Characteristics and outcomes of acute hepatitis of unknown etiology in Egypt: first report of adult adenovirus-associated hepatitis.

PURPOSE: Several outbreaks of acute hepatitis of unknown etiology (AHUE) in children were reported in 2022 in many countries, with adenovirus identified as the etiological agent in most of them. We aimed to evaluate the characteristics and outcomes of AHUE cases in Egypt. METHODOLOGY: Hospitalized patients with acute hepatitis were included in the study. Drug-induced, alcoholic hepatitis, autoimmune hepatitis, and Wilson's disease were identified either by medical history or by routine laboratory diagnosis. Molecular and serological approaches were used to investigate common viral causes of hepatitis, such as hepatitis A-E viruses, cytomegalovirus, Epstein-Barr virus, herpes simplex viruses (HSV1/2), adenovirus, parvovirus B19, and coxsackie virus. RESULTS: A total of 42 patients were recruited and divided into two groups: 24 cases of unknown hepatitis after excluding the common causes and 18 cases of known hepatitis. About two-thirds of the patients were male (61.9%), and the mean age was 34.55 ± 16.27 years. Jaundice, dark urine, abdominal pain and diarrhea were recorded at a higher incidence in group 1, while jaundice and fever were frequent in group 2. Fulminant hepatitis occurred in 28.6% of the cases, but the two groups did not differ significantly in terms of patient outcome, duration of hospitalization, ascites, and development of fulminant hepatitis. Adenovirus was detected in five cases (20.8%) in group 1, and one case co-infecting with hepatitis E virus in group 2. Herpes simplex virus 1/2, coxsackie virus, and parvovirus B19 were not detected in any case, while etiologies of 75% of the cases were still not confirmed. One out of the six adenovirus-infected patients died. The outcome significantly correlated with the severity of the liver disease. CONCLUSION: This is the first report describing etiologies and characteristics of AHUE cases in Egypt, and interestingly, adenovirus was detected in adults. Further studies are required to determine the prevalence of this newly emerging viral hepatitis pathogens.

Perineural Platelet-Rich Plasma for Diabetic Neuropathic Pain, Could It Make a Difference?

OBJECTIVE: To evaluate the clinical effect of perineural platelet-rich plasma (PRP) injection for pain and numbness alleviation in diabetic peripheral neuropathy (DPN). STUDY DESIGN: A randomized prospective clinical trial. SETTING: Pain clinic and Rheumatology and Rehabilitation Departments, Assiut University Hospital. METHODS: Sixty adult patients with type II DM accompanied by DPN of at least six months' duration were assessed by modified Toronto Clinical Neuropathy Score (mTCNS) and randomly allocated into two groups. Group I underwent ultrasound-guided perineural PRP injection and medical treatment, and Group II received medical treatment only. Patients were followed up at months 1, 3, and 6 with regard to pain and numbness visual analog scale (VAS) and mTCNS scores. RESULTS: Significant improvement was recorded in pain and numbness VAS scale scores in group I vs group II (P ≤ 0.001 during the whole study period for both parameters); at the same time, mTCNS improved in group I in comparison with group II with P = 0.01, 0.001, and <0.001 at months 1, 3, and 6, respectively. CONCLUSIONS: Perineural PRP injection is an effective therapy for alleviation of diabetic neuropathy pain and numbness and enhancement of peripheral nerve function.

Determinants of healing of diabetic foot ulcer comparing two offloading modalities: A randomized prospective study.

INTRODUCTION: Healing of Diabetic Foot ulcer is crucial to prevent amputation. Offloading is key treatment of diabetic foot ulcers, but choosing which offloading modality is still not clear. Besides, other factors that control ulcer healing, is a question that needs to be determined. OBJECTIVE: to assess factors that affect ulcer healing, comparing two commonly used offloading devices, removable walker and cast-shoe. METHODS: This is a Randomized Clinical Trial which recruited 87 patients with active diabetic foot ulcers randomly assigned to either a removable walker (W-arm) or a cast-shoe (C-arm) at 3:2 ratio. Both groups received the routine ulcer care, and were followed-up for 24 weeks. Different possible factors related to healing were assessed, and a regression model was built for the most predictive factors. RESULTS: The 24-week healing rate was 81% for the walker group and 62 % for the cast-shoe group. The mean adherence was 55 % ± 26 % and 46 % ± 29 for the walker and cast shoe groups respectively. Ulcer healing was significantly positively associated with: better adherence, device type (walker), less SINBAD score (2 or less), absence of ischemia, absence of infection, smaller ulcer area, superficial ulcer, better 4-week area reduction, and better blood glucose control. The most important predictors were adherence, total SINBAD score and 4-week area reduction. CONCLUSION: SINBAD score at initial presentation and the degree of adherence to offloading device, are two major determinants of ulcer healing. Ulcer area reduction at 4 weeks represents an important clinical parameter to predict and guide the success of ulcer management.

Clinical and Bacteriological Analyses of Biofilm-Forming Staphylococci Isolated from Diabetic Foot Ulcers.

Background: Diabetes mellitus is a chronic disease that is associated with increased morbidity and mortality. Unfortunately, foot ulcers and amputations due to diabetes are very common in developing countries. The purpose of this study was to characterize the clinical presentation of diabetic foot ulcer (DFU) infections, isolate the causative agent, and analyze the biofilm formation and distribution of biofilm-related genes among isolated Staphylococci. Material and Methods: The study included 100 diabetic patients suffering from DFUs attending Assiut University Hospital. Swabs were collected and antimicrobial susceptibility testing of the isolates was performed. Biofilm formation was tested phenotypically among staphylococcal isolates and the frequency of different biofilm genes was analyzed by PCR. Clinical presentations of diabetic foot ulcers were correlated with bacterial genetic characteristics. Spa types were determined using DNA Gear-a software. Results: Microbiological analysis showed that 94/100 of the DFUs were positive for bacterial growth. The majority of infections were polymicrobial (54%, n=54/100). Staphylococci were the most commonly detected organisms, of which S. aureus represented 37.5% (n=24/64), S. haemolyticus 23.4% (n=15/64), S. epidermidis 34.3% (n=22/64) and other CNS 4.7% (n=3/64). Interestingly, co-infection with more than one species of Staphylococci was observed in 17.1% (n=11/64) of samples. A high level of antibiotic resistance was observed, where 78.1% (n=50/64) of Staphylococci spp were multidrug-resistant (MDR). Phenotypic detection showed that all isolated Staphylococci were biofilm-formers with different grades. Analysis of biofilm-forming genes among Staphylococci showed that the most predominant genes were icaD, spa, and bap. Isolates with a higher number of biofilm-related genes were associated with strong biofilm formation. Sequencing of the spa gene in S. aureus showed that our isolates represent a collection of 17 different spa types. Conclusion: The majority of DFUs in our hospital are polymicrobial. Staphylococci other than S.aureus are major contributors to infected DFUs. MDR and biofilm formation are marked among isolates, which is paralleled by the presence of different categories of virulence-related genes. All severely infected wounds were associated with either strong or intermediate biofilm formers. The severity of DFU is directly related to the number of biofilm genes.

Fig latex inhibits the growth of pathogenic bacteria invading human diabetic wounds and accelerates wound closure in diabetic mice.

Impaired wound healing is one of the most critical complications associated with diabetes mellitus. Infections and foot ulcers are major causes of morbidity for diabetic patients. The current treatment of diabetic foot ulcers, commonly used antibiotics, is associated with the development of bacterial resistance. Hence, novel and more effective natural therapeutic antibacterial agents are urgently needed and should be developed against the pathogenic bacteria inhabiting diabetic wounds. Therefore, the current study aimed to investigate the impact of fig latex on pathogenic bacteria and its ability to promote the healing process of diabetic wounds. The pathogenic bacteria were isolated from patients with diabetic foot ulcers admitted to Assiut University Hospital. Fig latex was collected from trees in the Assiut region, and its chemical composition was analyzed using GC‒MS. The antibacterial efficacy of fig latex was assessed on the isolated bacteria. An in vivo study to investigate the effect of fig latex on diabetic wound healing was performed using three mouse groups: nondiabetic control mice, diabetic mice and diabetic mice treated with fig latex. The influence of fig latex on the expression levels of ß-defensin-1, PECAM-1, CCL2 and ZO-1 and collagen formation was investigated. The GC‒MS analysis demonstrated the presence of triterpenoids, comprising more than 90% of the total latex content. Furthermore, using a streptozotocin-induced diabetic mouse model, topical treatment of diabetic wound tissues with fig latex was shown to accelerate and improve wound closure by increasing the expression levels of ß-defensin-1, collagen, and PECAM-1 compared to untreated diabetic wounds. Additionally, fig latex decreased the expression levels of ZO-1 and CCL2.

The First Report of Coxiella burnetii as a Potential Neglected Pathogen of Acute Hepatitis of Unknown Causes in Egypt.

The World Health Organization (WHO) recently alerted the emergence of new pathogens causing acute hepatitis in children across several countries. This new situation directs us to the screening of neglected pathogens that cause acute hepatitis. Q-fever is a zoonotic disease, caused by Coxiella burnetii. Although a high seroprevalence of Coxiella burnetii was recorded in animals present in Egypt, Q-fever is still a neglected disease, and the diagnosis of Q-fever is not routinely performed in Egyptian hospitals. In this study, we performed a retrospective assessment for Coxiella burnetii in cases of hepatitis of unknown causes (HUC) enrolled in Assiut University hospitals, in Egypt. Out of 64 samples of HUC, 54 samples were negative for all hepatitis markers, labeled as acute hepatitis of unknown etiology (AHUE), and 10 samples tested positive for adenovirus and Hepatitis E virus (HEV). Q-fever was detected in 3 out of 54 (5.6%) of AHUE, and one sample was confirmed as coinfection of HEV/Q-fever. Jaundice was the most common clinical symptom developed in the patients. In conclusion, Coxiella burnetii was found to be a potential cause of acute hepatitis in HUC. The diagnosis of Q-fever should be considered in acute hepatitis cases in Egyptian hospitals.

Circulating microparticle subpopulation in metabolic syndrome: relation to oxidative stress and coagulation markers.

BACKGROUND: Circulating microparticles (MPs) contribute to the pathogenesis of atherothrombotic disorders and are raised in cardiovascular diseases. Herein, we aimed to investigate the effect of moderate metabolic abnormalities in an early stage of metabolic syndrome (MetS) on the level of MP subpopulations and to study relationships between MP subpopulations and both oxidative stress and coagulation markers. METHODS: Flow cytometry used to evaluate circulating MPs subpopulations in 40 patients with an early stage MetS and 30 healthy controls. ELISA was used to quantify plasminogen activator inhibitor type 1/tissue plasminogen activator (PAI-1/TPA) while plasma glutathione peroxidase (GPx) activity was measured spectrophotometrically. RESULTS: Total MPs were significantly elevated in MetS (P<0.001). Glutathione peroxidase and PAI1/TPA activity was significantly increased in subjects with MetS (P<0.001). Waist circumference, diastolic blood pressure, and total cholesterol positively influenced levels of total MPs, platelet-derived microparticles, and endothelium-derived microparticles. Fasting blood glucose, cholesterol, triglycerides, and low-density lipoprotein positively influenced the coagulation factors (TPA, PAI1). However, high-density lipoprotein negatively influenced platelet-derived MPs and factors associated with fibrinolysis (TPA, PAI1). CONCLUSION: Elevated circulating MPs are associated with MetS abnormalities, oxidative stress and coagulation factors and may act as early predictor of metabolic syndrome with risk of cardiovascular disease.

Risk factors for diabetic foot ulcer recurrence: A prospective 2-year follow-up study in Egypt.

OBJECTIVES: To determine the frequency of diabetic foot ulcer recurrence and its potential risk factors. METHODS: This study included 93 patients with type 2 diabetes and followed for 2 years after primary healed foot ulceration. Demographic, diabetes related, comorbid and ulcer related variables were investigated as risk factors. Multiple logistic regression analysis was used to identify independent risk factors. RESULTS: 61.3% of patients had recurrent ulcers particularly in the forefoot (33.3%) and big toe (24.6%). Peripheral neuropathy, peripheral arterial disease or both were reported in 69%, 12% and 19% of feet with recurrent ulcers respectively. In multivariate analysis, the significant independent potential risk factors for recurrence of foot ulcers were smoking (P=0.040), poor glycemic control [HbA1c cutoff of 10%] (P=0.010), peripheral neuropathy with lost ankle reflex (P=0.0001), peripheral arterial disease (P=0.0001) and previous ulcer location (P=0.050). CONCLUSION: The frequency rate of recurrent diabetic foot ulceration in patients with type 2 diabetes is high particularly in the first year despite regular follow-up and patient education.