Nevin Manimala

J Neurooncol. 2023 May 12. doi: 10.1007/s11060-023-04328-0. Online ahead of print.

ABSTRACT

BACKGROUND: The HIT-SKK protocol is used for low/standard-risk medulloblastomas in young children with the aim to eliminate cranial irradiation and its neuropsychological (NP) sequelae. This therapy includes IV and intraventricular (ITV) methotrexate (MTX) potentially responsible for leukoencephalopathy (LE) and neurocognitive disorders. This study describes the risk factors and course of LE, and investigates its correlation with neurocognitive impact.

METHODS: A retrospective, multicenter study was conducted in 35 children under 5 years old, with a median follow-up of 72 months (range 14 to 130). The main analysis was performed in 30 patients who received cumulative doses of MTX as per-protocol (group 1). Five patients who received higher cumulative doses of MTX were analyzed separately. All follow-up MRIs and NP assessments were centrally reviewed by experts.

RESULTS: Twenty patients in group 1 developed LE, grade 2 and 3 abnormalities did not correlate with higher cumulative doses of ITV-MTX (p = 0.698). Considering the most recent NP evaluation, the Full-Scale IQ (FSIQ) and Wechsler indices were in the average to lower average range. The FSIQ was deficient in 6/17 evaluable patients. Cumulative dose of ITV-MTX was almost associated with decreased processing speed competence (p = 0.055) which was the most frequently impaired neurocognitive domain. Neuropsychological assessment scores were not statistically lower in patients with persistent grade 2 LE at the end of follow-up.

CONCLUSION: This study described that the use of cumulative dose of MTX (IV and ITV) according to the HIT-SKK protocol resulted in LE that tented to decrease over time, without significant correlation with a decline in neuro-intellectual skills.

PMID:37171700 | DOI:10.1007/s11060-023-04328-0

Eur J Nucl Med Mol Imaging. 2023 May 12. doi: 10.1007/s00259-023-06240-1. Online ahead of print.

ABSTRACT

PURPOSE: To introduce a biomarker-based dosimetry method for the rational selection of a treatment activity for patients undergoing radioactive iodine ¹³¹I therapy (RAI) for metastatic differentiated thyroid cancer (mDTC) based on single-timepoint imaging of individual lesion uptake by ¹²⁴I PET.

METHODS: Patients referred for RAI therapy of mDTC were enrolled in institutionally approved protocols. A total of 208 mDTC lesions (in 21 patients) with SUV_max > 1 underwent quantitative PET scans at 24, 48, 72, and 120 h post-administration of 222 MBq of theranostic NaI-¹²⁴I to determine the individual lesion radiation-absorbed dose. Using a general estimating equation, a prediction curve for biomarker development was generated in the form of a best-fit regression line and 95% prediction interval, correlating individual predicted lesion radiation dose metrics, with candidate biomarkers (“predictors”) such as SUV_max and activity in microcurie per gram, from a single imaging timepoint.

RESULTS: In the 169 lesions (in 15 patients) that received ¹³¹I therapy, individual lesion cGy varied over 3 logs with a median of 22,000 cGy, confirming wide heterogeneity of lesion radiation dose. Initial findings from the prediction curve on all 208 lesions confirmed that a 48-h SUV_max was the best predictor of lesion radiation dose and permitted calculation of the ¹³¹I activity required to achieve a lesional threshold radiation dose (2000 cGy) within defined confidence intervals.

CONCLUSIONS: Based on MIRD lesion-absorbed dose estimates and regression statistics, we report on the feasibility of a new single-timepoint ¹²⁴I-PET-based dosimetry biomarker for RAI in patients with mDTC. The approach provides clinicians with a tool to select personalized (precision) therapeutic administration of radioactivity (MBq) to achieve a desired target lesion-absorbed dose (cGy) for selected index lesions based on a single 48-h measurement ¹²⁴I-PET image, provided the selected activity does not exceed the maximum tolerated activity (MTA) of < 2 Gy to blood, as is standard of care at Memorial Sloan Kettering Cancer Center.

TRIAL REGISTRATION: NCT04462471, Registered July 8, 2020. NCT03647358, Registered Aug 27, 2018.

PMID:37171634 | DOI:10.1007/s00259-023-06240-1

J Med Syst. 2023 May 12;47(1):62. doi: 10.1007/s10916-023-01947-y.

ABSTRACT

We aimed to assess the feasibility of developing three-dimensional (3D) models of pelvic organs using cross-sectional MRI images of patients with uterine fibroids and urinary symptoms and of obtaining anatomical information unavailable in 2D imaging modalities. We also aimed to compare two image processing applications. We performed a feasibility study analysing MRI scans from three women, aged 30 to 58 years old, with fibroids and urinary symptoms. Cross-sectional images were used to render 3D models of pelvic anatomy, including bladder, uterus and fibroids, using 3D Slicer and OsiriX. Dimensions, volumes and anatomical relationships of the pelvic organs were evaluated. Comparisons between anatomical landmarks and measurements obtained from the two image processing applications were undertaken. Rendered 3D pelvic models yielded detailed anatomical information and data on spatial relationships that were unobtainable from cross-sectional images. Models were rendered in sufficient resolution to aid understanding of spatial relationships between urinary bladder, uterus and fibroid(s). Measurements of fibroid volumes ranged from 5,336 to 418,012 mm³ and distances between the fibroid and urinary bladder ranged from 0.10 to 83.60 mm. Statistical analysis of measurements showed no significant differences in measurements between the two image processing applications. To date, limited data exist on the use of 3D volume reconstructions of routine MRI scans, to investigate pelvic pathologies such as fibroids in women with urinary symptoms. This study suggests that post-MRI image processing can provide additional information over standard MRI. Further studies are required to assess the role of these data in clinical practice, surgical planning and training. Three-dimensional reconstruction of routine two-dimensional magnetic resonance imaging provides additional anatomical information and may improve our understanding of anatomical relationships, their role in clinical presentations and possibly guide clinical and surgical management.

PMID:37171621 | DOI:10.1007/s10916-023-01947-y

Allergol Immunopathol (Madr). 2023 May 1;51(3):117-123. doi: 10.15586/aei.v51i3.820. eCollection 2023.

ABSTRACT

BACKGROUND: Urticaria is a common disorder, estimated to affect 2.1 to 6.7% of children and adolescents, and is a frequent cause of emergency department (ED) admissions.

METHODS: The aim of this study was to retrospectively characterize the clinical features of children and adolescents with a diagnosis of urticaria, evaluated in a tertiary care pediatric ED between 2015 and 2019. Statistical analysis was performed using IBM SPSS Statistics^®, version 27.0.

RESULTS: A total of 2254 episodes of urticaria were counted with 98.1% corresponding to acute urticaria (AU). A suspected trigger factor was identified in 51.6% of the episodes, namely infections (27.8%), drugs (9.9%) and food (7.6%). From these episodes, excluding infections, only 59.2% were referred to an Allergy Consultation for further study, with only 18.8% (drug) and 28.3% (food) confirmed as the AU trigger. Of the 43 episodes of chronic urticaria (CU), 79% were referred to consultation, with 23 being diagnosed with chronic spontaneous urticaria, 8 with inducible urticaria and 3 with both entities. Older age (p < 0.001), personal history of atopy (p = 0.019) and angioedema (p = 0.003) were factors associated with CU, while the presence of other accompanying symptoms (p = 0.007) was associated with AU. Older age (OR = 1.2; p < 0.001) and the presence of angioedema (OR = 2.7; p = 0.007) were identified as independent factors for CU.

CONCLUSION: The majority of episodes corresponded to AU. Infections were the main suspected trigger, followed by drugs and food, with an overall confirmation rate ranging from 18 to 30%, highlighting the importance of an allergologic follow-up evaluation.

PMID:37169569 | DOI:10.15586/aei.v51i3.820

Allergol Immunopathol (Madr). 2023 May 1;51(3):80-84. doi: 10.15586/aei.v51i3.790. eCollection 2023.

ABSTRACT

Lipid transfer protein (LTP) syndrome is an increasingly prevailing disease, especially in the young population, with severely affected quality of life. Since 2013, a specific treatment, called sublingual immunotherapy (SLIT), with peach extract (SLIT-peach^®) has been used, but with no long-term effectiveness studies. The main objective of the present study was to assess the long-term effectiveness of SLIT-peach^® and to relate the clinical evolution of patients. This was an ambispective study conducted for 3 years. A total of 25 patients with LTP syndrome were selected and treated with SLIT-peach^®. They underwent a provocation test in the first year with reintroduced foods that had produced symptoms in the past. Analytical determination of specific immunoglobulin E (IgE) and immunoglobulin G4 (IgG4) to peach (Pru p 3) was performed at the beginning of treatment, at the first year of initiation, and at the end of treatment. These data were compared with the control group comprising 14 patients with LTP syndrome without treatment. A statistically significant decrease in specific IgE to Pru p 3 at the end of the treatment and an increase in specific IgG4 to Pru p 3 1 year after treatment initiation were observed in the active group in relation to tolerance to foods with LTPs. These results indicate that food tolerance begins after the first year and is maintained after the end of 3 years of treatment. In conclusion, treatment with SLIT-peach^® for 3 years is effective for patients with LTP syndrome, preventing the evolution of the disease, allowing patients to restart a diet with plant foods, and improving their quality of life.

PMID:37169563 | DOI:10.15586/aei.v51i3.790

AJNR Am J Neuroradiol. 2023 May 11. doi: 10.3174/ajnr.A7865. Online ahead of print.

ABSTRACT

BACKGROUND AND PURPOSE: Surgical clipping and endovascular treatment are commonly used in patients with unruptured intracranial aneurysms. We compared the safety and efficacy of the 2 treatments in a randomized trial.

MATERIALS AND METHODS: Clipping or endovascular treatments were randomly allocated to patients with one or more 3- to 25-mm unruptured intracranial aneurysms judged treatable both ways by participating physicians. The study hypothesized that clipping would decrease the incidence of treatment failure from 13% to 4%, a composite primary outcome defined as failure of aneurysm occlusion, intracranial hemorrhage during follow-up, or residual aneurysms at 1 year, as adjudicated by a core lab. Safety outcomes included new neurologic deficits following treatment, hospitalization of >5 days, and overall morbidity and mortality (mRS > 2) at 1 year. There was no blinding.

RESULTS: Two hundred ninety-one patients were enrolled from 2010 to 2020 in 7 centers. The 1-year primary outcome, ascertainable in 290/291 (99%) patients, was reached in 13/142 (9%; 95% CI, 5%-15%) patients allocated to surgery and in 28/148 (19%; 95% CI, 13%-26%) patients allocated to endovascular treatments (relative risk: 2.07; 95% CI, 1.12-3.83; P = .021). Morbidity and mortality (mRS >2) at 1 year occurred in 3/143 and 3/148 (2%; 95% CI, 1%-6%) patients allocated to surgery and endovascular treatments, respectively. Neurologic deficits (32/143, 22%; 95% CI, 16%-30% versus 19/148, 12%; 95% CI, 8%-19%; relative risk: 1.74; 95% CI, 1.04-2.92; P = .04) and hospitalizations beyond 5 days (69/143, 48%; 95% CI, 40%-56% versus 12/148, 8%; 95% CI, 5%-14%; relative risk: 0.18; 95% CI, 0.11-0.31; P < .001) were more frequent after surgery.

CONCLUSIONS: Surgical clipping is more effective than endovascular treatment of unruptured intracranial aneurysms in terms of the frequency of the primary outcome of treatment failure. Results were mainly driven by angiographic results at 1 year.

PMID:37169541 | DOI:10.3174/ajnr.A7865

AJNR Am J Neuroradiol. 2023 May 11. doi: 10.3174/ajnr.A7867. Online ahead of print.

ABSTRACT

BACKGROUND AND PURPOSE: Important information regarding fluoroscopically guided lumbar puncture (FGLP) performance and referrals is lacking. The purpose of our study was to elucidate the success rate for initial FGLP attempts and re-attempts, reasons for unsuccessful FGLPs, and the relationship between clinical indications and whether patients will undergo a fluoroscopically guided re-attempt, among others.

MATERIALS AND METHODS: This retrospective study analyzed failed FGLP attempts in hospitalized adult patients at an academic hospital between June 2016 and March 2022. Unsuccessful FGLPs were labeled as insufficient CSF egress. FGLP reports and patients’ clinical charts were analyzed for pertinent information such as clinical indication, reason for failure, whether patients received IV fluid before fluoroscopically guided spinal puncture attempt, and which patients returned for another FGLP attempt. Patients’ ages and sex were analyzed using descriptive statistics. The OR was used to investigate the relationship between the clinical indications to perform FGLP and whether patients returned for a re-attempt.

RESULTS: Sixty-three of 1389 (4.5%) patients (median age, 62 years) had failed the initial FGLPs administered by 39 trainees. Twenty-eight of 63 (44.4%) patients (median age, 64 years) underwent a re-attempt within a median of 2 days after the first attempt, and 27/28 (96.4%) re-attempts were successful. A dry tap, no egress of CSF was the top reason (58.7%) for failed FGLP, and 12/13 of patients had a successful FGLP after IV hydration. Twenty-seven of 63 (43%) patients did not undergo a repeat attempt, and 100% were subsequently discharged from the hospital. There was no difference (P > .05) in the likelihood of patients returning for a repeat FGLP based on the clinical indications.

CONCLUSIONS: Initial and repeat FGLPs have very high success rates. No difference exists in the likelihood of patients returning for a re-attempt based on clinical indication.

PMID:37169540 | DOI:10.3174/ajnr.A7867

Psychiatry Clin Neurosci. 2023 May 11. doi: 10.1111/pcn.13565. Online ahead of print.

ABSTRACT

AIM: The main aim of this study was to investigate the additional effects of L-theanine, an amino acid in tea and an analog of glutamate with neuroprotective and anti-depressant properties, on obsessive-compulsive disorder (OCD) symptoms in combination with fluvoxamine.

METHODS: Patients from either sex aged between 18-60 years diagnosed with OCD, based on the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5), who had a Yale-Brown Obsessive Compulsive Scale (Y-BOCS) score of more than 21 were enrolled in a double-blinded, parallel-group, placebo-controlled, clinical trial of 10 weeks to receive either L-theanine (100 mg twice daily) and fluvoxamine (100 mg daily initially followed by 200 mg daily after week 5) or placebo and fluvoxamine. The primary outcome of interest in this study was the Y-BOCS total score decrease from baseline.

RESULTS: From a total of 95 evaluated patients, 50 completed our study; 30 were randomly assigned to each group. Multivariate analysis (ANOVA) showed a significant effect of time × treatment for L-theanine in obsession subscale (F = 5.51, p-value = 0.008) of the Y-BOCS score but not in the total and compulsion scores. Our results showed significantly more improvement in obsession subscale scores in L-theanine compared to placebo group (p = 0.007, Cohen’s d = 0.82). Also, total Y-BOCS scores were lower in L-theanine compared to placebo group at week 5 (p = 0.039, Cohen’s d = 0.60) and 10 (p = 0.008, Cohen’s d = 0.80). However, there was no significant between-group differences in compulsion subscale scores. Complete response was also more frequent in the L-theanine group (p = 0.0001).

CONCLUSION: Findings in this study suggest L-theanine as a relatively safe and effective adjuvant therapy for moderate to severe OCD. This article is protected by copyright. All rights reserved.

PMID:37169515 | DOI:10.1111/pcn.13565

BMJ Open. 2023 May 11;13(5):e065538. doi: 10.1136/bmjopen-2022-065538.

ABSTRACT

INTRODUCTION: Low dietary calcium intake is a risk factor for pre-eclampsia, a major contributor to maternal and perinatal mortality and morbidity worldwide. Calcium supplementation can prevent pre-eclampsia in women with low dietary calcium. However, the optimal dose and timing of calcium supplementation are not known. We plan to undertake an individual participant data (IPD) meta-analysis of randomised trials to determine the effects of various calcium supplementation regimens in preventing pre-eclampsia and its complications and rank these by effectiveness. We also aim to evaluate the cost-effectiveness of calcium supplementation to prevent pre-eclampsia.

METHODS AND ANALYSIS: We will identify randomised trials on calcium supplementation before and during pregnancy by searching major electronic databases including Embase, CINAHL, MEDLINE, CENTRAL, PubMed, Scopus, AMED, LILACS, POPLINE, AIM, IMSEAR, ClinicalTrials.gov and the WHO International Clinical Trials Registry Platform, without language restrictions, from inception to February 2022. Primary researchers of the identified trials will be invited to join the International Calcium in Pregnancy Collaborative Network and share their IPD. We will check each study’s IPD for consistency with the original authors before standardising and harmonising the data. We will perform a series of one-stage and two-stage IPD random-effect meta-analyses to obtain the summary intervention effects on pre-eclampsia with 95% CIs and summary treatment-covariate interactions (maternal risk status, dietary intake, timing of intervention, daily dose of calcium prescribed and total intake of calcium). Heterogeneity will be summarised using tau², I² and 95% prediction intervals for effect in a new study. Sensitivity analysis to explore robustness of statistical and clinical assumptions will be carried out. Minor study effects (potential publication bias) will be investigated using funnel plots. A decision analytical model for use in low-income and middle-income countries will assess the cost-effectiveness of calcium supplementation to prevent pre-eclampsia.

ETHICS AND DISSEMINATION: No ethical approvals are required. We will store the data in a secure repository in an anonymised format. The results will be published in peer-reviewed journals.

PROSPERO REGISTRATION NUMBER: CRD42021231276.

PMID:37169508 | DOI:10.1136/bmjopen-2022-065538

BMJ Open. 2023 May 11;13(5):e068969. doi: 10.1136/bmjopen-2022-068969.

ABSTRACT

OBJECTIVE: The purpose of this systematic review and meta-analysis was to investigate whether glucocorticoid might be beneficial after hepatectomy.

DESIGN: Systematic review and meta-analysis.

DATA SOURCES: PubMed, Embase, Cochrane Library and Web of Science.

ELIGIBILITY CRITERIA: We included studies assessing the efficacy of perioperative glucocorticoid administration in patients undergoing liver surgery.

DATA EXTRACTION AND SYNTHESIS: Four data bases were retrieved for all randomised controlled trials. We considered postoperative complications, hospital stay and postoperative chemistry evaluations as outcomes. Pooled effects of dichotomic variables were expressed as relative risk (RR) with a 95% CI. The mean difference was used for continuous variables and an inverse variance statistical method was adopted.

RESULTS: Fourteen studies with 1205 patients were included. Lower risk of overall complications was associated with glucocorticoid (RR, 0.77; 95% CI 0.64 to 0.92), while no difference was found in hospital stay (RR, 0.02; 95% CI -0.47 to 0.51). There were also improvements in postoperative chemistry evaluations including interleukin 6 on day 1 and 3, C reactive protein on day 1, 2 and 3, international normalised ratio on day 2, total bilirubin on day 1, 2, 3 and 5, albumin on day 1.

CONCLUSION: Current evidence indicated that perioperative glucocorticoid administration for patients undergoing hepatectomy reduced the risk of overall complications with inhibited postoperative inflammatory response and improved postoperative liver function.

PROSPERO REGISTRATION NUMBER: CRD42022307533.

PMID:37169506 | DOI:10.1136/bmjopen-2022-068969