Category: Statistics

J Allergy Clin Immunol Pract. 2025 Sep;13(9):2535. doi: 10.1016/j.jaip.2025.06.017.

NO ABSTRACT

PMID:40947180 | DOI:10.1016/j.jaip.2025.06.017

J Allergy Clin Immunol Pract. 2025 Sep;13(9):2460-2474. doi: 10.1016/j.jaip.2025.06.015.

ABSTRACT

BACKGROUND: Primary immunodeficiency diseases (PIDDs) are rare genetic disorders impairing immunity. Studies evaluating diagnostic rates of PIDDs in historically marginalized US populations are limited.

OBJECTIVE: To conduct a scoping review that identifies the extent of race and ethnicity reporting in US-based observational studies of people with PIDDs, and the demographic composition of study populations compared with the broader US population.

METHODS: We conducted pragmatic searches of MEDLINE in April 2024 and ultimately included studies dating back 10 years. Results were screened and extracted against prespecified eligibility criteria by a single reviewer. Included data were compared with US census data using χ² tests.

RESULTS: We identified 126 publications publishing observational PIDD studies that report patient characteristics, 62 of which (49%) reported race or ethnicity data. After grouping for data source and PIDD type to avoid overlapping studies, 25 publications were prioritized for extraction. Of these, seven were fully compliant with current Food and Drug Administration-recommended reporting guidelines. The populations of the extracted studies were not statistically representative of the broader US population, with overrepresentation of non-Hispanic White patients.

CONCLUSIONS: Primary immunodeficiency disease cohort and other studies inconsistently report demographic data on patient race and ethnicity according to current Food and Drug Administration recommendations. Efforts to improve understanding of the prevalence, characteristics, and diagnostic rates of PIDD in different US populations (as well as differences among study populations and overall US demographics) would likely be facilitated by a greater effort toward comprehensive demographic reporting.

PMID:40947178 | DOI:10.1016/j.jaip.2025.06.015

J Neurosurg. 2025 Sep 12:1-10. doi: 10.3171/2025.5.JNS243092. Online ahead of print.

ABSTRACT

OBJECTIVE: Prolactinomas are the most common type of pituitary adenoma. Historically, surgery was the primary treatment, but the introduction of dopaminergic agonists in the 1970s changed therapeutic practices. Recent guidelines (2023) from the Pituitary Society now recommend surgery as the first-line option for select prolactinomas, particularly those with certain grades as defined by the Knosp classification system. This systematic review and meta-analysis was performed to evaluate the safety of and the biochemical remission rates following resection of prolactinomas classified preoperatively by Knosp grade.

METHODS: A comprehensive literature search was conducted across the MEDLINE (via PubMed), Scopus, Web of Science, LILACS (Latin American and Caribbean Literature on Health Sciences), and Cochrane CENTRAL (Central Register of Controlled Trials) databases from inception to February 2024. Eligible studies reported individual participant data on the biochemical remission and surgical outcomes of patients with prolactinomas stratified by Knosp grade. A random effects meta-analysis was performed to synthesize biochemical remission rates and relative risks, with results presented in forest plots. Subgroup analyses were conducted according to Knosp grade, heterogeneity was assessed using the I2 statistic, prediction intervals were reported, and publication bias was evaluated through funnel plots and Egger’s test. This review was registered in the International Prospective Register of Systematic Reviews (registration no.: CRD42024602904) and followed the PRISMA guidelines.

RESULTS: Twelve studies involving 1010 patients with prolactinomas undergoing transsphenoidal surgery were included. Prolactinomas classified as Knosp grades 0-2 demonstrated significantly higher biochemical remission rates of 75% (95% CI 67%-82%, prediction interval 42%-96%, I2 = 81.5%, p < 0.0001) compared to 22% (95% CI 16%-31%, prediction interval 11%-38%, I2 = 17.2%, p = 0.57) for Knosp grades 3-4. Transsphenoidal surgery was associated with favorable outcomes characterized by low complication rates and no reported deaths.

CONCLUSIONS: Resection for Knosp grade 0-2 prolactinomas appears to be an effective first-line treatment option, resulting in favorable biochemical remission rates and low complication risks. These findings support considering surgery in appropriately selected patients, particularly at experienced medical centers. However, the high heterogeneity among and the observational design of most included studies limit the strength of the conclusions. Thus, further studies are needed to compare surgical and medical management strategies across Knosp grades and to refine patient selection.

PMID:40939216 | DOI:10.3171/2025.5.JNS243092

J Neurosurg. 2025 Sep 12:1-10. doi: 10.3171/2025.5.JNS243092. Online ahead of print.

ABSTRACT

OBJECTIVE: Prolactinomas are the most common type of pituitary adenoma. Historically, surgery was the primary treatment, but the introduction of dopaminergic agonists in the 1970s changed therapeutic practices. Recent guidelines (2023) from the Pituitary Society now recommend surgery as the first-line option for select prolactinomas, particularly those with certain grades as defined by the Knosp classification system. This systematic review and meta-analysis was performed to evaluate the safety of and the biochemical remission rates following resection of prolactinomas classified preoperatively by Knosp grade.

METHODS: A comprehensive literature search was conducted across the MEDLINE (via PubMed), Scopus, Web of Science, LILACS (Latin American and Caribbean Literature on Health Sciences), and Cochrane CENTRAL (Central Register of Controlled Trials) databases from inception to February 2024. Eligible studies reported individual participant data on the biochemical remission and surgical outcomes of patients with prolactinomas stratified by Knosp grade. A random effects meta-analysis was performed to synthesize biochemical remission rates and relative risks, with results presented in forest plots. Subgroup analyses were conducted according to Knosp grade, heterogeneity was assessed using the I2 statistic, prediction intervals were reported, and publication bias was evaluated through funnel plots and Egger’s test. This review was registered in the International Prospective Register of Systematic Reviews (registration no.: CRD42024602904) and followed the PRISMA guidelines.

RESULTS: Twelve studies involving 1010 patients with prolactinomas undergoing transsphenoidal surgery were included. Prolactinomas classified as Knosp grades 0-2 demonstrated significantly higher biochemical remission rates of 75% (95% CI 67%-82%, prediction interval 42%-96%, I2 = 81.5%, p < 0.0001) compared to 22% (95% CI 16%-31%, prediction interval 11%-38%, I2 = 17.2%, p = 0.57) for Knosp grades 3-4. Transsphenoidal surgery was associated with favorable outcomes characterized by low complication rates and no reported deaths.

CONCLUSIONS: Resection for Knosp grade 0-2 prolactinomas appears to be an effective first-line treatment option, resulting in favorable biochemical remission rates and low complication risks. These findings support considering surgery in appropriately selected patients, particularly at experienced medical centers. However, the high heterogeneity among and the observational design of most included studies limit the strength of the conclusions. Thus, further studies are needed to compare surgical and medical management strategies across Knosp grades and to refine patient selection.

PMID:40939216 | DOI:10.3171/2025.5.JNS243092

J Neurosurg Spine. 2025 Sep 12:1-10. doi: 10.3171/2025.5.SPINE25215. Online ahead of print.

ABSTRACT

OBJECTIVE: Mid- to long-term data on the natural history of degenerative lumbar spinal stenosis (LSS) remain limited as surgery is increasingly favored. The aim of this study was to characterize the prevalence of clinical deterioration over long-term follow-up and to identify risk and protective factors.

METHODS: In this retrospective cohort study, adult patients with symptomatic LSS and a follow-up period ≥ 5 years were analyzed. Clinical deterioration was defined by at least one of the following factors: myotomal lower limb weakness, sphincter disturbance, or a decrease in walking tolerance to ≤ 10 minutes due to neurogenic claudication. Radiological assessment included standing lumbar radiographs and lumbosacral MR images obtained after symptom onset. A univariate analysis was performed, with variables demonstrating significance levels of p < 0.1 included in the subsequent multivariable logistic regression analysis. Receiver operating characteristic (ROC) curves and Kaplan-Meier survival curves were plotted for statistically significant risk factors.

RESULTS: A total of 202 patients with symptomatic LSS and adequate follow-up were included. The mean age was 65.2 ± 4.2 years at the onset of neurological symptoms and the mean follow-up duration was 121 ± 40 months. Clinical deterioration occurred in 39 patients (19.3%). Among those with deterioration, 36 (92.3%) reported reduced walking tolerance due to neurogenic claudication, 8 (20.5%) had myotomal weakness, and 2 (5.1%) experienced sphincter disturbance. Upon multivariate analysis, the presence of lumbar developmental spinal stenosis was a risk factor for deterioration (p = 0.031), while an increased dural sac area was protective (p = 0.045); adjusted hazard ratios were 10.11 and 0.98, respectively. A dural sac area < 55 mm2 had an area under the ROC curve of 0.781 for predicting clinical deterioration within 5 years of symptom onset.

CONCLUSIONS: Patients with lumbar stenosis and neurogenic claudication mostly remained ambulatory without developing motor deficits or sphincter dysfunction. Conservative management is an option for patients with tolerable symptomatology and low functional expectations, especially in the absence of the identified risk factors of developmental narrowing of lumbar canal dimensions and critically reduced dural sac area over the most stenotic level.

PMID:40939213 | DOI:10.3171/2025.5.SPINE25215

Blood. 2025 Sep 12:blood.2025028823. doi: 10.1182/blood.2025028823. Online ahead of print.

ABSTRACT

The IELSG37 trial enrolled 545 patients with primary mediastinal B-cell lymphoma (PMBCL) and demonstrated that consolidation radiotherapy (RT) can be omitted in patients with complete metabolic response (CMR), defined by the Lugano classification as Deauville score (DS) 1-3. This report evaluates outcomes following different frontline rituximab- and doxorubicin-based immunochemotherapy regimens chosen according to local practice. Patients treated with R-CHOP21 showed a significantly higher percentage of DS 5 than those on other regimens (23.8% vs. 8.2% average, P< 0.001) as well as a trend toward additional unplanned treatments (53.2% vs. 46.9%, P=0.30). The increased risk of poor response was confirmed in a multinomial logistic regression analysis adjusted for age, sex, IPI score, and performance status. R-CHOP21 was also associated with smaller reductions in MTV and less pronounced decreases in SUVmax. Patients with DS 5 more often received additional treatment (RT and/or salvage chemotherapy with or without autologous consolidation) after induction immunochemotherapy (96% vs. 41%, P< 0.001) and experienced significantly poorer outcomes. Although differences in progression-free and overall survival between R-CHOP21 and more aggressive regimens were not statistically significant, R-CHOP21 may increase the risk of additional treatments and may be inadvisable as frontline therapy for PMBCL. NCT01599559.

PMID:40939190 | DOI:10.1182/blood.2025028823

JCO Glob Oncol. 2025 Sep;11:e2500180. doi: 10.1200/GO-25-00180. Epub 2025 Sep 12.

ABSTRACT

PURPOSE: Malignant apocrine and eccrine tumors (MAETs) are extremely rare cutaneous adnexal malignancies, accounting for only 0.005%-0.01% of all skin tumors. These tumors are highly metastatic, and evidence regarding optimal chemotherapy and prognostic outcomes remains limited. This study aimed to evaluate the efficacy of systemic chemotherapy and overall prognosis in Japanese patients with unresectable MAETs.

PATIENTS AND METHODS: We conducted a retrospective, multicenter study involving 81 patients with unresectable MAETs treated at 27 institutions across Japan. Patients received one of three primary chemotherapy regimens: platinum-based (cisplatin or carboplatin), taxane-based (docetaxel or paclitaxel), or TS-1 (tegafur/gimeracil/oteracil). Patient demographics, objective response rates (ORRs), overall survival (OS), and progression-free survival were assessed. Survival curves were estimated using the Kaplan-Meier method.

RESULTS: The estimated ORRs for the platinum-based, taxane-based, and TS-1 groups were 37.0%, 25.0%, and 22.2%, respectively, with no statistically significant differences among them (P = .527). The median OS and 5-year OS rate for the entire cohort were 29.0 months and 34.0%, respectively. The median OS and 5-year OS rates by regimen were as follows: platinum-based, 29.0 months and 36.2%; taxane-based, 22.0 months and 39.7%; and TS-1, 30.0 months and 13.9%, with no significant differences observed (P = .907). In addition, there were no significant differences in ORR or OS between patients receiving combined chemoradiotherapy and those receiving chemotherapy alone.

CONCLUSION: No single chemotherapeutic regimen demonstrated superior efficacy in patients with unresectable MAETs. These findings highlight the need for further investigations using larger, prospective cohorts and multidisciplinary approaches to establish optimal therapeutic strategies for this rare malignancy.

PMID:40939132 | DOI:10.1200/GO-25-00180

Neurology. 2025 Oct;105(7):e214070. doi: 10.1212/WNL.0000000000214070. Epub 2025 Sep 12.

ABSTRACT

BACKGROUND AND OBJECTIVES: The third Intensive Care Bundle with Blood Pressure Reduction in Acute Cerebral Hemorrhage Trial (INTERACT3) showed that the implementation of a care bundle improves the functional outcome of patients who experience acute intracerebral hemorrhage (ICH). However, uncertainty exists over the relative contribution of each component of the care bundle for the benefit.

METHODS: INTERACT3 used a stepped-wedge, cluster randomized controlled trial design, which was conducted in 5 lower and 4 upper middle-income countries and 1 high-income country. Compared with usual care, there was a statistically significant beneficial effect of the intervention, a care bundle comprising early control of elevated blood pressure (BP), glucose, and temperature and reversal of warfarin-related anticoagulation, on the primary outcome of functional recovery of ICH. We performed a model-based causal mediation analysis to assess the contribution of each component of the care bundle to the overall effect, as measured by the modified Rankin Scale (mRS) at 6 months after randomization. The mediation analysis considered whether protocol-specified treatment targets were reached as well as the actual achieved levels of physiologic control according to the summary measures of systolic BP (mean, variation over 1-24 hours, and reduction in 1 hour) and mean of blood glucose, body temperature, and international normalized ratio over 24 hours. The analyses were performed in the modified intention-to-treat population with available mRS data.

RESULTS: A total of 6,225 patients (mean age 61.9 years [SD 12.6], 2,284 women [36.5%]) with available primary outcome data were included in these analyses. Overall, only the control of BP and blood glucose contributed positively to the beneficial effect, with mediated proportions of 8.9% (95% CI 4.8-20.0) and 7.0% (1.1-17.0) for achieved systolic BP and blood glucose over 24 hours after randomization, respectively, and 4.0% (1.2-14.0) and 7.6% (2.2-15.0) for reaching the specified targets for systolic BP and blood glucose, respectively.

DISCUSSION: The major contributors to the effectiveness of the care bundle in INTERACT3 for improved functional outcomes after acute ICH were the control of systolic BP and blood glucose, as indicated by both the achieved levels and protocol targets being met.

TRIAL REGISTRATION INFORMATION: The name of the registry is “the Third, Intensive Care Bundle With Blood Pressure Reduction in Acute Cerebral Hemorrhage Trial (INTERACT3).” This trial was submitted for registration at ClinicalTrials.gov (NCT03209258) on July 1, 2017, and the Chinese Clinical Trial Registry (ChiCTR-IOC-17011787) on June 28, 2017. The first patient was enrolled on December 12, 2017.

PMID:40939125 | DOI:10.1212/WNL.0000000000214070

Glob Chang Biol. 2025 Sep;31(9):e70486. doi: 10.1111/gcb.70486.

ABSTRACT

Unsustainable soil management, climate change, and land degradation jeopardize soil biodiversity and soil-mediated ecosystem functions. Although the transition from conventional to organic agriculture has been proposed as a potential solution to alleviate these pressures, there is limited evidence of its effectiveness in enhancing belowground biodiversity across different biogeographical regions, climates, and land degradation levels. In this study, we holistically assessed the status of soil biodiversity, from microorganisms to meso- and macrofauna, in agroecosystems distributed across four continents. We identified the primary environmental community composition drivers and assessed the effects of the transition from conventional to organic management (no chemical inputs) on soil ecology. Our findings highlight the mean temperature and precipitation of the warmest and coldest quarters of the year, aridity, pH, and soil texture as the primary drivers of the different soil biodiversity components. Overall, organic farming has a significant but small impact on soil biodiversity compared to the other community drivers. On top of that, the results demonstrate the importance of a regional-specific context for a future generalized transition towards organic soil management. Specifically, under the most arid conditions in our study, organic management showed potential to buffer biodiversity loss in highly degraded soils, with a significant increase in diversity for prokaryotes and protists compared to conventionally managed soils. Therefore, the combination of a global and, simultaneously, regional-specific approach supports the hypothesis that a shift towards organic agriculture would maximize its beneficial impact on belowground diversity in highly degraded soils under arid conditions over the coming years, being a crucial tool to increase resilience and adaptation to global change for agriculture.

PMID:40939096 | DOI:10.1111/gcb.70486

Rev Med Virol. 2025 Sep;35(5):e70069. doi: 10.1002/rmv.70069.

ABSTRACT

The central nervous system is a potential target of the COVID-19 virus, and one of the devastating neurological consequences of this infection is cerebral haemorrhage (ICH). Cerebral haemorrhage is a leading cause of death worldwide. This study aimed to systematically review and analyse the existing literature on this topic and provide insights into the potential neurological consequences of COVID-19. A comprehensive search was conducted across the PubMed, Scopus, Web of Science, and Embase databases to extract relevant published data up to February 2025. This meta-analysis included 11 studies involving a total of 197,060 individuals. Subgroup analyses were performed based on the year of publication, hospital sampling wards, and study design. A critical appraisal was carried out using the Newcastle-Ottawa Scale (NOS) score. Risk was utilised as a measure of pooled effect size based on a random-effects model. In this analysis, we identified 11 articles that directly assessed the risk of cerebral haemorrhage. The reported risk of cerebral haemorrhage was five cases per 10,000 COVID-19 patients [0.005 (95% CI: 0.002-0.009), p < 0.001]. Notably, studies published in 2022 and 2023 indicated a significantly higher risk of cerebral haemorrhage compared to earlier years. COVID-19 patients admitted to the intensive care unit (ICU) faced an increased risk of cerebral haemorrhage compared to those admitted to general wards. Meta-regression analysis revealed a statistically significant association between the risk of cerebral haemorrhage and the type of wards in a hospital [0.0089 (95% CI: 0.0067-0.0112), p < 0.001], as well as the year of publication [0.0004 (95% CI: 0.0003-0.0008), p = 0.048]. Therefore, it is essential to evaluate COVID-19 patients admitted to the ICU in recent years for the potential occurrence of cerebral haemorrhage.

PMID:40939094 | DOI:10.1002/rmv.70069