Prognostic markers among Egyptian children with sepsis in the Intensive Care Units, Cairo University Hospitals.

BACKGROUND: Early identification of septic patients at risk of mortality is important in their prognosis. OBJECTIVE: Identification of septic patients at risk of mortality in Pediatric Intensive Care Units (PICUs) at Cairo University Hospitals, through measuring the levels of certain immunological parameters. METHODS: A hospital-based prospective cohort study was conducted in two PICUs at Cairo University Hospitals; all patients with diagnosis of severe sepsis or septic shock on admission were included. A total of 57 patients were prospectively followed at the selected PICUs and their demographic and clinical data were recorded. Microbiological and immunological workup (at days 1 and 7) was conducted for all patients to detect the causative organism of sepsis and to measure the levels of immunoglobulins (IgG, IgM and IgA), complement factors (C3 and C4), mature lymphocyte subpopulations (CD3+) and natural killer (NK) cells (CD3-CD16+CD56+), respectively. RESULTS: Mortality rate was 24.6%; the most frequent causes of death were multi-organ dysfunction and refractory shock. PELOD and PRISM III scores were significantly higher among non-survivors. At day 1, non-survivors had significantly higher levels of IgG, C4 and NK cells than survivors. However, from day 1 to day 7, survivors had a progressive increase in most of the immunological parameters (IgG, IgM, C4and CD3+ T lymphocytes). Survival curve analysis revealed the significant predictive ability of NK cells to detect early mortality. CONCLUSION: Monitoring the levels of cellular and humoral immunological parameters together with assessing PELOD and PRISM III scores can significantly affect prognosis and survival of septic children.

Expression of Toll­like receptors 3 and 9 in Egyptian systemic lupus erythematosus patients.

BACKGROUND: Systemic lupus erythematosus (SLE) is a common complex disease characterized by chronic generalized inflammation which may involve several tissues and organs. OBJECTIVE: The aim of this work was to study the expression of Toll-like receptors (TLR) 3 and 9 in SLE patients, and to investigate their relationship to clinical features, disease activity, and damage. PATIENTS AND METHODS: The current study included 24 Egyptian female SLE patients and 15 matched controls. Disease activity was assessed using the SLE Disease Activity Index (SLEDAI) and damage using the Systemic Lupus International Collaborating Clinics (SLICC) index. Expression of TLR3 and TLR9 in B- (CD19-positive) and T-lymphocytes (CD3-positive) was studied using flow cytometry. RESULTS: Patient age ranged between 17 and 42 years (mean 26.17 ± 5.78 years). There was a significant difference between patients and controls regarding TLR3/CD3, TLR3/CD19, TLR9/CD3, and TLR9/CD19 expression (p < 0.0001). There were significant correlations of TLR3/CD3, TLR3/CD19, and TLR9/CD19 with serum creatinine (r = 0.52, p = 0.009; r = 0.504, p = 0.012; and r = 0.58, p = 0.003; respectively) and negative correlations with ALT levels (r = -0.42, p = 0.04; r = -0.49, p = 0.016; and r = -0.472, p = 0.02; respectively). CONCLUSION: The results of the study suggest that TLR3 and TLR9 play a role in the pathogenesis of SLE, and have an impact on organ involvement in this disease. More studies concerning the biology and function of TLRs are required in larger patient cohorts, and may lead to development of a new class of drugs.

The potential therapeutic effect of metformin in type 2 diabetic patients with severe COVID-19.

OBJECTIVE: Type 2 diabetes mellitus (T2DM) is regarded as a chief risk factor for(coronavirus disease 2019 (COVID-19) owing to dysregulation of the expression of angiotensin-converting enzyme 2 (ACE2) and chronic low-grade inflammatory disorders. Metformin, an insulin-sensitizing agent for managing T2DM, has pleiotropic anti-inflammatory and oxidant potentials, which may lessen the risk of diabetic complications. So, we aimed to reveal the potential role of metformin monotherapy in treating T2DM patients with COVID-19. PATIENTS AND METHODS: In this prospective cohort study, 60 hospitalized T2DM patients with COVID-19 on metformin plus standard anti-COVID-19 treatments compared to 40 hospitalized T2DM patients with COVID-19 on other diabetic pharmacotherapy like insulin and sulfonylurea, were recruited. Inflammatory and oxidative stress biomarkers and radiological and clinical outcomes were assessed at admission time and at the time of discharge. RESULTS: The results of this study illustrated that metformin treatment in T2DM patients with COVID-19 was more effective in reducing inflammatory and oxidative stress biomarkers with significant amelioration of radiological scores and clinical outcomes compared to T2DM patients with COVID-19 on another diabetic pharmacotherapy. CONCLUSIONS: Our findings highlighted that metformin efficiently managed T2DM patients with COVID-19 by reducing inflammatory and oxidative stress with mitigating effects on the radiological scores and clinical outcomes.

A randomized placebo-controlled, double-blind study to investigate the effect of a high oral loading dose of cholecalciferol in non-alcoholic fatty liver disease patients, new insights on serum STAT-3 and hepassocin.

OBJECTIVE: Non-alcoholic fatty liver disease (NAFLD) is a common chronic liver metabolic disease affecting millions globally. This study aimed to assess the safety and efficacy of a high oral loading dose of cholecalciferol supplement on NAFLD patients and to investigate its potential role on serum inflammatory biomarkers. PATIENTS AND METHODS: One hundred patients with NAFLD and type 2 diabetes mellitus were involved in the study. Eligible patients were randomized among two equal groups. Group 1 received the standard conventional therapy in addition to a placebo. Group 2 received the conventional therapy plus cholecalciferol for 4 months. The improvement in the patients' glycaemic control parameters, liver function tests, lipid profile, and serum 25-hydroxy vitamin D at the end of the study was set as a primary outcome. The secondary outcome was the decrease in steatosis grade in the ultrasound and high-sensitivity C-reactive protein (hs-CRP), tumor necrosis factor-alpha (TNF-α), signal transducer and activator of factor-3 (STAT-3), nitric oxide (NO), malondialdehyde (MDA), and hepassocin serum levels at the end of the study. RESULTS: Group 2 revealed a significant reduction in the serum levels of lipid profile measures, hs-CRP, alanine aminotransferase (ALT), STAT-3, NO, hepassocin, and MDA compared to the baseline and group 1 results. Whereas group 1 did not show these significant changes. Both groups observed no significant changes in glycemic index, TNF-α, aspartate aminotransferase (AST), and albumin levels. CONCLUSIONS: Cholecalciferol is recommended as additional therapy to modulate lipid peroxidation and systemic inflammation alongside other NAFLD therapies.

Epidermal photoprotection: comparative study of narrowband ultraviolet B minimal erythema doses with and without stratum corneum stripping in normal and vitiligo skin.

BACKGROUND: Recent accumulating data in the literature have indicated a complex photoprotective role of the epidermis, and the role of melanin as the major epidermal photoprotective mechanism has become debatable. AIM: Comparative assessment of the photoprotective roles played by different epidermal structures and compounds. METHODS: In total, 64 participants, comprising patients with vitiligo (n = 32) and healthy volunteers (n = 32), with skin phototypes (SPTs) II to V, were enrolled in the study. Areas of skin were delineated; for both lesional and nonlesional skin, the stratum corneum (the SC) was stripped, followed 24 h later by exposure to narrowband ultraviolet B (NB-UVB) irradiation, to measure the minimal erythema dose (MED) in normal, stripped normal, vitiliginous and stripped vitiliginous skin models. These MED values were used to assess the photoprotective role of epidermal structures: melanin, viable epidermis (VE) and the SC. RESULTS: In the vitiligo group, the MED values were significantly (P < 0.05) different between the skin models, being highest in normal skin, followed by stripped normal, vitiliginous and stripped vitiliginous skin. A similar significance level was found within each SPT for almost all comparisons. There was also a significant (P < 0.001) positive correlation between MED and SPTs. There were also significant (P < 0.05) differences in MED values calculated for epidermal structures, being highest for VE, followed by melanin and then the SC, and there was a significant (P < 0.05) positive correlation between MED and SPTs. CONCLUSION: Epidermal photoprotection may extend beyond melanin production, involving several factors such as epidermal layer thickness, optical properties and chromophores. Such a role was perceived to be reactive to UV irradiation, and more efficient in those with higher SPTs.

The spectrum of paediatric dermatoses in a university hospital in Cairo, Egypt.

BACKGROUND: Epidemiological data on paediatric dermatoses in Egypt are scanty. OBJECTIVE: To study the spectrum of paediatric dermatoses in Cairo. METHODS: The medical records of children attending the dermatology outpatient clinics of Ain Shams University hospital for the year 2001 were retrieved. Data of 3049 patients were included. Demographic data (age and gender) and diagnoses were extracted, coded and analysed. RESULTS: Patients' attendance peaked in summer (42.57%) and revealed female predominance (1.3:1). Infections constituted most of dermatoses (52.87%) and impetigo was most common (12.04%). Hypersensitivity came after (18.6%), and contact dermatitis prevailed (6.03%). Females predominated in most dermatoses. Bacterial infections were the most common in both genders. Age distribution revealed prevalence of bacterial infections in infants and preschool children, parasitic infections in school children and sebaceous gland disorders in adolescents. Parasitic infections prevailed in winter and spring, whereas bacterial infections prevailed in summer and autumn. Most dermatoses peaked in summer except urticaria and chicken pox that peaked in spring. CONCLUSION: Infections outnumbered other paediatric dermatoses parallel to the situation in developing communities. Such diseases are potentially controllable and therefore strategies that target infections may represent a key to an efficient child health care programme.

Organophosphorus pollutants (OPP) in aquatic environment at Damietta Governorate, Egypt: implications for monitoring and biomarker responses.

The study was carried out from spring 1999 to spring 2001 to monitor the residue levels of organophosphorus pollutants (OPP) in aquatic environment of the drainage canal surrounding a pesticide factory at Damietta Governorate. Water, sediment, and fish samples were collected at six different seasonal periods. OPPs were analyzed by GLC and confirmed using GC-MS. Chlorpyrifos, chlorpyrifos-methyl, malathion, diazinon, pirimiphos-methyl and profenofos were detected in most samples. Chlorpyrifos was dominant in all water and sediment samples. It was ranged from 24.5 to 303.8 and 0.9 to 303.8 ppb in water and sediment samples, respectively. Diazinon level was slightly similar to chlorpyrifos in fish samples. Data based on the grand total concentration of OPP showed that the most polluted samples were collected either at spring 1999 or autumn 2000. They were 675.5 and 303.8 ppb in water samples and 43.0 and 52.2 ppb in fish collected at spring 1999 and autumn 2000, respectively. The obtained results are in parallel to that found in case of cholinesterase activity where the activity of both acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) was declined at these seasonal period. The activity levels of AChE and BuChE were found to be 77.18% and 59.67% of control at spring 1999 and 78.62% and 85.80% of control, at autumn 2000, respectively. Thus, AChE and BuChE could be used as biomarkers for tracing and biomonitoring OPP pollution.

Serum Th17 cytokines in leprosy: correlation with circulating CD4(+) CD25 (high)FoxP3 (+) T-regs cells, as well as down regulatory cytokines.

Leprosy is not only a bacteriological disease but also an immunological disease, in which T helper17 and CD4(+) CD25(high)FoxP3(+) regulatory T cells (T-regs), among others, may play a role. We aimed to evaluate serum levels of interleukin (IL)-17, IL-22 (Th17 cytokines), IL-10 and transforming growth factor (TGF)-ß (down regulatory cytokines) in 43 untreated leprosy patients and 40 controls by enzyme-linked immunosorbent assay, and to assess circulating CD4(+) CD25(high)FoxP3(+)T-regs in patients using flow cytometry. Patients were grouped into tuberculoid, pure neural, borderline, lepromatous, type 1 reactional leprosy, and erythema nodosum leprosum. IL-10 and TGF-ß were significantly higher in patients as compared to controls (p < 0.001), while IL-17, but not IL-22, was significantly lower (p < 0.001), with no significant difference comparing patients' subgroups. Significantly higher CD4(+) CD25(high)FoxP3(+)T-regs levels was detected in tuberculoid, type 1 reaction and pure neural leprosy, while the lowest levels in erythema nodosum leprosum (p < 0.001). TregsFoxP3 expression% was significantly lower in pure neural leprosy than other patients' subgroups (p < 0.05). T-regs/T-effs was lowest in erythema nodosum leprosum (p < 0.05). TGF-ß correlated negatively with TregsFoxP3 expression% and T-effs% (p = 0.009 and 0.018 respectively). Leprosy is associated with defective IL-17 and overproduction of IL-10 and TGF-ß. Tuberculoid, type 1 reaction and pure neural leprosy express significantly higher circulating T-regs, consistent with effector immune mechanisms activation, but with lower TregsFoxP3 expression (in pure neural leprosy). Erythema nodosum leprosum is characterized by deficient T-regs and increased TregsFoxP3 expression%. The present study pinpointed a potential role of Th17, CD4(+) CD25(high)FoxP3(+)T-regs, and probably CD4(+) CD25(+)IL-10(+) T regulatory cells 1 (Tr1), and Th3 in leprosy.

Endothelin-1 is significantly elevated in plasma of patients with vitiligo treated with psoralen plus ultraviolet A.

BACKGROUND: Recent evidence suggests that systemic psoralen plus ultraviolet A (PUVA) therapy may have a stimulatory effect on melanocytes, not only locally but also systemically. Aim. We aimed to assess endothelin-1 (ET-1), a potent melanocyte mitogen, in plasma of PUVA-treated paients with vitiligo. METHODS: ET-1 was sequentially assessed (using ELISA) in patients with nonsegmental vitiligo treated with PUVA (n = 20), at 8, 16 and 24 h following the PUVA session. Evaluations took place at 0, 1 and 3 months of therapy. Patients with psoriasis (n = 15) treated identically and healthy subjects not receiving any therapy (n = 15) served as controls. Vitiligo Area Scoring Index (VASI) and Psoriasis Area Severity Index (PASI) scores were simultaneously evaluated. RESULTS: ET-1 was significantly lower in vitiligo than in psoriasis at month 0 (8.2 +/- 3.6 vs. 13.7 +/- 5.4 pg/mL; P = 0.03) and it was significantly higher in both than in healthy controls at all time points of the PUVA sessions (P < 0.001). In vitiligo, it significantly increased at month 3 at 8 (8.2 +/- 3.6 vs. 10.8 +/- 2.7 pg/mL; P = 0.02) and 16 h (8.2 +/- 3.6 vs. 11.5 +/- 3.9 pg/mL; P < 0.01), whereas in psoriasis, it significantly decreased at month 3 at 8 (13.7 +/- 5.4 vs. 3.5 +/- 0.4 pg/mL; P < 0.01) and 16 h (13.7 +/- 5.4 vs. 6.3 +/- 4 pg/mL; P = 0.01). In contrast to psoriasis, sequential values of vitiligo revealed insignificant variance (P > 0.05). VASI score significantly decreased at month 3 (19 +/- 9.6 vs. 11.9 +/- 7.3; P < 0.01), whereas PASI score significantly decreased at months 1 (38.2 +/- 16.1 vs. 13.8 +/- 3; P < 0.05) and 3 (38.2 +/- 16.1 vs. 7 +/- 2.6; P = 0.03). There was a significant indirect correlation of ET-1 with VASI score (P < 0.01) and a significant direct correlation with PASI score (P < 0.01). CONCLUSION: Systemic PUVA therapy in vitiligo may have a generalized mitogenic effect on melanocytes through the release of ET-1 into the circulation.