Congenital laryngomalacia: Is it an inflammatory disease? The role of vitamin D.

OBJECTIVES/HYPOTHESIS: Laryngomalacia is the most common cause of stridor in infants. The exact pathophysiology is still not well understood. Our objective was to investigate whether laryngomalacia is an inflammatory disease, focusing on the possible role of vitamin D. STUDY DESIGN: Case-control study. METHODS: Sixty Egyptian infants and 60 mothers were included in this study. They were divided into four equal groups (n = 30 for each): infants with laryngomalacia (LM-infants), control infants (C-infants), mothers of the infants with laryngomalacia (LM-mothers), and mothers of the control infants (C-mothers). Laryngoscopy was performed and serum 25-hydroxyvitamin D (25[OH]-vitamin-D) and interleukin 6 (IL-6) were estimated. RESULTS: Significant increase of serum IL-6 associated with a significant decrease in serum 25(OH)-vitamin D was observed in the LM-infants compared to the C-infants (P < .001 for both). LM-mothers had significantly lower 25(OH)-vitamin D status compared to C-mothers (P < .001). CONCLUSIONS: Deficiency of 25(OH)-vitamin D in LM-infants may result in dysregulation of the immune responses with elevation of a proinflammatory cytokine (IL-6). Laryngomalacia could be an inflammatory disease due to 25(OH)-vitamin D deficiency as evidenced by the high level of IL-6. This finding may open the door to the appropriate prevention, diagnosis, and treatment, especially for moderate to severe laryngomalacia. LEVEL OF EVIDENCE: 3b Laryngoscope, 130:448-453, 2020.

Pattern and Outcome of Acute Disseminated Encephalomyelitis (ADEM) in Children: Experience in a Tertiary Center, Upper Egypt.

INTRODUCTION: Acute disseminated encephalomyelitis (ADEM) is an immune mediated disease of the brain. Although it occurs in all ages, most reported cases are in children and adolescents. The aims of this study were to study the clinical pattern and outcome of ADEM in children in a tertiary center in Upper Egypt and to determine the effect of combined use of steroids and IVIg on outcome. METHODS: This observational study was carried out from January 2014 through December 2014 in the Pediatric Department of Sohag University Hospital (Egypt). All children diagnosed as ADEM during a one year period were included in this study. The treatments used were IV methylprednisolone followed by oral prednisone taper and intravenous immunoglobulin for severe cases. All studied cases were followed up and reevaluated at three months and six months. We used SPSS version 10 and Chi Square, Spearman's test and t-test for data analysis. RESULTS: Eighteen children were included in this study (10 males and 8 females), the average age was 5.5 ± 0.9 years. Prodroma was found in 72.22% of the cases while the main complaint was encephalopathy (83.33%) followed by seizures (11.11%). The neurological findings were convulsions in 83.33%, quadriparesis (33.33%), hemiparesis (33.33), bladder involvement (both retention and incontinence) in 61.11%, and cranial nerve affection (11.11%). Demyelination patches were multifocal in 50%, mainly subcortical in 27.78%. Intelligence quotient (IQ) assessment after 6 months follow up showed that 50% were below average, 25% had mild MR while neurological evaluation showed that 75% of our patients were completely cured. The predictors of better outcome were; children related to the age group (1-4 years) (p = 0.01), children with higher GCS (6-14) (p = 0.01), and children who received steroids on the first day of symptoms and intravenous immunoglobulin in the first week (p = 0.03). CONCLUSION: The clinical pattern of acute disseminated encephalomyelitis is variable, and a disturbed level of consciousness was the most common presentation. The outcome is generally favorable although motor deficit and cognitive impairment were reported. The combined use of steroids and IVIg has substantial effect on the outcome in children with ADEM.

Outcome of Guillain - Barré Syndrome in Children: A prospective cohort study in a tertiary hospital in Upper Egypt.

INTRODUCTION: Guillain-Barré syndrome is the most common cause of acute flaccid paralysis in children, and defined as an acute inflammatory polyneuropathy. The objective of this study was to assess the clinico-laboratory profile, and outcome of Guillain-Barré syndrome in children at Sohag University Hospital. METHODS: This prospective cohort observational study was conducted in 2014-2015. The included children were subjected to through medical history and detailed systemic and neurological examination. Nerve conduction studies and cerebrospinal fluid analysis were done for all patients. Follow up was done at three and six months both clinically and by nerve conduction studies. RESULTS: This study included 50 patients (27 males/23 females) with median age of 2.92 years. Upper respiratory tract infections were the most common antecedent infections (50%) and the neurological findings were weakness of both lower limbs and pain in all patients (100%) followed by sphincteric dysfunction (26%) while cranial neuropathies were found in 4%. Nerve conduction study revealed that acute inflammatory demyelinating polyradiculoneuropathy was found in 52% of cases, acute motor axonal neuropathy in 36% of cases, whereas acute motor-sensory axonal neuropathy was found in 6% of cases. The outcome was good in about 78% of cases, Hughes motor scale revealed that 58% were healthy, 18% had minor signs or symptoms, 12% walked without support, 6% walked with support, and 6% were bed ridden. CONCLUSION: The outcome was favorable, although a minority of patients suffered neurological deficit. Immediate administration of intravenous immunoglobulin reduced mortality and disability.

Al-hijamah and oral honey for treating thalassemia, conditions of iron overload, and hyperferremia: toward improving the therapeutic outcomes.

Iron overload causes iron deposition and accumulation in the liver, heart, skin, and other tissues resulting in serious tissue damages. Significant blood clearance from iron and ferritin using wet cupping therapy (WCT) has been reported. WCT is an excretory form of treatment that needs more research efforts. WCT is an available, safe, simple, economic, and time-saving outpatient modality of treatment that has no serious side effects. There are no serious limitations or precautions to discontinue WCT. Interestingly, WCT has solid scientific and medical bases (Taibah mechanism) that explain its effectiveness in treating many disease conditions differing in etiology and pathogenesis. WCT utilizes an excretory physiological principle (pressure-dependent excretion) that resembles excretion through renal glomerular filtration and abscess evacuation. WCT exhibits a percutaneous excretory function that clears blood (through fenestrated skin capillaries) and interstitial fluids from pathological substances without adding a metabolic or detoxification burden on the liver and the kidneys. Interestingly, WCT was reported to decrease serum ferritin (circulating iron stores) significantly by about 22.25% in healthy subjects (in one session) and to decrease serum iron significantly to the level of causing iron deficiency (in multiple sessions). WCT was reported to clear blood significantly of triglycerides, low-density lipoprotein (LDL) cholesterol, total cholesterol, uric acid, inflammatory mediators, and immunoglobulin antibodies (rheumatoid factor). Moreover, WCT was reported to enhance the natural immunity, potentiate pharmacological treatments, and to treat many different disease conditions. There are two distinct methods of WCT: traditional WCT and Al-hijamah (WCT of prophetic medicine). Both start and end with skin sterilization. In traditional WCT, there are two steps, skin scarification followed by suction using plastic cups (double S technique); Al-hijamah is a three-step procedure that includes skin suction using cups, scarification (shartat mihjam in Arabic), and second skin suction (triple S technique). Al-hijamah is a more comprehensive technique and does better than traditional WCT, as Al-hijamah includes two pressure-dependent filtration steps versus one step in traditional WCT. Whenever blood plasma is to be cleared of an excess pathological substance, Al-hijamah is indicated. We will discuss here some reported hematological and therapeutic benefits of Al-hijamah, its medical bases, methodologies, precautions, side effects, contraindications, quantitative evaluation, malpractice, combination with oral honey treatment, and to what extent it may be helpful when treating thalassemia and other conditions of iron overload and hyperferremia.

Percutaneous excretion of iron and ferritin (through Al-hijamah) as a novel treatment for iron overload in beta-thalassemia major, hemochromatosis and sideroblastic anemia.

Iron overload is a big challenge when treating thalassemia (TM), hemochromatosis and sideroblastic anemia. It persists even after cure of TM with bone marrow transplantation. Iron overload results from increased iron absorption and repeated blood transfusions causing increased iron in plasma and interstitial fluids. Iron deposition in tissues e.g. heart, liver, endocrine glands and others leads to tissue damage and organ dysfunction. Iron chelation therapy and phlebotomy for iron overload have treatment difficulties, side effects and contraindications. As mean iron level in skin of TM patients increases by more than 200%, percutaneous iron excretion may be beneficial. Wet cupping therapy (WCT) is a simple, safe and economic treatment. WCT is a familiar treatment modality in some European countries and in Chinese hospitals in treating different diseases. WCT was reported to clear both blood plasma and interstitial spaces from causative pathological substances (CPS). Standard WCT method is Al-hijamah (cupping, puncturing and cupping, CPC) method of WCT that was reported to clear blood and interstitial fluids better than the traditional WCT (puncturing and cupping method, PC method of WCT). In other word, traditional WCT may be described as scarification and suction method (double S technique), while Al-hijamah may be described as suction, scarification and suction method (triple S technique). Al-hijamah is a more comprehensive treatment modality that includes all steps and therapeutic benefits of traditional dry cupping therapy and WCT altogether according to the evidence-based Taibah mechanism (Taibah theory). During the first cupping step of Al-hijamah, a fluid mixture is collected inside skin uplifting due to the effect of negative pressure inside sucking cups. This fluid mixture contains collected interstitial fluids with CPS (iron, ferritin and hemolyzed RBCs in thalassemia), filtered fluids (from blood capillaries) with iron and hemolyzed blood cells (hemolyzed RBCs, WBCs and platelets). That fluid mixture does not contain intact blood cells (having diameters in microns) that are too big to pass through pores of skin capillaries (6-12nm in diameter) and cannot be filtered. Puncturing skin upliftings and applying second cupping step excrete collected fluids. Skin scarifications (shartat mihjam in Arabic) should be small, superficial (0.1mm in depth), short (1-2mm in length), multiple, evenly distributed and confined to skin upliftings. Sucking pressure inside cups (-150 to -420mmHg) applied to skin is transmitted to around skin capillaries to be added to capillary hydrostatic pressure (-33mmHg at arterial end of capillaries and -13mmHg at venous end of capillaries) against capillary osmotic pressure (+20mmHg). This creates a pressure gradient and a traction force across skin and capillaries and increases filtration at arterial end of capillaries at net pressure of -163 to -433mmHg and at venous end of capillaries at net pressure of -143 to -413mmHg resulting in clearance of blood from CPS (iron, ferritin and hemolyzed blood cells). Net filtration pressure at renal glomeruli is 10mmHg i.e. Al-hijamah exerts a more pressure-dependent filtration than renal glomeruli. Al-hijamah may benefit patients through inducing negative iron balance. Interestingly, Al-hijamah was reported to decrease serum ferritin significantly (by about 22%) in healthy subjects while excessive traditional WCT was reported to cause iron deficiency anemia. Al-hijamah is a highly recommended treatment in prophetic medicine. In conclusion, Al-hijamah may be a promising adjuvant treatment for iron overload in TM, hemochromatosis and sideroblastic anemia.

A new method in the diagnosis of reflux esophagitis: confocal laser endomicroscopy.

BACKGROUND: The diagnosis of GERD is made by using a combination of clinical symptoms, pH study, endoscopy, and histology. Histologic changes include basal cell hyperplasia and papillary elongation. Confocal laser endomicroscopy (CLE) enables surface and subsurface imaging of living cells in vivo at ×1000 magnification and up to 250 µm below the tissue surface. In the esophagus, the distance between the surface to papillary (S-P) tip can be measured by using CLE. OBJECTIVE: To measure the S-P distance in the esophagus in patients with reflux esophagitis and controls by using CLE and comparing with histologic measurements. DESIGN: Retrospective analysis of a prospective database. SETTING: Endoscopy unit of a tertiary-care children's hospital. PATIENTS: This study involved 7 patients (5 female) with a median age of 7.6 years (range 1.8-15.5 years) and median weight of 23 kg (range 13.2-71 kg) and 16 controls with a median age of 12.0 years (range 2.2-15.3 years) and median weight of 38.2 kg (range 10.7-83 kg). INTERVENTION: S-P distance was measured both by CLE and histology and was corrected for height for both patients and controls and the results compared. MAIN OUTCOME MEASUREMENTS: To determine if there were significant differences in the S-P distance in patients with esophagitis and controls. RESULTS: The median confocal and histologic measurements for S-P distance, corrected for patient height, were 0.19 µm/cm (range 0.10-0.49 µm/cm) and 0.58 µm/cm (range 0.29-0.76 µm/cm) and for controls were 0.44 µm/cm (range 0.20-0.93 µm/cm) and 1.07 µm/cm (range 0.76-0.1.57 µm/cm), respectively. LIMITATIONS: Small numbers involved in the study, reliance on only papillary elongation in arriving at a diagnosis. CONCLUSION: Measurement of the S-P distance by CLE will enable real-time diagnosis of GERD-related esophagitis during ongoing endoscopy.

Role of confocal endomicroscopy in the diagnosis of celiac disease.

BACKGROUND AND AIMS: Confocal laser endomicroscopy (CLE) is a recent development that enables surface and subsurface imaging of living cells in vivo at 1000 x magnification. The aims of the present study were to define confocal features of celiac disease (CD) and to evaluate the usefulness of the CLE in the diagnosis of CD in children in comparison to histology. PATIENTS AND METHODS: Nine patients (8 girls) with a median age of 8.35 years (range 2-12.66 years) and a median weight of 28.3 kg (range 11-71 kg) were suspected with CD and 10 matched controls underwent oesophagogastroduodenoscopy using the confocal laser endomicroscope (EC3870CILK; Pentax, Tokyo, Japan). Histologic sections were compared with the confocal images of the same site by 2 experienced paediatric histopathologists and endoscopists, all of whom were blinded to the diagnosis. RESULTS: The median procedure time was 17 minutes (range 8-25 minutes). Confocal features of CD were defined and a score was developed. A total of 1384 confocal images were collected from 9 patients and 10 controls. Five images from each patient and control were selected and compared with the biopsy specimen of the same site. The sensitivity, specificity, and positive predictive value for the confocal images in comparison to the histology were 100%, 80%, and 81%. The kappa inter-observer agreement between the 2 endoscopists was 0.769 (P = 0.018) and between the 2 histopathologists was 0.571 (P = 0.05). CONCLUSIONS: Confocal endomicroscopy offers the prospect of diagnosis of CD during ongoing endoscopy. It also enables targeting biopsies to abnormal mucosa and thereby increasing the diagnostic yield, especially when villous atrophy is patchy in the duodenum.

Feasibility of confocal endomicroscopy in the diagnosis of pediatric gastrointestinal disorders.

AIM: To evaluate the feasibility and utility of confocal laser endomicroscopy (CLE) in the description of normal gastrointestinal (GI) mucosa and in the diagnosis of GI disorders in children, in comparison to histology. METHODS: Forty-four patients (19 female) median age 10.9 years (range 0.7-16.6 years) with suspected or known GI pathology underwent esophago-gastro-duodenoscopy (OGD) (n = 36) and/or ileocolonoscopy (IC) (n = 31) with CLE using sodium fluorescein and acriflavine as contrast agents. Histological sections were compared with same site confocal images by two experienced pediatric and GI histopathologists and endoscopists, respectively. RESULTS: Duodenum and ileum were intubated in all but one patient undergoing OGD and IC. The median procedure time was 16.4 min (range 7-25 min) for OGD and 27.9 min (range 15-45 min) for IC. A total of 4798 confocal images were compared with 153 biopsies from the upper GI tract from 36 procedures, and 4661 confocal images were compared with 188 biopsies from the ileocolon from 31 procedures. Confocal images were comparable to conventional histology both in normal and in pathological conditions such as esophagitis, Helicobacter pylori gastritis, celiac disease, inflammatory bowel disease, colonic heterotopia, and graft versus host disease. CONCLUSION: CLE offers the prospect of targeting biopsies to abnormal mucosa, thereby increasing diagnostic yield, reducing the number of biopsies, decreasing the burden on the histopathological services, and reducing costs.