Factors affecting timing of hypothyroidism following radioactive iodine therapy (RAIT) for patients with Graves' disease: A 12-month observational study.

BACKGROUND: This retrospective study analyzed factors influencing hypothyroidism development after radioactive iodine therapy for Graves' disease. PATIENTS AND METHODS: Three hundred and three patients with Graves' disease treated with radioactive iodine (RAI) from 2013 to 2022 at two Egyptian hospitals were included. Data collected included demographics, lab values, thyroid imaging, RAI doses, and outcomes. Patients were followed for ≥1 year to assess hypothyroidism onset. RESULTS: At the end of 1 year, around 79.5% of the individuals developed hypothyroidism while 12.5% continued to experience hyperthyroidism. The onset of hypothyroidism occurred earlier in those with thyroid volume (≤75.5 cm 3 ), lower thyroid weight (≤84.7 g), thyroid uptake (≤18.8%), and higher RAI dose/volume (≥0.1022 mCi/ml) ( P  < 0.001). Additionally, there was a correlation between anti-thyroid peroxidase (anti-TPO) antibodies and faster development of hypothyroidism compared to those who were negative for antibodies (2.9 vs 8.9 months, P  = 0.001). When considering factors in analysis it was found that anti-TPO antibodies were the only independent predictor, for developing hypothyroidism (hazard risk 30.47, P  < 0.001). Additionally, thyroid volume and uptake independently predicted successful treatment outcomes ( P  < 0.05). CONCLUSION: Positive anti-TPO antibodies strongly predict hypothyroidism risk after RAI therapy for Graves' disease. Smaller thyroid size, lower uptake, and higher RAI dose/volume correlate with earlier hypothyroidism onset but are less significant predictors than anti-TPO status. Findings can guide RAI therapy personalization to optimize outcomes.

The Use of Transesophageal Doppler and Central Venous Oxygen Saturation as Predictors of Weaning Success.

OBJECTIVES: Weaning individuals from mechanical ventilation (MV) is a challenge to physicians. Respiratory failure is the main reason for weaning failure (WF), but heart failure plays a pivotal role as well. Transesophageal Doppler (TED) is a minimally invasive method of hemodynamic tracking with fewer problems. The study authors evaluated the role of TED in predicting WF. DESIGN: An observational study. SETTING: A university teaching hospital. PARTICIPANTS: Weaning individuals. INTERVENTIONS: TED was applied before initiating the spontaneous breathing trial (SBT). Hemodynamic parameters, arterial blood gases, and TED (peak velocity [PV], cardiac output [COP]) were reported while cases were on MV before initiating the SBT, and at the successful completion of SBT. Succeeded (group S) and failed individuals (group F, who needed reintubation within 48 hours) were compared. The sensitivity, specificity, and area under the receiver operating curve were calculated. A subgroup of patients with cardiac comorbidities and impaired cardiac contractility was further analyzed. MEASUREMENTS AND MAIN RESULTS: The authors included 39 critically ill patients for weaning from MV. The reintubation rate was 54.8%. In patients with cardiac morbidity, delta change (dC) in PV and COP as predictors of WF showed 100% sensitivity and specificity, with 18% and 14% cut-offs after initiating the SBT (dC between the beginning and end of the successful SBT), respectively. Central venous oxygen saturation revealed a significant difference between patients with cardiac morbidity and noncardiac patients with lower sensitivity and specificity in the prediction of WF. CONCLUSIONS: TED could be a helpful method for the weaning of patients with cardiac morbidity from MV. The dC in PV and COP >18% and >14% were significant predictors of WF in these subjects, respectively.

Admission SpO2 and ROX index predict outcome in patients with COVID-19.

BACKGROUND: This study aimed to evaluate the accuracy of pulse oximetry-derived oxygen saturation (SpO2) on room air, determined at hospital admission, as a predictor for the need for mechanical ventilatory support in patients with Coronavirus Disease-2019 (COVID-19). METHODS: In this retrospective observational study, demographic and clinical details of the patients were obtained during ICU admission. SpO2 and respiratory rate (RR) on room air were determined within the first 6 h of hospital admission. As all measurements were obtained on room air, we calculated the simplified respiratory rate­oxygenation (ROX) index by dividing the SpO2 by the RR. Based on the use of any assistance of mechanical ventilator (invasive or noninvasive), patients were divided into mechanical ventilation (MV) group and oxygen therapy group. The accuracy of the SpO2, CT score, and ROX index to predict the need to MV were determined using the Area under receiver operating curve (AUC). RESULTS: We included 72 critically ill patients who tested COVID-19-positive. SpO2 on the room air could predict any MV requirement (AUC [95% confidence interval]: 0.9 [0.8-0.96], sensitivity: 70%, specificity 100%, cut-off value ≤78%, P < 0.001). Within the MV group, the use of noninvasive ventilation (NIV) was successful in 37 (74%) patients, whereas 13 patients (26%) required endotracheal intubation. The cut-off ROX value for predicting early NIV failure was ≤1.4, with a sensitivity of 85%, a specificity of 86%, and an AUC of 0.86 (95% confidence interval of 0.73-0.94, P < 0.0001). CONCLUSIONS: A baseline SpO2 ≤78% is an excellent predictor of MV requirement with a positive predictive value of 100%. Moreover, the ROX index measured within the first 6 h of hospital admission is a good indicator of early NIV failure.

Changes in the co-expressions of interleukin 29 (IL-29), IFN-inducible protein 10 (IP-10) and monokine induced by IFNγ (MIG) genes in chronic hepatitis C Egyptian patients untreated and treated with DAAs.

Direct acting antiviral agents (DAAs) are a group of antiviral drugs that inhibit specific non-structural proteins of the virus and disrupt viral replication and infection. DAAs regimens for hepatitis C virus (HCV) infection provide a particular event to tackle mechanistic intracellular relationships between the innate immunity and HCV, potentially providing perceptions about the rate of the viral replication and complex decay. Interleukin 29 (IL-29) prevents the replication of HCV. IFN-inducible protein 10 (IP-10) plays a significant role in the pathogenesis of HCV infection. MIG/CXCL9 are produced by inflammatory and stromal cells such as hepatocytes following either stimulation by interferon lambda (IFNγ) or viral infection. This study aimed to evaluate the co-expression of IL-29, IP-10 and MIG in peripheral blood mononuclear cells (PBMCs) from untreated and treated chronic HCV patients with DAAs. This study included group of twenty naïve HCV patients, group of twenty sustained viral response (SVR) patients and a control group that consisted of 10 healthy subjects. All subjects were tested for liver enzymes, serum albumin level, total serum bilirubin, platelet count, prothrombin activity and viral load. Relative gene expression of IL-29, IP-10, and MIG in PBMCs from all subjects was determined using real time PCR. The mean value of IL-29, IP-10 and MIG gene expression significantly increased in both naïve HCV and SVR groups of patients as compared to normal subjects. The corresponding value was significantly lower in patients with SVR compared to naïve HCV patients. Infection with HCV significantly trigged the co-expression of IL-29, IP-10, and CXCL9 (MIG) genes in PBMCs of chronic hepatitis C patients and significantly down-regulated in those who achieved SVR after successful DAAs therapy. Keywords: IP10; MIG; IL29; HCV; DAAs; gene expression.

Predictive Factors Increasing the Risk of Radiation Toxicity in Patients with Early Breast Cancer.

OBJECTIVES: Radiation induces adverse events on healthy tissues which may be augmented by certain factors. This study aimed to assess patients; tumor and treatment-related factors which increase the risk of radiation-induced toxicity in breast cancer patients. METHODS: This prospective study included postmenopausal early breast cancer patients treated at the clinical oncology department, Assiut University, Egypt between January 2015 and December 2018. Patients treated with mastectomy followed by conventional radiotherapy (25x 2 Gy) and either concurrent or sequential letrozole. Acute and late radiation toxicity was scored according to EORTC/RTOG and risk factors were analyzed. RESULTS: A total of 75 patients were included in the study. After a median follow-up of 24 months, 12 patients had > grade 2 acute dermatitis, 5 patients had > grade 2 cardiac toxicity and 3 patients had > grade 2 lung toxicity. Multivariate analysis revealed that trastuzumab use was associated with a decrease risk of acute dermatitis (p= 0.01) but boost irradiation was significantly associated with increased risk of acute dermatitis (p= 0.01). Late toxicity > grade 2 was observed in 6 patients, 14 patients, and 2 patients for skin, heart, and lung respectively. CONCLUSION: The use of boost irradiation was associated with increased risk of acute dermatitis, in the contrary; the use of trastuzumab seemed to be protective as observed in this study.

FAK inhibition radiosensitizes pancreatic ductal adenocarcinoma cells in vitro.

INTRODUCTION: Focal adhesion kinase (FAK) is a nonreceptor tyrosine kinase protein frequently overexpressed in cancer and has been linked to an increase in the stem cell population of tumors, resistance to therapy, and metastatic spread. Pharmacological FAK inhibition in pancreatic cancer has received increased attention over the last few years, either alone or in combination with other therapeutics including chemotherapy and immunotherapy. However, its prognostic value and its role in radioresistance of pancreatic ducal adenocarcinoma (PDAC) is unknown. METHODS AND MATERIALS: Using the TCGA and GTEx databases, we investigated the genetic alterations and mRNA expression levels of PTK2 (the encoding-gene for FAK) in normal pancreatic tissue and pancreatic cancer and its impact on patient survival. Furthermore, we evaluated the expression of FAK and its tyrosine domain Ty-397 in three pancreatic cancer cell lines. We went further and evaluated the role of a commercial FAK tyrosine kinase inhibitor VS-4718 on the viability and radiosensitization of the pancreatic cell lines as well as its effect on the extracellular matrix (ECM) production from the pancreatic stellate cells. Furthermore, we tested the effect of combining radiation with VS-4718 in a three-dimensional (3D) multicellular pancreatic tumor spheroid model. RESULTS: A database analysis revealed a relevant increase in genetic alterations and mRNA expression of the PTK2 in PDAC, which were associated with lower progression-free survival. In vitro, there was only variation in the basal phosphorylation level of FAK in cell lines. VS-4718 radiosensitized pancreatic cell lines only in the presence of ECM-producing pancreatic stellate cells and markedly reduced the ECM production in the stromal cells. Finally, using a 3D multicellular tumor model, the combination of VS-4718 and radiotherapy significantly reduced the growth of tumor aggregates. CONCLUSION: Pharmacological inhibition of FAK in pancreatic cancer could be a novel therapeutic strategy as our results show a radiosensitization effect of VS-4718 in vitro in a multicellular 2D- and in a 3D-model of pancreatic cancer.

Evaluation of peripheral perfusion index and heart rate variability as early predictors for intradialytic hypotension in critically ill patients.

BACKGROUND: Intradialytic hypotension is a serious complication during renal replacement therapy in critically ill patients. Early prediction of intradialytic hypotension could allow adequate prophylactic measures. In this study we evaluated the ability of peripheral perfusion index (PPI) and heart rate variability (HRV) to predict intradialytic hypotension. METHODS: A prospective observational study included 36 critically ill patients with acute kidney injury during their first session of intermittent hemodialysis. In addition to basic vital signs, PPI was measured using Radical-7 (Masimo) device. Electrical cardiometry (ICON) device was used for measuring cardiac output, systemic vascular resistance, and HRV. All hemodynamic values were recorded at the following time points: 30 min before the hemodialysis session, 15 min before the start of hemodialysis session, every 5 min during the session, and 15 min after the conclusion of the session. The ability of all variables to predict intradialytic hypotension was assessed through area under receiver operating characteristic (AUROC) curve calculation. RESULTS: Twenty-three patients (64%) had intradialytic hypotension. Patients with pulmonary oedema showed higher risk for development of intradialytic hypotension {Odds ratio (95% CI): 13.75(1.4-136)}. Each of baseline HRV, and baseline PPI showed good predictive properties for intradialytic hypotension {AUROC (95% CI): 0.761(0.59-0.88)}, and 0.721(0.547-0.857)} respectively. CONCLUSIONS: Each of low PPI, low HRV, and the presence of pulmonary oedema are good predictors of intradialytic hypotension.

Relation between microRNA-21, transforming growth factor ß and response to treatment among chronic hepatitis C patients.

BACKGROUND: Persistence of hepatitis C virus (HCV) infection and response to antiviral therapy has been shown to be associated with inappropriate levels of cytokines and microRNAs (miRNAs). miRNA levels have been reported to fluctuate during treatment. Thus they could be useful predictors for responses to treatment among HCV infected patients, thereby reducing ineffective treatments. AIM: The current study aimed to investigate the relation between miRNA-21 expression profiles, transforming growth factor ß (TGF-ß) serum levels and response to treatment with the new direct antiviral drugs (sofosbuvir + daclatasvir ± ribavirin), among HCV infected Egyptian patients. SUBJECTS AND METHODS: This prospective study was conducted on 50 HCV infected patients (before and after treatment) and 20 healthy volunteers. miRNA expression profiles were determined by real-time polymerase chain reaction and TGF-ß1 serum levels were measured by using enzyme-linked immunosorbent assay. RESULTS: There was a significant increase in serum albumin, platelets count and a significant decrease in liver enzymes, serum bilirubin, and prothrombin time after treatment. Significant reduction of viral load among HCV patients after receiving the treatment was reported. Concomitantly, there was an increase in the relative quantity of miRNA-21 (P = .001*) and serum levels of TGF-ß1 ( P = .337) among HCV patients after receiving treatment. CONCLUSION: Nearly all responders to direct antiviral drugs showed increased levels of both miRNA-21 and TGF-ß1. This may indicate an interplay between TGF-ß1 and miRNA-21 during remission or progression of viral infection. Thus miRNA-21 could be used as promising serum biomarker, for assessment of antiviral treatment efficacy and improvement of fibrosis among chronically infected HCV patients.

Helicobacter pylori infection and risk of salmonella infection.

Helicobacter pylori (H pylori) infection is the most frequent infection worldwide and it has been postulated that it predisposes to multiple enteric pathogens and diarrheal diseases. Salmonella infection is common in tropical and under developed communities and is associated with wide range of diseases from gastroenteritis to typhoid fever. This study aimed at detecting the impact of H pylori infection on the incidence of salmonella infections.The study participants were sampled from cohorts of patients in four university hospitals in different Egyptian Governorates. Their age ranged from 20 to 59 years and followed up for a rising Widal test. Case patients (n = 109) were subjects who visited the outpatient clinic because of diarrhea and typhoid like illness. They were either positive for H pylori stool antigen (n = 53) or negative to it (n = 56). All patients were subjected to thorough history taking, clinical examination, routine laboratory investigations, abdominal ultrasonography, H pylori stool antigen detection, and serial Widal test assay.The proportion of salmonella-infected subjects was lower among case patients with H pylori infection (22.6%) than among those negative for H pylori (33.9%) albeit not statistically significant (adjusted odds ratio [OR], 0.57; 95% confidence interval [CI], 0.24-1.33; P = .21). The association persisted nonsignificant after adjusting for sociodemographic variables (adjusted OR, 0.5; 95% CI, 0.18-1.39; P = .18). In a multivariate analysis that adjusted for sex, dietary habits, socioeconomic status, and educational level subjects who eat outdoors were associated with a significantly greater risk of salmonella typhi infection.Our findings suggest that there is no association between H pylori infection and salmonella infection in patients presented with typhoid fever or typhoid like illness.

Comparison of Free and Immobilized L-asparaginase Synthesized by Gamma-Irradiated Penicillium cyclopium.

Gamma irradiation is used on Penicillium cyclopium in order to obtain mutant cells of high L-asparaginase productivity. Using gamma irradiation dose of 4 KGy, P. cyclopium cells yielded L-asparaginase with extracellular enzyme activity of 210.8 ± 3 U/ml, and specific activity of 752.5 ± 1.5 U/mg protein, which are 1.75 and 1.53 times, respectively, the activity of the wild strain. The enzyme was partially purified by 40-60% acetone precipitation. L-asparaginase was immobilized onto Amberlite IR-120 by ionic binding. Both free and immobilized enzymes exhibited maximum activity at pH 8 and 40 degrees C. The immobilization process improved the enzyme thermal stability significantly. The immobilized enzyme remained 100% active at temperatures up to 60 degrees C, while the free asparaginase was less tolerant to high temperatures. The immobilized enzyme was more stable at pH 9.0 for 50 min, retaining 70% of its relative activity. The maximum reaction rate (V(max)) and Michaelis-Menten constant (K(m)) of the free form were significantly changed after immobilization. The K(m) value for immobilized L-asparaginase was about 1.3 times higher than that of free enzyme. The ions K+, Ba2+ and Na+ showed stimulatory effect on enzyme activity with percentages of 110%, 109% and 106% respectively.

Total serum immunoglobulin E in patients with alopecia areata.

CONTEXT: Alopecia areata (AA) is a common form of localized, non-scarring hair loss. The pathogenesis of the disease is unknown. Previous evidence suggested the involvement of Th2 cytokines in disease pathogenesis. AIM: To determine serum level of total IgE, this is mainly influenced by Th2 cytokines, in Egyptian patients with AA. MATERIALS AND METHODS: Fifty subjects with AA (28 males and 22 females) were selected from Dermatology Outpatient Clinic, Menoufiya University Hospital from February 2012 to December 2012. Subjects with other conditions that might elevate serum IgE were excluded from the study. Fifty age- and sex-matched healthy subjects were selected as a control group. Venous blood samples were taken from cases and controls for measurement of total serum IgE by enzyme-linked immunosorbent assay. Skin biopsy was taken from every case from an active area of hair loss. RESULTS: Total serum IgE was elevated in 27 (54%) cases. Its values among patients ranged from 13.5 IU/ml to 780 IU/ml. There was a statistically significant difference between cases and controls with regard to mean value of serum IgE (P < 0.05). Mean value of IgE did not vary significantly with disease severity, patients' age, patients' gender, disease duration, site of lesions, and positive family history of AA. No correlation was found between serum IgE levels and histopathological changes detected in examined cases. CONCLUSIONS: Total serum IgE is elevated in AA. This elevation is not related to age, gender, disease duration, disease severity, site of affection or family history of AA.

Prevalence of extensively drug-resistant gram negative bacilli in surgical intensive care in Egypt.

INTRODUCTION: The prevalence of extensively drug resistant gram negative bacilli (XDR-GNB) is rapidly progressing; however in Egypt data are sparse. We conducted the present study to quantify the incidence, risk factors and outcome of patients harboring XDR-GNB. METHODS: A one year prospective study was done by collecting all the bacteriological reports for cultures sent from the surgical intensive care unit, Cairo university teaching hospital. XDR-GNB were defined as any gram negative bacilli resistant to three or more classes of antimicrobial agents. Patients with XDR-GNB compared with those sustaining non extensively drug-resistant infection. A multivariate logistic regression model was created to identify independent predictors of multi-resistance. RESULTS: During one-year study period, a total of 152 samples (65%) out of 234 gram negative bacilli samples developed extensively drug resistant infection. XDR strains were significantly higher in Acinetobacterspp (86%), followed by Pseudomonas (63%), then Proteus (61%), Klebsiella (52%), and E coli (47%). Fourth generation cephalosporine (Cefipime) had the lowest susceptibility (10%) followed by third generation cephalosporines (11%), Quinolones (31%), Amikacin (42%), Tazobactam (52%), Carbapinems (52%), and colistin (90%). Relaparotomy was the only significant risk factor for acquisition of XDR infection. CONCLUSION: Extensively drug-resistant gram negative infections are frequent in our ICU. This is an alarming health care issue in Egypt which emphasizes the need to rigorously implement infection control practices.