Median Dose Research Articles

Risk of Cardiovascular Disease in Patients With Classical Hodgkin Lymphoma: A Danish Nationwide Register-Based Cohort Study.

Risk of cardiovascular disease (CVD) in patients with classical Hodgkin lymphoma (cHL) undergoing contemporary treatment is unclear. cHL patients ≥ 18 years at diagnosis treated with doxorubicin-containing chemotherapy between 2000 and 2022 were matched 1:5 with comparators on birth year, sex, and Charlson Comorbidity Index at time of matching (score of 0 or ≥ 1). Cause-specific cumulative incidence of a composite of CVDs with corresponding 95% confidence intervals (CIs) were computed with death and lymphoma relapse as competing events (i.e., by censoring individuals at such occurrences) using the Aalen-Johansen estimator. A total of 1905 patients and 9525 comparators with a median follow-up of 10 years (interquartile range, [IQR]: 5.9-17.4). Median age was 39 years (IQR: 27-56), median cumulative doxorubicin dose was 250 mg/m2 (IQR: 200-300). The CVD cumulative incidences were 4.7% (95% CI: 3.6-5.7) for patients versus 2.6% (95% CI: 2.3-2.9) for comparators at 5 years, 8.9% (95% CI: 7.2-10.5) versus 5.5% (95% CI: 4.9-6.0) at 10 years, and 17.0% (95% CI: 14.1-19.9) versus 8.2% (95% CI: 7.4-9.0) at 15 years. CVD remains a substantial effect after contemporary treatment for cHL, suggesting that awareness of symptoms and a low threshold for referral to diagnostic examination are still important measures during survivorship.

Once-a-Week Ablative Radiotherapy as Replacement of Prolonged Fractionation in Frail Patients: Feasibility and Toxicity Results.

The aim of this work was to explore the use of an original once-weekly radiotherapy fractionation in elderly or frail patients with recurrence or metastasis from different solid malignancies. A retrospective analysis was conducted on 29 patients treated from 2011 to 2019 with a once-weekly radiotherapy schedule. Patients received a median dose of 27.5 Gy, with weekly fractions of 4-5 Gy over 7-10 weeks. The treatment aimed at both palliative and cytoreductive objectives. Primary endpoints were feasibility and compliance, secondary outcome was acute toxicity. All patients completed the planned radiotherapy without interruptions. Acute toxicity was mild, with only one patient developing grade 3 toxicity (bowel perforation). Three months post-treatment, 74% of patients experienced symptom relief and tumor response. One-year local control rates were 26.7%, and treatment was generally well-tolerated. This once-weekly hypofractionated radiotherapy regimen demonstrated feasibility, good tolerance, and promising tumor response in frail and elderly patients. Although limited by a small sample size, the approach offers a practical alternative for patients unable to undergo conventional daily radiotherapy. Further studies on larger cohorts are required to validate these findings.

Therapeutic drug monitoring of posaconazole delayed-release tablets and injections in pediatric patients.

This study aimed to investigate the dose and trough concentration (Cmin) of posaconazole delayed-release tablets and injections, and their correlation with efficacy and safety in pediatric patients. Patients younger than 18 years old received posaconazole delayed-release tablets or injections for prophylaxis or treatment of invasive fungal disease (IFD). Blood samples were collected to determine the plasma Cmins, and dose regimen adjustments were made if necessary. Clinical data were collected. A total of 210 Cmins of 113 pediatric patients were detected. The median Cmins were 1.0 and 1.3 mg/L for tablets and injections, respectively (P < 0.05). The median doses required to achieve the target Cmin were about 6.0 mg/kg of body weight/day, and no statistical difference was observed between different age groups, formulations, or indications (P > 0.05). Concomitant treatment of tacrolimus and diarrhea were found to affect Cmins of tablets, while age, gender, and BMI were found to be correlated with Cmins of injections. IFD breakthrough occurred in 9.2% of patients with a median Cmins of 0.74 mg/L for prophylaxis, and infection progression occurred in 43.2% of patients with a median Cmins of 0.97 mg/L for treatment, respectively. Transaminitis was the most common adverse event. Posaconazole delayed-release tablets and injections are safe for prophylaxis and treatment of IFD in pediatric patients. An empirical initial dose of 6.0 mg/kg of body weight/day is appropriate for prophylaxis, while a higher dose should be required for the treatment of IFD. It is necessary to adjust the dose regimen according to the results of therapeutic drug monitoring.This study is registered with chictr.gov.cn under identifier ChiCTR2300070008.

The Validity of Impressions as a Media Dose Metric in a Tobacco Public Education Campaign Evaluation: Observational Study.

Evaluation research increasingly needs alternatives to target or gross rating points to comprehensively measure total exposure to modern multichannel public education campaigns that use multiple channels, including TV, radio, digital video, and paid social media, among others. Ratings data typically only capture delivery of broadcast media (TV and radio) and excludes other channels. Studies are needed to validate objective cross-channel metrics such as impressions against self-reported exposure to campaign messages. This study aimed to examine whether higher a volume of total media campaign impressions is predictive of individual-level self-reported campaign exposure in California. We analyzed over 3 years of advertisement impressions from the California Tobacco Prevention Program's statewide tobacco education campaigns from August 2019 through December 2022. Impressions data varied across designated market areas (DMAs) and across time. These data were merged to individual respondents from 45 waves of panel survey data of Californians aged 18-55 years (N=151,649). Impressions were merged to respondents based on respondents' DMAs and time of survey completion. We used logistic regression to estimate the odds of respondents' campaign recall as a function of cumulative and past 3-month impressions delivered to each respondent's DMA. Cumulative impressions were positively and significantly associated with recall of each of the Flavors Hook Kids (odds ratio [OR] 1.15, P<.001), Dark Balloons and Apartment (OR 1.20, P<.001), We Are Not Profit (OR 1.36, P<.001), Tell Your Story (E-cigarette, or Vaping, product use Associated Lung Injury; OR 1.06, P<.05), and Thrown Away and Little Big Lies (OR 1.05, P<.01) campaigns. Impressions delivered in the past 3 months were associated with recall of the Flavors Hook Kids (OR 1.13, P<.001), Dark Balloons and Apartment (OR 1.08, P<.001), We Are Not Profit (OR 1.14, P<.001), and Thrown Away and Little Big Lies (OR 1.04, P<.001) campaigns. Past 3-month impressions were not significantly associated with Tell Your Story campaign recall. Overall, magnitudes of these associations were greater for cumulative impressions. We visualize recall based on postestimation predicted values from our multivariate logistic regression models. Variation in cumulative impressions for California Tobacco Prevention Program's long-term multichannel tobacco education campaign is predictive of increased self-reported campaign recall, suggesting that impressions may be a valid proxy for potential campaign exposure. The use of impressions for purposes of evaluating public education campaigns may help address current methodological limitations arising from the fragmented nature of modern multichannel media campaigns.

Treatment satisfaction and effectiveness of Lurasidone on quality of life and functioning in adult patients with schizophrenia in the real-world Italian clinical practice: a prospective 3-month observational study.

Although second-generation antipsychotics (SGAs) have proven to be effective therapeutic options for patients with schizophrenia, there is a notable lack of evidence on patients' subjective perspectives regarding their well-being, quality of life, and satisfaction with these medications. This study aimed to evaluate the treatment satisfaction and effectiveness of lurasidone on quality of life and functioning in adult patients with schizophrenia in real-world Italian clinical practice. This was a multicentre, national, non-interventional, single-arm, 3-month prospective study. Patients who were naive to lurasidone treatment and whose treating physician had decided to start them on this medication were enrolled and evaluated over a 3-month period. Eligible patients were adults (≥ 18 years of age) with a primary diagnosis of schizophrenia who were being treated with lurasidone (for the first time [i.e., they were lurasidone naive]) as part of routine clinical practice. Efficacy endpoints were changes in patient/caregiver treatment satisfaction (seven-point Likert scale from the Treatment Satisfaction Questionnaire for Medication), patient quality of life and functioning (QLS), investigator-rated global assessment of functioning (CGI-S, IAQ) after 6 weeks and 3 months of lurasidone, and number of relapses and hospitalizations. Sixty-one patients were enrolled and 59 completed the study. The median dosage of lurasidone at baseline was 37.00mg/day. The median duration of titration was 86.0 days (Min 28; Max 115 days); the median number of dosage changes was 1.0. At the end of 3-month observation period, the median dose of lurasidone was 74.00mg/day. QoL and Functioning Score showed a trend of improvement over time, reaching a mean change from baseline of 9.8 at the end of the study. According to the CGI-S, the percentage of patients who were "markedly or severely ill" showed a continuous decrease from baseline to 3 months, from 62.29% to 8.20%. Patient satisfaction increased over time, with 80.32% of patients reporting that they were somewhat, fairly, or very satisfied (including 63.93% who were completely or very satisfied) at the end of the study. No relapses/hospitalizations for psychiatric reasons were reported. Lurasidone was well tolerated with no safety concerns or discontinuations due to AEs. Lurasidone represents a valid option for the treatment of schizophrenia and positively affects subjective well-being, quality of life and satisfaction. NCT06527885 retrospectively registered (01/08/2024).

Benefits of combining SGLT2 inhibitors and pioglitazone on risk of MASH in type 2 diabetes-A real-world study.

Both pioglitazone and glucagon-like peptide 1 receptor agonists (GLP1RA) alone improve metabolic dysfunction-associated steatohepatitis (MASH) in randomized clinical trials, whereas preclinical studies suggested MASH benefits with sodium glucose co-transporter 2 inhibitors (SGLT2i). In the real world, patients with type 2 diabetes often require multiple agents for glycaemic control. Here, we investigated the benefits of combining these agents on risks of MASH. Longitudinal changes in FibroScan-aspartate aminotransferase (FAST) score were measured in 888 patients with type 2 diabetes. Use of pioglitazone, GLP1RA and/or SGLT2i was defined as continuous prescriptions of ≥180 days prior to their last reassessment FibroScan. Multivariable logistic regression analysis was conducted to evaluate the associations between use of these agents and FAST score changes. Over a median follow-up of 3.9 years, the increasing number of these agents used was significantly associated with more reductions in FAST score (p for trend <0.01). Dual combination was independently associated with a higher likelihood of achieving low FAST score at reassessment than single use of any of these agents (odds ratio [OR] 2.84, p = 0.01). Among the different drug combinations, using SGLT2i and pioglitazone (median dose 15 mg daily) together, as compared to not using any of these three agents, was associated with a higher likelihood of both low FAST score at reassessment (OR 6.51, p = 0.008) and FAST score regression (OR 12.52, p = 0.009), after adjusting for changes in glycaemic control and body weight during the study. Combining SGLT2i and pioglitazone is a potentially useful strategy to ameliorate 'at-risk' MASH in patients with type 2 diabetes.

Evaluation of Crushed Posaconazole Delayed Release Tablets in Lung Transplant Recipients.

Invasive fungal infections can cause serious complications after lung transplant; therefore, prophylaxis with posaconazole is common. The posaconazole delayed-release (DR) tablet is preferred. Although the package insert states DR tablets cannot be crushed, recent data suggest it is reasonable. We hypothesized that crushed posaconazole DR tablets could reach therapeutic levels in lung transplant recipients. A retrospective study of lung transplant recipients between January 2018 and July 2023, who received crushed posaconazole DR for at least 5 days was completed. Posaconazole troughs were evaluated, and differences were compared between subjects who were therapeutic to those who were subtherapeutic. A cost analysis was also performed. Thirty subjects received crushed posaconazole DR and 50% were therapeutic. The median trough was 1mg/L for those who were therapeutic and 0.4mg/L for those who were not (p < 0.001). The median cumulative dose was 2000mg, and there were no significant differences in the incidence of diarrhea or tube feeds. More subjects in the therapeutic group were loaded (33%vs. 13%), although this was not statistically significant (p = 0.39). No subjects had breakthrough aspergillus one month after starting crushed therapy. Crushed posaconazole DR tablets are a viable and cost savings option, but loading doses and higher maintenance doses may be required to reach therapeutic levels. Those who received loading doses (intravenously or crushed) followed by a daily crushed dose of 400mg were more likely to be therapeutic. Limitations of our study include that it is single-center, small in sample size, and retrospective.

Initial feasibility cohort of temporally modulated pulsed proton re-irradiation (TMPPR) for recurrent high-grade intracranial malignancies

Recurrent high-grade intracranial malignancies have a grim prognosis and uniform management guidelines are lacking. Re-irradiation is underused due to concerns about irreversible side effects. Pulsed-reduced dose rate radiotherapy (PRDR) aims to reduce toxicity while improving tumor control by exploiting dose-rate effects. We share our initial experience with temporally modulated pulsed proton re-irradiation (TMPPR), focusing on workflow, safety, feasibility, and outcomes for the first patient cohort. TMPPR was administered to patients with recurrent or progressive central nervous system malignancies using intensity modulated proton therapy with three fields. Patient and treatment data were collected, responses categorized using RANO assessment, and toxicities graded using CTCAE v5.0. Five patients received TMPPR between October 2022 and May 2023, with a median age of 54 years (Range: 32–72), and a median time from initial radiotherapy to re-RT of 23 months (Range 14–40). Treatment was completed without delay, with a median dose of 60 GyRBE in 30 fractions. Initial treatment response assessment showed complete (n = 1) or partial (n = 3) responses. Limited toxicity was observed, primarily grade 2 alopecia and one case of radiation necrosis graded at 2. This early experience demonstrates the feasibility of TMPPR delivery, highlighting the importance of prospective evaluations in the re-irradiation setting.

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.

Build-a-Bio-Strip: An Online Platform for Rapid Toxicity Assessment in Chemical Synthesis.

The increasing need to understand and control the environmental impact of chemical processes has revealed the challenge in efficient evaluation of toxicity of the vast number of chemical compounds and their varying effects on biological systems. In this study, we introduce "Build-a-bio-Strip", a novel online service designed to carry out a quick initial analysis of the toxic impact of chemical processes. This platform enables users to automatically generate toxicity characteristics of chemical reactions using their own data on cytotoxicity or median lethal doses of the substances involved or computational predictions based on SMILES strings. The service calculates the toxicity metrics such as bio-Factors and cytotoxicity potentials, which can be used to identify the substances with significant contributions to the overall toxicity of a particular process. This facilitates the selection of safer synthetic routes and the optimization of chemical processes from a toxicity perspective. "Build-a-bio-Strip" represents a step toward safer and more sustainable chemical practices. It is available free-of-charge at http://app.ananikovlab.ai:8080/.

Time to Next Treatment Following Sub-Ablative Progression Directed Radiation Therapy for Oligoprogressive Non-Small-Cell Lung Cancer

We aimed to evaluate whether progression-directed radiation therapy (PDRT) can prolong the initiation of a subsequent systemic therapy regimen in a cohort of patients with oligoprogressive NSCLC. A retrospective analysis was conducted on NSCLC patients who underwent PDRT for extracranial oligoprogressive NSCLC, defined as limited (up to five) progressing lesions following initial complete, partial, or stable response to systemic therapy according to REC1ST 1.1 and/or PERCIST 1.0 criteria. Cox proportional hazard regressions were performed to identify factors influencing time to next treatment (TTNT), which was considered the primary endpoint. Forty patients were analyzed. First, second, and ≥3 lines of systemic therapy were administered in 22 (58.2%), 14 (27.2%), and 4 (14.6%) cases, respectively. The median total dose was 36 Gy (range: 12–60) in five fractions (1–10), with a median biological effective dose for tumor control (BED10) of 52 Gy (26.4–151.2). After a median follow-up of 11 months (2–50), PDRT delayed further systemic therapy in 32 (80.0%) treatments. Median TTNT was not reached at 8 months (1–47) with a one-year Kaplan–Meier estimate of 81.4% (95% CI: 75.0% to 87.8%). No &gt;grade 3 adverse event was observed. On multivariate analysis, patients with ≥3 lines of systemic therapy and/or with larger CTV volumes did not benefit from PDRT. Despite the use of sub-ablative doses, our findings show that PDRT represents an effective, safe, and viable option for oligoprogressive NSCLC. Patients irradiated early during their systemic treatment course, with a low volume of disease and nonmetastatic oligoprogression, could derive substantial benefits from PDRT.

Cribriform Pattern Is a Predictive Factor of PSA Recurrence in Patients Receiving Radiotherapy After Prostatectomy.

In prostate cancer, robotic total prostatectomy is a popular treatment modality. However, prostate-specific antigen (PSA) recurrence after prostate cancer surgery remains a concern. Salvage radiotherapy is commonly used to treat PSA recurrence, but the recurrence rate after salvage radiotherapy is high, highlighting the need for better predictive markers. This study aimed to retrospectively evaluate the association between cribriform pattern and PSA recurrence in patients receiving radiotherapy after radical prostatectomy. Data of 50 patients who underwent radiotherapy after total prostatectomy between January 2010 and May 2020 were retrospectively evaluated. The median age was 67 years. Among these patients, two cases involved postoperative irradiation, while 48 cases involved salvage irradiation after postoperative PSA recurrence. The median time from surgery to PSA recurrence was 38.3 months. The median radiation dose was 64 Gy in 32 fractions. Three-dimensional conformal radiation therapy was administered in 38 cases and intensity-modulated radiation therapy was used in 12 cases. Combined hormone therapy was administered in 21 cases. PSA levels were measured every 3 months after treatment. Statistical analysis between groups was performed by a t-test. The median follow-up period after radiotherapy was 31 months. No local recurrences were observed at the prostate bed, and no deaths related to prostate cancer were recorded during follow-up. However, 18 patients (36.0%) had PSA recurrence. The PSA recurrence rate based on the cribriform pattern was 17.6% in the none to moderate group (34 patients) and 75.0% in the severe cribriform pattern group (16 patients). The PSA recurrence rate was significantly higher in patients with a severe invasive cribriform pattern (p=0.001). No significant differences were observed in other histopathological characteristics. The cribriform pattern in surgical pathology specimens was found to be a useful predictor of PSA recurrence after postoperative radiotherapy.

Association Between ABCC2 -24C>T and Nab-Paclitaxel-induced Peripheral Neuropathy in Japanese Patients With Pancreatic Cancer.

Nab-paclitaxel is used to treat patients with pancreatic cancer. However, it frequently induces peripheral neuropathy. Notably, pharmacokinetic factors may be associated with neuropathic symptoms as the onset depends on the cumulative dose. Therefore, we prospectively examined the association between the cumulative dose of nab-paclitaxel at the onset of peripheral neuropathy and polymorphisms of hepatic transporter genes. Patients with pancreatic cancer receiving nab-paclitaxel (125 mg/m2) and gemcitabine (1,000 mg/m2) were enrolled. Peripheral neuropathy was assessed using the Common Terminology Criteria for Adverse Events (CTCAE), Patient-Reported Outcomes CTCAE (PRO-CTCAE), and Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity (FACT/GOG-Ntx), every 2-12 weeks, and every 4 weeks thereafter. solute carrier organic anion transporter family member 1B1 (SLCO1B1) 521T>C, 388A>G; SLCO1B3 rs11045585; ATP-binding cassette transporters, subfamily B, member 1 (ABCB1) 1236C>T, 2677G>T/A, 3435C>T; ABCC1 rs2644983; ABCC2 24C>T; and ABCG2 421C>A were analyzed by direct sequencing. Correlations between transporter genotypes and cumulative dose at symptom onset were assessed using Kaplan-Meier and log-rank tests. In total, 25 patients were enrolled. The lowest median cumulative dose for nab-paclitaxel at peripheral neuropathy onset using PRO-CTCAE was 593 mg. By CTCAE it was 800 mg, and by FACT/GOG-Ntx it was 1,090 mg (p<0.0001). At symptom onset, patients with ABCC2 -24C/T genotype had received a significantly lower median cumulative dose by PRO-CTCAE (540 mg) than those with C/C (720 mg) (p=0.0188). However, the other polymorphisms studied were not associated with symptoms. Herein, we found for the first time that ABCC2 -24C/T genotype was significantly associated with the onset of nab-paclitaxel-induced peripheral neuropathy detected with PRO-CTCAE.

Acute and sub-acute toxicity of ethanol leaf extract from Acrostichum aureum in rats

Acrostichum aureum L. (A.aureum) is a medicinal plant that has anti-cancer, anti-inflammatory, and anti-bacterial activities and has been widely used traditionally in the treatment of many diseases. However, there is a dearth of information on the plant's safety. The present investigation was carried out to evaluate the acute and sub-acute toxicity of ethanol leaf extract of A. aureum (ELAA) in female Sprague Dawley (SD) rats. Oral acute toxicity was studied in female SD rats administered a single dose of 5000 mg kg-1 body weight ELAA. The sub-acute toxicity evaluation was also conducted orally with 100, 200, 500, and 750 mg kg-1 body weight of ELAA for 28 days in female SD rats. The impact of sub-acute treatment on body weight, gross histology, relative organ weight, urinalysis, hematology, plasma biochemistry, and histopathology was assessed following treatment. The ELAA did not cause death or signs of toxicity after acute treatment. Similarly, all the parameters evaluated during acute and sub-acute administration of ELAA did not significantly differ from the control. Therefore, the median lethal dose (LD50) of the ethanol extract of Acrostichum aureum is greater than 5000 mg kg-1 body weight. Its oral sub-acute administration is also non-toxic and safe at the tested doses.

CT surveillance for type 1 autoimmune pancreatitis: cumulative radiation dose and diagnostic performance for disease relapse.

Long-term follow-up is essential for type 1 autoimmune pancreatitis (AIP) patients due to high relapse rates. The cumulative radiation dose from repeated CT scans during follow-up should not be ignored. We aim to investigate the cumulative radiation dose in AIP patients undergoing CT surveillance and the diagnostic performance of CT in detecting disease relapse. The diagnostic performance of MRI from a secondary cohort during the same period was also investigated. This retrospective single-institutional study included 247 type 1 AIP patients with one or more follow-up CT scans, and 120 patients with MR follow-ups. Four metrics were utilized to report the radiation dose, including the volume computed tomography dose index, the dose length product, size-specific dose estimate and effective dose. The diagnostic performance for AIP relapse was assessed, taking the final clinical diagnosis in retrospect as the reference standard. With a median 2.3-year follow-up period, AIP patients followed up with CT exhibited a median cumulative radiation dose of 37.5 mSv. 11.3% of patients have accumulated doses exceeding 100 mSv. For the 169 patients followed over a year, 30.8% sustained an average annual radiation dose surpassing 20 mSv. The sensitivity/specificity/accuracy of CT for detecting abdominal organ relapse was 64.1%/99.6%/97.0%. For AIP patients followed up with MRI, the sensitivity for detecting disease relapse was 90.5%. Considering the accumulation of radiation dose in AIP patients and the insufficient sensitivity in detecting disease relapse with CT, safer and more sensitive imaging follow-up strategies should be explored. Question CT, as the primary imaging modality for autoimmune pancreatitis (AIP) follow-up, raises concerns regarding radiation exposure and lacks reported diagnostic performance in detecting AIP relapse. Findings CT in AIP follow-up causes significant cumulative radiation exposure and exhibits insufficient sensitivity in relapse detection. Clinical relevance Type 1 AIP necessitates long-term imaging follow-up, yet current guidelines lack consensus regarding the prioritization of CT or MRI for such follow-up. CT is widely used but has radiation concerns and limited sensitivity, calling for safer, efficient strategies.

The Role of Radiotherapy in Indolent Ocular Adnexal and Orbital Lymphomas.

This study evaluates the oncological outcomes and toxicities of indolent ocular adnexal and orbital lymphomas (OOLs) treated with radiotherapy (RT) ± systemic therapy. A retrospective analysis of 44 patients with indolent OOLs treated with RT was conducted. Most patients (87%) had early-stage disease. Treatment involved RT alone (34%) or RT + systemic therapy (66%). The median RT dose was 30 Gy, with a median follow-up of 45 months. Local and systemic recurrence rates were 4% and 9%, respectively. Five-year overall and disease-free survival (DFS) rates were 96.2% and 83.6%. Early-stage patients showed similar DFS rates regardless of whether they received RT alone or RT plus systemic therapy. No grade 3 RT-related toxicity occurred, but systemic therapy led to grade 3 toxicity in 17% of patients. RT is essential for treating indolent OOLs, and combination with systemic therapies does not enhance outcomes for early-stage patients.

Retrospective analysis of carboplatin-induced cumulative neutropenia in cancer-bearing dogs.

To determine the clinical significance of performing repeated postchemotherapy CBC for cancer-bearing dogs receiving ≥ 4 carboplatin treatments. The secondary aim was to identify risk factors associated with cumulative carboplatin-induced neutropenia in those dogs. 40 client-owned dogs diagnosed with cancer. A retrospective study using medical records from a single academic institution during 2012 to 2023. Dogs that received ≥ 4 doses of carboplatin with pre- and postchemotherapy CBCs available were included. Signalment and possible risk factors were recorded. Veterinary Cooperative Oncology Group-Common Terminology Criteria for Adverse Events was used for neutropenia grading. 40 dogs met the inclusion criteria, with a total of 206 prechemotherapy and 188 postchemotherapy CBC results available. The median carboplatin dosage was 300 mg/m2 (range, 200 to 300 mg/m2). The median interval between carboplatin administration and the postchemotherapy CBC was 10 days (range, 6 to 38 days). Eleven dogs developed a grade 2 or higher neutropenia, with 5 dogs developing multiple neutropenic events, for a total of 18 separate events (18/394). Only 2 of 18 neutropenic events were recorded at the 10- to 14-day postchemotherapy CBC. The yield of detecting neutropenia at a postchemotherapy CBC at any carboplatin chemotherapy after the second dose was < 1% (1/149). Dogs that developed neutropenia at the pre-2nd chemotherapy CBC had a significantly higher risk of developing another neutropenic event at subsequent prechemotherapy CBC (P < .001). The incidence of cumulative neutropenia after 4 to 6 doses of carboplatin is low in cancer-bearing dogs. If a grade 2 or higher neutropenia is observed at or before the second prechemotherapy CBC, the dog is at a higher risk of developing neutropenia following future treatments.

Risk of late radiation necrosis more than 5 years after stereotactic radiosurgery.

Radiation necrosis (RN) is a well-recognized late complication most commonly occurring within 2 years of stereotactic radiosurgery (SRS); however, late RN (LRN), RN occurring or recurring > 5 years after SRS, has been poorly described. This study analyzes the incidence of and risk factors for LRN occurring > 5 years after SRS. This retrospective analysis included patients treated with linear accelerator-based SRS for tumors or arteriovenous malformations with > 5 years of clinical and serial MRI follow-up. LRN was defined as new neurological symptoms with neuroanatomically correlated imaging findings without disease recurrence. Univariate and multivariate analyses for LRN were performed using the Cox proportional hazards model. The authors identified a cumulative 297 lesions in 219 patients treated to a median dose of 17 Gy with a median follow-up of 7.4 years. In total, 290 (97.6%) lesions were treated in a single fraction, and 64 (21.5%) were treated after resection. The LRN occurred in 19 (8.7%) patients and in 23 (7.7%) lesions at a median of 6.1 years (range 5.1-13.9 years) after SRS. Fifteen of the 23 (65.2%) lesions were managed with steroids, bevacizumab, and/or antiepileptic drugs. The remaining 8 (34.8%) were resected; histopathology confirmed necrosis without disease recurrence in each. On multivariate analysis, only > 5-cm3 volume of the brain receiving 12 Gy (brain V12Gy) (HR 6.01, 95% CI 1.77-20.48; p = 0.004) and a history of early, previously resolved RN (HR 9.53, 95% CI 2.00-45.61; p = 0.005) remained significantly associated with LRN. RN risk persists well beyond 5 years after SRS, and recognizing LRN as an entity has important implications in managing these patients. LRN risk was highest in those with a brain V12Gy > 5 cm3 and a history of early RN after SRS, warranting close follow-up in perpetuity for select patients.

Late gestation maternal infection with bovine viral diarrhea virus impacts offspring feedlot performance, digestion, blood parameters, and hot carcass weights.

Fetal infection with bovine viral diarrhea virus (BVDV) after 150 d results in transient fetal infections (TI). Twenty-five unvaccinated, yearling Hereford heifers, seronegative for antibodies to BVDV1 and BVDV2, were bred by artificial insemination with X chromosome-bearing sperm from one Angus sire to examine the impact of TI on postnatal growth, estimated dry matter digestibility, blood parameters, and carcass characteristics. On d 175 of pregnancy, dams were intranasally inoculated with either sham control or 4.0 log median tissue culture infectious dose noncytopathic type2 BVDV to generate control or TI offspring, respectively. All control dams remained seronegative and all BVDV-inoculated dams seroconverted by d 14 post-inoculation. All control offspring were seronegative and all TI offspring were seropositive for antibodies to type 2 BVDV at birth. All offspring were raised on pasture until weaning. At weaning, all calves were transported to our research feedlot facility, housed in three pens, and transitioned to a high-energy concentrate-based diet. Heifer body weights (BW) and jugular blood samples were collected every 28 d. On d 84 of the feeding period, titanium dioxide was added to the diet of 12, age-paired, individually fed, heifers (6 control and 6 TI heifers; approximately 1 yr. of age) for 28 d and used to estimate dry matter digestibility. On d 105 and 240 ruminal fluid (approximately 900ml) was collected from every animal using a stomach pump and analyzed for short chain fatty acids (SCFA). After approximately 287 d on feed, heifers were transported to a USDA-inspected abattoir and harvested. TI heifers had lighter final BW (P < 0.04) when compared to control heifers. Average daily gain was greater (P < 0.01) in control compared to TI heifers. TI heifers had a 2.2% lesser (P < 0.05) apparent dry matter digestibility, lighter (P < 0.01) hot carcass weights, but similar ruminal SCFA compared to controls. Blood glucose concentrations were similar (P > 0.8) between control and TI heifers. Ceruloplasmin activity (P < 0.03) and the oxidized form of glutathione (GSSG; P < 0.01), indicators of chronic inflammation, were increased in plasma from TI heifers compared to controls. Other indicators of oxidative stress were not impacted (P > 0.10) by TI status. These data suggest that fetal BVDV transient infection negatively impacts growth throughout the feeding period, possibly by impacting gastrointestinal tract function and increasing systemic inflammation.

Crushed posaconazole delayed-release tablets for antifungal prophylaxis and treatment in children.

Therapeutic drug monitoring (TDM) is recommended for posaconazole to achieve target concentrations of ≥0.7 mg/L and ≥1.0 mg/L for prophylaxis and treatment of invasive fungal infection (IFI), respectively. However, target attainment is challenging with the oral suspension, particularly in children. Here, we describe our experience using crushed delayed-release tablet (DRT) in a paediatric cohort, with a focus on TDM. We undertook a retrospective audit of crushed posaconazole DRT administration via enteral feeding tubes (EFTs) for patients aged ≤18 years over 18 months at The Royal Children's Hospital Melbourne who had at least one trough concentration measured at steady state. Details of patient demographics, posaconazole dosing, monitoring and adverse effects were recorded. Twelve patients with a median age of 9 years (range 2 to 14) received posaconazole DRT via EFT for prophylaxis (n = 8) or treatment (n = 4). All children achieved target concentration, with a median dose of 7 mg/kg/day (range 5 to 11) for prophylaxis and 13 mg/kg/day (range 9 to 20) for treatment. The median time to reach therapeutic levels was 7 days (range 5 to 14) for prophylaxis and 20 days (range 15 to 35) for treatment. One child had blockage of their EFT, which was attributed to posaconazole. No other adverse effects were observed. Crushed posaconazole DRT administered via EFT may be used as a method of attaining therapeutic posaconazole concentrations in children for antifungal prophylaxis and treatment.