CTD.

Study on Machine Learning-based Prediction of Lime Dosage for Mine Drainage Treatment

Study on Machine Learning-based Prediction of Lime Dosage for Mine Drainage Treatment

The influence of daily imaging and target margin reduction on secondary cancer risk in image-guided and adaptive proton therapy.

Image-guided and adaptive proton therapy rely on daily CBCT or CT imaging, which increases radiation dose and radiation-induced cancer risk. Online adaptation however also reduces setup uncertainty, and the additional risk might be compensated by reducing the setup robustness margin. 
This work developed a framework to investigate how much this robustness margin should be reduced to offset the secondary cancer risk from additional imaging dose and applied it to proton therapy for head-and-neck cancer. 

Approach:For five patients with head-and-neck cancer, voxel-wise CT and CBCT imaging doses were estimated with Monte Carlo radiation transport simulations, calibrated with air and PMMA phantom measurements. The total dose of several image-guided and adaptive treatments protocols was calculated by summing the planning CT dose, daily and weekly CBCT or CT dose, and therapy dose, robustly optimized with setup margins between 0 and 4 mm. These were compared to a reference protocol with 4 mm setup margin without daily imaging. All plans further used 3% range robustness. Organ-wise excess absolute risk (EAR) of cancer was calculated with three models to determine at which setup margin the total EAR of image-guided and adaptive treatment protocols was equal to the total EAR of the reference.

Results:The difference between the simulated and measured CT and CBCT doses was within 10%. Using the Monte Carlo models, we found that a 1 mm setup margin reduction was sufficient for most patients, treatment protocols, and cancer risk models to compensate the additional risk \imposed by daily and weekly imaging. For some protocols, even a smaller reduction sufficed, depending on the imaging frequency and type. The risk reduction by reducing the margin was mainly due to reducing the risk for carcinomas in the brain and, for some patients, the oral cavity.

Significance: Our framework allows to compare an increased imaging dose with the reduced treatment dose from margin reductions in terms of radiation-induced cancer risk. It is extendable to different treatment sites, modalities, and imaging protocols, in clinic-specific or even patient-specific assessments.

The Effect of Different Antenatal Betamethasone Regimens on Neonatal Outcomes

Objective: Preterm births sometimes occur before the completion of antenatal steroid therapy. Some specialists recommend administering betamethasone at 12-h intervals when birth is expected to occur quickly. The purpose of this study was to compare neonatal outcomes in pregnancies in which betamethasone was administered at 12-or 24-h intervals. Material and Methods: Neonates born at <34 gestational weeks were included in this retrospective study. They were assigned to groups based on antenatal betamethasone therapy: those receiving no steroid, a single dose, and two doses at 12 or 24-h intervals. Results: Six hundred forty-four babies were enrolled including 536 Turkish and 108 refugee pregnant women. The antenatal steroid treatment rate was lower in the refugee group (p<0.05), while 12-h interval treatment was similar between Turkish and refugee groups. Intubation at birth among no steroid, a single dose and two-dose treatment groups (12- or 24-h) were 53/136 (38.9%), 62/222 (28%), and 65/286 (22.7%), and mortality rates were 34/136 (27.9%), 48/222 (21.6%), and 50/286 (17.5%), respectively (p<0.05). Thirty-six (n: 286) of the patients received two doses of betamethasone as 12-h intervals (n:36) and 24-h intervals (n:250). Times elapsing from first betamethasone administration to birth in the 12 and 24-h groups were 22 h and 92 h, respectively (p<0,001). Median gestational week and birth weight were lower in the 24-h interval group than 12-h interval group (29 and 30 weeks, p=0.007; 1190 and 1362 g, p=0.015, respectively). Conclusion: Antenatal betamethasone administered at 12-h intervals may be a suitable option when preterm birth is expected within 24 hours. This regimen is associated with better neonatal outcomes, including lower intubation and mortality rates, as well as higher gestational age and birth weight, compared to the 24-h interval group.

Integrating Organ-on-Chip Models In Drug Discovery: A Comprehensive Review on Innovations and Implications

This review article examines the current developments in applying microfluidic technologies in cancer therapy and personalized medicine. This includes the fabrication of cancer cells onto the microfluidic chips, preclinical cancer model simulation development, biomarker detection, tumor heterogeneity detection, integration of microfluidics in robotic drug delivery systems, Artificial Intelligence (AI), and discuss the use of techniques such as Machine Learning (ML) to predict pharmacokinetics and pharmacodynamics of cancer cells. This review article also highlights how integrating cancer models with microfluidic devices helps to simulate disease progression more accurately, thereby improving treatment options. These devices also enable researchers to identify suitable doses for cancer treatment. Moreover, microfluidics chips facilitate cell transformation in many types of cancer, which is important for patient-specific therapy. Microfluidics technology in robotic drug delivery enables precise delivery of targeted drugs, thus reducing the potential side effects of the drugs. Integrating these fields into the medical and pharmaceutical fields helps researchers to develop the pharmaceutical product faster than the traditional method of drug discovery. Overall, this review article highlights the integration of interdisciplinary technologies in the healthcare field, which may decrease the timeline of drug discovery and provide efficient drugs to patients.

Oxygen enriched PAni-based counter electrode network toward efficient dye-sensitized solar cells (DSSCs)

Dye-sensitized solar cells (DSSCs) have great potential as a renewable energy technology assisting combat climate change due to its low cost, adaptability, and sustainability. Oxygen plasma ion doping is a promising strategy to improve the capacity of a low-cost, platinum-free counter-electrodes (CEs) to absorb photons and drive high-performance DSSCs via generating an abundance of active absorption sites. In this instance, novel PAni–ZnO (PZ) composite layers were designed as a CE material and received various in-situ oxygen plasma dosages, including 0, 2, 4, 6, 8, and 10 min, to improve their physiochemical and microstructural feature for the first time, to the best of our knowledge. Physical evaluations of the microstructure, porosity, morphology, contact angle, roughness, electrical, and optical, electrochemical impedance spectroscopy (EIS) features of CEs were conducted in along with an evaluation of J–V variables. Compared to pristine CE substance, the surface nature of the modified hybrids was gradually enhanced as the plasma level rose, reaching an optimum after 8 min (i.e. 0.2 µm for average pore size and average roughness Ra = 7.21 µm). Expanded plasma treatment doses also improved PV cell performance even further: after 4 min at a plasma level, η = 5.41% was obtained, and after 6 min in a oxygen plasma environment, η = 5.81% was obtained. Mixing high energetic plasma ions increased the mobility of charge carriers in PAni composites along with lowered charge carrier recombination through generating an environment that was conducive to charge dissociation. Therefore, longer lifespans and more effective charge transfer inside the photovoltaic cell as a consequence of the increased mobility less resistive losses. In this respect, following 8 min of plasma surface modification of the PZ CE, the optimized efficiency of 6.31% and Jsc of 15.6 mA/cm2 were obtained. The improvement in efficiency equated to a proportion growth of 77% versus a pristine one. This gain was explained by the reality that suffusing a quantity of oxygen plasma free radicals into the PAni system developed continuous channels that enabled the mixture to move electrons more rapidly, hence raising the photovoltaic efficiency. Overall, this study highlights the advantages of regulating heteroatom species and their co-doping, offering a new perspective for the application of heteroatom-doped CE in DSSCs.

Lyme disease in UK primary care: a knowledge, attitude and practice survey.

Lyme disease (LD) cases in the UK most commonly present within the primary care setting. Despite an upward trend of incidence, little is known regarding general practitioner (GP) experience with diagnosis and treatment. This study aims to describe baseline primary care clinician Knowledge, Attitude and Practice (KAP) in Scotland and England. Online KAP survey on Lyme disease for UK based practising GPs. An online KAP questionnaire was developed for use in UK primary care. The survey was distributed through UK based research networks, professional societies and via social media. 191 complete responses were analysed (England n=130, Scotland n=61). The Scotland-based respondent group had more relevant consultations in the previous 3 years. Respondents from Scotland demonstrated a greater awareness that erythema migrans (EM) is pathognomonic for Lyme disease and that serological testing of this patient group is not indicated. Less common cardiac and neurological symptoms were not as well associated with Lyme disease by both respondent groups for the former and England-based respondents for the latter. Prescribing according to the National institute for Health and Care Excellence (NICE) guidance was identified in 70% of Scotland and 42% of England-based GP responses. Targeted resources may improve clinician confidence on exposure risk, symptom recognition, testing limitations and treatment dose and duration. Scotland-based respondents' better survey performance potentially reflects greater clinical exposure and public awareness of the disease, due to high endemicity within the nation.

Colchicine prevents post-ablation atrial fibrillation recurrence: a systematic review and meta-analysis

Abstract Background Catheter ablation for atrial fibrillation (AF) is a commonly performed procedure with appreciable effectiveness; however, post-AF ablation recurrence is often observed. The pathophysiology behind this recurrence is often inflammation and oxidative stress triggered during the ablation procedure. Colchicine is a potent anti-inflammatory agent that has emerged as a promising therapeutic for preventing post-ablation AF recurrence; however, the data available on its efficacy are limited. Purpose This meta-analysis aimed to investigate the outcomes of post-ablation AF patients who received colchicine in the postoperative period. Methods A comprehensive literature search spanning major bibliographic databases was conducted to retrieve studies comparing outcomes in post-ablation AF patients who received colchicine versus those who did not. The outcomes of interest included AF recurrence, pericarditis, gastrointestinal side effects, and hospitalization. AF recurrence was determined with a 12-lead electrocardiogram and/or Holter monitoring. Odds ratios (ORs) and the corresponding 95% confidence intervals (CIs) were pooled from all studies using the DerSimonian and Laird random-effects model. Statistical significance was set at p ≤ 0.05. Results Six studies were included with 1791 patients (721 in the colchicine group and 1070 in the placebo group). Patients who received colchicine had significantly lower odds of AF recurrence on follow-up [OR: 0.62; 95% CI: 0.48, 0.79; p=0.0001] but had higher gastrointestinal side effects [OR: 2.67; 95% CI: 1.00, 7.12; p=0.05]. There were no statistically significant differences in acute pericarditis [OR: 0.54; 95% CI: 0.27, 1.05; p=0.07] or hospitalization [OR: 1.03; 95% CI: 0.73, 1.45; p=0.87]. Conclusion Prophylactic use of colchicine after catheter ablation in patients with AF leads to a reduction in AF recurrence, albeit with increased gastrointestinal side effects such as diarrhea and nausea. Colchicine use did not lead to a reduction in the rates of pericarditis and hospitalization after ablation. Large randomized controlled trials are necessary to evaluate the efficacy of colchicine in the prevention of AF recurrence, particularly focusing on the dose and duration of treatment to optimize the side effect profile.

Treatment approaches and survival outcomes in elderly colorectal cancer patients: a single-center comparative study.

Geriatric patients account for nearly half of new colorectal cancer (CRC) cases. This study compares clinicopathological features, treatments, outcomes, and frailty in elderly (≥ 70) and younger (< 70) CRC patients at our center. Patients diagnosed with non-metastatic or de novo metastatic CRC between January 2015 and April 2024 were included. Demographic, pathological, and survival data were retrospectively collected. Analyses were performed using SPSS version 25, with statistical significance set at P < 0.05. Of the 414 non-metastatic CRC patients, 26.6% were aged ≥ 70. Elderly patients received less perioperative chemotherapy (60% vs. 81.6%, P < 0.001) and had more dose reductions (41.6% vs. 19.2%, P < 0.001). Frailty reduced perioperative chemotherapy in elderly non-metastatic patients (54.5% vs. 92.1%, P < 0.001) but did not affect dose reduction (37.9% vs. 33.3%, P = 0.764) or treatment duration (median 24weeks for both groups, P = 0.909). In metastatic patients, frailty shortened chemotherapy duration (9.5 vs. 15.5weeks, P = 0.129). Elderly patients had lower 5- and 8-year overall survival (OS) rates (64.7%, 60.1% vs. 83.0%, 78.8%, P = 0.004). In the de novo metastatic cohort (135 patients), age did not affect OS (19.4 vs. 17.3months, P = 0.590) or PFS (9.8 vs. 7.5months, P = 0.209). Rectal cancer (HR: 2.751, P = 0.005) and early chemotherapy termination (HR: 4.138, P < 0.001) worsened OS in non-metastatic CRC, while absence of RAS (HR: 2.043, P = 0.047), BRAF mutations (HR: 8.263, P = 0.010), and metastasectomy (HR: 3.650, P = 0.036) improved OS in metastatic CRC. Age does not independently worsen CRC survival, though early chemotherapy discontinuation impacts outcomes. Reduced-dose chemotherapy or monotherapy can help minimize adverse effects in elderly patients.

First-line sunitinib treatment modification in patients with mRCC: nationwide analysis of the Swedish population.

Aim: Assess first-line sunitinib dosing for treatment of metastatic renal cell carcinoma in Swedish clinical practice (2006-2019).Materials & methods: Retrospective analysis of three sunitinib dosing regimens: 2-weeks on, 1-week off (2:1 Start); standard 4-weeks on, 2-weeks off (4:2) and 4:2 start with switch to 2:1 (2:1 Switch).Results: Time-to-treatment discontinuation (95% CI) differed significantly (p<0.001): 6.2 (5.6-7.2), 13.9 (8.1-20.6)and 4.6 (4.3-5.6) months for 2:1 Start (n=320), 2:1 Switch (n=71)and 4:2 (n=704), respectively. Overall survival (95% CI) differed significantly (p<0.001): 21.8 (18.1-26.1), 32.2 (25.1-48.3)and 13.5 (12.3-15.8) months for 2:1 Start (n=320), 2:1 Switch (n=71)and 4:2 (n=704), respectively.Conclusion: Alternative dosing does not compromise clinical efficacy and may provide advantages in terms of improved treatment outcomes. However, due to the changing treatment patterns during this long-term study, and the absence of patient risk category data, caution is required when interpreting the main outcomes.

Nanoplatforms for Magnetic-Photo-Heating of Thermo-Resistant Tumor Cells: Singular Synergic Therapeutic Effects at Mild Temperature.

A self-assemble amphiphilic diblock copolymer that can incorporate iron oxide nanocubes (IONCs) in chain-like assemblies as heat mediators for magnetic hyperthermia (MHT) and tuneable amounts of IR780 dye as agent for photothermal therapy (PTT) is developed. MHT-heating performance of photobeads in viscous media have the same heat performances in water at magnetic field conditions of clinical use. Thanks to IR780, the photobeads are activated by infrared laser light within the first biological window (808nm) with a significant enhancement of photo-stability of IR780 enabling the raise of the temperature at therapeutic values during multiple PTT cycles and showing unchanged optical features up to 8 days. Moreover, the photobeads fluorescent signal is preserved once internalized by glioblastoma multiforme (GBM) cells. Peculiarly, the photobeads are used as toxic agents to eradicate thermo-resistant GBM cells at mild heat, as low as 41°C, with MHT and PTT both of clinical use. Indeed, a high U87 GBM cell mortality percentage is obtained only with dual MHT/PTT while each single treatment dose not provide the same cytotoxic effects. Only for the combined treatment, the cell death mechanism is assigned to clear sign of apoptosis as observed by structural/morphological cell studies and enhanced lysosome permeability.

Pemphigus relapse: Mechanisms, risk factors, and agents associated with disease recurrence.

Pemphigus represents a spectrum of potentially life-threatening autoimmune-mediated skin blistering conditions caused by antibody production against desmoglein 1 and 3 (anti-DSG 1 and 3) in keratinocytes. Greater than 50% of pemphigus patients experience relapse, which complicates long-term medical management, including risks associated with re-treatment and complications such as infection and dehydration. This review aims to elucidate mechanisms, risk factors, and medications associated with pemphigus relapse. Mechanisms of relapse include the persistence of auto-reactive B-cell populations post-treatment and CD20- B-cell populations that reactivate after B-cell depletion therapy. Risk factors for relapse include high body surface area (BSA) of pemphigus involvement, high body mass index, high severity according to the Pemphigus Disease Area Index (PDAI) at onset, treatment delay, and high anti-DSG1 and DSG3 titers post-treatment. Targeted B-cell localization is associated with better clinical outcomes, including less frequent relapses. Rituximab is currently the gold standard of treatment for moderate-severe pemphigus and has relapse rates of 11%-44% in selected studies, with a mean time to relapse of 5.8 months to 36 months following treatment. Relapse rates across lymphoma dosing (375 mg/m2) versus rheumatoid arthritis dosing (1 g dosing weekly) was inconsistent; however, more frequent dosing, earlier treatment, and higher cumulative dosing were associated with lower relapse rates. Alternative agents that have clinical efficacy include corticosteroid monotherapy, mycophenolate mofetil, azathioprine, and intravenous immunoglobulin. Future studies should include head-to-head comparators over long follow-up periods to identify the best treatment agents associated with the least relapse risk.

Effect of Various Nitrogen Doses and Plant Growth Regulators on Nutrient Uptake and Productivity of Wheat (Triticum aestivum L)

A field experiment was conducted at Research Farm of Bihar Agricultural University, Sabour, Bhagalpur, Bihar, during season of 2019-20, to find out the effect of optimization of nitrogen doses for high yield potential of wheat with plant growth regulators. The experiment was laid out in randomized block and replicated thrice. The experiment ten treatment of different doses of fertilizer with plant growth regulators chlormequat chloride and tebuconazole applied at 0.2% and 0.1% respectively. Experimental revealed that application of 150% recommended doses of NPK resulted significantly higher available nitrogen (171.82 kg ha-1), available phosphorus (27.01 kg ha-1) and available potassium (192.27 kg ha-1) in soil after the harvest of wheat significantly highest nitrogen, phosphorus and potassium uptake by wheat recorded with 150% RDF of NPK with chlormequat chloride (0.2%) and tebuconazole (0.1%). Significantly highest grain and straw yield recorded with 150% NPK + chlormequat chloride (0.2%) and tebuconazole (0.1%) at par with 100% RDF as compare to other treatments harvest index was recorded 125% RDF of N and chlormequat chloride (0.2%) and tebuconazole (0.1%) and 150% RDF of N and chlormequat chloride (0.2%) and tebuconazole (0.1%). The uptake of key nutrients, nitrogen, phosphorus and potassium followed a similar pattern, with 150% recommended doses of NPK along chlormequat chloride (0.2%) and tebuconazole (0.1%). optimal NPK application resulted in positive nutrient balance in the soil. This investigation that managing nutrient with growth regulator in wheat is an economically viable and ecologically sound approach to improve both crop production and soil health through balanced nutrition.

Azacitidine in combination with shortened venetoclax treatment cycles in patients with acute myeloid leukemia.

The combination of venetoclax with hypomethylating agents is currently the standard of care for elderly patients with acute myeloid leukemia (AML) ineligible for intensive chemotherapy. Despite its favorable efficacy, clinical use is often associated with post-remission cytopenia, frequently necessitating treatment delays and dose modifications. This study aims to evaluate the efficacy and safety of shortened venetoclax treatment durations. A multicenter analysis was conducted involving 20 adult AML patients receiving venetoclax (7 or 14 days with 9 and 11 patients, respectively) combined with 5-azacitidine (5-7 days) between 2021 and 2024. The cohort included patients from four German academic centers all treated in first line. Outcome measures included bone marrow response, transfusion dependence, overall survival (OS) and progression-free survival (PFS). Median age was 73.5 years, with 70% of patients having secondary AML. Adverse molecular risk was observed in 75% of patients. The overall response rate (ORR) was 100%, with a composite complete remission rate of 78%. No significant differences in response rates were observed between the 7-day and 14-day venetoclax regimens. Median OS for the cohort was 15 months. Infection-related complications were observed in 55% of patients, with severe sepsis in 20% of cases. In this cohort, shortened venetoclax regimens demonstrated efficacy comparable to standard treatment protocols, with a potential reduction in hematologic toxicity. These findings support the individualization of treatment regimens to optimize clinical outcomes while potentially minimizing adverse effects.

The Effect of Different Doses of Nitrogen and Seed Treatment with Biofertilizers on Growth, Yield and Seed Quality of Sunflower (Helianthus annus L.)

Aims: To study the effect of Different Doses of Nitrogen and Seed Treatment with Biofertilizers on Growth, Yield and Seed Quality of Sunflower. Study Design: The experiment was laid out in a randomized block design with eleven treatments replicated thrice. Place and Duration of Study: The field experiment was conducted during rabi season of 2019-20, 2020-21, 2021-22 and 2022-2023 in the Instructional Farm of Ramkrishna Ashram Krishi Vigyan Kendra, Nimpith, South 24 Parganas, West Bengal. Methodology: The experiment was carried out in randomized block design with eleven treatments and replicated thrice. The treatments were Control, 50% N, 100% N (90 kg N/ha), Azospirillum (seed treatment), Azatobacter (seed treatment), Azospirillum +Azatobacter (seed treatment), 50% N + Azospirillum (seed treatment), 50% N + Azatobacter (seed treatment), 50% N +Azospirillum + Azatobacter (seed treatment), 75% N + Azospirillum + Azatobacter (seed treatment) and 100% N + Azospirillum + Azatobacter (seed treatment). A common dose of Nitrogen@ 90kg/ha, phosphorus @90kg/ha and potash @40kg/ha were applied. Results: Higher head diameter (13.82 cm), 1000 seed weight (65.50 g), seed yield (1830 kg/ha), oil yield (628.80 kg/ha), gross return (Rs.48581), net return (Rs.26368) and B:C (2.19) than all other treatment followed by T10 (75% N + Azospirillum + Azotobacter) and T3 (100% N) which were statistically at par with each other. Conclusion: On the basis of all parameter as well as economics it can be concluded that treatment T10 (75% N + Azospirillum + Azotobacter) can be recommended for better benefit and sustainable production of sunflower. The results of this experiment showed that use of chemical fertilizers can be reduced by using a combination of bio-fertilizers and inorganic nitrogen fertilizer.