Multisystem inflammatory syndrome in children (MIS-C) secondary to COVID-19 mRNA vaccination - A case report from Qatar.

COVID-19 vaccines are generally proven safe in all population and are highly recommended. However, rare adverse events have been reported. We hereby present a case of an 18-year-old man who presented to emergency department with fever, meningitis like symptoms, shortness of breath, chest pain, skin rash, and extreme fatigue. He had cardiac manifestations including hypotension, elevated troponin, and reduced ejection fraction. High inflammatory markers were also noted. He was initially worked up for and treated as a possible infectious etiology, but the microbiological studies were negative and there was no response to treatment. Since he had recently received booster dose of Pfizer-BioNTech COVID-19 vaccination three weeks prior to onset of symptoms, a possibility of Multisystem inflammatory syndrome in children (MIS-C) was made. His presentation fulfilled all the diagnostic criteria. The possibility for MIS-C being related to vaccination was proposed after relevant serological tests showed that the antibodies, he had were due to COVID-19 vaccine, not to a prior infection. After he received appropriate immunomodulatory treatment (IVIG and methylprednisolone) as per the guideline, he showed marked clinical improvement. Our case report highlights the need to consider MIS-C as a potential differential in young patients who present with unexplained multisystem illness with increased inflammatory markers and negative microbiologic work-up. MIS-C can be secondary to COVID-19 vaccination as well as to prior COVID-19 infection.

Treatment planning facilitates clinical decision making for hyperthermia treatments.

Background: Treatment quality is important in clinical hyperthermia. Guideline-based treatment protocols are used to determine system settings and treatment strategies to ensure effective tumor heating and prevent unwanted treatment-limiting normal tissue hot spots. Realizing both these goals can prove challenging using generic guideline-based and operator-dependent treatment strategies. Hyperthermia treatment planning (HTP) can be very useful to support treatment strategies. Although HTP is increasingly integrated into the standard clinical workflow, active clinical application is still limited to a small number of hyperthermia centers and should be further stimulated.Purpose: This paper aims to serve as a practical guide, demonstrating how HTP can be applied in clinical decision making for both superficial and locoregional hyperthermia treatments.HTP in clinical decision making: Seven problems that occur in daily clinical practice are described and we show how HTP can enhance insight to formulate an adequate treatment strategy. Examples use representative commercially available hyperthermia devices and cover all stages during the clinical workflow. Problems include selecting adequate phase settings, heating ability analysis, hot spot suppression, applicator selection, evaluation of target coverage and heating depth, and predicting possible thermal toxicity in case of an implant. Since we aim to promote a general use of HTP in daily practice, basic simulation strategies are used in these problems, avoiding a need for the application of dedicated advanced optimization routines that are not generally available.Conclusion: Even fairly basic HTP can facilitate clinical decision making, providing a meaningful and clinically relevant contribution to maintaining and improving treatment quality.

Effect of vitamin B17 on experimentally induced colon cancer in adult male albino rat.

BACKGROUND: Colon cancer is considered to be the third most common cancer worldwide. At diagnosis of colon cancer, 3.7-11% developed bone metastasis. Diet based strategies are important for prevention and treatment of colon cancer. This study investigated the effect of vitamin B17 on a DMH induced rat model of colon cancer. MATERIALS AND METHODS: Eighty young adult male albino rats were divided into five groups: group I (control group), group II (vitamin B17), group III (colon cancer), group IV (protected) and group V (treated). Distal colon sections were prepared for light and scanning electron microscopic examination. Lumbar vertebrae specimens were prepared for light microscopic study. Morphometric and statistical analysis were done. RESULTS: In comparison with the control, both colon cancer and treated groups showed invasion of the colonic tissue by pleomorphic branching colonic glands of variable shapes and sizes lined with dysplastic elongated hyperchromatic nuclei with frequent mitotic figures or stratified multi-layered crowded nuclei with an extremely significant (p < 0.0001) reduction of goblet cell number when compared to the control together with major pathological bone changes were observed in colon cancer and the treated groups. CONCLUSIONS: While the protected group showed impressive improvement of all previously mentioned diameters.

Case Report: Ischemic Colitis in Severe COVID-19 Pneumonia: An Unforeseen Gastrointestinal Complication.

Clinical manifestations and complications of SARS-CoV-2 are still emerging and variant. Gastrointestinal (GI) manifestations and complications are hugely under-recognized. The presence of angiotensin converting enzyme-2 receptors in the intestinal enterocytes, the receptors primarily involved in the pathogenesis of COVID-19 pneumonia, maybe the key factor contributing to the pathogenesis of GI manifestations. Ischemic colitis, although the most common ischemic pathology of the GI tract, is relatively rare, occurring as a result of colonic hypoperfusion. The innumerable causes of colonic ischemia are categorized into occlusive and nonocclusive pathologies. Here, we have discussed a case of severe COVID-19 pneumonia, developing ischemic colitis, as a rare GI complication. The cause of ischemia in COVID-19 pneumonia is multifactorial, including hypercoagulable state, coagulopathy leading to thromboembolic complications, and use of vasopressors in severely ill patients with hemodynamic compromise.

A case report of TB versus idiopathic granulomatous mastitis with erythema nodosum, reactive arthritis, cough, and headache.

Tuberculous mastitis (TBM) is relatively rare disease with an incidence ranging between 0.1 and 4%. Most of the cases are culture negative and often mistaken with chronic benign idiopathic granulomatous mastitis (IGM). It is very crucial to distinguish culture negative TBM from other causes of mastitis as the treatment differs tremendously. We describe here in a young woman originally from India and residing in Qatar; a non endemic area of tuberculosis; for more then fifteen years. She presented with 2 months history of right breast mass, followed by low grade fever, dry cough, headache, erythema nodosum, arthritis, and arthralgia. In view of the origin of the patient, positive family history for tuberculosis and positive quantiferon, the patient was started empirically on anti-tuberculous treatment (ATT). One week later she developed paradoxical reaction to ATT. This case illustrates unusual and rare manifestations of primary TBM and highlights the importance of differentiating and treating culture negative TBM from IGM.

Incidence and clinical outcome of Cryptococcosis in a nation with advanced HIV surveillance program.

BACKGROUND: Cryptococcosis is a major opportunistic invasive mycosis that mostly affects immunocompromised patients. METHODS: This was an observational study of all culture-confirmed cases of cryptococcosis conducted in the State of Qatar from January 2005 to December 2016. Cryptococcus fungi were identified using Matrix-Assisted Laser Desorption Ionization-Time of Flight Mass Spectrometry (MALDI-TOF MS). RESULTS: Fourteen culture-confirmed cases of cryptococcosis were identified during the study period. Four patients had a Human Immunodeficiency Virus (HIV) infection with low CD4 count and five were receiving immunosuppressant medications. The rest of the patients were apparently immuno-competent. The central nervous system was the most common site of infection (57%) followed by bloodstream infection (36%) and pneumonia (14%). One patient had a cryptococcal scrotal infection. Twelve isolates were Cryptococcus neoformans and 2 were Cryptococcus laurentii. All isolates were within the wild type ECV values to amphotericin B and fluconazole. Only 2 patients with bloodstream infection (HIV negative) died. The rest were cured of the infection. CONCLUSION: Cryptococcosis is a rare fungal disease in the State of Qatar, mostly diagnosed in Asian immigrants. The central nervous system is the most common site of infection. The presence of the fungus in the blood carries a high mortality.

Regional deep hyperthermia: quantitative evaluation of predicted and direct measured temperature distributions in patients with high-risk extremity soft-tissue sarcoma.

BACKGROUND: Temperature distributions resulting from hyperthermia treatment of patients with high-risk soft-tissue sarcoma (STS) were quantitatively evaluated and globally compared with thermal simulations performed by a treatment planning system. The aim was to test whether the treatment planning system was able to predict correct temperature distributions. METHODS: Five patients underwent computed tomography (CT) fluoroscopy-guided placement of tumor catheters used for the interstitial temperature measurements. For the simulations, five 3 D patient models were reconstructed by segmenting the patient CT datasets into different tissues. The measured and simulated data were evaluated by calculating the temperature change ( ΔT ), T90, T50, T20, Tmean, Tmin and Tmax, as well as the 90th percentile thermal dose (CEM43T90). In order to measure the agreement between both methods quantitatively, the Bland-Altman analysis was applied. RESULTS: The absolute difference between measured and simulated temperatures were found to be 2°, 6°, 1°, 4°, 5° and 4 °C on average for Tmin, Tmax, T90, T50, T20 and Tmean, respectively. Furthermore, the thermal simulations exhibited relatively higher thermal dose compared to those that were measured. Finally, the results of the Bland-Altman analysis showed that the mean difference between both methods was above 2 °C which is considered to be clinically unacceptable. CONCLUSION: Given the current practical limitations on resolution of calculation grid, tissue properties, and perfusion information, the software SigmaHyperPlan™ is incapable to produce thermal simulations with sufficient correlation to typically heterogeneous tissue temperatures to be useful for clinical treatment planning.

Quality assurance guidelines for interstitial hyperthermia.

Quality assurance (QA) guidelines are essential to provide uniform execution of clinical hyperthermia treatments and trials. This document outlines the clinical and technical consequences of the specific properties of interstitial heat delivery and specifies recommendations for hyperthermia administration with interstitial techniques. Interstitial hyperthermia aims at tumor temperatures in the 40-44 °C range as an adjunct to radiation or chemotherapy. The clinical part of this document imparts specific clinical experience of interstitial heat delivery to various tumor sites as well as recommended interstitial hyperthermia workflow and procedures. The second part describes technical requirements for quality assurance of current interstitial heating equipment including electromagnetic (radiative and capacitive) and ultrasound heating techniques. Detailed instructions are provided on characterization and documentation of the performance of interstitial hyperthermia applicators to achieve reproducible hyperthermia treatments of uniform high quality. Output power and consequent temperature rise are the key parameters for characterization of applicator performance in these QA guidelines. These characteristics determine the specific maximum tumor size and depth that can be heated adequately. The guidelines were developed by the ESHO Technical Committee with participation of senior STM members and members of the Atzelsberg Circle.

Lean body weight dosing avoids excessive systemic exposure to proton pump inhibitors for children with obesity.

BACKGROUND: Children with obesity are more likely to suffer gastroesophageal reflux disease, requiring acid-suppression therapy with proton pump inhibitors (PPIs) and no guidelines regarding dosing. OBJECTIVE: To prospectively evaluate lean-body-weight-based (LBW) dosing of the PPI pantoprazole for children with and without obesity. METHODS: Methods: Sixty-two children (6-17 years) received a one-time oral dose of liquid pantoprazole (1.2 mg kg-1 LBW). Plasma pantoprazole concentrations were measured at 10 time points over 8 h and pharmacokinetic (PK) profiles generated using non-compartmental techniques, in order to compare PK parameters of interest between children with and without obesity, while accounting for CYP2C19 genotype. RESULTS: Adjusted for milligram-per-kilogram total body weight (TBW) pantoprazole received, apparent drug clearance (CL/F) was reduced 50% in children with vs. without obesity (p=0.03). LBW-based dosing compensated for this reduction in CL/F (p = 0.15). CONCLUSION: To achieve comparable systemic PPI exposures for children with and without obesity, we recommend using LBW, rather than TBW-based dosing for pantoprazole.

Measurement of stretched penile length in prepubertal boys in Egypt.

BACKGROUND: Early diagnosis of penile size abnormalities is both medically and psychologically important. It is important in the diagnosis of penile problems. Therefore, a current established reference for penile size in newborns and children is vital for diagnosis and early management of micropenis. OBJECTIVES: The aim of the present study was to establish reference values for penile length in newborn and prepubertal boys at different ages in Minia Governorate, Egypt. METHODS: The study was conducted on 1000 boys with ages ranging from 1 day to 13 years. Stretched penile length (SPL) was measured in mm by using a ruler with markings along the dorsum of the penis. The suprapubic fat tissue was pressed with one end of the ruler through the pubic ramus, and the penis was fully stretched and measured. RESULTS: The mean SPL increased with age from newborn to 5 years, with a rapid growth observed in the first 8 months of life. After 5 years, SPL showed a slower growth rate until the age of 10 years, where it started to increase significantly again. DISCUSSION: Comparison of the SPL in different age groups revealed significant statistical differences between most groups. It showed a noticeable and significant increase, especially from birth to the age of 5 years. Although there was a mild increase in SPL from 5 to 10 years, it showed a significant level in few age groups, indicating that the change is trivial. After that, high growth rate occurred again and statistical differences remained from age 10-13 years. CONCLUSION: An updated reference for normal SPL in Egyptian boys from birth to 13 years old was provided in this study.

Enhancement of broodstock health and maternal immunity in gilthead seabream (Sparus aurata L.) using ExcelMOS®.

The current study was conducted to investigate the effect of ExcelMOS® in enhancing the immune system of Sparus aurata broodstock and their impact on offspring health through displaying the maternal transfer of immunity. Broodstock were divided into two groups: one was injected intraperitoneally with ExcelMOS® 1 month before spawning, while the other group was used as a control (without injection). Comprehensive increase in survival rate was observed for larvae hatched from ExcelMOS®-injected broodstock than those of the control (P ≤ 0.05). Hematological analysis showed increases in leukocyte count and hematocrit percentage (P ≤ 0.05) and significant enhancement in immune assays as phagocytic, respiratory burst, lysozyme activities in ExcelMOS®-injected broodstock (P ≤ 0.05). Additionally, total immunoglobulin levels in the serum, eggs, and larvae resulted from ExcelMOS®-injected broodstock were highly significant (P ≤ 0.05) than those in the control ones. Transmission electron microscopy and semi-thin sections in posterior intestine of ExcelMOS®-injected broodstock revealed reinforcement of the epithelial barrier structure, intestinal integrity, and functionality in combination with the stimulation of innate immune system. In conclusion, immunostimulation of Sparus aurata broodstock using ExcelMOS® has improved survival of larvae and enhanced both innate and adaptive immune defense mechanisms. Further investigations are required to show the effect of ExcelMOS® on fish cultured in intensive culture systems.

Baclofen systemic toxicity: Experimental histopathological and biochemical study.

OBJECTIVE: The present study was designed to highlight the toxic impact of baclofen on both biochemical and histopathological aspects in rats' liver, gastric, lung, kidney, and brain tissues. METHODS: The study was performed on 30 healthy adult male albino rats divided into four groups with 5 rats in each control group, and 10 rats in either experimental groups (two experimental and two control groups). Five rats (negative control) were kept in a quite non-stressful environment, provided with food ad libitum and free access to water. Normal saline (1 ml) was given orally as placebo in the positive control group ( n = 5). Experimental group III, baclofen acute toxicity group (10 rats): Each animal received a single dose of lethal dose (LD50) of baclofen orally by gavage. It equals 145 mg/kg body weight. The rats were observed for acute toxicity manifestations as well as for LD50 deaths. Group IV, (baclofen-dependent group, 10 rats): Each animal received baclofen (1/10th LD50) in gradually increasing doses for 1 month. RESULTS: The levels of blood urea nitrogen, creatinine kinase, alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, γ-glutamyl transpeptidase, cardiac troponin I, and prothrombin time in both baclofen-treated groups showed significant elevation when compared to controls. There were brain, lung, gastric, hepatic, and renal histopathological changes in baclofen-treated rats whose severity varied between the two experimental groups. CONCLUSION AND RECOMMENDATION: Baclofen toxicity is an under diagnosed emergency. Physicians should consider baclofen toxicity in users having hepatorenal dysfunction, presenting with altered mental status, bradycardia, and hypotension.

Solidification of cinnarizine self-nanoemulsifying drug delivery systems by fluid bed coating: optimization of the process and formulation variables.

Self-nanoemulsifying drug delivery systems (SNEDDS) offer an efficient choice to improve the poor dissolution and erratic bioavailability of poorly-water soluble drugs. However, liquid SNEDDS experience some manufacturing and stability limitations. To overcome these limitations, the current study aims to investigate and optimize the solidification of cinnarizine (CN) liquid SNEDDS onto pellets by fluid bed coating. The study involved optimization of process and formulation variables. The coated self-nanoemulsifying pellets (SNEP) were characterized, their droplet size and dissolution profiles were compared to the corresponding liquid SNEDDS. Higher spray/microclimate air pressure led to minimal agglomeration and minimal spray drying. However, slight increase in inlet air volume above 35 m3/h led to extensive spray drying. The optimized coating formula included oleic acid/Imwitor308/Cremophor El (25/25/50) as liquid SNEDDS, HPMC E3 as coating polymer and Plasacryl™T20 as anti-tacking agent. The optimum concentration of coating solution was 15% and optimum SNEDDS proportion in the coating layer was 40%. The droplet size of reconstituted SNEP was significantly (p < 0.05) higher than liquid SNEDDS, yet the SNEP aqueous dispersion was still within the nano-metric scale. Pure CN showed sharp precipitation upon shifting the media from pH 1.2 to 6.8. In contrast, Both SNEP and liquid SNEDDS maintained >85% CN in solution, even at pH 6.8. Therefore, CN-SNEP seems to be an excellent dosage form that maintains the solubilization benefits of liquid SNEDDS, overcomes their limitations along with the additional benefits of solid dosage form.

Potential effect of Olea europea leaves, Sonchus oleraceus leaves and Mangifera indica peel extracts on aromatase activity in human placental microsomes and CYP19A1 expression in MCF-7 cell line: Comparative study.

Aromatase inhibitors (AIs) provide novel approaches to the adjuvant therapy for postmenopausal women with estrogen-receptor-positive (ER+) breast cancers. In this study, different plant extracts from Olea europaea leaves (OLE), Sonchus oleraceus L. (SOE) and Mangifera indica peels (MPE) were prepared to identify phytoconstituents and measure antioxidant capacities. The effects of these three extracts on aromatase activity in human placental microsomes were evaluated. Additionally, the effects of these extracts on tissue-specific promoter expression of CYP19A1 gene in cell culture model (MCF-7) were assessed using qRT-PCR. Results showed a concentration-dependent decrease in aromatase activity after treatment with OLE and MPE, whereas, SOE showed a biphasic effect. The differential effects of OLE, SOE and MPE on aromatase expression showed that OLE seems to be the most potent suppressor followed by SOE and then MPE. These findings indicate that OLE has effective inhibitory action on aromatase at both the enzymatic and expression levels, in addition to its cytotoxic effect against MCF-7 cells. Also, MPE may be has the potential to be used as a tissue-specific aromatase inhibitor (selective aromatase inhibitor) and it may be promising to develop a new therapeutic agent against ER+ breast cancer.

A biological timer in the fat body comprising Blimp-1, ßFtz-f1 and Shade regulates pupation timing in Drosophila melanogaster.

During the development of multicellular organisms, many events occur with precise timing. In Drosophila melanogaster, pupation occurs about 12 h after puparium formation and its timing is believed to be determined by the release of a steroid hormone, ecdysone (E), from the prothoracic gland. Here, we demonstrate that the ecdysone-20-monooxygenase Shade determines pupation timing by converting E to 20-hydroxyecdysone (20E) in the fat body, which is the organ that senses nutritional status. The timing of shade expression is determined by its transcriptional activator ßFtz-f1. The ßftz-f1 gene is activated after a decline in the expression of its transcriptional repressor Blimp-1, which is temporally expressed around puparium formation in response to a high titer of 20E. The expression level and stability of Blimp-1 is critical for the precise timing of pupation. Thus, we propose that Blimp-1 molecules function like sand in an hourglass in this precise developmental timer system. Furthermore, our data suggest that a biological advantage results from both the use of a transcriptional repressor for time determination and the association of developmental timing with nutritional status of the organism.

Single dose, CYP2D6 genotype-stratified pharmacokinetic study of atomoxetine in children with ADHD.

The effect of CYP2D6 genotype on the dose-exposure relationship for atomoxetine has not been well characterized in children. Children 6-17 years of age diagnosed with attention-deficit hyperactivity disorder (ADHD) were stratified by CYP2D6 genotype into groups with 0 (poor metabolizers [PMs], n = 4), 0.5 (intermediate metabolizers [IMs], n = 3), one (extensive metabolizer [EM]1, n = 8) or two (EM2, n = 8) functional alleles and administered a single 0.5 mg/kg oral dose of atomoxetine (ATX). Plasma and urine samples were collected for 24 (IM, EM1, and EM2) or 72 hours (PMs). Dose-corrected ATX systemic exposure (area under the curve [AUC]0-∞ ) varied 29.6-fold across the study cohort, ranging from 4.4 ± 2.7 µM*h in EM2s to 5.8 ± 1.7 µM*h, 16.3 ± 2.9 µM*h, and 50.2 ± 7.3 µM*h in EM1s, IMs, and PMs, respectively (P < 0.0001). Simulated steady state profiles at the maximum US Food and Drug Administration (FDA)-recommended dose suggest that most patients are unlikely to attain adequate ATX exposures. These data support the need for individualized dosing strategies for more effective use of the medication.

Plasma ghrelin and liquid gastric emptying in children with functional dyspepsia consistent with post-prandial distress syndrome.

BACKGROUND: Adult studies indicate a role for ghrelin in functional dyspepsia (FD) mediated through ghrelin's effect on gastric emptying (GE). This study examines the relationship between ghrelin, liquid GE, and pain in children with FD. METHODS: Thirteen FD patients reporting symptoms consistent with post-prandial distress syndrome (PDS) and 17 healthy controls were enrolled. All participants received a liquid meal containing (13) C-sodium acetate. Pain severity, liquid GE utilizing exhaled (13) CO2 from the sodium acetate breath tests (ABT), plasma acyl ghrelin (AG), and des-acyl ghrelin concentrations were measured at specific intervals over 240 min following ingestion. KEY RESULTS: FD-PDS patients demonstrated lower mean baseline AG (14.8 ± 9.7 vs 27.2 ± 14.0 fmol/mL; p = 0.013), AG Cmax (24.6 ± 8.2 vs 40.5 ± 16.8 fmol/mL; p = 0.007), and AG flux (18.2 ± 7.8 vs 32.7 ± 17.3 fmol/mL; p = 0.015) than controls. The time to reach maximum exhaled (13) CO2 concentration (T max ) was longer in FD patients than controls (47.5 ± 18.5 vs 35.8 ± 11.8 min; p = 0.046). Significant relationships between ghrelin analyte ratios and ABT parameters were largely confined to control participants. CONCLUSIONS & INFERENCES: FD-PDS in children is associated with lower fasting and maximum AG concentrations, and dampened AG flux. These data suggest a possible role for altered ghrelin physiology in the pathogenesis of PDS.

Function of the nuclear receptor FTZ-F1 during the pupal stage in Drosophila melanogaster.

The nuclear receptor ßFTZ-F1 is expressed in most cells in a temporally specific manner, and its expression is induced immediately after decline in ecdysteroid levels. This factor plays important roles during embryogenesis, larval ecdysis, and early metamorphic stages. However, little is known about the expression pattern, regulation and function of this receptor during the pupal stage. We analyzed the expression pattern and regulation of ftz-f1 during the pupal period, as well as the phenotypes of RNAi knockdown or mutant animals, to elucidate its function during this stage. Western blotting revealed that ßFTZ-F1 is expressed at a high level during the late pupal stage, and this expression is dependent on decreasing ecdysteroid levels. By immunohistological analysis of the late pupal stage, FTZ-F1 was detected in the nuclei of most cells, but cytoplasmic localization was observed only in the oogonia and follicle cells of the ovary. Both the ftz-f1 genetic mutant and temporally specific ftz-f1 knockdown using RNAi during the pupal stage showed defects in eclosion and in the eye, the antennal segment, the wing and the leg, including bristle color and sclerosis. These results suggest that ßFTZ-F1 is expressed in most cells at the late pupal stage, under the control of ecdysteroids and plays important roles during pupal development.