Enhancing Diagnostic Accuracy Through Neuroimaging Revisions in Pediatric Pseudotumor Cerebri Syndrome: A Cross-Sectional Study.

BACKGROUND: This cross-sectional study aimed to report all neuroimaging findings suggestive of raised intracranial pressure in children with pseudotumor cerebri syndrome (PTCS), before and after re-review by two neuroradiologists. METHODS: We included 48 children aged <18 years diagnosed with PTCS between 2016 and 2021. Clinical and radiological data were obtained from their medical files. Two neuroradiologists independently re-reviewed all neuroimages, and the average of their assessments was compared with the initial neuroimaging reports; an additional review was done to analyze inter- and intraclass correlation. RESULTS: The initial neuroimaging reports showed under-reporting of findings, with only 26 of 48 (54.1%) patients identified with abnormal reports. After revision, the proportion of the reported findings increased to 44 of 48 (91.6%). Distention of the perioptic space was the most commonly reported finding after revision (36.5 of 48; 76%). Flattening of the posterior globe and empty sella were initially under-reported but improved after revision. Moreover, several findings suggestive of increased intracranial pressure not mandated by Friedman criteria were identified, such as narrowing of the Meckel cave, posterior displacement of the pituitary stalk, and narrowing of the cavernous sinus. Analysis of associations between neuroimaging findings and demographic and clinical characteristics yielded no statistically significant results. The inter- and intraclass correlation results demonstrated a significant agreement between raters and within each rater's assessment (P < 0.05). CONCLUSIONS: This study highlights the impact of image revision in enhancing PTCS diagnosis. Intra- and interclass correlations underscore the reliability of the review process, emphasizing the importance of meticulous image analysis in clinical practice.

XPO1 mutations identify early-stage CLL characterized by shorter time to first treatment and enhanced BCR signalling.

Here we evaluated the epigenomic and transcriptomic profile of XPO1 mutant chronic lymphocytic leukaemia (CLL) and their clinical phenotype. By ATAC-seq, chromatin regions that were more accessible in XPO1 mutated CLL were enriched of binding sites for transcription factors regulated by pathways emanating from the B-cell receptor (BCR), including NF-κB signalling, p38-JNK and RAS-RAF-MEK-ERK. XPO1 mutant CLL, consistent with the chromatin accessibility changes, were enriched with transcriptomic features associated with BCR and cytokine signalling. By combining epigenomic and transcriptomic data, MIR155HG, the host gene of miR-155, and MYB, the transcription factor that positively regulates MIR155HG, were upregulated by RNA-seq and their promoters were more accessible by ATAC-seq. To evaluate the clinical impact of XPO1 mutations, we investigated a total of 957 early-stage CLL subdivided into 3 independent cohorts (N = 276, N = 286 and N = 395). Next-generation sequencing analysis identified XPO1 mutations as a novel predictor of shorter time to first treatment (TTFT) in all cohorts. Notably, XPO1 mutations maintained their prognostic value independent of the immunoglobulin heavy chain variable status and early-stage prognostic models. These data suggest that XPO1 mutations, conceivably through increased miR-155 levels, may enhance BCR signalling leading to higher proliferation and shorter TTFT in early-stage CLL.

Liquid biopsy in hematological malignancies: current and future applications.

The assessment of the cancer mutational profile is crucial for patient management, stratification, and therapeutic decisions. At present, in hematological malignancies with a solid mass, such as lymphomas, tumor genomic profiling is generally performed on the tissue biopsy, but the tumor may harbor genetic lesions that are unique to other anatomical compartments. The analysis of circulating tumor DNA (ctDNA) on the liquid biopsy is an emerging approach that allows genotyping and monitoring of the disease during therapy and follow-up. This review presents the different methods for ctDNA analysis and describes the application of liquid biopsy in different hematological malignancies. In diffuse large B-cell lymphoma (DLBCL) and Hodgkin lymphoma (HL), ctDNA analysis on the liquid biopsy recapitulates the mutational profile of the tissue biopsy and can identify mutations otherwise absent on the tissue biopsy. In addition, changes in the ctDNA amount after one or two courses of chemotherapy significantly predict patient outcomes. ctDNA analysis has also been tested in myeloid neoplasms with promising results. In addition to mutational analysis, liquid biopsy also carries potential future applications of ctDNA, including the analysis of ctDNA fragmentation and epigenetic patterns. On these grounds, several clinical trials aiming at incorporating ctDNA analysis for treatment tailoring are currently ongoing in hematological malignancies.

Assessing pharmacists and other healthcare providers' knowledge of hand sanitization during COVID-19 pandemic in Jordan: A comparative study.

BACKGROUND: Health care providers including pharmacists are often on the first line when dealing with COVID -19; they can be under threat of contracting and spreading the disease. We aimed to assess and compare their knowledge of hand sanitization during COVID-19 pandemic to improve quality of care. METHODS: A cross-sectional study was conducted in Jordan, on healthcare providers in different settings from 27 October till 3 December 2020, using a pre-validated electronic questionnaire. Participants (n = 523) were healthcare providers practicing in different settings. Descriptive and association statistical analyses were produced on the data using SPSS 26. Chi square was used for the categorical variables, and One way ANOVA was used on the continuous and categorical variables. RESULTS: A significant difference was recorded in total knowledge mean according to gender (59.78 vs 61.79 p = 0.030) in favor of men, and between pharmacists and other healthcare providers in favor of the latter (59.22 vs 61.45, p = 0.02). No significant difference was generally noticed between those who attended hand hygiene training and those who did not. CONCLUSION: Healthcare providers' knowledge of hand hygiene was generally good among participants, regardless of training and it was possibly increased because of fear of COVID-19 infection. Physicians were the most knowledgeable in regard of hand hygiene while pharmacists were the least among healthcare providers. Thus, structured, more frequent, and tailored training on hand sanitization in addition to new educational strategies are recommended for healthcare providers, in particular, pharmacists for better quality of care especially in pandemics.

Clonally unrelated Richter syndrome are truly de novo diffuse large B-cell lymphomas with a mutational profile reminiscent of clonally related Richter syndrome.

Richter syndrome (RS) is mostly due to the direct transformation of the chronic lymphocytic leukaemia (CLL) clone, as documented by the same immunoglobulin heavy-chain variable region (IGHV) rearrangement in both CLL and RS cells. In rare cases characterized by a better outcome, the RS clone harbours a different IGHV rearrangement compared to the CLL phase. We investigated the CLL phase of clonally unrelated RS to test whether the RS clone was already identifiable prior to clinicopathologic transformation, albeit undetectable by conventional approaches. CLL cells of eight patients with unrelated RS were subjected to an ultra-deep next-generation sequencing (NGS) approach with a sensitivity of 10-6 . In 7/8 cases, the RS rearrangement was not identified in the CLL phase. In one case, the RS clone was identified at a very low frequency in the CLL phase, conceivably due to the concomitance of CLL sampling and RS diagnosis. Targeted resequencing revealed that clonally unrelated RS carries genetic lesions primarily affecting the TP53, MYC, ATM and NOTCH1 genes. Conversely, mutations frequently involved in de novo diffuse large B-cell lymphoma (DLBCL) without a history of CLL were absent. These results suggest that clonally unrelated RS is a truly de novo lymphoma with a mutational profile reminiscent, at least in part, of clonally related RS.

Pseudotumor cerebri syndrome in children: Clinical characteristic and re-classification.

AIM: To describe the clinical characteristics of children with pseudotumor cerebri syndrome (PTCS) who were diagnosed according to the modified Dandy criteria and to reclassify them according to the newly proposed diagnostic criteria by Freidman. METHODOLOGY: This retrospective study included the period from January 2016-to July 2021. RESULTS: 50 patients were included; 34 males and 16 females with a male to female ratio of 2.1:1. The average age at onset of symptoms was 8 years. Obesity was noticed in 6 (12%) patients; 34 (68%) had symptoms upon presentation. The most common presenting symptom was headache (28 patients; 56%), papilledema was present in 33 (66%) patients. Most patients (37; 74%) had an initial cerebrospinal fluid (CSF) pressure ≥280 mmH2O. At last follow-up, papilledema resolved in 11/32 (34.3%) patients, and headache resolved in 17/23 (74%) patients. 22/50 (44%) patients fulfilled the definite criteria proposed by Freidman, 11/50 (22%) fulfilled the probable, 10/50 (20%) were categorized as possible, and 7 (14%) patients were categorized as unmet. CONCLUSION: PTCS is a chronic condition. Managing patients who do not have papilledema or who do not meet the newly proposed higher CSF pressure is challenging. Although, applying the newly proposed criteria captured most of our patients, however, around one quarter were managed based on clinical experience. This study indicates a strong need for future guidelines tailored specifically for children, taking into consideration that the cut-off point of CSF pressure might not be similar for all populations.

Druggable Molecular Pathways in Chronic Lymphocytic Leukemia.

Chronic lymphocytic leukemia (CLL), the most common type of leukemia in adults, is characterized by a high degree of clinical heterogeneity that is influenced by the disease's molecular complexity. The genes most frequently affected in CLL cluster into specific biological pathways, including B-cell receptor (BCR) signaling, apoptosis, NF-κB, and NOTCH1 signaling. BCR signaling and the apoptosis pathway have been exploited to design targeted medicines for CLL therapy. Consistently, molecules that selectively inhibit specific BCR components, namely Bruton tyrosine kinase (BTK) and phosphoinositide 3-kinase (PI3K) as well as inhibitors of BCL2, have revolutionized the therapeutic management of CLL patients. Several BTK inhibitors and PI3K inhibitors with different modes of action are currently used or are in development in advanced stage clinical trials. Moreover, the restoration of apoptosis by the BCL2 inhibitor venetoclax offers meaningful clinical activity with a fixed-duration scheme. Inhibitors of the BCR and of BCL2 are able to overcome the chemorefractoriness associated with high-risk genetic features, including TP53 disruption. Other signaling cascades involved in CLL pathogenesis, in particular NOTCH signaling and NF-kB signaling, already provide biomarkers for a precision medicine approach to CLL and may represent potential druggable targets for the future. The aim of the present review is to discuss the druggable pathways of CLL and to provide the biological background of the high efficacy of targeted biological drugs in CLL.

Mucormycosis: The hidden and forgotten disease.

Mucormycosis is a rare but serious fungal infection caused by a group of moulds called mucormycetes. More attention has recently been paid to it due to its association with coronavirus disease 2019 (COVID-19). Thus, it is important to review the progress of studies on mucormycosis and highlight the important findings in relation to epidemiology, clinical manifestation, major risk factors, diagnostic strategies and management. An electronic literature search was performed in PubMed using the keywords: Rhizopus, Mucorales, mucormycosis, zygomycosis, zygomycetes, COVID-19, the drugs (azoles, posaconazole, isavuconazole, amphotericin B pharmaceutical preparations and caspofungin), combination therapy, diagnosis and clinical manifestations. Studies written in the English language from January 1960 to 2021 were considered for this review article. All search results were reviewed, and the relevance of each article was determined by the authors independently. The review emphasized the fact that the diagnosis of mucormycosis is difficult, it is necessary to have a high index of suspicion to identify it, surgical debridement should be done prior to the dissemination of infection to improve clinical outcomes and identifying underlying risk factors is important for proper treatment. Moreover, antifungal therapeutic options are few with polyenes and their combinations should be appropriate for empirical therapy while posaconazole and isavuconazole are best reserved for de-escalation, refractory cases or patients intolerant to amphotericin B.

Adverse pregnancy outcomes during the COVID-19 lockdown. A descriptive study.

BACKGROUND: The ongoing spread coronavirus disease worldwide has caused major disruptions and led to lockdowns. Everyday lifestyle changes and antenatal care inaccessibility during the coronavirus disease 2019 (COVID-19) pandemic have variable results that affect pregnancy outcomes. This study aimed to assess the alterations in stillbirth, neonatal-perinatal mortality, preterm birth, and birth weight during the COVID-19 national lockdown. METHODS: We used the data from the Jordan stillbirths and neonatal death surveillance system to compare pregnancy outcomes (gestational age, birth weight, small for gestational age, stillbirth, neonatal death, and perinatal death) between two studied periods (11 months before the pandemic (May 2019 to March 2020) vs. 9 months during the pandemic (April 2020 to March 1st 2020). Separate multinomial logistic and binary logistic regression models were used to compare the studied outcomes between the two studied periods after adjusting for the effects of mother's age, income, education, occupation, nationality, health sector, and multiplicity. RESULTS: There were 31106 registered babies during the study period; among them, 15311 (49.2%) and 15795 (50.8%) births occurred before and during the COVID-19 lockdown, respectively. We found no significant differences in preterm birth and stillbirth rates, neonatal mortality, or perinatal mortality before and during the COVID-19 lockdown. Our findings report a significantly lower incidence of extreme low birth weight (ELBW) infants (<1kg) during the COVID-19 lockdown period than that before the lockdown (adjusted OR 0.39, 95% CI 0.3-0.5: P value <0.001) CONCLUSIONS: During the COVID-19 lockdown period, the number of infants born with extreme low birth weight (ELBW) decreased significantly. More research is needed to determine the impact of cumulative socio-environmental and maternal behavioral changes that occurred during the pandemic on the factors that contribute to ELBW infants.

Assessment of intrinsic vulnerability to contamination for Gaza coastal aquifer, Palestine.

Gaza coastal aquifer (GCA) is the major source of fresh water for the 1.5 million residents of Gaza Strip, Palestine. The aquifer is under deteriorating quality conditions mainly due to the excessive application of fertilizers. The intrinsic vulnerability of GCA to contamination was assessed using the well-known DRASTIC method. Detailed analysis of the intrinsic vulnerability map of GCA was carried out and did consider different relationships between the vulnerability indices and the on-ground nitrogen loadings and land use classes. In addition, correlation between vulnerability values and the nitrate concentrations in GCA was studied. Based on the vulnerability analysis, it was found that 10% and 13% of Gaza Strip area is under low and high vulnerability of groundwater contamination, respectively, while more than 77% of the area of Gaza Strip can be designated as an area of moderate vulnerability of groundwater contamination. It was found that the density of groundwater sampling wells for nitrate concentration is high for the moderate and high vulnerability zones. The highest first quartile, median, mean, and third quartile of nitrate concentrations are reported in the high vulnerability zones. Results of sensitivity analysis show a high sensitivity of the high vulnerability index to the depth to water table.

Multi-criteria decision analysis for the optimal management of nitrate contamination of aquifers.

We present an integrated methodology for the optimal management of nitrate contamination of ground water combining environmental assessment and economic cost evaluation through multi-criteria decision analysis. The proposed methodology incorporates an integrated physical modeling framework accounting for on-ground nitrogen loading and losses, soil nitrogen dynamics, and fate and transport of nitrate in ground water to compute the sustainable on-ground nitrogen loading such that the maximum contaminant level is not violated. A number of protection alternatives to stipulate the predicted sustainable on-ground nitrogen loading are evaluated using the decision analysis that employs the importance order of criteria approach for ranking and selection of the protection alternatives. The methodology was successfully demonstrated for the Sumas-Blaine aquifer in Washington State. The results showed the importance of using this integrated approach which predicts the sustainable on-ground nitrogen loadings and provides an insight into the economic consequences generated in satisfying the environmental constraints. The results also show that the proposed decision analysis framework, within certain limitations, is effective when selecting alternatives with competing demands.