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Introduction: Functional gastrointestinal disorders (FGIDs) encompass a wide spectrum of disorders that may be diagnosed using the Rome criteria. Aim: To identify the prevalence and risk factors for the development of FGIDs in Jordanian infants. Material and methods: We conducted a cross-sectional study to investigate the prevalence of FGIDs among infants and characterise any possible risk factors. Between 1 January 2020, and 30 December 2020, patients who presented to the paediatric follow-up clinic at King Abdullah University Hospital were recruited. Parents were interviewed and asked to complete an Arabic version of the Rome IV diagnostic questionnaire for pediatric gastrointestinal disorders for neonates and toddlers. Data regarding the parents' gastrointestinal symptoms and children's medical history were collected. Children's electronic medical files were also reviewed. Results: The study included 127 children, 78 (61%) were males. The median age was 40 days. According to the Rome IV criteria eighty-two (64%) of the infants fit the diagnosis for at least one disorder. The most prevalent disorder was functional constipation (n = 78, 95%) followed by infant dyschezia (n = 11, 13%). Compared to infants who did not meet the diagnostic criteria, herb intake and circumcision rates were significantly higher among those who did. Univariate analyses revealed that Infants with FGIDs were more likely to ingest herbs. Conclusions: FGIDs were common among young infants. Functional constipation was the most commonly diagnosed FGID. Infants with with FGIDs were more likely to intake herbs to ease the symtpoms.
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The association between primary immunodeficiencies and autoinflammatory disorders has been popularized over the past decade. In this report, we illustrated the co-infection of cytomegalovirus (CMV) and Epstein-Barr virus (EBV) in a three-year-old Jordanian male patient with an extremely rare variant of the CYBB gene (c.125C>G, p.Thr42Arg) associated with chronic granulomatous disease (CGD) coexisting with familial Mediterranean fever (FMF). CGD and FMF co-existence induced early-onset inflammatory bowel disease mainly resembling Crohn's disease.
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Cell cycle regulatory proteins plays a pivotal role in the development and progression of many human malignancies. Identification of their biological functions as well as their prognostic utility presents an active field of research. As a continuation of the ongoing efforts to elucidate the molecular characteristics of clear cell renal cell carcinoma (ccRCC); we present a comprehensive bioinformatics study targeting the prognostic and mechanistic role of cyclin-dependent kinase inhibitor 3 (CDKN3) in ccRCC. The ccRCC cohort from the Cancer Genome Atlas Program was accessed through the UCSC Xena browser to obtain CDKN3 mRNA expression data and their corresponding clinicopathological variables. The independent prognostic signature of CDKN3 was evaluated using univariate and multivariate Cox logistic regression analysis. Gene set enrichment analysis and co-expression gene functional annotations were used to discern CDKN3-related altered molecular pathways. The tumor immune microenvironment was evaluated using TIMER 2.0 and gene expression profiling interactive analysis. CDKN3 upregulation is associated with shortened overall survival (hazard ratio [HR] = 2.325, 95% confident interval [CI]: 1.703-3.173, P < .0001) in the Cancer Genome Atlas Program ccRCC cohort. Univariate (HR: 0.426, 95% CI: 0.316-0.576, P < .001) and multivariate (HR: 0.560, 95% CI: 0.409-0.766, P < .001) Cox logistic regression analyses indicate that CDKN3 is an independent prognostic variable of the overall survival. High CDKN3 expression is associated with enrichment within the following pathways including allograph rejection, epithelial-mesenchymal transition, mitotic spindle, inflammatory response, IL-6/JAK/STAT3 signaling, spermatogenesis, TNF-α signaling via NF-kB pathway, complement activation, KRAS signaling, and INF-γ signaling. CDKN3 is also associated with significant infiltration of a wide spectrum of immune cells and correlates remarkably with immune-related genes. CDKN3 is a poor prognostic biomarker in ccRCC that alters many molecular pathways and impacts the tumor immune microenvironment.
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Carcinoma de Células Renales , Proteínas Inhibidoras de las Quinasas Dependientes de la Ciclina , Neoplasias Renales , Humanos , Carcinoma de Células Renales/genética , Biología Computacional , Quinasas Ciclina-Dependientes , Fosfatasas de Especificidad Dual , Neoplasias Renales/genética , Pronóstico , Microambiente Tumoral , Regulación hacia ArribaRESUMEN
Anoctamin 1 (ANO1)-related intestinal dysmotility syndrome (OMIM: 620045) is an extremely rare disorder with only 2 cases reported in the medical literature. We present the clinical scenario of a 2-month-old male infant that presented to our center with diarrhea, vomiting, and abdominal distension. Routine investigations did not yield a clear diagnosis. Whole-exome sequencing showed a novel homozygous nonsense ANO1 pathogenic variant (c.1273G>T) with a protein alternation of p.Glu425Ter that fits the patient's phenotype. Sanger sequencing revealed the same ANO1 variant in both parents in a heterozygous form confirming an autosomal recessive mode of inheritance. The patient experienced multiple bouts of diarrhea-related metabolic acidosis, dehydration, and severe electrolyte imbalances that required intensive care unit monitoring. The patient was managed conservatively and being followed regularly in an outpatient setting.
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Renal cell carcinoma (RCC) exhibits a propensity for unusual wide metastasis. Cutaneous metastasis from RCC is a rare and poorly recognized clinical entity. We present a case of cutaneous metastasis of poorly differentiated RCC in 49-year-old male patient. In the presented case, the skin lesion was the first sign of widely spread RCC. After the establishment of the diagnosis using radiological and histopathological assessments, the patient was labeled as a terminal case and was referred for pain management. He deceased after 6 months of the initial presentation.
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Background: Over the past decade, transcriptome profiling has elucidated many pivotal pathways involved in oncogenesis. However, a detailed comprehensive map of tumorigenesis remains an enigma to solve. Propelled research has been devoted to investigating the molecular drivers of clear cell renal cell carcinoma (ccRCC). To add another piece to the puzzle, we evaluated the role of anoctamin 4 (ANO4) expression as a potential prognostic biomarker in non-metastasized ccRCC. Methods: A total of 422 ccRCC patients with the corresponding ANO4 expression and clinicopathological data were obtained from The Cancer Genome Atlas Program (TCGA). Differential expression across several clinicopathological variables was performed. The Kaplan-Meier method was used to assess the impact of ANO4 expression on the overall survival (OS), progression-free interval (PFI), disease-free interval (DFI), and disease-specific survival (DSS). Univariate and multivariate Cox logistic regression analyses were conducted to identify independent factors modulating the aforementioned outcomes. Gene set enrichment analysis (GSEA) was used to discern a set of molecular mechanisms involved in the prognostic signature. Tumor immune microenvironment was estimated using xCell. Results: ANO4 expression was upregulated in tumor samples compared to normal kidney tissue. Albeit the latter finding, low ANO4 expression is associated with advanced clinicopathological variables such as tumor grade, stage, and pT. In addition, low ANO4 expression is linked to shorter OS, PFI, and DSS. Multivariate Cox logistic regression analysis identified ANO4 expression as an independent prognostic variable in OS (HR: 1.686, 95% CI: 1.120-2.540, p = 0.012), PFI (HR: 1.727, 95% CI: 1.103-2.704, p = 0.017), and DSS (HR: 2.688, 95% CI: 1.465-4.934, p = 0.001). GSEA identified the following pathways to be enriched within the low ANO4 expression group: epithelial-mesenchymal transition, G2-M checkpoint, E2F targets, estrogen response, apical junction, glycolysis, hypoxia, coagulation, KRAS, complement, p53, myogenesis, and TNF-α signaling via NF-κB pathways. ANO4 expression correlates significantly with monocyte (ρ = -0.1429, p = 0.0033) and mast cell (ρ = 0.1598, p = 0.001) infiltration. Conclusions: In the presented work, low ANO4 expression is portrayed as a potential poor prognostic factor in non-metastasized ccRCC. Further experimental studies should be directed to shed new light on the exact molecular mechanisms involved.
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Background and Objectives: Chemotherapy-induced febrile neutropenia is the most widespread oncologic emergency with high morbidity and mortality rates. Herein we present a retrospective risk factor identification study to evaluate the prognostic role of lymphocyte-based measures and ratios in a cohort of chemotherapy-induced febrile neutropenia patients following granulocyte colony-stimulating factor (G-CSF) therapy. Materials and Methods: The electronic medical records at our center were utilized to identify patients with a first attack of chemotherapy-induced febrile neutropenia and were treated accordingly with G-CSF between January 2010 to December 2020. Patients' demographics and disease characteristics along with laboratory tests data were extracted. Prognosis-related indicators were the absolute neutrophil count (ANC) at admission and the following 6 days besides the length of stay and mortality rate. Results: A total of 80 patients were enrolled, which were divided according to the absolute lymphocyte count at admission into two groups, the first includes lymphopenia patients (n = 55) and the other is the non-lymphopenia group (n = 25) with a cutoff point of 700 lymphocytes/µL. Demographics and baseline characteristics were generally insignificant among the two groups but the white blood cell count was higher in the non-lymphopenia group. ANC, neutrophils percentage and ANC difference in reference to admission among the two study groups were totally insignificant. The same insignificant pattern was observed in the length of stay and the mortality rate. Univariate analysis utilizing the ANC difference compared to the admission day as the dependent variable, revealed no predictability role in the first three days of follow up for any of the variables included. However, during the fourth day of follow up, both WBC (OR = 0.261; 95% CI: 0.075, 0.908; p = 0.035) and lymphocyte percentage (OR = 1.074; 95% CI: 1.012, 1.141; p = 0.019) were marginally significant, in which increasing WBC was associated with a reduction in the likelihood of ANC count increase, compared to the lymphocyte percentage which exhibited an increase in the likelihood. In comparison, sequential ANC difference models demonstrated lymphocyte percentage (OR = 0.961; 95% CI: 0.932, 0.991; p = 0.011) and monocyte-to-lymphocyte ratio (OR = 7.436; 95% CI: 1.024, 54.020; p = 0.047) reduction and increment in the enhancement of ANC levels, respectively. The fifth day had WBC (OR = 0.790; 95% CI: 0.675, 0.925; p = 0.003) to be significantly decreasing the likelihood of ANC increment. Conclusions: we were unable to determine any concrete prognostic role of lymphocyte-related measures and ratios. It is plausible that several limitations could have influenced the results obtained, but as far as our analysis is concerned ALC role as a predictive factor for ANC changes remains questionable.
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Neutropenia Febril Inducida por Quimioterapia , Humanos , Pronóstico , Estudios Retrospectivos , Factor Estimulante de Colonias de Granulocitos/uso terapéutico , Linfocitos , Neutrófilos , Protocolos de Quimioterapia Combinada AntineoplásicaRESUMEN
RATIONALE: Cellular angiofibroma (CA) is a rare tumor of the soft tissue classified as a benign fibroblastic/myofibroblastic tumor. Considering this, the literature regarding CA mainly, but not exclusively, comprises single case reports and case series. Here, we report a case of giant CA of the vulva with comprehensive literature review. PATIENT CONCERNS: We present a case of a massive vulvar CA arising in 53-year-old woman with no notable medical or surgical history. The mass has grown considerably over time, causing pain and difficult urination, defecation, and movement. The patient had normal regular menstrual cycle with no previous contraception use. Vaginal examination exposed a right-sided large tender vulvar mass with normal-looking vagina. DIAGNOSES: Pelvic magnetic resonance imaging with contrast revealed a large right vulvar heterogeneously enhancing soft tissue mass measuring 13.1â ×â 10.9â ×â 10.7 cm expending the left vulva, with internal and peripheral voids resembling feeding vessels. The mass was surgically removed, and subsequent histopathology showed skin-covered dermal-based lesion composed of fibroblast-like bland and spindle cell proliferation with thin-walled blood vessels of various sizes. Immunohistostaining of CD34 and smooth muscle antigen were both positive, while desmin was found to be negative. A diagnosis of vulvar angiofibroma was made based on the clinical scenario, imaging, and histopathology. INTERVENTIONS: Mass vulvectomy was performed starting with a circumferential incision at the base of the mass and structural dissection to separate the mass from the vulvar wall. The incision was successfully closed, and subcuticular stitches were applied to the skin. OUTCOMES: The patient's complaints were significantly relieved with no postoperative complications and the patient is being followed regularly in an outpatient setting. LESSONS: Due to its extremely benign nature of CA, and the implausible ability of its recurrence, it was decided to surgically excise it. Despite its rarity, it can be readily identified at its earlier stages preventing the vexing and exasperating symptoms accompanied with increased size as mentioned.
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Angiofibroma , Neoplasias de Cabeza y Cuello , Neoplasias de la Vulva , Angiofibroma/patología , Angiofibroma/cirugía , Diagnóstico Diferencial , Femenino , Neoplasias de Cabeza y Cuello/diagnóstico , Humanos , Persona de Mediana Edad , Vulva/patología , Vulva/cirugía , Neoplasias de la Vulva/patologíaRESUMEN
Cerebral venous sinus thrombosis secondary to inflammatory bowel disease is a clinically rare and challenging entity with serious sequela. We preset a case of a 15-year-old female patient who was recently diagnosed with ulcerative colitis and had been suffering from headache for 4 days duration. During the diagnostic workup, computed tomography (CT) venography revealed Dural venous sinus thrombosis in the left transverse sinus extending into the left sigmoid sinus and the upper third of the left internal jugular vein as well as into the sinus confluence with non-occlusive filling defects in the superior sagittal sinus. Anticoagulant therapy with enoxaparin was initiated and the patient is being monitored in an outpatient setting regularly. Post-discharge disease course was uneventful. CT venography performed after 3 months illustrated partial recanalization of both left transverse and sigmoid sinuses. CVST is a rare extraintestinal manifestation of ulcerative colitis with significant morbidity and mortality which requires a high level of suspicion to establish a clear diagnosis. In spite the fact that CVST is rare, it should be ruled out in inflammatory bowel disease patients with new onset seizures, headache, along with focal, and non-focal neurologic symptoms.
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Carbonic anhydrase II deficiency is a rare autosomal recessive disorder with a classical triad of renal tubular acidosis, intracerebral calcifications and osteopetrosis. We present a case of a 6-year and 4-months old male patient presented to our pediatric gastroenterology outpatients' clinic with parental concern of poor growth. The patient is a known case of unexplained global developmental delay, recurrent fractures and constipation since birth. As a result of the patient's hyperactivity, he hit his head with the clinic's door resulting in a cut wound. Brain computed tomography scan showed abnormal symmetrical calcifications seen in both basal ganglia, thalami and subcortical white matter associated with increased bone density of the skull and upper cervical spine reassembling osteopetrosis. The suspicion of carbonic anhydrase II deficiency was confirmed by arterial blood gases revealing a marked metabolic acidosis fulfilling the diagnostic triad. The patient was discharged on sodium bicarbonate therapy, lactulose and vitamin D3 supplements and has been followed up regularly.
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Resorcylic acid lactones (RALs) are fungal polyketides that consist of a ß-resorcylic acid residue (2,4-dihydroxybenzoic acid) embedded in a macrolactone ring. RALs exhibit a broad range of biological activities, including anticancer activities. Following discovery of the selective Hsp90 inhibition activity of radicicol, the kinase inhibition activity of hypothemycin, monocillin II, 5Z-7-oxo-zeaenol, and L-783,277 RALs, and the nuclear factor kappa B (NF-κB) inhibition activity of the RAL zearalenone, have attracted great attention as potential therapeutics for cancer treatment. In this minireview, we focus on natural RALs that possess cytotoxic activities [IC50 values < 10 µM (or 4-5 µg/ml)], discussing their structures, isolation, occurrence, biological activities, and anticancer molecular mechanisms.
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Lactonas , FN-kappa B , Biología , Lactonas/química , Lactonas/farmacología , Estructura MolecularRESUMEN
OBJECTIVE: The aim of this study is to compare the respiratory neonatal outcomes utilizing antenatal dexamethasone sodium phosphate (DSP) versus a mixture of betamethasone dipropionate and betamethasone sodium phosphate (B-DP/SP) for preterm births. PATIENTS AND METHODS: All neonatal intensive care unit (NICU) admissions for prematurity were retrospectively identified at our center in the period between September 2016 and September 2018. Pregnant women expected to give preterm birth and received steroid injections whether it is DSP or B-DP/SP were included in the study. Maternal and obstetrical data along with the corresponding respiratory neonatal outcomes were extracted and analyzed. The population was categorized according to the gestational age into extremely preterm (less than 28 weeks), very preterm (28 up to 32 weeks) and moderate or late preterm (32 up to 37 weeks) in which the repository outcomes were compared in each sub-group. RESULTS: A total of 650 premature neonates were included in the analysis. B-DP/SP illustrated a significant reduction in the occurrence of respiratory distress syndrome (RDS) among moderate or late preterm neonates (P = 0.003) compared to DSP. In contrast, a non-significant difference was observed between B-DP/SP and DSP regarding apnea of prematurity and transient tachypnea of the newborn. The number of neonates developed chronic lung disease has been remarkably reduced when using DSP in extremely (P = 0.038) and very (P = 0.046) preterm neonates when compared to B-DP/SP. CONCLUSION: The dual acting B-DP/SP formulation could possess a significant potential in reducing RDS in moderate or late preterm neonates, while DSP groups exhibit a favorable result in the development of chronic lung disease in extreme and very preterm cohorts. Such findings emphasize the need of further clinical trials, pharmacokinetics, pharmacodynamics and cost effectiveness studies to evaluate the durability of these findings.
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OBJECTIVE: Chemotherapy-induced febrile neutropenia is a common and serious oncological emergency which carries a substantial mortality and morbidity. The main objective of this study is to evaluate the usage of absolute monocyte count (AMC) at presentation as a prognostic factor for patients with chemotherapy-induced febrile neutropenia who were subsequently treated with granulocyte colony-stimulating factor (G-CSF). STUDY DESIGN: The electronic medical records of our center were used retrospectively to identify patients diagnosed with unprecedented chemotherapy-induced febrile neutropenia treated with G-CSF between January 2010 to December 2020 and diagnosed with solid and hematological malignancies. Patient's demographics, disease characteristics and laboratory investigations were extracted. Disease progression measures were statistically compared between the study groups in the short-term period of follow-up (six days) including absolute neutrophil count (ANC), ANC difference compared to the baseline readings, hospitalization period, and mortality. RESULTS: A total of 80 patients were identified and categorized into two groups namely monocytopenia (n = 34) and non-monocytopenia (n = 46) with an AMC cutoff point of 0.1×109 cells/L. The monocytopenia group exhibited a worse prognosis with lower ANC values and slower improvement illustrated by the low ANC difference values at all follow up points (P-value ≤ 0.05) apart from day 5. A statistically significant lower hospitalization period was also observed in the non-monocytopenia group (P-value = 0.006). Linear regression analysis evaluated the association between AMC values at admission and ANC values at admission along with subsequent days of follow up which were found to be statistically significant (P-value ≤ 0.05). Receiver operating characteristic curves suggest a satisfactory predictability of ANC changes by AMC values at admission, days1, 2, 3, 4 and 6. CONCLUSION: Monocytopenia holds a worse prognosis in chemotherapy-induced febrile neutropenia patients treated with G-CSF. In addition, AMC values at presentation represents a potential risk factor that can predict short-term changes regarding ANC measures.
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Seaweeds have attracted attention in the past decade as a biological source of highly diverse secondary metabolites with great potential in the industrial and pharmaceutical sciences. Herein, we represent a comprehensive cheminformatics study to compare the chemical diversity of seaweed metabolites based on their taxonomic source. Seaweed Metabolite Database (SWMD) was utilized in this study. The compounds were manually categorized into three datasets, namely red algae (Rhodophyta, n = 645), brown algae (Phaeophyta, n = 220), and green algae (Chlorophyta, n = 32). The compounds in each dataset were curated to generate six chemical descriptors of pharmaceutical interest for each molecule, which were later used to visualize the chemical space of these metabolites by principal component analysis. Scaffolds were generated by removing side chains and keeping the core part of each molecule. Scaffold diversity among the tested datasets was quantified using Cyclic System Retrieval Curves. Green algae metabolites in SWMD possessed the highest scaffold diversity followed by brown and red algae metabolites, respectively. Three structural binary fingerprints, including ECFP_4, MACCS keys, and PubChem were computed indicating that the red algae metabolites had the highest fingerprint diversity followed by the green and brown algae metabolites respectively. Finally, Consensus Diversity Plots were generated to assess the global diversity considering both scaffold and fingerprint diversity. It was concluded that green algae metabolites in the SWMD are the most diverse regarding chemical descriptors of pharmaceutical relevance and scaffolds. While red algae possess the highest fingerprint diversity.