Oxytocin regimen used for induction of labor and pregnancy outcomes.

BACKGROUND: Following the results of the ARRIVE trial, which demonstrated a reduction in cesarean delivery with no increase in adverse perinatal outcomes after elective induction of labor (IOL) in low-risk nulliparous patients at 39 weeks' gestation compared with expectant management, the use of induction has increased. Current evidence is insufficient to recommend mid-high-dose over low-dose regimens for routine IOL. OBJECTIVE(S): We sought to evaluate the association of oxytocin regimen with cesarean delivery and an adverse perinatal composite outcome in low-risk nulliparous patients undergoing IOL at 39 weeks of gestation or greater. STUDY DESIGN: This is a secondary analysis of the NICHD Maternal-Fetal Medicine Units Network ARRIVE randomized trial. Patients induced with a mid-to high-dose oxytocin regimen (MHD; starting or incremental increase >2 mU/min) were compared with those receiving a low-dose oxytocin regimen (LD; starting and incremental increase ≤2 mU/min). The co-primary outcomes for this secondary analysis were 1) cesarean delivery and 2) composite of perinatal death or severe neonatal complications. Multivariable Poisson regression was used to estimate adjusted relative risks (aRR) and 97.5% confidence intervals (CI) for the co-primary endpoints, 95% CI for binomial outcomes and multinomial logistic regression was used to estimate adjusted odds ratios (aOR) and 95% CIs for multinomial outcomes. RESULTS: Of 6,106 participants enrolled in the primary trial, 2,933 underwent induction with oxytocin: 861 in the MHD group and 2,072 in the LD group. The lower frequency of cesarean delivery in the MHD group compared with the LD group (20.3% vs. 25.2%, RR 0.81, 95%CI (0.69-0.94)) was not significant after adjustment (aRR 0.90, 97.5%CI (0.76-1.07)). The composite of perinatal death or severe neonatal complications was more frequent in the MHD group compared with the LD group (6.7% vs. 4.3%, RR 1.55, 95%CI (1.13-2.14)) and remained significant after adjustment (aRR 1.61, 97.5%CI (1.11-2.35)). The majority of the cases in the composite were from the respiratory support (5.2% vs. 3.1%) component with an increase in transient tachypnea of the newborn (3.8% vs. 2.5%, aRR 1.63, 95% CI (1.04-2.54)). The duration of neonatal respiratory support for one day was significantly higher in the MHD group compared with the LD group (3.5% vs. 1.4%, aRR 2.59, 95%CI (1.52-4.39)); however, support beyond one day was not different between the two groups. The MHD group, when compared with the LD group had a higher operative vaginal delivery rate (10.0% vs. 7.0%, aRR 1.54, 95%CI (1.18-2.00)) and shorter duration of time from start of oxytocin to delivery [crude median (interquartile range) 12 (8-17) vs. 13 (9-19) hours, adjusted median difference -2 (-2 to -1), p<0.001], respectively. CONCLUSION(S): Mid-high-dose oxytocin regimen use for IOL in nulliparas at ≥ 39 weeks' gestation was not associated with improved maternal or neonatal outcomes compared with low-dose regimens. Although mid-high-dose oxytocin regimen use was associated with a shorter duration of labor, there was an increase in self-limited neonatal respiratory support and no difference in cesarean rates. More evidence is needed to define the magnitude of potential maternal and neonatal benefits and risks associated with oxytocin regimens.

Immunogenicity, safety, and persistence induced by triple- and standard-strength four-dose hepatitis B vaccination regimens in hemodialysis patients: A multicenter, randomized, parallel-controlled trial in Six cities in Shanxi Province.

BACKGROUND: Hemodialysis (HD) patients represent a high-risk group for hepatitis B infection. It is crucial to administer hepatitis B vaccination and stimulate higher and more sustained levels of anti-HBs. Our aim is to enhance the immunogenicity and persistence by implementing high-dose and prolonged hepatitis B vaccine schedule regimen in HD patients. METHODS: We conducted this multicenter, randomized, parallel-controlled trial between July 2020 and February 2023 at 11 hospitals in Shanxi province, China. A total of 504 HD patients were enrolled. All participants randomly allocated in a ratio of 1:1:1 to receive recombinant HBV vaccine of 3 standard doses (20 µg) at 0-1-6 months (IM20×3 group), 4 standard doses at 0-1-2-6 months (IM20×4 group), or 4 triple doses (60 µg) at 0-1-2-6 months (IM60×4 group). RESULTS: The vaccine-elicited antibody response peaked at month 7. The follow-up outcomes ranging from month 7 to 30 revealed that the response rates of anti-HBs decreased from 85.9% (134/156) to 33.0% (33/100) in IM20×3 group, from 92.5% (135/146) to 53.9% (56/104) in IM20×4 group and from 95.4% (145/152) to 57.3% (55/96) in IM60×4 group. The duration of vaccine-induced response with 75% of patients maintained protective antibody were 21.0 months in IM20×3 group, 25.7 months in IM20×4 group (vs. IM20×3 group, P=0.056) and 29.2 months in IM60×4 group (vs. IM20×3 group, P=0.034). All the adverse reactions were mild. CONCLUSIONS: The four-triple-dose hepatitis B vaccination regimens could enhance the immunogenicity and 2-year duration in HD patients.The trial was registered with Clinical Trials.gov, number NCT03962881. https://classic.clinicaltrials.gov/ct2/show/NCT03962881?term=NCT03962881&draw=2&rank=1.

Dosimetric calibration of anatomy-specific ultra-high dose rate electron irradiation platform for preclinical FLASH radiobiology experiments.

BACKGROUND: FLASH radiation therapy (RT) offers a promising avenue for the broadening of the therapeutic index. However, to leverage the full potential of FLASH in the clinical setting, an improved understanding of the biological principles involved is critical. This requires the availability of specialized equipment optimized for the delivery of conventional (CONV) and ultra-high dose rate (UHDR) irradiation for preclinical studies. One method to conduct such preclinical radiobiological research involves adapting a clinical linear accelerator configured to deliver both CONV and UHDR irradiation. PURPOSE: We characterized the dosimetric properties of a clinical linear accelerator configured to deliver ultra-high dose rate irradiation to two anatomic sites in mice and for cell-culture FLASH radiobiology experiments. METHODS: Delivered doses of UHDR electron beams were controlled by a microcontroller and relay interfaced with the respiratory gating system. We also produced beam collimators with indexed stereotactic mouse positioning devices to provide anatomically specific preclinical treatments. Treatment delivery was monitored directly with an ionization chamber, and charge measurements were correlated with radiochromic film measurements at the entry surface of the mice. The setup for conventional dose rate irradiation utilized the same collimation system but at increased source-to-surface distance. Monte Carlo simulations and film dosimetry were used to characterize beam properties and dose distributions. RESULTS: The mean electron beam energies before the flattening filter were 18.8 MeV (UHDR) and 17.7 MeV (CONV), with corresponding values at the mouse surface of 17.2 and 16.2 MeV. The charges measured with an external ion chamber were linearly correlated with the mouse entrance dose. The use of relay gating for pulse control initially led to a delivery failure rate of 20% (± 1 pulse); adjustments to account for the linac latency improved this rate to < 1/20. Beam field sizes for two anatomically specific mouse collimators (4 × 4 cm2 for whole-abdomen and 1.5 × 1.5 cm2 for unilateral lung irradiation) were accurate within < 5% and had low radiation leakage (< 4%). Normalizing the dose at the center of the mouse (∼0.75 cm depth) produced UHDR and CONV doses to the irradiated volumes with > 95% agreement. CONCLUSION: We successfully configured a clinical linear accelerator for increased output and developed a robust preclinical platform for anatomically specific irradiation, with highly accurate and precise temporal and spatial dose delivery, for both CONV and UHDR irradiation applications.

High-dose rifampicin for 3 months after culture conversion for drug-susceptible pulmonary tuberculosis.

BACKGROUND: This study aimed to determine whether a shorter high-dose rifampicin regimen is non-inferior to the standard 6-month tuberculosis regimen. METHOD: This multicenter, randomized, open-label, non-inferiority trial enrolled participants with respiratory specimen positivity by Xpert MTB/RIF assay or Mycobacterium tuberculosis culture without rifampicin-resistance. Participants were randomized at 1:1 to the investigational or control group. The investigational group received high-dose rifampicin (30 mg/kg/day), isoniazid, and pyrazinamide until culture conversion, followed by high-dose rifampicin and isoniazid for 12 weeks. The control group received the standard 6-month regimen. The primary outcome was the rate of unfavorable outcomes at 18 months post-randomization. The non-inferiority margin was set at <6% difference in unfavorable outcomes rates. RESULTS: Between 4 November 2020 and 3 January 2022, 76 participants were enrolled. Of these, 58 were included in the modified intention-to-treat analysis. Unfavorable outcomes occurred in 10 (31.3%) of 32 in the control group and 10 (38.5%) of 26 in the investigational group. The difference was 7.2% (95% confidence interval, ∞ to 31.9%), failing to prove non-inferiority. Serious adverse events and grade 3 or higher adverse events did not differ between the groups. CONCLUSIONS: The shorter high-dose rifampicin regimen failed to demonstrate non-inferiority but had an acceptable safety profile. Trial registration ClinicalTrials.gov NCT04485156.

A multidisciplinary view of FLASH irradiation.

The delivery of ultra-high dose rates of radiation, called FLASH irradiation or FLASH-RT, has emerged as a new modality of radiotherapy shaking up the paradigm of proportionality of effect and dose whatever the method of delivery of the radiation. The hallmark of FLASH-RT is healthy tissue sparing from the side effects of radiation without decrease of the antitumor efficiency in animal models. In this review we will define its specificities, the molecular mechanisms underlying the FLASH effect and the ongoing developments to bring this new modality to patient treatment.

Mimicking large spot-scanning radiation fields for proton FLASH preclinical studies with a robotic motion platform.

Previously, a synchrotron-based horizontal proton beamline (87.2 MeV) was successfully commissioned to deliver radiation doses in FLASH and conventional dose rate modes to small fields and volumes. In this study, we developed a strategy to increase the effective radiation field size using a custom robotic motion platform to automatically shift the positions of biological samples. The beam was first broadened with a thin tungsten scatterer and shaped by customized brass collimators for irradiating cell/organoid cultures in 96-well plates (a 7-mm-diameter circle) or for irradiating mice (1-cm2 square). Motion patterns of the robotic platform were written in G-code, with 9-mm spot spacing used for the 96-well plates and 10.6-mm spacing for the mice. The accuracy of target positioning was verified with a self-leveling laser system. The dose delivered in the experimental conditions was validated with EBT-XD film attached to the 96-well plate or the back of the mouse. Our film-measured dose profiles matched Monte Carlo calculations well (1D gamma pass rate >95%). The FLASH dose rates were 113.7 Gy/s for cell/organoid irradiation and 191.3 Gy/s for mouse irradiation. These promising results indicate that this robotic platform can be used to effectively increase the field size for preclinical experiments with proton FLASH.

Bivalirudin versus heparin in patients with or without bail-out GPI use: a pre-specified subgroup analysis from the BRIGHT-4 trial.

BACKGROUND: Conflicting results comparing bivalirudin versus heparin anticoagulation in patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI), in part due to the confounding effect of glycoprotein IIb/IIIa inhibitors (GPI). The aim of the study was to compare the safety and effectiveness of bivalirudin plus a post-PCI high-dose infusion vs heparin with or without bail-out GPI use. METHODS: We conducted a pre-specified subgroup analysis from the BRIGHT-4 trial that randomized 6016 STEMI patients who underwent primary PCI to receive either bivalirudin plus a post-PCI high-dose infusion for 2-4 h or heparin monotherapy. GPI use was only reserved as bail-out therapy for procedural thrombotic complications. The primary outcome was a composite of all-cause death or Bleeding Academic Research Consortium (BARC) types 3-5 bleeding at 30 days. RESULTS: A total of 5250 (87.4%) patients received treatment without GPI while 758 (12.6%) received bail-out GPI. Bail-out GPI use was associated with an increased risk of the primary outcome compared to non-GPI use (5.28% vs. 3.41%; adjusted hazard ratio (aHR), 1.62; 95% confidence interval (CI), 1.13-2.33; P = 0.009) and all-cause death (5.01% vs. 3.12%; aHR, 1.74; 95% CI, 1.20-2.52; P = 0.004) but not in the risk of BARC types 3-5 bleeding (0.53% vs. 0.48%; aHR, 0.90; 95% CI, 0.31-2.66; P = 0.85). Among patients without GPI use, bivalirudin was associated with lower rates of the primary outcome (2.63% vs. 4.21%; aHR, 0.55; 95% CI, 0.39-0.77; P = 0.0005), all-cause death (2.52% vs. 3.74%; aHR, 0.58; 95% CI, 0.41-0.83; P = 0.003), and BARC types 3-5 bleeding (0.15% vs. 0.81%; aHR, 0.19; 95% CI, 0.06-0.57; P = 0.003) compared with heparin. However, among patients requiring bail-out GPI, there were no significant differences observed in the rates of the primary outcome (5.76% vs. 4.87%; aHR, 0.77; 95% CI, 0.36-1.66; P = 0.50; Pinteraction = 0.07) or its individual components between bivalirudin and heparin groups. CONCLUSIONS: Bivalirudin plus a post-PCI high-dose infusion was associated with significantly reduced 30-day composite rate of all-cause death or BARC types 3-5 bleeding compared with heparin monotherapy in STEMI patients undergoing primary PCI without GPI use. However, these benefits might be less pronounced in patients requiring bail-out GPI due to thrombotic complications during primary PCI. TRIAL REGISTRATION: ClinicalTrials.gov NCT03822975.

Characterizing second line and beyond therapies for primary central nervous system lymphomas.

Primary central nervous system (CNS) lymphoma (PCNSL) is a rare and aggressive lymphoma that affects the CNS without other systemic involvement. High-dose methotrexate (HDMTX)-based regimens are recommended frontline treatment, followed by consolidation with either high-dose chemotherapy, whole brain radiation (WBRT) +/- sequential temozolomide (TMZ), or autologous stem cell transplant (autoSCT). Despite advancements with HDMTX and rituximab, up to half of patients will relapse. Treatment for relapsed or refractory (R/R) disease varies widely as preferred regimens are not well-established. Our study aimed to provide real-world characterization of R/R PCNSL therapies. The secondary objective was characterization of consolidation methods after frontline treatment. This retrospective, descriptive analysis included 54 adult PCNSL patients that received a HDMTX-based frontline regimen between 4/1/2016 and 7/1/2022. Patients receiving HDMTX for the purpose of secondary CNS lymphoma, non-B cell origin PCNSL, and intraocular lymphoma were excluded. Thirty-one patients (57%) received consolidation therapy with rituximab and high-dose cytarabine (R-HDAC), WBRT, or both. Thirteen patients (24%) proceeded with autoSCT. Twenty-five patients had disease progression, with 17 patients receiving second line treatment. The second line treatments were WBRT (24%), clinical trial (18%), rituximab with lenalidomide (R2; 18%), re-induction with HDMTX-based regimens (18%), ibrutinib with rituximab (12%) and R-HDAC (12%). Seven patients progressed, and all received third line treatment. Treatments varied, including R2; ibrutinib +/- HDMTX; rituximab, methotrexate, and cytarabine; R-HDAC; R-nivolumab; and WBRT. Five patients received a fourth line regimen of R +/- lenalidomide, R-HDMTX, or nivolumab monotherapy. Regimens used for the three patients who received fifth line treatment and beyond included R-TMZ and pembrolizumab monotherapy in addition to previously described regimens. Regimen selection is varied and highly dependent on physician preference and patient factors, including clinical trial eligibility, prior therapies, performance status, organ function, and treatment intent. Prospective clinical trials are needed to guide optimal management.

Adjuvant Therapy in Acral Melanoma: A Systematic Review.

Background: Acral melanoma presents distinct biological characteristics compared to cutaneous melanoma. While adjuvant therapeutic strategies for high-risk resected acral melanoma closely resemble those for cutaneous melanoma, the evidence supporting the clinical application of adjuvant therapy for acral melanoma remains inadequate. Our aim was to systematically analyze the efficacy and safety profile of adjuvant therapy in acral melanoma. Methods: This systematic review adhered to a pre-registered protocol. We comprehensively searched four electronic databases and reference lists of included articles to identify eligible studies. The primary outcome was therapeutic efficacy, and the secondary outcome was adverse events (AEs). Results: This systematic review included 11 studies with 758 acral melanoma patients undergoing adjuvant therapy. High-dose interferon α-2b (IFN) regimens showed no significant difference in recurrence-free survival (RFS), though the longer regimen was linked to increased hepatotoxicity. Adjuvant anti-PD-1 therapy demonstrated varying efficacy, with improved RFS in patients who experienced immune-related AEs. Targeted therapy with dabrafenib plus trametinib achieved high 12-month RFS in patients with BRAF-mutated acral melanoma. Comparative studies suggested that adjuvant anti-PD-1 therapy is similarly effective to IFN in prolonging survival for high-risk acral melanoma patients. Additionally, prior treatment with pegylated IFN enhanced RFS in patients receiving adjuvant pembrolizumab. Conclusion: High-dose IFN was widely used as adjuvant therapy for acral melanoma, but serious AEs prompted the search for alternatives. Adjuvant anti-PD-1 therapy shows promise, though it may be less effective than in non-acral melanoma. Further prospective studies are needed to determine the optimal adjuvant treatment for acral melanoma.

Optimizing clinical outcomes: The journey of twins with CRIM-negative infantile-onset Pompe disease on high-dose enzyme replacement therapy and immunomodulation.

Infantile-onset Pompe disease (IOPD) is caused by a deficiency in the enzyme acid alpha-glucosidase (GAA). It is characterized by severe and progressive hypertrophic cardiomyopathy and muscle weakness with death in the first 2 years of life if left untreated. Enzyme replacement therapy (ERT) with alglucosidase-alfa is lifesaving, but its effectiveness is influenced by the patient's cross-reactive immunologic material (CRIM) status, dose of ERT, and the development of high antibody titers, which can reduce the therapy's efficacy. The inability of CRIM-negative IOPD patients to produce native GAA exposes them to a high risk of development of anti-rhGAA IgG antibody titers, leading to treatment failure. We present the case of CRIM-negative dizygotic twins treated with high-dose alglucosidase-alfa (40 mg/kg/week), initiated at 28 days (Twin A) and 44 days (Twin B). Both twins received immune tolerance induction (ITI) with rituximab, methotrexate, and IVIG to mitigate antibody response. Initial evaluations revealed elevated left ventricular mass index (LVMI) and elevated biomarkers (urine glucose tetrasaccharide (Glc4), creatine kinase (CK), and aspartate aminotransferase (AST)) in both twins. Following treatment, cardiac function and biomarkers normalized within several months, with a slight delay in Twin B compared to Twin A, likely attributed to the later initiation of ERT. Both twins safely tolerated ITI, achieving immune tolerance with low antibody titers. At 28 months, the twins transitioned to avalglucosidase-alfa (40 mg/kg every other week (EOW)), which was well tolerated without an increase in antibody titers. At 39 months, both twins exhibited normal cardiac function, LVMI, and biomarkers. Motor skills continued to improve, though some kinematic concerns persisted. These cases underscore the importance of early, high-dose ERT combined with ITI in managing CRIM-negative IOPD. While transitioning to avalglucosidase-alfa at 40 mg/kg/EOW was beneficial and well-tolerated in our patients, further studies are needed to confirm its long-term efficacy compared to the high-dose weekly 40 mg/kg alglucosidase-alfa.

Sparing Effect on Cell Survival Under Normoxia Using Ultra-high Dose Rate Proton Beams from a Compact Superconducting AVF Cyclotron.

BACKGROUND/AIM: The purpose of this study was to evaluate whether the sparing effect on cell survival is observed under normoxia. MATERIALS AND METHODS: A superconducting spiral sector-type azimuthally varying field (AVF) cyclotron produced 230 MeV proton beams at 250 Gy/s as ultra-high dose rate (uHDR) and 1 Gy/s as normal dose rate (NDR) to irradiate tumor and normal cell lines (HSGc-c5 and HDF up to 24 Gy at the center of spread-out Bragg peak (SOBP). The Advanced Markus chamber and Gafchromic film were used to measure the examined absolute dose and field sizes. Colony formation assay and immunofluorescence staining were conducted to evaluate the sparing effect. RESULTS: A homogeneous field was achieved at the center of the SOBP for both uHDR and NDR scanned proton beams, and dose reproducibility and linearity were adequate for experiments. There were significant differences in cell surviving fractions of HSGc-C5 and HDF cells irradiated at uHDRs compared to NDRs at 20 Gy and 24 Gy. Increasing γ-H2AX foci were observed for both cell lines at NDR. CONCLUSION: The sparing effect on cell survival was first observed under normoxic conditions for tumor and normal cells with doses exceeding 20 Gy, using proton irradiation at 250 Gy/s extracted from a superconducting AVF cyclotron. This study marks a significant milestone in advancing our understanding of the underlying mechanism behind the sparing effect.

Early Urinary Potassium Level Predicts High-dose Methotrexate Elimination Delay in Primary Central Nervous System Lymphoma.

BACKGROUND/AIM: Treatment of primary central nervous system lymphoma (PCNSL) includes high dose methotrexate-based polychemotherapy (HD-MTX). This study aimed to identify early predictive factors of methotrexate (MTX) delayed elimination. PATIENTS AND METHODS: We prospectively included all patients with newly-diagnosed PCNSL. Daily serum and urinary creatinine and ionogram were collected. We generated two independent cohorts: a training cohort (TC) and a confirmatory cohort (CC). RESULTS: We included for analysis 64 cures of HD-MTX (20 patients) in the TC and 59 cures (22 patients) in the CC. Median elimination time of MTX was 95 h and 96 h in the TC and CC, respectively. In multivariate analysis, older age (p=0.004), low Karnofsky Performance Status (p=0.036) and high urinary K+ (p=0.001) were associated with delayed MTX elimination. An optimal cutoff for urinary K+ was defined. In the CC, we confirmed that high urinary K+ (p=0.004) remained associated with delayed MTX elimination. CONCLUSION: High urinary K+ may be predictive of delayed MTX elimination in primary central nervous system lymphoma. Its relevance as a decision-making factor needs to be validated in additional prospective studies.

Efficacy of initial and repeat DCB angioplasty of restenotic arteriovenous fistulas compared with plain angioplasty.

PURPOSE: To evaluate the effect of drug-coated balloon (DCB) with high-dose paclitaxel for the treatment of restenotic dysfunctional arteriovenous fistulas (AVFs). MATERIALS AND METHODS: In this single-arm, multicenter, prospective, observational study, 334 patients using IN.PACT AV DCB (Medtronic Inc., Plymouth, MN) for the first time in the restenotic lesion of dysfunctional AVF between April 2021 and March 2022 were registered. RESULTS: Procedural success, defined as <30% residual stenosis, was achieved in 96.7% of cases. During a median follow-up of 7.4 months, 179 target lesion reinterventions (TLRs) were observed, and the 6-month freedom from TLR was 73.2% (68.2%-78.2%). When compared with the previous plain percutaneous transluminal angioplasty, the median time to reintervention was significantly longer with DCB (9.1 [8.0-10.6] versus 3.2 [3.0-3.4] months; P<.001). Baseline characteristics that were independently associated with TLR were: months from the last intervention (adjusted hazard ratio, 0.50 [95% confidence interval, 0.40-0.62] per doubling; P<.001), partial lesion coverage by DCB (2.13 [1.10-4.12]; P=.024), and residual stenosis after DCB (2.19 [1.53-3.12] per 15% increase; P<.001) with its time interaction (0.91 [0.86-0.97] per month; P=.003). Of the 179 TLRs, 84 used DCB once again. The median time to reintervention was significantly longer for TLR using DCB (7.1 [6.2-9.7] versus 3.3 [3.1-4.0] months; P<.001). CONCLUSIONS: DCB with high-dose paclitaxel is effective at both the initial treatment in the restenotic lesion of dysfunctional AVF and during TLR after DCB use. However, partial lesion coverage by DCB and residual stenosis should be avoided.

Clinical Outcome Comparison between CT-Guided Versus all MRI-Guided Scenarios in Brachytherapy for Cervical Cancer: A Single-Institute Experience.

OBJECTIVES: Image-guided adaptive brachytherapy (IGABT) is the standard of care for patients with cervical cancer. The objective of this study was to compare the treatment outcomes and adverse effects of computed tomography (CT)-guided and magnetic resonance imaging (MRI)-guided scenarios. MATERIALS AND METHODS: Data of patients with cervical cancer treated using external beam radiotherapy followed by IGABT from 2012 to 2016 were retrospectively reviewed. CT-guided IGABT was compared with the three modes of MRI-guided IGABT: pre-brachytherapy (MRI Pre-BT) without applicator insertion for fusion, planning MRI with applicator in-place in at least 1 fraction (MRI ≥1Fx), and MRI in every fraction (MRI EveryFx). Patient characteristics, oncologic outcomes, and late radiation toxicity were analyzed using descriptive, survival, and correlation statistics. RESULTS: Overall, 354 patients were evaluated with a median follow-up of 60 months. The 5-year overall survival (OS) rates were 61.5%, 65.2%, 54.4%, and 63.7% with CT-guided, MRI PreBT, MRI ≥1Fx, and MRI EveryFx IGABT, respectively with no significant differences (p = 0.522). The 5-year local control (LC) rates were 92.1%, 87.8%, 80.7%, and 76.5% (p = 0.133), respectively, with a significant difference observed between the CT-guided and MRI ≥1Fx (p = 0.018). The grade 3-4 late gastrointestinal toxicity rates were 6% in the CT-guided, MRI ≥1Fx, and MRI EveryFx, and 8% in MRI PreBT. The grade 3-4 late genitourinary toxicity rates were 4% in the CT-guided, 2% in MRI PreBT, 1% in MRI ≥1Fx, and none in MRI EveryFx. No significant differences were observed in the oncologic and toxicity outcomes among MRI PreBT, MRI ≥1Fx, and MRI EveryFx. CONCLUSIONS: CT-guided IGABT yielded an acceptable 5-year OS, LC, and toxicity profile compared with all MRI scenarios and is a potentially feasible option in resource-limited settings.

High-Dose-Rate Brachytherapy in Cervical and Endometrial Cancer Patients: A Retrospective Study From a Tertiary Cancer Center in the UAE.

Purpose This study evaluates the therapeutic outcomes and practical application of high-dose-rate (HDR) brachytherapy in managing cervical and endometrial cancers at a tertiary hospital in the UAE, focusing on treatment efficacy, safety, and patient-reported outcomes. Methods A retrospective analysis was conducted on 368 female patients treated between January 2008 and January 2022. Data included demographic information, cancer type, histopathology, treatment details, and survival outcomes. Statistical analyses were performed using descriptive and inferential statistics. Results The cohort comprised 275 cervical cancer patients (74.73%) and 93 endometrial cancer patients (25.27%). The majority were non-nationals (79.62%). The mean age was 57 years. Squamous cell carcinoma was the most common histopathological type (63.59%). HDR brachytherapy was administered to 290 patients (79.89%). The 12-month survival probability was significantly higher in the HDR-Brachy group (75%, 95% CI: 60% to 85%) compared to the noHDR-Brachy group (50%, 95% CI: 35% to 65%), with a hazard ratio of 0.953 (p=0.0035). At the last review, 86.68% of patients were alive, and disease progression was observed in 37.88% of patients. Conclusion HDR brachytherapy significantly improves survival outcomes in cervical and endometrial cancer patients. Continued efforts to enhance access and standardize brachytherapy protocols are essential to optimize treatment efficacy and patient outcomes in similar healthcare settings.

Insulin aspart plus high-dose vitamin D supplementation for gestational diabetes mellitus: analysis of efficacy and risk factors for maternal and infant outcomes.

BACKGROUND: Gestational diabetes mellitus (GDM) presents not only immediate challenges affecting maternal and infant health but also long-term consequences. Effective prevention and treatment of GDM are crucial for minimizing the short- and long-term health impacts. OBJECTIVES: This retrospective study evaluated the effects of insulin aspart injection plus high-dose vitamin D (HD-VD) supplementation on treatment outcomes and maternal - infant outcomes in patients with GDM. METHODS: A total of 129 GDM patients admitted to the Zhongshan Hospital Xiamen University from December 2021 to December 2023 were included in this study. According to the intervention regimen, the patients were divided into two groups: a control group of 59 patients receiving insulin aspart injection plus low-dose vitamin D (LD-VD) supplementation and a research group of 70 cases receiving insulin aspart injection plus HD-VD supplementation. The curative effect, blood glucose metabolism (fasting blood glucose [FPG], 2-hour postprandial blood glucose [2hPG], and glycosylated hemoglobin [HbA1c]), homocysteine (HCY), and cystatin C (Cys C), maternal and infant outcomes (maternal outcomes: hypoglycemia, cesarean section, polyhydramnios, and premature rupture of membranes; neonatal outcomes: stillbirth, macrosomia, neonatal respiratory distress syndrome, and Apgar score) were recorded and compared between the two groups. Risk factors affecting maternal and infant outcomes were analyzed. RESULTS: The research group demonstrated a higher overall effective rate in compared to the control group (P<0.05). Post-treatment measurements of FPG, 2hPG, HbA1c, HCY, and Cys C in the research group were statistically lower than the pre-treatment levels and those in the control group (all P<0.05). Additionally, the research group showed better maternal and neonatal outcomes, with fewer adverse pregnancy-related conditions and better neonatal health indicators, including higher Apgar scores (P<0.05). Besides, insulin aspart injection plus high-dose vitamin D was a protective factor for maternal and infant outcomes (P<0.05). CONCLUSIONS: Insulin aspart injection plus HD-VD supplementation markedly enhances treatment efficacy and improves maternal and infant outcomes in GDM.

Individual curved-needle interstitial template created using three-dimensional printing for brachytherapy for distal parauterine tumor recurrence.

BACKGROUND: Achieving a clinically acceptable dose distribution with commercial vaginal applicators for brachytherapy of recurrent parauterine tumors is challenging. However, the application of three-dimensional (3D) printing technology in brachytherapy has been widely acknowledged and can improve clinical treatment outcomes. PURPOSE: This study aimed to introduce an individual curved-needle interstitial template (ICIT) created using 3D printing technology for high-dose-rate (HDR) brachytherapy with interstitial treatment to provide a clinically feasible approach to distal parauterine and vaginal cuff tumors. The entire workflow, including the design, optimization, and application, is presented. METHODS: Ten patients with pelvic cancer recurrence were examined at our center. The vaginal topography was filled with gauze strips soaked in developer solution, and images were obtained using computed tomography (CT) and magnetic resonance imaging (MRI). Curved needle paths were designed, and ICITs were 3D-printed according to the high-risk clinical target volume (HRCTV) and vaginal filling model. The dose and volume histogram parameters of the HRCTV (V100, V200, D90, and D98) and organs at risk (OARs) (D2cc) were recorded. RESULTS: All patients completed interstitial brachytherapy treatment with the 3D-printed ICIT. One patient experienced vaginal cuff tumor recurrence, and nine patients experienced parametrial tumor recurrence (four on the left and five on the right). We used two to five interstitial needles, and the maximum angle of the curved needle was 40°. No source obstruction events occurred during treatment of these 10 patients. The doses delivered to the targets and OARs of all patients were within the dose limits and based on clinical experience at our center. CONCLUSION: The ICIT is a treatment option for patients with distal parauterine tumor recurrence. This method addresses the limitations of vaginal intracavitary and standard interstitial applicators. The ICIT has the advantages of biocompatibility, personalization, and magnetic resonance imaging compatibility.

Eradication rate and safety of vonoprazan-amoxicillin dual therapy for helicobacter pylori eradication: a randomized controlled trial.

BACKGROUND: Helicobacter pylori (H. pylori), prevalent in developing regions, is a key factor in gastrointestinal diseases. Despite the common use of bismuth-based quadruple therapy, its drawbacks have prompted the search for alternatives. Recently, vonoprazan, a novel acid suppressant, has shown promise in combination with antibiotics as a dual therapy for H. pylori eradication. This study aimed to assess the therapeutic outcomes and adverse events of vonoprazan-amoxicillin dual therapy compared to quadruple therapy. METHODS: A randomized controlled trial (RCT) enrolled H. pylori-infected patients at Zhejiang Hospital. Participants were randomly assigned to dual and quadruple therapy groups. The primary endpoints were H. pylori eradication and adverse events. RESULTS: Of the 400 patients studied from April 2022 to June 2023, In the intention-to-treat (ITT) analysis, the eradication rates of H. pylori in vonoprazan-amoxicillin dual therapy group and quadruple therapy group were 94.0% and 87.0%, respectively, p = 0.017. In the per-protocol (PP) analysis were 97.9% and 93.0%, p = 0.022. Additionally, the dual therapy group had a significantly lower incidence of adverse events (19%) compared to the quadruple therapy group (53%) (p < 0.001). CONCLUSION: Vonoprazan-amoxicillin dual therapy demonstrates superior eradication efficacy and reduced adverse events compared to quadruple therapy in H. pylori-infected patients, suggesting its potential for clinical application and promotion.

Early therapeutic drug monitoring of methotrexate and its association with acute kidney injury: A retrospective cohort study.

INTRODUCTION: High-dose methotrexate (HDMTX) use can be limited by the development of acute kidney injury (AKI). Early AKI detection is paramount to prevent further renal injury and irreversible toxicities. This study sought to determine whether early elimination patterns of MTX would be useful as a biomarker of AKI in HDMTX treatment. METHODS: This retrospective cohort study included two sites that collected ≥2 MTX levels within 16 h from completion of MTX infusion. Early levels were tagged and MTX elimination half-life (t½) were calculated from combinations of two of three different early time periods. Receiver operating characteristic (ROC) curves were synthesized for each elimination t½ (biomarker) with respect to AKI and delayed methotrexate elimination (DME); the biomarker with the highest area under the ROC curve (AUC) was tested in a multiple variable logistic regression model. RESULTS: Data from 169 patients who received a total of 556 courses of HDMTX were analyzed. ROC analysis revealed MTX elimination t½ calculated from the second and third time periods had the highest AUC for AKI at 0.62 (interquartile range [IQR] 0.56-0.69) and DME at 0.86 (IQR 0.73-1.00). After adjusting for age, sex, dose (mg/m2), infusion duration, HDMTX course, and baseline estimated glomerular filtration rate, it remained significant for AKI with an OR of 1.29 and 95% confidence interval of 1.03-1.65. CONCLUSION: Early MTX elimination t½ measured within 16 h of infusion completion was significantly associated with the development of AKI and serves as an early clearance biomarker that may identify patients who benefit from increased hydration, augmented leucovorin rescue, and glucarpidase administration.