Objective: To report a patient with an unusual presentation of autoimmune polyendocrinopathy-cand... more Objective: To report a patient with an unusual presentation of autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) and severe keratopathy. Case History: An Egyptian male sustained an injury to the left eye at 13 years of age and was found to have corneal damage which was attributed to the injury. Subsequently, however, he continued to have sore eyes with photophobia. A year later he became weak with pigmentation and episodes of collapse, and investigation showed that he had Addison’s disease together with mucocutaneous candidiasis. At 15 years of age he developed carpo-pedal spasm and was found to have hypoparathyroidism with intracranial calcification. At 20 years of age the ophthalmic diagnosis was revised to keratopathy by which time the patient had corneal opacity and problems with visual acuity, especially in the right eye. Investigation at 22 years of age showed that he was homozygous for an R139X mutation in the gene encoding the AIRE protein, a mutation which to date has only been found in Sardinian patients. Conclusions: Keratopathy can be an early and severe manifestation of APECED, requiring expert ophthalmic care. Its presence should prompt a search for other components of APECED, some of which are life-threatening.
trials was conducted to evaluate efficacy and safety of using Absorb BVS system for patients with... more trials was conducted to evaluate efficacy and safety of using Absorb BVS system for patients with STEMI. Taking into account the hypothesis of superior effectiveness of Absorb BVS system for patients with STEMI for pharmacoeconomic analysis was chosen "cost-effectiveness" analysis. MS Excel based model was performed to asses 2 strategies: strategy 1-patients with primary percutaneous coronary intervention (PPCI) with Absorb BVS system; strategy 2-patients received thrombolytic therapy in the hospital. The 1 LYG and 1 surviving patient were included into the model as the effectiveness criteria. Direct costs included emergency, inpatient and outpatient treatment, rehabilitation and cost of PPCI with Absorb BVS system. All the direct costs were calculated from the Russian healthcare system perspective. Results: According to published trials the using of Absorb BVS system for patients with STEMI did not lead to different rates of composite patient-oriented and device-oriented adverse events. Strategy 1 has a higher efficiency-the proportion of survivors at 1 year will be the maximum-92.7%, as well as the LYG-5.4.
OBJECTIVE: We aimed to investigate if endothelin 1 concentration at day 3 postnatal age could be ... more OBJECTIVE: We aimed to investigate if endothelin 1 concentration at day 3 postnatal age could be used as a predictive marker for development of bronchopulmonary dysplasia in preterm neonates with respiratory distress syndrome. METHODS: This prospective observational study was done on 69 preterm neonates with gestational ages between 28 and 34 weeks and diagnosed as having respiratory distress syndrome. Serum concentrations of endothelin 1 was measured for all patients at day 3 of life and they were divided into BPD and No-BPD groups according to whether they developed bronchopulmonary dysplasia or not. RESULTS: A total of 17 infants were in the BPD group and 52 infants were in the No-BPD group. Serum endothelin 1 was significantly higher in the BPD group (435.39 ± 172.88) compared with the No-BPD group (302.65 ± 49.32) (p < 0.001). Serum endothelin 1 correlated significantly with days spent on mechanical ventilation (r = 0.379, p = 0.022) and days spent on CPAP (r = 0.391, p = 0.001). A serum endothelin 1 cut off value of 302.7 ng/L could predict preterm that will develop bronchopulmonary dysplasia with a sensitivity of 88.24%, and specificity of 61.54%. CONCLUSION: Serum endothelin 1 is significantly increased at day 3 of life in preterm neonates with respiratory distress syndrome who later develop bronchopulmonary dysplasia (BPD). It seems to be a promising predictive marker for BPD but further studies are needed to find the appropriate time for its measurement.
Autoimmune polyendocrinopathy candidiasis ectodermal dystrophy (APECED) is a monogenic autosomal ... more Autoimmune polyendocrinopathy candidiasis ectodermal dystrophy (APECED) is a monogenic autosomal recessive disease caused by mutations in the autoimmune regulator (AIRE) gene and, as a syndrome, is characterized by chronic mucocutaneous candidiasis and the presentation of various autoimmune diseases. During the last decade, research on APECED and AIRE has provided immunologists with several invaluable lessons regarding tolerance and autoimmunity. This review describes the clinical and immunological features of APECED and discusses emerging alternative models to explain the pathogenesis of the disease.
Background: The presented evidence-based clinical practice guideline (CPG) is proposed as a Natio... more Background: The presented evidence-based clinical practice guideline (CPG) is proposed as a National CPG using an evidence-based and formal CPG adaptation methodology. The purpose of this study was to adapt the international CPGs' recommendations for term and late preterm neonates with severe hyperbilirubinemia to suit the healthcare system in the Egyptian context. This CPG provides a framework for prediction, prevention and management of severe hyperbilirubinemia in newborn infants of 35 or more weeks of gestation. The quality of evidence and strength of recommendations are indicated. The guideline adaptation group was chosen from various Egyptian Universities. There was an active involvement of a Multidisciplinary Review Committee following a standardized process. The Neonatology Guideline Adaptation Group (NGAG) was assigned individual health questions to cover the different sections of the required CPG. A literature search for source CPGs was carried out. The NGAG studied several guidelines. Critical appraisal was done by AGREE II (Appraisal of Guidelines for Research and Evaluation) Instrument to rate and select the appropriate guidelines. Results: The NGAG decided to adapt mainly the American Academy of Pediatrics Guideline (2004, 2009 & 2011) and for the questions which were not answered; the best and most relevant evidence available was used. Implementation tools were sought for to facilitate the application of the adapted CPG. Conclusion: The finalized CPG offers healthcare providers with applicable evidence-based guidance for severe neonatal hyperbilirubinemia in the Egyptian context. The Adapted ADAPTE method emphasized the value of collaborative clinical and methodological expert groups' efforts for adaptation of national guidelines.
Background The presented evidence-based clinical practice guideline (CPG) is proposed as a Nation... more Background The presented evidence-based clinical practice guideline (CPG) is proposed as a National CPG using an evidence-based and formal CPG adaptation methodology. The purpose of this study was to adapt the international CPGs’ recommendations for children with bronchiolitis to suit the healthcare system in the Egyptian context. This CPG, ‘diagnosis, treatment, and prevention of Bronchiolitis’, applies to children from 1 through 23 months of age. Other exclusions are noted. The quality of evidence, benefit-harm relationship, and strength of recommendations are indicated. This study is part of a larger collaborative initiative with the faculty staff of pediatric departments of 15 Egyptian universities and a national research center to formulate a national Committee (EPG) that aims to define the topics of, assign authors to, and assist in the adaptation of pediatric evidence-based CPGs according to a national strategic plan. The committee is guided by a formal CPG adaptation methodo...
Background: Hypogonadism is a key feature of Prader-Willi syndrome (PWS) but clear strategies for... more Background: Hypogonadism is a key feature of Prader-Willi syndrome (PWS) but clear strategies for hormone replacement are lacking. Objective: To evaluate gonadal status and outcome in patients attending a Scottish PWS clinic from 1991-2019. Methods: In 93 (35F:56M) patients, median follow-up 11.2 years, gonadal and pubertal status were assessed clinically. Pelvic ultrasound findings and basal/stimulated gonadotrophins were compared with age-matched controls. Results: Females: Of 22 patients aged >11, 9 had reached B4-5, while 5 were still at B2-3, and 6 remained prepubertal. Eight patients experienced menarche aged 9.8-21.4 years, none with a normal cycle. Uterine length and ovarian volumes were normal but uterine configuration remained immature, with low follicular counts. Gonadotrophins were unremarkable, serum estradiol 129 (70 – 520) pmol/L. Only 5 patients received oestrogen replacement. Males: Fifty-four (96%) patients were cryptorchid (9 unilateral). Weekly hCG injections ...
Abstract In order to evaluate the effect of different types of phototherapy on oxidant/antioxidan... more Abstract In order to evaluate the effect of different types of phototherapy on oxidant/antioxidant status in hyperbilirubinemic neonates, an interventional randomized control trial was conducted on 120 neonates ≥35 weeks’ gestational age with indirect hyperbilirubinemia reaching phototherapy level. This study is registered with ClinicalTrials.gov as NCT03074292. Neonates were assigned to three groups; 40 neonates received conventional phototherapy, 40 received intensive phototherapy and 40 received blue light-emitting diodes (LED) phototherapy. Complete blood count (CBC), total serum bilirubin (TSB), total antioxidant capacity (TAC), malondialdehyde (MDA), nitric oxide (NO), copper (Cu), zinc (Zn), and iron (Fe) levels were measured before and 24 hours after phototherapy. TSB decreased postphototherapy in all three groups (p < .05 for all), with significantly lower levels following intensive and LED phototherapy compared to conventional phototherapy (p < .05 for both). TAC decreased postphototherapy in the three groups (p < .05 for all). MDA and NO increased postphototherapy (p < .05 for all), with the intensive phototherapy group having the highest levels followed by the conventional while LED phototherapy group showed the lowest levels in comparison to the other groups (p < .05). Cu, Zn and Fe increased postphototherapy in all three groups (p < .05 for all). Positive correlations were found between postphototherapy TSB with TAC, Cu and Zn (p < .05) and negative correlations with MDA, NO and Fe (p < .05) among neonates of the 3 studied groups. In conclusion, different photo therapies have an impact on oxidant/antioxidant balance and are associated with increased oxidative stress markers with the LED phototherapy being the safest.
Communicated by Jurgen Horst Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APEC... more Communicated by Jurgen Horst Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) is a rare recessive disorder that results in several autoimmune diseases due to the mutations in the AIRE (autoimmune regulator) gene. APECED patients develop several autoimmune endocrine disorders and are characterized by the high titer autoantibodies to organ-specific antigens such as the steroidogenic P450 cytochromes. So far, 38 mutations have been identified in the AIRE gene. We report here the genetic and autoantibody analysis of 27 APECED patients of Eastern and Central European origins and one Egyptian patient. From 54 analyzed APECED chromosomes, eight mutations were detected, four of which (T16M, W78R, IVS1_IVS4, 3053dup23bp) are novel. The most prevalent reason for APECED in these populations was the occurrence of R257X (36 chromosomes) that has been described earlier as a common and recurrent mutation in several other populations. The analysis of humoral immunity to steroidogenic P450 cytochromes by the immunoblotting of E. coli expressed antigens in the 18 APECED patients showed that 67%, 44%, and 61% of the Eastern and Central European APECED patients had autoantibodies to P450c17,
Objective: To report a patient with an unusual presentation of autoimmune polyendocrinopathy-cand... more Objective: To report a patient with an unusual presentation of autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) and severe keratopathy. Case History: An Egyptian male sustained an injury to the left eye at 13 years of age and was found to have corneal damage which was attributed to the injury. Subsequently, however, he continued to have sore eyes with photophobia. A year later he became weak with pigmentation and episodes of collapse, and investigation showed that he had Addison’s disease together with mucocutaneous candidiasis. At 15 years of age he developed carpo-pedal spasm and was found to have hypoparathyroidism with intracranial calcification. At 20 years of age the ophthalmic diagnosis was revised to keratopathy by which time the patient had corneal opacity and problems with visual acuity, especially in the right eye. Investigation at 22 years of age showed that he was homozygous for an R139X mutation in the gene encoding the AIRE protein, a mutation which to date has only been found in Sardinian patients. Conclusions: Keratopathy can be an early and severe manifestation of APECED, requiring expert ophthalmic care. Its presence should prompt a search for other components of APECED, some of which are life-threatening.
trials was conducted to evaluate efficacy and safety of using Absorb BVS system for patients with... more trials was conducted to evaluate efficacy and safety of using Absorb BVS system for patients with STEMI. Taking into account the hypothesis of superior effectiveness of Absorb BVS system for patients with STEMI for pharmacoeconomic analysis was chosen "cost-effectiveness" analysis. MS Excel based model was performed to asses 2 strategies: strategy 1-patients with primary percutaneous coronary intervention (PPCI) with Absorb BVS system; strategy 2-patients received thrombolytic therapy in the hospital. The 1 LYG and 1 surviving patient were included into the model as the effectiveness criteria. Direct costs included emergency, inpatient and outpatient treatment, rehabilitation and cost of PPCI with Absorb BVS system. All the direct costs were calculated from the Russian healthcare system perspective. Results: According to published trials the using of Absorb BVS system for patients with STEMI did not lead to different rates of composite patient-oriented and device-oriented adverse events. Strategy 1 has a higher efficiency-the proportion of survivors at 1 year will be the maximum-92.7%, as well as the LYG-5.4.
OBJECTIVE: We aimed to investigate if endothelin 1 concentration at day 3 postnatal age could be ... more OBJECTIVE: We aimed to investigate if endothelin 1 concentration at day 3 postnatal age could be used as a predictive marker for development of bronchopulmonary dysplasia in preterm neonates with respiratory distress syndrome. METHODS: This prospective observational study was done on 69 preterm neonates with gestational ages between 28 and 34 weeks and diagnosed as having respiratory distress syndrome. Serum concentrations of endothelin 1 was measured for all patients at day 3 of life and they were divided into BPD and No-BPD groups according to whether they developed bronchopulmonary dysplasia or not. RESULTS: A total of 17 infants were in the BPD group and 52 infants were in the No-BPD group. Serum endothelin 1 was significantly higher in the BPD group (435.39 ± 172.88) compared with the No-BPD group (302.65 ± 49.32) (p < 0.001). Serum endothelin 1 correlated significantly with days spent on mechanical ventilation (r = 0.379, p = 0.022) and days spent on CPAP (r = 0.391, p = 0.001). A serum endothelin 1 cut off value of 302.7 ng/L could predict preterm that will develop bronchopulmonary dysplasia with a sensitivity of 88.24%, and specificity of 61.54%. CONCLUSION: Serum endothelin 1 is significantly increased at day 3 of life in preterm neonates with respiratory distress syndrome who later develop bronchopulmonary dysplasia (BPD). It seems to be a promising predictive marker for BPD but further studies are needed to find the appropriate time for its measurement.
Autoimmune polyendocrinopathy candidiasis ectodermal dystrophy (APECED) is a monogenic autosomal ... more Autoimmune polyendocrinopathy candidiasis ectodermal dystrophy (APECED) is a monogenic autosomal recessive disease caused by mutations in the autoimmune regulator (AIRE) gene and, as a syndrome, is characterized by chronic mucocutaneous candidiasis and the presentation of various autoimmune diseases. During the last decade, research on APECED and AIRE has provided immunologists with several invaluable lessons regarding tolerance and autoimmunity. This review describes the clinical and immunological features of APECED and discusses emerging alternative models to explain the pathogenesis of the disease.
Background: The presented evidence-based clinical practice guideline (CPG) is proposed as a Natio... more Background: The presented evidence-based clinical practice guideline (CPG) is proposed as a National CPG using an evidence-based and formal CPG adaptation methodology. The purpose of this study was to adapt the international CPGs' recommendations for term and late preterm neonates with severe hyperbilirubinemia to suit the healthcare system in the Egyptian context. This CPG provides a framework for prediction, prevention and management of severe hyperbilirubinemia in newborn infants of 35 or more weeks of gestation. The quality of evidence and strength of recommendations are indicated. The guideline adaptation group was chosen from various Egyptian Universities. There was an active involvement of a Multidisciplinary Review Committee following a standardized process. The Neonatology Guideline Adaptation Group (NGAG) was assigned individual health questions to cover the different sections of the required CPG. A literature search for source CPGs was carried out. The NGAG studied several guidelines. Critical appraisal was done by AGREE II (Appraisal of Guidelines for Research and Evaluation) Instrument to rate and select the appropriate guidelines. Results: The NGAG decided to adapt mainly the American Academy of Pediatrics Guideline (2004, 2009 & 2011) and for the questions which were not answered; the best and most relevant evidence available was used. Implementation tools were sought for to facilitate the application of the adapted CPG. Conclusion: The finalized CPG offers healthcare providers with applicable evidence-based guidance for severe neonatal hyperbilirubinemia in the Egyptian context. The Adapted ADAPTE method emphasized the value of collaborative clinical and methodological expert groups' efforts for adaptation of national guidelines.
Background The presented evidence-based clinical practice guideline (CPG) is proposed as a Nation... more Background The presented evidence-based clinical practice guideline (CPG) is proposed as a National CPG using an evidence-based and formal CPG adaptation methodology. The purpose of this study was to adapt the international CPGs’ recommendations for children with bronchiolitis to suit the healthcare system in the Egyptian context. This CPG, ‘diagnosis, treatment, and prevention of Bronchiolitis’, applies to children from 1 through 23 months of age. Other exclusions are noted. The quality of evidence, benefit-harm relationship, and strength of recommendations are indicated. This study is part of a larger collaborative initiative with the faculty staff of pediatric departments of 15 Egyptian universities and a national research center to formulate a national Committee (EPG) that aims to define the topics of, assign authors to, and assist in the adaptation of pediatric evidence-based CPGs according to a national strategic plan. The committee is guided by a formal CPG adaptation methodo...
Background: Hypogonadism is a key feature of Prader-Willi syndrome (PWS) but clear strategies for... more Background: Hypogonadism is a key feature of Prader-Willi syndrome (PWS) but clear strategies for hormone replacement are lacking. Objective: To evaluate gonadal status and outcome in patients attending a Scottish PWS clinic from 1991-2019. Methods: In 93 (35F:56M) patients, median follow-up 11.2 years, gonadal and pubertal status were assessed clinically. Pelvic ultrasound findings and basal/stimulated gonadotrophins were compared with age-matched controls. Results: Females: Of 22 patients aged >11, 9 had reached B4-5, while 5 were still at B2-3, and 6 remained prepubertal. Eight patients experienced menarche aged 9.8-21.4 years, none with a normal cycle. Uterine length and ovarian volumes were normal but uterine configuration remained immature, with low follicular counts. Gonadotrophins were unremarkable, serum estradiol 129 (70 – 520) pmol/L. Only 5 patients received oestrogen replacement. Males: Fifty-four (96%) patients were cryptorchid (9 unilateral). Weekly hCG injections ...
Abstract In order to evaluate the effect of different types of phototherapy on oxidant/antioxidan... more Abstract In order to evaluate the effect of different types of phototherapy on oxidant/antioxidant status in hyperbilirubinemic neonates, an interventional randomized control trial was conducted on 120 neonates ≥35 weeks’ gestational age with indirect hyperbilirubinemia reaching phototherapy level. This study is registered with ClinicalTrials.gov as NCT03074292. Neonates were assigned to three groups; 40 neonates received conventional phototherapy, 40 received intensive phototherapy and 40 received blue light-emitting diodes (LED) phototherapy. Complete blood count (CBC), total serum bilirubin (TSB), total antioxidant capacity (TAC), malondialdehyde (MDA), nitric oxide (NO), copper (Cu), zinc (Zn), and iron (Fe) levels were measured before and 24 hours after phototherapy. TSB decreased postphototherapy in all three groups (p < .05 for all), with significantly lower levels following intensive and LED phototherapy compared to conventional phototherapy (p < .05 for both). TAC decreased postphototherapy in the three groups (p < .05 for all). MDA and NO increased postphototherapy (p < .05 for all), with the intensive phototherapy group having the highest levels followed by the conventional while LED phototherapy group showed the lowest levels in comparison to the other groups (p < .05). Cu, Zn and Fe increased postphototherapy in all three groups (p < .05 for all). Positive correlations were found between postphototherapy TSB with TAC, Cu and Zn (p < .05) and negative correlations with MDA, NO and Fe (p < .05) among neonates of the 3 studied groups. In conclusion, different photo therapies have an impact on oxidant/antioxidant balance and are associated with increased oxidative stress markers with the LED phototherapy being the safest.
Communicated by Jurgen Horst Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APEC... more Communicated by Jurgen Horst Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) is a rare recessive disorder that results in several autoimmune diseases due to the mutations in the AIRE (autoimmune regulator) gene. APECED patients develop several autoimmune endocrine disorders and are characterized by the high titer autoantibodies to organ-specific antigens such as the steroidogenic P450 cytochromes. So far, 38 mutations have been identified in the AIRE gene. We report here the genetic and autoantibody analysis of 27 APECED patients of Eastern and Central European origins and one Egyptian patient. From 54 analyzed APECED chromosomes, eight mutations were detected, four of which (T16M, W78R, IVS1_IVS4, 3053dup23bp) are novel. The most prevalent reason for APECED in these populations was the occurrence of R257X (36 chromosomes) that has been described earlier as a common and recurrent mutation in several other populations. The analysis of humoral immunity to steroidogenic P450 cytochromes by the immunoblotting of E. coli expressed antigens in the 18 APECED patients showed that 67%, 44%, and 61% of the Eastern and Central European APECED patients had autoantibodies to P450c17,
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Papers by Sameh Tawfik