bluuebunny/crossref_metadata_2025 huggingface dataset:
P18.10.B WHICH MENINGIOMAS BENEFIT MOST FROM METHYLATION PROFILING?
Authors: Ruiz F , D'Antona L , Dutt M , Mariathasan P , Merve A , Jaunmuktane Z , Sahm F , Brandner S
Published: September 2023

BACKGROUND

methylation profiling combined with copy number assay provide a better prognostication than WHO grade alone. Profiling all meningiomas is financially unsustainable in most centres, therefore pathologists and clinicians ask for guidance which meningiomas to analyse. Here, we analysed how the WHO grades resolve into methylation classes and risk strata, to provide guidance on which meningiomas to profile

MATERIAL AND METHODS

From 2018-2023 a subset of meningiomas diagnosed within our institution, and all referred meningiomas underwent methylation profiling with copy number assay. Using the classifier 12.6 we determined how the 3 CNS WHO grades (in short G1, G2, G3), resolve into the methylation classes (MC) benign, intermediate, or malignant, or the risk strata low, intermediate, and high [PMID 36377252, 34618539]

RESULTS

Of 1408 locally diagnosed meningiomas, 309 (22%) underwent profiling and 393 meningiomas were referred. Of these 702 meningiomas, 545 had a calibrated score of >0.90. Of 253 G1 meningiomas 231 (91%) allocated to MC benign, and 22 (9%) into MC intermediate. Instead, of the 214 G2 meningiomas, 124 (58%) allocated to MC benign, 77 (36%) to MC intermediate and 13 (6%) into MC malignant. The 17 G3 meningiomas distributed approximately equally into the 3 MC’s. Similarly, when analysing the allocation to integrated risk scores, of the 214 G2 meningiomas, 71 (33 %) were low, 106 (50%) intermediate, and 37 (17 %) high risk. None of the 16 G3 meningiomas had a low risk score, whilst 5 had an intermediate, and 11 a high risk score. When stratifying G2 meningiomas by grading criterium (brain invasion, mitotic count, histological type) there was a similar risk score distribution across the 3 criteria.

CONCLUSION

G2 meningiomas show the most notable discrepancy between grade and methylation class or risk score, and thus should preferentially undergo methylation profiling. Instead, most G1 meningiomas have a low, and most G3 meningiomas a high risk score.
P19.03.B IMPLEMENTATION OF RESECT CATEGORIES FOR EXTENT OF RESECTION STRESS THE LONG-TERM CLINICAL BENEFIT OF SUPRAMAXIMAL CONTRAST ENHANCING RESECTION IN A RETROSPECTIVE COHORT OF NEWLY DIAGNOSED IDH WT GLIOBLASTOMA PATIENTS
Authors: Gambacciani C , Nizzola M G , Calvanese F , Villanacci F , Pieri F , Grimod G , Aquila F , Scudieri C , Cupini S , Stasi I , Zucchi V , Giusti A , Lastrucci L , Vannozzi F , Giuri A , Farina L , Pichiecchio A , Di Stefano A L , Santonocito O S
Published: September 2023

BACKGROUND

to assess the long-term benefit associated with supramarginal CE resection and to apply ReSECT criteria for extent of resection in patients with primary glioblastoma IDH wild-type.

MATERIAL AND METHODS

We performed a retrospective search in the institutional of Livorno Hospital for adult patients with primary GBM IDH wild-type. We assess residual tumor volumetry in the early post-operative magnetic resonance imaging by the 3dslicer software. We attributed EOR classes according to ReSECT criteria based on residual contrast and non-contrast enhancing tumor volumes. We performed multivariate analysis by Cox regression including main known prognostic factors and MGMT promoter status assessed by pyrosequencing. IDH wild-type status was defined on both IDH1 and IDH2 genes.

RESULTS

We identified 173 patients who underwent surgery for confirmed primary glioblastoma IDH wild-type in our institutions from 2016 and 2022. Male/female ratio was 1.6, median age at diagnosis 68 years old (yo) (range 30-83), median KPS before surgery was 80 (range 30-100) with no significant variation at the post-operative stage. Forty out of 173 (23%) patients received a supramarginal CE resection (class 1) in the whole cohort; prevalence of class 1 resection was the highest in the subgroup of patients aged ≤ 65 yo (27%) than the subgroup of >65 ≤ 75 yo (22%) and the subgroup of >75 yo (14%). The rate of class 1 resection was not different between patients with tumors located in the right and in left hemisphere (24% and 23% respectively). We analysed survival in patients treated with adjuvant RT-TMZ and found a significant longer OS in patients operated with resection class 1 (16.7 months) than other classes (p<0.0001). Long term benefit resulted the strongest in the subgroup of patients aged ≤ 65 yo (median OS 23.8 months). Multivariate analysis confirmed EOR according to the ReSECT criteria as the strongest independent predictor factor of OS (HR 0.6, p=0.004).

CONCLUSION

We efficiently implemented ReSECT criteria for EOR in our retrospective cohort of patients with primary GBM IDH wild-type. Supramarginal CE resection defined as no residual CE and ≤ 5 cm of nCE on the post-operative imaging emerged as the strongest predictive factor of survival.
P19.07.A EXPRESSION STUDY OF SYNAPTIC PROTEINS BASSOON, DLG4, DLG1, MAGI2, SHANK1, AND HOMER1 IN GLIOMA
Authors: Timmer M , Lauer N , Kuhl S , Goldbrunner R
Published: September 2023

BACKGROUND

To thrive, glioma cells exploit pathways that are active in normal CNS cells, as well as in normal neurotransmitter signaling. In healthy excitatory synapses the postsynaptic submembrane space consists of multiprotein complexes called the postsynaptic density (PSD). The PSD is responsible for the structural organization, the functioning, and the regulation of neuronal signaling. The five MAGUK Proteins DLG4, DLG1, Magi2, Shank1, and Homer1 are part of the healthy PSD complex and play a crucial role not only in NMDA and AMPA receptor signaling. Investigating the role of these MAGUK proteins in glioma biology could bring further insight into which principal neurobiological features, including organization in communicating networks, are recapitulated by tumor cells of different stages in gliomas.

MATERIAL AND

Methods qPCR was used to determine expression levels of DLG4, DLG1, Magi2, Shank1, and Homer1 in 7 different glioma groups (GII, GIII, primary GBM before and after chemotherapy, secondary glioblastoma recurrence with and without chemotherapy). Western Blot was done for DLG4, DLG1, and Homer1. Immunohistochemical staining of frozen sections, paraffin sections and in vitro cells was performed. Results The expression levels of DLG4, DLG1, Magi2, Shank1, and Homer1 were reduced especially in high grade glioma compared to control tissue. A tendency of decreasing protein levels with increasing malignancy is visible for the majority of proteins. In cell culture all proteins were also present. siRNA experiments are ongoing. Conclusion The presence of these synaptic proteins in glioma tissue and moreover also primary cell culture could indicate a role in tumor biology and the connection of glioma cells with neuronal tissue.
P20.06.B SYSTEMIC CHEMOTHERAPY IN ADULT PATIENTS WITH DIFFUSE MIDLINE GLIOMA H3K27-ALTERED
Authors: Lombardi G , Simonelli M , Minniti G , Di Nunno V , Cerretti G , Di Muzio A , Asioli S , Antonelli M , Padovan M , Dipasquale A , Corrà M , De Biase D , Persico P , Caccese M , Tosoni A , Fernandes B , Franceschi E
Published: September 2023

BACKGROUND

Adult Diffuse midline glioma (DMG) is a very rare disease. DMGs are currently treated with radiotherapy and temozolomide even if only a few retrospective studies assessed the impact on survival of these approaches.

MATERIAL AND METHODS

We carried out a multicentric retrospective study of adult patients with DMG to assess the effective role of concurrent and adjuvant chemotherapy. All patients had a diagnosis of DMG - H3K27 altered. Results Overall we included 27 DMG H3K27 mutated patients with a median age of 40 years (range 20-66). Thalamus was the most frequent location (n =10, 37%). Overall, 16 patients (59.3%) underwent biopsy, 9 partial resections (33.3%), and 2 (7.4%) complete resections. The molecular assessment revealed TP53 as the most frequently altered gene (n = 4, 14.8%) followed by PIK3R (n = 2, 7.4%) and NF1 (n = 2, 7.4%). MGMT was methylated in 4 patients (14.8%). After surgery, 22 patients (81.5%) received postoperative radiation therapy (RT). Moreover, 12 patients received concurrent temozolomide (44.4%) and 11 (40.7%) adjuvant temozolomide. Patients receiving adjuvant temozolomide had a significantly longer overall survival (25.3 vs 10.5 months, HR 0.16, 95% CI 0.1 - 0.8, p= 0.02). Adjuvant temozolomide was confirmed to be associated with improved survival also when adjusted for age, surgery received, or tumor location. Conclusion In this multicentric retrospective study, the treatment with adjuvant temozolomide seems to prolong survival in DMG H3K27 altered patients. Further studies are needed to improve survival in these patients.
P20.08.B CLINICAL AND MOLECULAR ANALYSES OF A SERIES OF ADULT PILOCYTIC ASTROCYTOMA
Authors: Manzano-Benito I , Moreno Torres B , Cantero D , Hernández-Laín A , Romo Á , Rodríguez de Lope Á , Mollejo M , Meléndez B
Published: September 2023

BACKGROUND

Pilocytic astrocytoma (PA) is a rare, grade 1 subtype of glioma. It is most frequent during the first two decades of life, the incidence rate decreasing with age. PAs are usually located in the cerebellum, although they have also been described in other sites. They are circumscribed, solid-cystic, with low cellularity and generally slow-growing tumours with good prognosis in the paediatric age group. PA is associated with MAPK pathway dysregulation, most often showing BRAF gene alterations. PA is very rare in older adults and is associated in some cases with a worse prognosis. In this work we set out to analyse a series of adult PA from a clinical, morphological and molecular point of view.

MATERIAL AND METHODS

Clinical data were collected from a group of adult patients diagnosed with PA. Nucleic acid extraction was performed by automated extraction and the samples were analysed through a 30-gene targeted panel for gliomas by using Next-Generation Sequencing. Tandem duplication causing fusion of KIAA1549 and BRAF genes (K-B fusion) was analysed by RT-PCR.

RESULTS

Thirty-four patients were included, with a mean age of 34.4 years (range, 18-57 years). The male/female ratio was 26/8. Mean overall survival was 150.5 months, with more than 10 years of mean follow-up. At the time of the last review, 91% (30/33) of the patients remained alive, while the remaining 9% (3/33) died. Neuroanatomic locations (31 cases) were as follows: cerebrum/lobar 23% (7), cerebellum 39% (12), brainstem 10% (3), ventricle 6% (2), spinal cord 10% (3), optic nerve 13% (4). The K-B fusion was detected in 44% of cases (8/18). Of these, 87.5% (7/8) and 12.5% (1/8) showed fusions involving exons 16:9 and 15:9, respectively. K-B positive cases had a mean age of 40 years. Analyses by NGS revealed mutations in NF1 (15%), BRAF (11%), PDGFRA (11%), EGFR (7%) and PIK3CA (7%). Other variants observed in 4% of cases involved ATRX, CIC, IDH1, KEL, KRAS, MET, MSH6, PTPN11 and RB1. No alterations were detected in 3 of the cases, suggesting that other untested driver alterations could be present.

CONCLUSION

In this series, no significant differences with childhood PA in the frequency of molecular alterations were observed, in contrast to other gliomas where there are strong differences in the molecular alterations between adult and paediatric tumours. The most common genetic alterations in adult PA involved the MAPK pathway, as previously reported. In contrast to other adult PA studies, the frequency of K-B fusion was similar to that of paediatric PA. Molecular alterations related to an aggressive behaviour or to other glioma types were identified, such as mutations of ATRX, PDGFRA, NF1 or PI3KCA, which can suggest other tumour types. Our results suggest the need for multilayer histological and molecular diagnosis to appropriately manage adult PA.
P20.09.A FRACTIONATED STEREOTACTIC RADIOTHERAPY (FSRT) AS A TREATMENT FOR TRIGEMINAL SCHWANNOMAS
Authors: ARMIJOS L F , Maciá M , Lucas A , García N
Published: September 2023

BACKGROUND

Trigeminal schwannomas (TS) represent 1-8% of all intracranial schwannomas and 0.1-0.5% of all intracranial tumors Treatment strategies are mainly based on limited published data and case reports. The most common treatment is surgical resection. However, it can rarely be completed. Fractionated stereotactic radiotherapy (FSRT) has the potential to be a valuable and safe alternative to control growing or symptomatic TS. The aim of this review is to analyze clinical

RESULTS

, toxicity and tumor control rates obtained with this technique when treating this pathology in our short series of cases.

MATERIAL AND METHODS

Medical records of 18 patients treated from January 2007 to December 2018 were reviewed. 15 of them presented symptoms at the moment of diagnosis (83.3%) and the remaining 3 were radiological findings. Surgery was previously performed in 2 cases. Regarding radiotherapy scheme, all patients received 1.8-2Gy daily fractions to a median of 50,0 Gy. The median follow-up time was 62.7 months.

RESULTS

The outcome after radiotherapy was favourable in 16 of 18 patients (88.8%), clinical improvement was achieved in 52.94% while stability of symptoms was reached in 35.29%. Tumor growth was controlled in 82.35% of cases, even with tumor decrease observed in 5.88%. Acute toxicity was detected in 23.53% and it consisted in increased pain, sensitive alterations and diplopia. All well tolerated with adjusted corticoids and pain medication scheme. Clinical worsening and radiographic progression was shown in 2 out 17 patients and surgery was needed as salvage treatment in both cases (11.76%). However, one of them presented these outcomes in a period in which pseudoprogression could not be excluded (less than 2 years after treatment).

CONCLUSION

FSRT such as primary or adjuvant treatment accomplishes good clinical results and tumoral control, being an alternative for those patients with comorbidities not suitable for a surgical treatment or who preferred a non-invasive treatment. Regarding toxicity, FSRT is mainly a well tolerated treatment among patients. Prospective multicenter studies should be run in order to accomplish statistically significant results. Also, it is the second case series that reports the flare effect.
P20.13.A AUTOGRAFTED HUMAN CORTICAL SLICE MODEL REVEALS MESENCHYMAL-LIKE TRANSITION IN BRAF-MUTATED GLIOBLASTOMA UNDER TARGETED THERAPY
Authors: Zhang J , Joseph K , Beck J , Schnell O , Ravi V M , Heiland D H
Published: September 2023

BACKGROUND

The emergence of personalized therapy, which targets oncogenic drivers, has provided a novel adjunct to the standard-of-care therapy for glioblastoma, the most common central nervous system malignancy. Among the less frequently observed oncogenic drivers in glioblastoma are mutations in the proto-oncogene B-Raf. Although treatment options for BRAF-mutated malignancies have been extensively investigated, the implications of BRAF and MEK inhibition in gliomas remain ambiguous. In this study, we present a model system designed to predict cellular temporal trajectories, employing human neocortical slice models and patient-derived tumor cells, coupled with spatially resolved and single-cell transcriptomic analyses for comprehensive computational modeling.

MATERIAL AND METHODS

Non-neoplastic cortical tissue was procured from a BRAF(V600E) mutant glioblastoma patient during surgical intervention. The tissue was sectioned and inoculated with autologous glioblastoma cells to establish an ex-vivo personalized brain slice model. To facilitate adequate tumor growth, slices were cultured for seven days with clinically approved BRAF/MEK inhibitors and respective controls. For high-dimensional analysis, the tumor specimen and slices in all treatment conditions were profiled using live cell imaging, spatially resolved transcriptomics (Visium 10X) and single nucleus RNA-sequencing (10X). Advanced computational modeling techniques, encompassing graph neural networks and single-cell deconvolution, were employed to scrutinize the spatio-temporal evolution of the tumor and its microenvironment.

RESULTS

Live cell imaging showed varied treatment responses in tumor growth during culture. Immunofluorescence and immunohistochemistry analyses (using NeuN, GFAP, and Iba-1 cell markers) indicated no toxic effects from drug combinations on the tumor microenvironment. Single nucleus profiling revealed a tumoral trajectory towards induction of mesenchymal-like transcriptional programs under BRAF/MEK inhibition along with up-regulation of alternative receptor tyrosine kinases such as HER2/3 and EGFR. Spatial projection of single cell trajectories using cytospace confirmed the escape mechanism of BRAF/MEK inhibition due to acquisition of anti-inflammatory myeloid cells in close proximity to the tumor niches and enhancement of mesenchymal transcriptional programs. In line with the experimental set-up, we observed a rapid progression of the tumor und BRAF/MEK inhibition in the patient.

CONCLUSION

Our reported model system, employing high-dimensional readouts and advanced computational modeling, showcases a promising avenue to address uncertainties in personalized medicine, emphasizing that conventional oncological drivers may necessitate alternative treatment strategies in central nervous system malignancies.
P21.01.A EPIDEMIOLOGY OF ISCHEMIC LESIONS AFTER RESECTION OF LOW-GRADE GLIOMAS
Authors: Dunås T , Lipatnikova A , Thurin E , Jakola A
Published: September 2023

BACKGROUND

Diffuse low-grade gliomas are slow-growing malignant brain tumors that mainly affect people in their 30s and 40s, usually resulting in death within a decade. The standard treatment is surgery, which has a moderate risk of neurological sequelae. Clinical experience indicates that not all sequels are directly related to the resected area but rather caused by collateral damage, such as tissue- and vascular damages at the surgical site, causing ischemic lesions in the surrounding tissue. In this study, the epidemiology of these lesions is investigated, in terms of how common they are and how they are related to the size, type and location of the tumor.

MATERIAL AND METHODS

One hundred and sixty-six patients who underwent resection for grade II glioma (WHO 2007 or 2016) between 2012 and 2017 at any of nine hospitals in Sweden and Norway and had a postoperative MRI scan including diffusion-weighted imaging within three days after surgery, were included in this study. Lesions were segmented on the b1000 image, using the ADC and T1 image to exclude hyperintense areas caused by other factors than ischemia. Statistical analyses were performed using IBM SPSS Statistics version 27.0 (IBM Corp., Armonk, NY, USA). Analyses were carried out with ischemic lesion size as a continuous variable, and since the volumes were not normally distributed, non-parametric tests were used.

RESULTS

Ischemic lesions were found in 146 out of 166 (88%) cases, the median volume of the segmented lesions was 1.9 ml, with an interquartile range (IQR) of 0.95-4.5 ml. Patients with new or worsened deficits did have significantly larger ischemic volumes than does who did not (1.7 vs 2.8 ml, p=0.03). Ischemic volume was significantly correlated to both pre- and post-operative tumor volume (Spearmans rho = 0.370 and 0.304, p<0.001). No difference in ischemic volume was found between astrocytoma and oligodendroglioma, based on reported histopathologic diagnosis (p=0.43) or molecular status (p=0.44), neither between main tumor local (frontal (60%) vs temporal (19%), parietal (8%) or insular (12%), p>0.37).

CONCLUSION

Ischemic lesions after glioma resection are very common, but mostly small and restricted to a region close to the resection cavity. Large ischemic regions were associated with new or worsened neurological deficits and were mostly found in association with large tumors. More fine-tuned measures might be needed to find potential associations between tumor local and ischemic lesions.
Therapeutic effects of high-dose vitamin C supplementation in patients with COVID-19: a meta-analysis
Authors: Sun Lei , Zhao Jia-Hao , Fan Wen-Yi , Feng Bo , Liu Wen-Wen , Chen Rui-Qin , Ban Chuang , Dang Ao-Gui , Wang Miao , Luo Kang-Ting , Zhou Guo-Yu , Yu Fang-Fang , Ba Yue
Published: September 2023

Context

Coronavirus disease 2019 (COVID-19) could induce the “cytokine storm” due to overactivation of immune system and accompanied by acute respiratory distress syndrome as a serious complication. Vitamin C has been effective in improving lung function of patients by reducing inflammation.

Objective

The aim was to explore the therapeutic effects of high-dose vitamin C supplementation for patients with COVID-19 using meta-analysis.

Data Sources

Published studies were searched from PubMed, Cochrane Library, Web of Science, EMBASE, and China National Knowledge Infrastructure databases up to August 2022 using the terms “vitamin C” and “COVID-19”. Data analyses were performed independently by 2 researchers using the PRISMA guidelines.

Data Extraction

Heterogeneity between the included studies was assessed using I2 statistics. When I2 ≥50%, the random-effects model was used; otherwise, a fixed-effects model was applied. Stata 14.0 software was used to pool data by standardized mean differences (SMDs) with 95% CIs or odds ratios (ORs) with 95% CIs.

Data Analysis

The 14 studies had a total of 751 patients and 1583 control participants in 7 randomized controlled trials and 7 retrospective studies. The vitamin C supplement significantly increased ferritin (SMD = 0.272; 95% CI: 0.059 to 0.485; P = 0.012) and lymphocyte count levels (SMD = 0.376; 95% CI: 0.153 to 0.599; P = 0.001) in patients with COVID-19. Patients administered vitamin C in the length of intensive care unit staying (SMD = 0.226; 95% CI: 0.073 to 0.379; P = 0.004). Intake of vitamin C prominently alleviate disease aggravation (OR = 0.344, 95%CI: 0.135 to 0.873, P = 0.025).

Conclusions

High-dose vitamin C supplementation can alleviate inflammatory response and hinder the aggravation of COVID-19.
Reevaluating Adjuvant Capecitabine for Resected Biliary Tract Cancer
Authors: Benjamin David J , Prasad Vinay
Published: September 2023

Highlighting concerns about the acceptance of oncologic therapies with no proven benefit, this article compares the interpretation of the clinical trial results of several studies conducted to identify a better therapy for patients with biliary tract cancer.
Outcomes in Premenopausal Patients with HR+/HER2− Breast Cancer and Lymph Node Micrometastasis Based on the 21-Gene Recurrence Score
Authors: Bilani Nadeem , Patel Rima , Crowley Fionnuala , Tiersten Amy
Published: September 2023

Background

Postmenopausal patients with hormone receptor positive, HER2-negative (HR+/HER2−) early breast cancer (EBC) and 21-gene OncotypeDX (ODX) recurrence scores (RS) <26 do not benefit from chemoendocrine therapy (“CET”) compared to endocrine monotherapy (“E”), regardless of nodal status. In premenopausal patients, nodal status is significant in interpretation of RS. However, guidelines are not explicit in recommendations for patients with micrometastasis (“pN1mi” staging).

Methods

A cohort of patients aged <50 years with HR+/HER2− EBC who underwent ODX testing was identified within the National Cancer Database 2004-2019 dataset. We confirmed the prognostic value of ODX in pN1mi disease with multivariate Cox regression for overall survival (OS). We explored how patterns of practice differed by nodal status in cases of low RS (<26) with chi-squared testing. Finally, we performed Kaplan-Meier models comparing OS for those with RS <26 receiving E versus CET, controlling for nodal status.

Results

Of 72 068 patients aged <50 years with HR+/HER2− EBC, 6.1% (n = 4402) had micrometastasis. Multivariate Cox regression confirmed prognostic value of ODX in this pN1mi cohort (P < .001). In the context of RS <26, CET was used most commonly in patients with 1-3 involved lymph nodes (“pN1a-c” disease), less frequently in pN1mi disease, and least in node-negative (“pN0”) disease. A benefit in OS was observed in cases with RS <26 and pN1a-c receiving CET vs. E (P = .017), but not in pN1mi (P = .49) or pN0 (P = .57) disease.

Conclusion

Our large registry analysis found CET was associated with improved OS in pN1a-c, but not in pN1mi or pN0 disease.
A Bayesian spatiotemporal approach to modelling arboviral diseases in Mexico
Authors: Bukhari Moeen Hamid , Shad Muhammad Yousaf , Nguyen Uyen-Sa D T , Treviño C Jesús A , Jung Woojin , Bajwa Waheed U , Gallego-Hernández Ana Lucía , Robinson Renee , Corral-Frías Nadia Sarai , Hamer Gabriel L , Wang Penghua , Annan Esther , Ra Chaelin K , Keellings David , Haque Ubydul
Published: September 2023

Background

The objective of this study was to evaluate the spatial and temporal patterns of disease prevalence clusters of dengue (DENV), chikungunya (CHIKV) and Zika (ZIKV) virus and how socio-economic and climatic variables simultaneously influence the risk and rate of occurrence of infection in Mexico.

Methods

To determine the spatiotemporal clustering and the effect of climatic and socio-economic covariates on the rate of occurrence of disease and risk in Mexico, we applied correlation methods, seasonal and trend decomposition using locally estimated scatterplot smoothing, hotspot analysis and conditional autoregressive Bayesian models.

Results

We found cases of the disease are decreasing and a significant association between DENV, CHIKV and ZIKV cases and climatic and socio-economic variables. An increment of cases was identified in the northeastern, central west and southeastern regions of Mexico. Climatic and socio-economic covariates were significantly associated with the rate of occurrence and risk of the three arboviral disease cases.

Conclusion

The association of climatic and socio-economic factors is predominant in the northeastern, central west and southeastern regions of Mexico. DENV, CHIKV and ZIKV cases showed an increased risk in several states in these regions and need urgent attention to allocate public health resources to the most vulnerable regions in Mexico.
Lens epithelial cell‐derived exosome inhibits angiogenesis in ocular pathological neovascularization through its delivery of miR‐146a‐5p
Authors: Pan Ting , Wu Yan , Zhang Xu , Wang Jingfan , Wang Xingxing , Gu Qinyuan , Xu Changlin , Fan Yuanyuan , Li Xinsheng , Xie Ping , Liu Qinghuai , Hu Zizhong
Published: September 2023

Abnormal ocular neovascularization, a major pathology of eye diseases, leads to severe visual loss. The role of lens epithelial cell (LEC)‐derived exosomes (Lec‐exo) is largely unknown. Thus, we aimed to investigate whether Lec‐exo can inhibit abnormal ocular neovascularization and explore the possible mechanisms. In our study, we proved the first evidence that exosomes derived from LECs attenuated angiogenesis in both oxygen‐induced retinopathy and laser‐induced choroidal neovascularization mice models. Further in vitro experiments proved that Lec‐exo inhibited proliferation, migration, and tube formation capability of human umbilical vein endothelial cells in high glucose condition. Further high‐throughput miRNAs sequencing analysis detected that miR‐146a‐5p was enriched in Lec‐exo. Mechanistically, exosomal miR‐146a‐5p was delivered to endothelial cells and bound to the NRAS coding sequence, which subsequently inactivated AKT/ERK signaling pathway. We successfully elucidated the function of Lec‐exo in inhibiting abnormal ocular neovascularization, which may offer a promising strategy for treatment of abnormal ocular neovascularization.
Perioperative Malnutrition
Authors: Booth Alexander T. , Curran Thomas
Published: September 2023

CASE SUMMARY:

A 61-year-old man presented with penetrating Crohn’s ileocolitis and neoterminal ileal fibrostenotic stricture. He developed an anastomotic leak after a redo ileocolic resection and now has a chronic low-output enterocutaneous fistula. He was transferred from an outside institution for further management and is currently without Crohn’s disease (CD)–related medical therapy. The fistula output is 25 to 50 mL/day of GI contents. His weight dropped by 25 pounds in 6 months after surgery with a current BMI of 19.1, albumin of 2.0 g/dL, and hemoglobin of 9.7 g/dL. During a 3-month period, he was optimized for surgery with local wound care, initiation of infliximab, and nutritional support with exclusive enteral nutrition (EEN). He gained 9 pounds (BMI 20.4). Albumin improved to 3.4 g/dL and hemoglobin to 12.1 g/dL. He underwent a successful open takedown of the enterocutaneous fistula with ileocolic anastomosis.
Aplastic anemia from past to the present: A bibliometric analysis with research trends and global productivity during 1980 to 2022
Authors: Bulduk Tuba
Published: September 2023

There is no bibliometric study in the literature on Aplastic Anemia (AA). In the present study, the purpose was to summarize the intellectual structure of the subject, uncover the global productivity in this respect, and identify the latest research trends by performing a bibliometric analysis of the articles published on AA. For this purpose, outputs for different research components of scientific outputs (i.e., countries, institutions, journals, and authors) were analyzed. A total of 3221 articles on Aplastic Anemia published between 1980 and 2022 were analyzed by using various statistical methods and bibliometric approaches. The Spearman Correlation Coefficient was used for correlation analysis and bibliometric network visualization maps were used to identify trending topics, citation analysis, and international collaborations. The top 3 contributing countries to the literature were the USA in this respect (800, 24.8%), China (514, 15.9%), and Japan (442, 13.7%). The top 3 most active institutions were the National Institutes of Health USA (n = 177), National Heart Lung Blood Institute (n = 153), and Udice French Research Universities (n = 136). The top 3 most productive journals were the British Journal of Haematology (n = 239), Blood (n = 181), and Bone Marrow Transplantation (n = 137). The most prolific author was Neal Stuart Young (n = 130). Specific keywords that were most frequently used in articles were severe aplastic anemia, immunosuppressive therapy, pediatrics/children, anti-thymocyte globulin, cyclosporine, hematopoietic stem cell transplantation, myelodysplastic syndromes, Paroxysmal Nocturnal Hemoglobinuria, hepatitis-associated aplastic anemia, allogeneic stem cell transplantation, haploidentical hematopoietic stem cell transplantation, pancytopenia, eltrombopag, fludarabine, Graft-Versus-Host Disease, survival, apoptosis, cytokines, and cyclophosphamide. It was determined that the trend topics in recent years were eltrombopag, COVID-19, Treg, Th17, thrombopoietin receptor agonists, haploidentical hematopoietic stem cell transplantation, haploidentical donor/transplantation, and posttransplantation cyclophosphamide. In the formation of the AA literature, it was determined that the research leadership belonged to the USA, China, Japan, European countries (United Kingdom, Italy, Germany, France, Switzerland), India, and South Korea, which have large economies.
The association between Helicobacter pylori infection and inflammatory bowel disease in children: A systematic review with meta-analysis
Authors: Kong Guiping , Liu Zhifeng , Lu Yan , Li Mei , Guo Hongmei
Published: September 2023

Background:

Available literature has reported the association of Helicobacter pylori (H pylori) infection with inflammatory bowel disease (IBD) in adults. However, only a few studies have addressed the disease in children.

Aim:

To ascertain the correlation of H pylori infection with IBD among children.

Methods:

The aim of this systematic review and meta-analysis is to assess the association between H pylori infection and IBD in children. We searched databases including Cochrane, EMBASE, Google Scholar, PubMed, Medline, and Web of Science to select relevant studies. Ultimately, based on predetermined inclusion criteria, we included 6 studies that met the requirements. Review Manager and Stata software were used to extract and analyze the data from the relevant studies. In the methods, we employed both qualitative and quantitative approaches for comprehensive analysis. Qualitative analysis involved describing study designs, sample characteristics, and results, while quantitative analysis involved statistical tests such as calculating pooled risk ratios and 95% confidence intervals to evaluate the association between H pylori infection and IBD in children. Lastly, by combining the results of the individual studies, our objective is to provide a comprehensive understanding of the relationship between H pylori infection and IBD in children.

Results:

In totality, we involved 2236 participants that were recruited in 6 studies. We detected no significant difference in H pylori prevalence (9.8% vs 12.7%, P = .12) by comparing the children IBD group to controls. Among the IBD children, we estimated odds ratio (OR) of H pylori infection to 0.62 [(95% confidence interval (CI) of 0.34–1.12)]. In children suffering from ulcerative colitis (UC) and Crohn disease (CD), the H pylori infection rates were higher than in those with IBD-unclassified (IBDU).When analyzed stratified by disease of study design, In CD group [OR = 1.42, 95% CI: 0.72–2.80)] (I
2 = 0%, P = .64). but no significant difference in CD group.

Conclusions:

No correlation was found between H pylori infection and the occurrence of IBD in children.
Electroencephalography-based parietofrontal connectivity modulated by electroacupuncture for predicting upper limb motor recovery in subacute stroke
Authors: Li Mingfen , Zheng Su , Zou Weigeng , Li Haifeng , Wang Chan , Peng Li
Published: September 2023

Background:

Predicting motor recovery in stroke patients is essential for effective rehabilitation planning and goal setting. However, intervention-specific biomarkers for such predictions are limited. This study investigates the potential of electroacupuncture (EA) – induced brain network connectivity as a prognostic biomarker for upper limb motor recovery in stroke.

Methods:

A randomized crossover and prospective observational study was conducted involving 40 stroke patients within 30 days of onset. Patients underwent both EA and sham electroacupuncture (SEA) interventions. Simultaneously, resting electroencephalography signals were recorded to assess brain response. Patients’ motor function was monitored for 3 months and categorized into Poor and proportional (Prop) recovery groups. The correlations between the targeted brain network of parietofrontal (PF) functional connectivity (FC) during the different courses of the 2 EA interventions and partial least squares regression models were constructed to predict upper limb motor recovery.

Results:

Before the EA intervention, only ipsilesional PF network FC in the beta band correlated with motor recovery (r = −0.37, P = .041). Post-EA intervention, significant correlations with motor recovery were found in the beta band of the contralesional PF network FC (r = −0.43, P = .018) and the delta and theta bands of the ipsilesional PF network FC (delta: r = −0.59, P = .0004; theta: r = −0.45, P = .0157). No significant correlations were observed for the SEA intervention (all P > .05). Specifically, the delta band ipsilesional PF network FC after EA stimulation significantly differed between Poor and Prop groups (t = 3.474, P = .002, Cohen’s d = 1.287, Poor > Prop). Moreover, the partial least squares regression model fitted after EA stimulation exhibited high explanatory power (R
2 = 0.613), predictive value (Q
2 = 0.547), and the lowest root mean square error (RMSE = 0.192) for predicting upper limb proportional recovery compared to SEA.

Conclusion:

EA-induced PF network FC holds potential as a robust prognostic biomarker for upper limb motor recovery, providing valuable insights for clinical decision-making.
Sorafenib exhibits lower toxicity and comparable efficacy to sunitinib as a first-line treatment for metastatic renal cell carcinoma: A systematic review and meta-analysis
Authors: Li Dailong , Wan Sha , Li Wanqiang , Cheng Chunlai , Xu Lu , Gu Peng
Published: September 2023

Background:

To assess the safety and efficacy of sorafenib and sunitinib as first-line treatments for metastatic renal cell carcinoma (mRCC), to provide evidence-based support for clinical decision-making regarding rational drug use.

Methods:

Until May 10, 2023, a comprehensive search was conducted across PubMed, EMBASE, Cochrane Library, ClinicalTrials.gov, China National Knowledge Infrastructure, and Wanfang databases to identify clinical studies comparing sorafenib with sunitinib as first-line treatment for mRCC. The literature was screened, data extracted, and quality evaluated independently by 2 researchers. Meta-analysis was conducted using Revman5.4 software.

Results:

A total of 3741 patients were enrolled in 20 studies. The meta-analysis results indicated that there were no significant differences in the 2- and 5-year progression-free survival (PFS) and overall survival (OS) rates between the sorafenib and sunitinib groups (P > .05). The disease control rate (DCR) was comparable between the 2 groups (P > .05), while the objective response rate (ORR) was higher in the sunitinib group (P = .03). However, subgroup analysis revealed no significant differences in ORR, DCR, 2- and 5-year PFS, and OS rates between sorafenib and sunitinib among both Asian populations as well as European and American populations (P > .05). In terms of drug-related adverse events, the incidence of grade ≥ 3 hypertension, leukopenia, neutropenia, thrombocytopenia, anemia, nausea and vomiting were significantly lower in the sorafenib group compared to the sunitinib group (P < .05).

Conclusion:

In the first-line treatment of mRCC, sorafenib exhibits comparable efficacy to sunitinib but with lower toxicity.
Effectiveness and safety of non-vitamin K antagonist oral anticoagulant in the treatment of patients with morbid obesity or high body weight with venous thromboembolism: A meta-analysis
Authors: Zhang Hongxia , Xie Hua , Wang Xiaoyan , Zhu Zonghong , Duan Feng
Published: September 2023

Background:

Venous thromboembolism (VTE) poses a significant health risk to patients with morbid obesity or high body weight. Non-vitamin K antagonist oral anticoagulants (NOACs) are emerging treatments, but their effectiveness and safety compared with vitamin K antagonists (VKAs) in this population are yet to be thoroughly studied.

Methods:

We conducted a systematic review and meta-analysis, adhering to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Four electronic databases were searched for relevant studies comparing the efficacy and safety of NOACs and VKAs in treating patients with VTE with a body mass index > 40 kg/m2 or body weight > 120 kg. Eligible studies were scored for quality using the Newcastle-Ottawa Scale.

Results:

Thirteen studies were included. The meta-analysis results showed that compared to VKAs, NOACs significantly decreased the risk of VTE occurrence (odds ratio = 0.72, 95% CI: 0.57–0.91, I
2 = 0%, P < .001) and were associated with a lower risk of bleeding (odds ratio = 0.74, 95% CI: 0.58–0.95, I
2 = 0%, P < .05). Subgroup analysis showed that in the cancer patient subgroup, both risks of VTE occurrence and bleeding were lower in the NOAC group than in the VKA group. In patients without cancer, the risk of VTE was significantly lower in the NOAC group.

Conclusion:

NOACs appear to be more effective and safer than VKAs in patients with morbid obesity or a high body weight with VTE. However, further large-scale randomized controlled trials are required to confirm these findings.
RB1 gene mutations and genetic spectrum in retinoblastoma cases
Authors: Akdeniz Odemis Demet , Kebudi Rejin , Bayramova Jamila , Kilic Erciyas Seda , Kuru Turkcan Gozde , Tuncer Seref Bugra , Sukruoglu Erdogan Ozge , Celik Betul , Kurt Gultaslar Busra , Buyukkapu Bay Sema , Tuncer Samuray , Yazici Hulya
Published: September 2023

The aim of the study was to investigate the frequency and types of mutations on the retinoblastoma gene (RB1 gene) in Turkish population. RB1 gene mutation analysis was performed in a total of 219 individuals (122 probands with retinoblastoma, 14 family members with retinoblastoma and 83 clinically healthy family members). All 27 exons and close intronic regions of the RB1 gene were sequenced for small deletions and insertions using both the Sanger sequencing or NGS methods, and the large deletions and duplications were investigated using the MLPA analysis and CNV algorithm. The bilateral/trilateral retinoblastoma rate was 66% in the study population. The general frequency of RB1 gene mutation in the germline of the patients with retinoblastoma was 41.9%. Approximately 51.5% of the patients were diagnosed earlier than 12 months old, and de novo mutation was found in 32.4% of the patients. Germline small genetic rearrangement mutations were detected in 78.9% of patients and LGRs were detected in 21.1% of patients. An association was detected between the eye color of the RB patients and RB1 mutations. 8 of the mutations detected in the RB1 gene were novel in the study.
Managing Older Adults' Chronic Pain
Authors: Arnstein Paul , Shade Marcia , Herr Keela A. , Young Heather M. , Fishman Scott M.
Published: September 2023

This article is part of a series, Supporting Family Caregivers: No Longer Home Alone, published in collaboration with the AARP Public Policy Institute. Results of focus groups, conducted as part of the AARP Public Policy Institute's No Longer Home Alone video project, supported evidence that family caregivers aren't given the information they need to manage the complex care regimens of family members. This series of articles and accompanying videos aims to help nurses provide caregivers with the tools they need to manage their family member's health care at home.

This new group of articles provides practical information nurses can share with family caregivers of persons living with pain. To use this series, nurses should read the articles first, so they understand how best to help family caregivers. Then they can refer caregivers to the informational tear sheet—Information for Family Caregivers—and instructional videos, encouraging them to ask questions. For additional information, see Resources for Nurses. Cite this article as: Arnstein, P., et al. Managing Older Adults' Chronic Pain: Higher-Risk Interventions. Am J Nurs 2023; 123 (4): 56-61.
Opportunistic PSA-free prostate cancer screening utilising biparametric MRI (VISIONING)
Authors: Wetterauer C. , Matthias M. , Pueschel H. , Deckart A. , Bubendorf L. , Mortezavi A. , Arbelaez E. , Winkel D.J. , Heye T. , Boll D.T. , Merkle E. , Hayoz S. , Seifert H.H. , Rentsch C.A.
Published: September 2023

Background

Literature suggests that prostate MRI exhibits better predictive capabilities compared to prostate-specific antigen (PSA) in detecting prostate cancer (PCa). Based on this, our present study investigates biparametric MRI (bpMRI) as a PSA-independent screening tool for PCa.

Objective

The primary endpoint was to assess the efforts and effectiveness of identifying 20 participants with clinically significant prostate cancer (csPCa) using bpMRI.

Design, Setting, and Participants

Biopsy-naïve men aged over 45 years were included. All participants underwent 3 Tesla bpMRI, PSA and digital rectal examination (DRE). Targeted-only biopsy was performed in participants with a suspicious lesion (PI-RADS≥3). Men with a negative bpMRI but suspicious DRE or elevated PSA had template biopsies. Pre-intended protocol adjustments were made post-interim analysis for PI-RADS 3 lesions: follow-up mpMRI after 6 months, biopsy only if lesions persisted or upgraded.

Outcome Measurements and Statistical Analysis

Biopsy results underwent comparison using Fisher’s exact test and univariable logistic regression to pinpoint prognostic factors for positive biopsy.

Results and Limitations

A total of 229 participants were enrolled in this analysis. Among these, 77 displayed suspicious PI-RADS lesions. A total of 79 participants underwent a biopsy. PCa was detected in 29 participants, of whom 21 had csPCa.

BpMRI detected all 21 csPCa, whereas PSA and DRE missed 66.7%. Protocol adjustment led to a 54.6 % biopsy reduction in PI-RADS 3 lesions. Overall, 10.9 bpMRIs were needed to identify one participant with csPCa. A major limitation of the study is the lack of a control cohort undergoing template biopsies.

Conclusions

Opportunistic screening utilising bpMRI as primary tool reveals participants with csPCa that traditional methods might overlook, even at low PSA levels.

Patient summary

Screening with bpMRI and targeted biopsy identified csPCa in every 11thman, regardless of PSA levels. Preselecting patients based on PSA > 1 ng/ml and positive family history of PCa as well as other potential blood tests may further improve the effectiveness of bpMRI in this setting.
Comparison of Different PCR Methods for the Detection of SARS-CoV-2 RNA in Wastewater Based on the Reported Incidence of COVID-19 in Finland
Authors: Länsivaara Annika , Lehto Kirsi-Maarit , Hyder Rafiqul , Janhonen Erja , Lipponen Anssi , Heikinheimo Annamari , Pitkänen Tarja , Oikarinen Sami ,   the WastPan Study Group
Published: September 2023

The spatial and temporal changes of the COVID-19 pandemic have been monitored with wastewater-based surveillance, which many countries have applied to their national public health monitoring measures. The most commonly used methods for the detection of SARS-CoV-2 in wastewater are RT-qPCR and RT-ddPCR. Previous comparisons of the two methods have produced conflicting results; some found RT-ddPCR to be more sensitive, one found RT-qPCR to be more sensitive, and others found them to be equal in sensitivity. This research was conducted to further study these two methods as well as two different RNA extraction methodologies and gene assays for the detection of SARS-CoV-2 in wastewater. We compared two RT-qPCR kits and RT-ddPCR based on sensitivity, variability, and the correlation of SARS-CoV-2 gene copy numbers in wastewater with the incidence of COVID-19. Our results indicate that the most sensitive and low-variance method to detect SARS-CoV-2 in wastewater was RT-ddPCR. However, we obtained the best correlation between COVID-19 incidence and SARS-CoV-2 gene copy number in wastewater using RT-qPCR (CC = 0.697, p < 0.001). We found a significant difference in sensitivity between the two RT-qPCR kits, one having a significantly lower limit of detection and a higher percentage of positive samples than the other. Furthermore, the CDC N1 primers and probe were the most sensitive for both RT-qPCR kits, while there was no significant difference between the tested gene targets using RT-ddPCR. For the most sensitive RT-qPCR, the use of different RNA extraction kits affected the result. All methods showed a trend between COVID-19 incidence and SARS-CoV-2 gene copy numbers in wastewater. In addition, we tested an isothermal amplification method for the detection of SARS-CoV-2 RNA in wastewater. It proved to be a viable option if results are expected quickly, resources are limited, and presence–absence information is sufficient.

Highlights

Using different RNA extraction kits, detection kits, and gene assays to detect SARS-CoV-2 in wastewater produces differing results.

SARS-CoV-2 gene copies in wastewater correlate with the reported incidence of COVID-19 in Finland.

RT-ddPCR was the most sensitive and repeatable method to detect SARS-CoV-2 in wastewater, whereas RT-qPCR had the best correlation to the incidence of COVID-19.

RT-SIBA is a viable option for the detection of SARS-CoV-2 in wastewater in low-resource settings.

All methods have high result variability when the amount of SARS-CoV-2 in wastewater is low.

Graphical abstract

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