The wide variety of methotrexate dosing regimens for the treatment of atopic dermatitis: a systematic review.

Background:Methotrexate is an off-label therapy for atopic dermatitis. A lack of consensus on dosing regimens poses a risk of underdosing and ineffective treatment or overdosing and increased risk of side effects. This systematic review summarizes the available evidence on dosing regimens.Materials and methods:A literature search was conducted, screening all randomized controlled trials (RCTs) and guidelines published up to 6 July 2023, in the MEDLINE, Embase, and Cochrane Library databases.Results:Five RCTs and 21 guidelines were included. RCTs compared methotrexate with other treatments rather than different methotrexate dosing regimens. The start and maintenance doses in RCTs varied between 7.5-15 mg/week and 14.5-25 mg/week, respectively. Despite varied dosing, all RCTs demonstrated efficacy in improving atopic dermatitis signs and symptoms. Guidelines exhibited substantial heterogeneity but predominantly proposed starting doses of 5-15 mg/week for adults and 10-15 mg/m2/week for children. Maintenance doses suggested were 7.5-25 mg/week for adults and 0.2-0.7 mg/kg/week for children. One guideline suggested a test dose and nearly half advised folic acid supplementation.Conclusion:This systematic review highlights the lack of methotrexate dosing guidelines for atopic dermatitis. It identifies commonly recommended and utilized dosing regimens, serving as a valuable resource for clinicians prescribing methotrexate off-label and providing input for an upcoming consensus study.

Heart Rate Characteristics Monitoring for Late-Onset Sepsis in Preterm Infants: A Systematic Review.

BACKGROUND: Early diagnosis of late-onset sepsis (LOS) and necrotizing enterocolitis (NEC) by monitoring heart rate characteristics (HRC) of preterm infants might reduce the risk of death and morbidities. We aimed to systematically assess the effects of HRC monitoring on death, LOS, and NEC. METHODS: A systematic search was performed in MEDLINE, Embase, Cochrane Library, and Web of Science. RESULTS: Fifteen papers were included in this review. Three of these papers reported results from the only identified randomized controlled trial (RCT). This RCT showed that HRC monitoring resulted in a small but significant reduction in mortality (absolute risk reduction 2.1% [95% confidence interval 0.01-4.14]) without any differences in neurodevelopmental impairment. The risk of bias was rated high due to performance and detection bias and failure to correct for multiple testing. Most diagnostic cohort studies showed high discriminating accuracy in predicting LOS but lacked sufficient quality and generalizability. No studies for the detection of NEC were identified. CONCLUSION: Supported by multiple observational cohort studies, the RCT identified in this systematic review showed that HRC monitoring as an early warning system for LOS might reduce the risk of death in preterm infants. However, methodological weaknesses and limited generalizability do not justify implementation of HRC in clinical care. A large international RCT is warranted.

Neo-adjuvant chemotherapy in fertility-sparing cervical cancer treatment.

The current review provides a literature overview of studies assessing the oncological and fertility outcomes of treatment with neo-adjuvant chemotherapy followed by fertility-sparing surgery in patients with cervical cancer >2 cm. Six cohort studies were included showing severe heterogeneity regarding patient selection, chemotherapy regimen, and surgical approach. In total, 111 patients were studied, with overall favorable characteristics. Patients were on average 29 years old, had a tumor of 36 mm, no lymph node metastasis, and response to chemotherapy. In approximately 5-year follow-up, the recurrence rate was 13% (0%-21%) and overall death rate 2.7% (0%-10%). Three patients were alive with recurrent disease (2.7% and 0%-11%). Of the 111 patients, 90 underwent successful fertility-sparing treatment (83%). Roughly one-third conceived and one-fourth had a healthy live-born child. More research is essential to determine proper selection criteria for fertility-sparing treatment of cervical cancer >2 cm and the optimal treatment management.

Data on vessel wall thickness measurements of intracranial arteries derived from human circle of Willis specimens.

In this article, we report data on vessel wall thickness parameters derived from different arterial segments of the circle of Willis and its primary branches in patients with and without cerebrovascular disease. Also data on inter-rater reliability and agreement of the derived vessel wall parameters are reported. For further interpretation and discussion please refer to the research article "ex vivo vessel wall thickness measurements of the human circle of Willis using 7T MRI" (Harteveld et al., in press) [1].

Ex vivo vessel wall thickness measurements of the human circle of Willis using 7T MRI.

BACKGROUND AND AIMS: MRI can detect intracranial vessel wall thickening before any luminal stenosis is present. Apart from representing a vessel wall lesion, wall thickening could also reflect normal (age-related) variations in vessel wall thickness present throughout the intracranial arterial vasculature. The aim of this study was to perform vessel wall thickness measurements of the major intracranial arteries in ex vivo circle of Willis (CoW) specimens using 7T MRI, to obtain more detailed information about wall thickness variations of the intracranial arteries. METHODS: Fifteen human CoW specimens were scanned at 7T MRI with an ultrahigh-resolution T1-weighted sequence. Five specimens were used for validation of MRI measurements with histology and evaluation of inter-rater reliability and agreement. The other 10 specimens from patients with (n = 5) and without (n = 5) cerebrovascular disease were used for vessel wall thickness measurements over the entire length of the major arterial segments of the CoW using MRI only. RESULTS: MRI measurements showed excellent agreement with histology. Mean wall thickness varied from 0.45 to 0.66 mm, minimum wall thickness from 0.31 to 0.42 mm, maximum wall thickness from 0.52 to 0.86 mm, and normalized wall index from 0.64 to 0.75. On average, vessel walls were thicker for symptomatic patients compared to asymptomatic patients. CONCLUSIONS: High-resolution MRI enables accurate measurement of vessel wall thickness in ex vivo CoW specimens. Vessel wall thickness measurements over the entire length of segments showed considerable variation both within and between arterial segments of patients.

Atherosclerosis in the circle of Willis: Spatial differences in composition and in distribution of plaques.

BACKGROUND AND AIMS: Intracranial atherosclerosis is one of the main causes of ischemic stroke. However, the characteristics of intracranial arteries and atherosclerosis have rarely been studied. Therefore, we systematically investigated atherosclerotic changes in all arteries of the Circle of Willis (CoW). METHODS: Sixty-seven CoWs obtained at autopsy from randomly chosen hospital patients (mean age, 67.3 ± 12.5 years), of which a total of 1220 segments were collected from 22 sites. Atherosclerotic plaques were classified according to the revised American Heart Association classification and were related to local vessel characteristics, such as the presence of an external and internal elastic lamina and the elastic fibre density of the media. RESULTS: 181 out of the 1220 segments had advanced plaques (15%), which were mainly observed in large arteries such as the internal carotid, middle cerebral, basilar and vertebral artery. Only 11 out of 1220 segments (1%) showed complicated plaques (p < 0.001). Six of these were intraplaque hemorrhages (IPH) and observed only in patients who had cardiovascular-related events (p = 0.015). The frequency of characteristics such as the external elastic lamina and a high elastin fibre density in the media was most often associated with the vertebral artery. Only 3% (n = 33) of the CoW arteries contained calcification (p < 0.001), which were mostly observed in the vertebral artery (n = 13, 12%). CONCLUSIONS: Advanced atherosclerotic plaques in the CoW are relatively scarce and mainly located in the 4 large arteries, and mostly characterized by an early and stable phenotype, a low calcific burden, and a low frequency of IPH.