This document discusses Gastro Esophageal Reflux Disease (GERD) in infants. It provides definitions of key terms like GER and GERD. It reviews the epidemiology and natural history of GER in infants, noting that the prevalence of daily regurgitation peaks between 1-6 months of age in around 70% of infants. It discusses the anatomy and physiology involved in GER and reviews approaches to diagnosing GERD in infants, including history, physical exam, upper GI imaging, endoscopy, and pH monitoring. Non-pharmacological and pharmacological treatment options are also covered.
Teduglutida en el síndrome de intestino corto. Experiencia en PediatríaJavier González de Dios
La teduglutida, un análogo del péptido-2 similar al glucagón, pertenece a una nueva familia terapéutica y representa el primer abordaje no sintomático del síndrome de intestino corto.
En los ensayos clínicos realizados hasta la fecha se ha demostrado que la teduglutida recupera la función de absorción intestinal y que reduce significativamente la dependencia de la nutrición parenteral, consiguiendo incluso la independencia total en algunos pacientes. En el artículo adjunto se constata la experiencia española en 17 pacientes pediátricos en España, y esta efectividad en la vida real es superior en la población pediátrica que en adultos.
Teduglutida en el síndrome de intestino corto. Experiencia en PediatríaJavier González de Dios
La teduglutida, un análogo del péptido-2 similar al glucagón, pertenece a una nueva familia terapéutica y representa el primer abordaje no sintomático del síndrome de intestino corto.
En los ensayos clínicos realizados hasta la fecha se ha demostrado que la teduglutida recupera la función de absorción intestinal y que reduce significativamente la dependencia de la nutrición parenteral, consiguiendo incluso la independencia total en algunos pacientes. En el artículo adjunto se constata la experiencia española en 17 pacientes pediátricos en España, y esta efectividad en la vida real es superior en la población pediátrica que en adultos.
Report Back from SGO 2024: What’s the Latest in Cervical Cancer?bkling
Are you curious about what’s new in cervical cancer research or unsure what the findings mean? Join Dr. Emily Ko, a gynecologic oncologist at Penn Medicine, to learn about the latest updates from the Society of Gynecologic Oncology (SGO) 2024 Annual Meeting on Women’s Cancer. Dr. Ko will discuss what the research presented at the conference means for you and answer your questions about the new developments.
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- Video recording of this lecture in English language: https://youtu.be/lK81BzxMqdo
- Video recording of this lecture in Arabic language: https://youtu.be/Ve4P0COk9OI
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Title: Sense of Taste
Presenter: Dr. Faiza, Assistant Professor of Physiology
Qualifications:
MBBS (Best Graduate, AIMC Lahore)
FCPS Physiology
ICMT, CHPE, DHPE (STMU)
MPH (GC University, Faisalabad)
MBA (Virtual University of Pakistan)
Learning Objectives:
Describe the structure and function of taste buds.
Describe the relationship between the taste threshold and taste index of common substances.
Explain the chemical basis and signal transduction of taste perception for each type of primary taste sensation.
Recognize different abnormalities of taste perception and their causes.
Key Topics:
Significance of Taste Sensation:
Differentiation between pleasant and harmful food
Influence on behavior
Selection of food based on metabolic needs
Receptors of Taste:
Taste buds on the tongue
Influence of sense of smell, texture of food, and pain stimulation (e.g., by pepper)
Primary and Secondary Taste Sensations:
Primary taste sensations: Sweet, Sour, Salty, Bitter, Umami
Chemical basis and signal transduction mechanisms for each taste
Taste Threshold and Index:
Taste threshold values for Sweet (sucrose), Salty (NaCl), Sour (HCl), and Bitter (Quinine)
Taste index relationship: Inversely proportional to taste threshold
Taste Blindness:
Inability to taste certain substances, particularly thiourea compounds
Example: Phenylthiocarbamide
Structure and Function of Taste Buds:
Composition: Epithelial cells, Sustentacular/Supporting cells, Taste cells, Basal cells
Features: Taste pores, Taste hairs/microvilli, and Taste nerve fibers
Location of Taste Buds:
Found in papillae of the tongue (Fungiform, Circumvallate, Foliate)
Also present on the palate, tonsillar pillars, epiglottis, and proximal esophagus
Mechanism of Taste Stimulation:
Interaction of taste substances with receptors on microvilli
Signal transduction pathways for Umami, Sweet, Bitter, Sour, and Salty tastes
Taste Sensitivity and Adaptation:
Decrease in sensitivity with age
Rapid adaptation of taste sensation
Role of Saliva in Taste:
Dissolution of tastants to reach receptors
Washing away the stimulus
Taste Preferences and Aversions:
Mechanisms behind taste preference and aversion
Influence of receptors and neural pathways
Impact of Sensory Nerve Damage:
Degeneration of taste buds if the sensory nerve fiber is cut
Abnormalities of Taste Detection:
Conditions: Ageusia, Hypogeusia, Dysgeusia (parageusia)
Causes: Nerve damage, neurological disorders, infections, poor oral hygiene, adverse drug effects, deficiencies, aging, tobacco use, altered neurotransmitter levels
Neurotransmitters and Taste Threshold:
Effects of serotonin (5-HT) and norepinephrine (NE) on taste sensitivity
Supertasters:
25% of the population with heightened sensitivity to taste, especially bitterness
Increased number of fungiform papillae
These simplified slides by Dr. Sidra Arshad present an overview of the non-respiratory functions of the respiratory tract.
Learning objectives:
1. Enlist the non-respiratory functions of the respiratory tract
2. Briefly explain how these functions are carried out
3. Discuss the significance of dead space
4. Differentiate between minute ventilation and alveolar ventilation
5. Describe the cough and sneeze reflexes
Study Resources:
1. Chapter 39, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 34, Ganong’s Review of Medical Physiology, 26th edition
3. Chapter 17, Human Physiology by Lauralee Sherwood, 9th edition
4. Non-respiratory functions of the lungs https://academic.oup.com/bjaed/article/13/3/98/278874
Tom Selleck Health: A Comprehensive Look at the Iconic Actor’s Wellness Journeygreendigital
Tom Selleck, an enduring figure in Hollywood. has captivated audiences for decades with his rugged charm, iconic moustache. and memorable roles in television and film. From his breakout role as Thomas Magnum in Magnum P.I. to his current portrayal of Frank Reagan in Blue Bloods. Selleck's career has spanned over 50 years. But beyond his professional achievements. fans have often been curious about Tom Selleck Health. especially as he has aged in the public eye.
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Introduction
Many have been interested in Tom Selleck health. not only because of his enduring presence on screen but also because of the challenges. and lifestyle choices he has faced and made over the years. This article delves into the various aspects of Tom Selleck health. exploring his fitness regimen, diet, mental health. and the challenges he has encountered as he ages. We'll look at how he maintains his well-being. the health issues he has faced, and his approach to ageing .
Early Life and Career
Childhood and Athletic Beginnings
Tom Selleck was born on January 29, 1945, in Detroit, Michigan, and grew up in Sherman Oaks, California. From an early age, he was involved in sports, particularly basketball. which played a significant role in his physical development. His athletic pursuits continued into college. where he attended the University of Southern California (USC) on a basketball scholarship. This early involvement in sports laid a strong foundation for his physical health and disciplined lifestyle.
Transition to Acting
Selleck's transition from an athlete to an actor came with its physical demands. His first significant role in "Magnum P.I." required him to perform various stunts and maintain a fit appearance. This role, which he played from 1980 to 1988. necessitated a rigorous fitness routine to meet the show's demands. setting the stage for his long-term commitment to health and wellness.
Fitness Regimen
Workout Routine
Tom Selleck health and fitness regimen has evolved. adapting to his changing roles and age. During his "Magnum, P.I." days. Selleck's workouts were intense and focused on building and maintaining muscle mass. His routine included weightlifting, cardiovascular exercises. and specific training for the stunts he performed on the show.
Selleck adjusted his fitness routine as he aged to suit his body's needs. Today, his workouts focus on maintaining flexibility, strength, and cardiovascular health. He incorporates low-impact exercises such as swimming, walking, and light weightlifting. This balanced approach helps him stay fit without putting undue strain on his joints and muscles.
Importance of Flexibility and Mobility
In recent years, Selleck has emphasized the importance of flexibility and mobility in his fitness regimen. Understanding the natural decline in muscle mass and joint flexibility with age. he includes stretching and yoga in his routine. These practices help prevent injuries, improve posture, and maintain mobilit
Ozempic: Preoperative Management of Patients on GLP-1 Receptor Agonists Saeid Safari
Preoperative Management of Patients on GLP-1 Receptor Agonists like Ozempic and Semiglutide
ASA GUIDELINE
NYSORA Guideline
2 Case Reports of Gastric Ultrasound
Lung Cancer: Artificial Intelligence, Synergetics, Complex System Analysis, S...Oleg Kshivets
RESULTS: Overall life span (LS) was 2252.1±1742.5 days and cumulative 5-year survival (5YS) reached 73.2%, 10 years – 64.8%, 20 years – 42.5%. 513 LCP lived more than 5 years (LS=3124.6±1525.6 days), 148 LCP – more than 10 years (LS=5054.4±1504.1 days).199 LCP died because of LC (LS=562.7±374.5 days). 5YS of LCP after bi/lobectomies was significantly superior in comparison with LCP after pneumonectomies (78.1% vs.63.7%, P=0.00001 by log-rank test). AT significantly improved 5YS (66.3% vs. 34.8%) (P=0.00000 by log-rank test) only for LCP with N1-2. Cox modeling displayed that 5YS of LCP significantly depended on: phase transition (PT) early-invasive LC in terms of synergetics, PT N0—N12, cell ratio factors (ratio between cancer cells- CC and blood cells subpopulations), G1-3, histology, glucose, AT, blood cell circuit, prothrombin index, heparin tolerance, recalcification time (P=0.000-0.038). Neural networks, genetic algorithm selection and bootstrap simulation revealed relationships between 5YS and PT early-invasive LC (rank=1), PT N0—N12 (rank=2), thrombocytes/CC (3), erythrocytes/CC (4), eosinophils/CC (5), healthy cells/CC (6), lymphocytes/CC (7), segmented neutrophils/CC (8), stick neutrophils/CC (9), monocytes/CC (10); leucocytes/CC (11). Correct prediction of 5YS was 100% by neural networks computing (area under ROC curve=1.0; error=0.0).
CONCLUSIONS: 5YS of LCP after radical procedures significantly depended on: 1) PT early-invasive cancer; 2) PT N0--N12; 3) cell ratio factors; 4) blood cell circuit; 5) biochemical factors; 6) hemostasis system; 7) AT; 8) LC characteristics; 9) LC cell dynamics; 10) surgery type: lobectomy/pneumonectomy; 11) anthropometric data. Optimal diagnosis and treatment strategies for LC are: 1) screening and early detection of LC; 2) availability of experienced thoracic surgeons because of complexity of radical procedures; 3) aggressive en block surgery and adequate lymph node dissection for completeness; 4) precise prediction; 5) adjuvant chemoimmunoradiotherapy for LCP with unfavorable prognosis.
Knee anatomy and clinical tests 2024.pdfvimalpl1234
This includes all relevant anatomy and clinical tests compiled from standard textbooks, Campbell,netter etc..It is comprehensive and best suited for orthopaedicians and orthopaedic residents.
Explore natural remedies for syphilis treatment in Singapore. Discover alternative therapies, herbal remedies, and lifestyle changes that may complement conventional treatments. Learn about holistic approaches to managing syphilis symptoms and supporting overall health.
New Directions in Targeted Therapeutic Approaches for Older Adults With Mantl...i3 Health
i3 Health is pleased to make the speaker slides from this activity available for use as a non-accredited self-study or teaching resource.
This slide deck presented by Dr. Kami Maddocks, Professor-Clinical in the Division of Hematology and
Associate Division Director for Ambulatory Operations
The Ohio State University Comprehensive Cancer Center, will provide insight into new directions in targeted therapeutic approaches for older adults with mantle cell lymphoma.
STATEMENT OF NEED
Mantle cell lymphoma (MCL) is a rare, aggressive B-cell non-Hodgkin lymphoma (NHL) accounting for 5% to 7% of all lymphomas. Its prognosis ranges from indolent disease that does not require treatment for years to very aggressive disease, which is associated with poor survival (Silkenstedt et al, 2021). Typically, MCL is diagnosed at advanced stage and in older patients who cannot tolerate intensive therapy (NCCN, 2022). Although recent advances have slightly increased remission rates, recurrence and relapse remain very common, leading to a median overall survival between 3 and 6 years (LLS, 2021). Though there are several effective options, progress is still needed towards establishing an accepted frontline approach for MCL (Castellino et al, 2022). Treatment selection and management of MCL are complicated by the heterogeneity of prognosis, advanced age and comorbidities of patients, and lack of an established standard approach for treatment, making it vital that clinicians be familiar with the latest research and advances in this area. In this activity chaired by Michael Wang, MD, Professor in the Department of Lymphoma & Myeloma at MD Anderson Cancer Center, expert faculty will discuss prognostic factors informing treatment, the promising results of recent trials in new therapeutic approaches, and the implications of treatment resistance in therapeutic selection for MCL.
Target Audience
Hematology/oncology fellows, attending faculty, and other health care professionals involved in the treatment of patients with mantle cell lymphoma (MCL).
Learning Objectives
1.) Identify clinical and biological prognostic factors that can guide treatment decision making for older adults with MCL
2.) Evaluate emerging data on targeted therapeutic approaches for treatment-naive and relapsed/refractory MCL and their applicability to older adults
3.) Assess mechanisms of resistance to targeted therapies for MCL and their implications for treatment selection
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2. Learning Objectives
To review the definitions, natural history and mechanisms of GER and
GERD
To discuss the diagnosis of GERD in infants
To discuss the management options for physiologic GER and GERD
3. Outline
1. Introduction
2. Epidemiology and natural history
3. Evaluation & Diagnosis
4. Non-Pharmacological treatment
5. Medication and surgery
6. Take home messages
4. DEFINITIONS
Gastroesophageal reflux (GER): passage of gastric contents into the
esophagus
Gastroesophageal reflux disease (GERD): Refers to reflux that has
pathologic consequences, such as esophagitis, nutritional compromise
with weight loss, or respiratory complications
Regurgitation: Describes effortless reflux up to the oropharynx or above.
Vomiting: Describes forceful emptying of the stomach
Refractory GERD: Unresponsive to medical treatment
The New Rome IV Criteria for Functional Gastrointestinal Disorders in Infants and Toddlers. Zeevenhooven J, Koppen IJ, Benninga MA Pediatr Gastroenterol Hepatol Nutr. 2017;20(1):1.
5. Introduction
The GI tract is a one-way passage, food and
water enter through the mouth and exist, after
multiple digestion processes, through the
anus.
The digestive system is equipped with a series
of sphincters and valves to prevent backward
circulation
The only exception is the lower esophageal
sphincter (LES) which through relaxation allows
the exist of air that inadvertently went in, with
food through swallowing (17-30 x/day)
7. Prevalence of Regurgitation in Infancy
0
10
20
30
40
50
60
70
0-3 4-6 7-9 10-12
Age (months)
% of
Infants
1 time a day
4 times a day
Adapted from Nelson SP, Chen EH, Syniar GM, et al. Prevalence of symptoms of gastroesophageal reflux during infancy. A
pediatric practice-based survey. Pediatric Practice Research Group. Arch Pediatr Adolesc Med. 1997;151(6):569–572
n=948
8. Natural history of gastroesophageal reflux in infancy:
new data from a prospective cohort
Methods: a prospective cohort study including all full-term
living neonates born at Besançon Teaching Hospital, France.
Regurgitation was based on the answer to the first question
of the I-GERQ-R as anything coming out of the mouth daily.
157/347 births were included
Curien-Chotard and Jantchou BMC Pediatrics (2020) 20:152
9. Natural history of gastroesophageal reflux in infancy:
new data from a prospective cohort
Methods: a prospective cohort study including all full-term
living neonates born at Besançon Teaching Hospital, France.
Regurgitation was based on the answer to the first question
of the I-GERQ-R as anything coming out of the mouth daily.
157/347 births were included
Curien-Chotard and Jantchou BMC Pediatrics (2020) 20:152
10. Natural history of gastroesophageal reflux in infancy:
new data from a prospective cohort
Results: The prevalence of regurgitation
at least once a day was 45.7% overall.
In total: 72, 69, 56, 18, and 13% of
infants regurgitated at least once a day
at 1, 3, 6, 10, and 12 months of age,
respectively.
Two risk factors were identified: family
history of GER and exposure to passive
smoking.
Curien-Chotard and Jantchou BMC Pediatrics (2020) 20:152
11. Incidence of GER and GERD between one and
twelve months of age
Curien-Chotard and Jantchou BMC Pediatrics (2020) 20:152
12. The estimated prevalence of GERD
Age Incidence (%)
Low risk High Risk
0-23 months 2.2 12.3
2-11 years 0.6 4.1
12-17 years 0.8 7.6
Martigne L, Delaage PH, Thomas-Delecourt F, et al. Prevalence and management of gastroesophageal reflux disease in children and adolescents: a
nationwide cross-sectional observational study. Eur J Pediatr 2012;171(12):1767–73.
13. High Risk Populations
1. Neurologically impaired
2. Neuromuscular diseases
3. Obese infants and children
4. Certain genetic syndromes
5. Esophageal atresia
6. Chronic lung diseases
7. Prematurity
Vandenplas Y, Rudolph CD, Di Lorenzo C, et al. Pediatric gastroesophageal reflux clinical practice guidelines: joint recommendations of the North American Society for Pediatric Gastroenterology,
Hepatology, and Nutrition (NASPHAN) and the European Society for Pediatric Gastroenterology, Hepatology, and Nutrition (ESPGHAN). J Pediatr Gastroesophageal Nutr. 2009;49(4):548–557
14. • Pulmonologists were most likely to report that respiratory
symptoms are caused by GERD
• Neonatologists were least likely to report that a
therapeutic trial of pharmacologic agents would be useful
for diagnosing GERD or that lansoprazole, ranitidine, or
cimetidine are safe or effective
• No pharmacologic therapy had 50% of respondents
supporting its effectiveness.
Pediatric Specialists’ Beliefs About Gastroesophageal
Reflux Disease in Premature Infants
Catherine A. Golski et al. www.pediatrics.org/cgi/doi/10.1542/peds.2008-3841
RESULTS : A total of 1021 neonatologists, 232 pediatric pulmonologists, and
222 pediatric gastroenterologists participated in the study
16. Anatomy of the esophagus
Pandolfino, J. E. and A. J. Gawron (2015). "Achalasia: a systematic review." JAMA 313(18): 1841-1852.
17. A) Pandolfino, J. E. and A. J. Gawron (2015). "Achalasia: a systematic review." JAMA 313(18): 1841-1852.
Anatomy of the Lower Esophageal Sphincter
Mittal RK, Balaban DH. The esophagogastric junction. N Engl J Med. 1997 Mar 27;336(13):924-32.
• Healthy adult – LES 3cm in
length, at level of diaphragm
• Neonate – LES 1.5cm in
length, above the diaphragm
18.
19. 1. Esophageal peristalsis and relaxation of the
lower esophageal sphincter induced by
swallowing result from the excitation of
receptors in the pharynx.
2. The afferent stimulus travels to the sensory
nucleus, the nucleus solitarius (small inset).
3. A programmed set of events from the dorsal
vagal nucleus and the nucleus ambiguus
mediates esophageal peristalsis and
sphincter relaxation.
4. The vagal efferent fibers communicate with
myenteric neurons that mediate relaxation
(large inset).
5. The postganglionic transmitters are nitric
oxide (NO) and vasoactive intestinal peptide
(VIP).
Ach: acetylcholine
(+) signs: excitatory effects
(-) signs: inhibitory effects
RAVINDERK. MITTAL, M.D., NEJM; March 27, 1997
Neurologic control
20. 6. Transient relaxation of the lower
esophageal sphincter, appears to use the
same pathway.
7. The afferent signals for such relaxation
may originate in the pharynx, the larynx,
or the stomach.
8. The efferent pathway is in the vagus
nerve, and nitric oxide is the
postganglionic neurotransmitter.
9. Contraction of the crural diaphragm is
controlled by the inspiratory center in
the brain stem and the nucleus of the
phrenic nerve.
10.The crural diaphragm is innervated by
the right and left phrenic nerves through
nicotinic cholinergic receptors.
Ach: acetylcholine
(+) signs: excitatory effects
(-) signs: inhibitory effects
RAVINDERK. MITTAL, M.D., NEJM; March 27, 1997
21. Why do Infants regurgitate?
Supine position
Fed frequently (6-8 meals per day)
Limited capacity of their stomach
Parents want to be sure they’re giving maximum amount of milk
Crying is interpreted as a sign of hunger
Questionable immaturity of LES especially in preterm babies
22. Adult
Esophageal Capacity
Infant
Weaver TL. Anatomy and embryology. In: Walker WA, Durie PR, Hamilton JR, et al, eds. Pediatric Gastrointestinal Disease, 1st ed. Philadelphia: BC Decker; 1991:195-216.
11 cm at birth, with a diameter of 5 mm
24-30 cm long, with lateral and anteroposterior
diameters of 30 and 19 mm
23. Colo-Gastric Break
Background & aims: Patients with constipation frequently complain of dyspeptic
symptoms that may be explained by reflex inhibition of upper-gastrointestinal motor
activity by colonic stimuli (Colo-Gastric break).
Methods: 42 children (mean age, 80.5 month) affected by FD (Rome II criteria).
All subjects underwent ultrasonographic measurement of the total gastric emptying time
(TGEt) at baseline (T0) and after 3 months (T3).
Children's bowel habits and the dyspeptic symptomatic score were evaluated at entry and
after 1 (T1), 2 (T2), and 3(T3) months.
Constipated patients were treated with osmotic laxatives for 3 months.
Dyspeptic children without constipation represented the comparison group.
Gabriella Bocia et al,Clin Gastroenterol Hepatol. 2008 May;6(5):556-60.
TGEt: Total gastric emptying time
FC: Functional constipation
FD: Functional dyspepsia
24. Colo-Gastric Break
Results:
1. FC was present in 28 of 42 (66.6%) patients.
2. Constipated dyspeptic children had significantly more prolonged total gastric emptying
time (TGEt) than subjects without constipation
3. Patients on osmotic laxatives had a significant decrease in TGEt at 3 months (P < .001).
4. The median dyspeptic symptomatic score as well as the number and consistency of
evacuations per week significantly improved at T1 in comparison with T0 and even more
at T2 and T3 (P < .001, for each).
Conclusions: FC was associated with delayed gastric emptying. Normalization of bowel
habit may improve gastric emptying as well as dyspeptic symptoms.
Gabriella Bocia et al,Clin Gastroenterol Hepatol. 2008 May;6(5):556-60.
TGEt: Total gastric emptying time
FC: Functional constipation
FD: Functional dyspepsia
26. History and Physical Exam
Symptoms and signs associated with GER are non-specific
Exclude other worrisome disorders that present with vomiting
Recognize complications of GERD
Severity of reflux or esophagitis found on diagnostic testing does not
directly correlate with symptom severity
In infants and toddlers, there is no symptom or group of symptoms
that can reliably diagnose GERD or predict treatment response
Vandenplas Y, Rudolph CD, Di Lorenzo C, et al. Pediatric gastroesophageal reflux clinical practice guidelines: joint recommendations of the North American Society for Pediatric
Gastroenterology, Hepatology, and Nutrition (NASPHAN) and the European Society for Pediatric Gastroenterology, Hepatology, and Nutrition (ESPGHAN). J Pediatr Gastroesophageal
Nutr. 2009;49(4):548–557
27. Obtain a Feeding and Vomiting History
Feeding and dietary history
Amount/frequency (overfeeding)
Preparation of formula
Recent changes in feeding type or
technique
Position during feeding
Burping
Behavior during feeding: choking,
gagging, cough, arching, discomfort,
refusal
Timing of smpx
Refluxate quality
Pattern of vomiting
Frequency/amount
Pain
Forceful or not
Blood or bile
Associated fever, lethargy,
diarrhea
28. 1. Bilious vomiting
2. Hematemesis, hematochezia
3. Consistently forceful vomiting
4. Onset of vomiting after six months of life
5. Constipation and/or Diarrhea
6. Abdominal tenderness, distension
7. Poor weight gain or weight loss
Red Flags
29. The challenging clinical overlap
1. Functional gastrointestinal disorders (FGID)
2. Gastrointestinal reflux disease (GERD)
3. Cow’s milk allergy (CMA)
4. Eosinophilic esophagitis (EoE)
PPI: proton pump inhibitor
AAF: amino acid-based formula
CM: cow’s milk
GI: gastrointestinal tract
eHF: extensively hydrolyzed formula
Salvatore S, Agosti M, Baldassarre ME, et al. Cow's milk allergy or gastroesophageal reflux disease- Can
we solve the dilemma in infants? Nutrients 2021; 13:297.
30. The challenging clinical overlap
1. Functional gastrointestinal disorders (FGID)
2. Gastrointestinal reflux disease (GERD)
3. Cow’s milk allergy (CMA)
4. Eosinophilic esophagitis (EoE)
PPI: proton pump inhibitor
AAF: amino acid-based formula
CM: cow’s milk
GI: gastrointestinal tract
eHF: extensively hydrolyzed formula
Salvatore S, Agosti M, Baldassarre ME, et al. Cow's milk allergy or gastroesophageal reflux disease- Can
we solve the dilemma in infants? Nutrients 2021; 13:297.
31. Upper GI Radiography
Advantage
Useful for detecting anatomic
abnormalities
Limitation
Cannot discriminate between
physiologic and non-physiologic
GER episodes
Pyloric stenosis
Malrotation
Reflux
32. Upper GI Radiography
Advantage
Useful for detecting anatomic
abnormalities
Limitation
Cannot discriminate between
physiologic and non-physiologic
GER episodes
Pyloric stenosis
Malrotation
Reflux
Not
recommended
33. Esophagogastroduodenoscopy (EGD)
Advantages
• Enables visualization and biopsy of esophageal epithelium
• Determines presence of esophagitis, other complications
• Discriminates between reflux and non-reflux esophagitis
Limitations
• Need for sedation or anesthesia
• Endoscopic grading systems not yet validated for
pediatrics
• Poor correlation between endoscopic appearance and
histopathology
Lundell LR, Dent J, Bennett JR, et al. Endoscopic assessment of oesophagitis: clinical and functional correlates and further validation of the Los Angeles classification. Gut 1999;45:172-80.
34. Esophagogastroduodenoscopy (EGD)
Advantages
• Enables visualization and biopsy of esophageal epithelium
• Determines presence of esophagitis, other complications
• Discriminates between reflux and non-reflux esophagitis
Limitations
• Need for sedation or anesthesia
• Endoscopic grading systems not yet validated for
pediatrics
• Poor correlation between endoscopic appearance and
histopathology
Lundell LR, Dent J, Bennett JR, et al. Endoscopic assessment of oesophagitis: clinical and functional correlates and further validation of the Los Angeles classification. Gut 1999;45:172-80.
Not
recommended
35. Esophageal pH probe
Assessment of three methods of pH probe positioning in preterm infants. Emmerson AJ, Chant T, May J, Vales P ;J Pediatr Gastroenterol Nutr. 2002;35(1):69.
• Advantages
• Detects episodes of reflux
• Determines temporal association between acid GER and symptoms
• Limitations
• Cannot detect nonacidic reflux
• Not useful in detecting association between GER and apnea unless
combined with other techniques
• The wide spectrum of size of infants makes placement of the
catheter challenging, as misplacement may result in under- or
overestimation of acid reflux
• Placement is confirmed radiographically.
36. Esophageal pH probe
Assessment of three methods of pH probe positioning in preterm infants. Emmerson AJ, Chant T, May J, Vales P ;J Pediatr Gastroenterol Nutr. 2002;35(1):69.
• Advantages
• Detects episodes of reflux
• Determines temporal association between acid GER and symptoms
• Limitations
• Cannot detect nonacidic reflux
• Not useful in detecting association between GER and apnea unless
combined with other techniques
• The wide spectrum of size of infants makes placement of the
catheter challenging, as misplacement may result in under- or
overestimation of acid reflux
• Placement is confirmed radiographically.
Not
recommended
37. Multiple Intraluminal Impedance
Advantages
• Detects nonacidic GER episodes
• Detects brief (< 15 s) acidic GER episodes
• Useful for studying respiratory symptoms and GER in infants
Limitations
• Normal values in pediatric age groups not yet defined
• Analysis of tracings time-consuming
• Portable device unavailable for outpatient studies
Wenzl TG. Investigating esophageal reflux with the intraluminal impedance technique. J Pediatr Gastroenterol Nutr 2002;34:261-8.
39. Characterization of GER events during pH-impedance
A. Liquid acid characterized by retrograde drop in
impedance and pH drop below 4. Note this is not full-
column GER (does not reach Z1). Bolus clearance time
(BCT) determines bolus contact and clearance efficiency.
B. Gas nonacid characterized by rapid rise in impedance
reaching the most proximal impedance channel (Z1) and
pH > 4. Crying is associated with this GER event
C. Mixed acid characterized by liquid and gas components
with pH < 4. Acid clearance time (ACT) measures
esophageal acid contact time. As numerous iterations are
possible, it is important to discern the true cause of
symptoms for effective diagnosis and therapies.
Sudarshan R. Jadcherla Clin Perinatol 47 (2020) 243–263
40. Characterization of GER events during pH-impedance
A. Liquid acid characterized by retrograde drop in
impedance and pH drop below 4. Note this is not full-
column GER (does not reach Z1). Bolus clearance time
(BCT) determines bolus contact and clearance efficiency.
B. Gas nonacid characterized by rapid rise in impedance
reaching the most proximal impedance channel (Z1) and
pH > 4. Crying is associated with this GER event
C. Mixed acid characterized by liquid and gas components
with pH < 4. Acid clearance time (ACT) measures
esophageal acid contact time. As numerous iterations are
possible, it is important to discern the true cause of
symptoms for effective diagnosis and therapies.
Sudarshan R. Jadcherla Clin Perinatol 47 (2020) 243–263
Useful in severe
GERD
but not available
41. Rosen et al. Pediatric Gastroesophageal Reflux Clinical Practice Guidelines. JPGN 2018;66: 516–554
Other diagnostic interventions for GERD
Salivary pepsin • Not to be used for the diagnosis of GERD in infants and children
Manometry • To consider only when a motility disorder is suspected.
Scintigraphy • Not to be used for the diagnosis of GERD in infants and children
42. Testing for Reflux Disorders
No one test can be used to diagnose reflux
Reflux tests are useful
To document the presence of GER(D)
To detect complications
To establish a causal relationship between GER and symptoms
To evaluate therapy
To exclude other conditions
Vandenplas Y, Rudolph CD, Di Lorenzo C, et al. Pediatric gastroesophageal reflux clinical practice guidelines: joint recommendations of the North American Society for Pediatric Gastroenterology,
Hepatology, and Nutrition (NASPHAN) and the European Society for Pediatric Gastroenterology, Hepatology, and Nutrition (ESPGHAN). J Pediatr Gastroesophageal Nutr. 2009;49(4):548–557
44. AR Formulas
Pre-thickened infant milks, so-called “anti-regurgitation‘ (AR) milks, have
been proposed for several years.
These AR formulations already contain a thickener, selected from rice,
starch and carob gum, at the origin of the viscosity of the reconstituted
milk and thus having an anti-regurgitation effect.
However, these milks have drawbacks: they very often have secondary
effects like constipation or diarrhea
45. Thickeners
The preparations based on carob flour are known to cause abdominal pain,
colic and diarrhea Subsequent to the fermentation of carob in the colon
(Cane et al., Arch Dis Child 1985, 60: 71-75).
Carob induces frequent, liquid and gelatinous stools. Although rare, serious
complications such as acute intestinal obstruction or necrotizing
enterocolitis have been reported in premature and newly born infants
(Vandenplas et al., “The Diagnosis and management of gastro-esophageal
reflux in infants. Early Hum Dev 2005, 81: 1011-24).
46. Rosen et al. Pediatric Gastroesophageal Reflux Clinical Practice Guidelines. JPGN 2018;66: 516–554
Rice readily absorbs arsenic from the environment, about 10 times more
than other grains.
Safety concerns were raised because of elevated levels of inorganic arsenic
in all forms of rice including infant cereals.
Arsenic exposure
Neurotoxicity
Long-term cancer
Rice Based Thickeners
47. At a pH between 6 and 3.5, viscosity is comprised
between 150 and 1,600 mPas*
*Mpas: Milli Pascals per second
Cold-soluble carob
The so-called “cold-soluble' carob is distinguished
from native carob, notably in that it has a lower
average molecular weight of carob than that of
native carob.
This particular weight average molecular weight may
for example be obtained by breaking the glycoside
bonds with the purpose of producing shorter chains.
ANT-REGURGITATION COMPOSITION MANTAINING GUT MOTILITY International Patent
Application No. PCT/EP2014/059312
48. • Purpose: The aim of the study was to evaluate the efficacy of a new anti-regurgitation (AR)
formula (Novalac), thickened with an innovative complex including Carob and fibers, on the
daily number of regurgitations and to assess its impact on stool consistency and frequency.
• Methods: Infants < 5 months, presenting at least 5 regurgitations/day were recruited. The
efficacy of the new formula on regurgitation (daily number and Vandenplas score), stool
frequency and consistency were assessed at day 14 and 90.
• Results: In all infants, regurgitations improved after 2 weeks. The daily number of
regurgitations decreased significantly. There was no significant change in stool consistency
at day 14. After 3 months, 97.5% of infants had formed or soft stools. Growth was
appropriate
• Conclusion: The new AR formula thickened with an innovative complex is very effective in
reducing the daily number of regurgitations without having a negative impact on stools
consistency.
Christophe Dupont, Yvan Vandenplas Pediatr Gastroenterol Hepatol Nutr 2016 June 19(2):104-109
Efficacy and Tolerance
of a New Anti-Regurgitation Formula
49. Effect of Thickening Milk Formula Feedings With
Rice Cereal
0.0
0.5
1.0
Adapted from Orenstein SR, Magill HL, Brooks P. Thickening of infant feedings for therapy of gastroesophageal reflux. J Pediatr. 1987;110(2):181–186
Caloric Density
(cal/cc)
Vomiting
(episodes/90 min)
Sleep Time
(min asleep/90 min)
Crying Time
(min crying/90 min)
Unthickened Thickened
p=.015 p=.026 p=.042
0
1
2
3
4
5
0
10
20
30
40
50
0
5
10
15
20
25
n=20
50. Esophageal pH probe study
parameters, outcome:
Reflux index
(percentage of time pH < 4).
KwokTC, OjhaS, DorlingJ. Feed thickener for infants up to six months of age with gastro-oesophageal reflux. Cochrane Database of Systematic Reviews 2017, Issue 12. Art. No.: CD003211.
63. The Effect of Body Positioning on Gastroesophageal Reflux
in Premature Infants
Study design Premature infants with frequent regurgitation and
postprandial desaturation (n = 22) underwent a 24-hour recording
of MII-pH. With the infants in 4 different positions: supine (S), prone
(P), on the right side (RS), and on the left side (LS).
Results All infants were analyzed for 20 hours. The mean number of
recorded GER episodes was 109. The LS position showed the lowest
esophageal acid exposure (0.8%) in the early postprandial period,
and the P position showed the lowest esophageal acid exposure
(5.1%) in the late postprandial period.
Conclusion Placing premature infants in the left lateral position in
the postprandial period is a simple intervention to limit GER.
GIACOMO FALDELLA, et al. J Pediatr 2007;151:591-6
Acid
reflux
Non-Acid
reflux
Supine 17.6 1.3
Prone 4.4 0.3
Left side 7.5 0.7
Right side 21.4 1.2
64. Effect of Sleep Position on GER in Infants and Sudden
Infant Death Syndrome (SIDS) Mortality
Reflux Index1
(% time pH <4)
Supine 15.3 0.05* 2.3 1.0
Left side 7.7 0.05* 1.1 3.5†
Right side 12.0 0.05* 1.8 3.5†
Prone 6.7 4.4 1.0 13.9
*Mortality rate for all non-prone positions combined
†Combined odds ratio
1 Tobin JM, McCloud P, Cameron DJ. Posture and gastro-oesophageal reflux: a case for left lateral positioning. Arch Dis Child. 1997;76(3):254–358
2 Skadberg BT, Morild I, Markestad T. Abandoning prone sleeping: Effect on the risk of sudden infant death syndrome. J Pediatr. 1998;132(2):340–343
3 Oyen N, Markestad T, Skaerven R, et al. Combined effects of sleeping position and prenatal risk factors in sudden infant death syndrome: the Nordic Epidemiological SIDS Study. Pediatrics. 1997;100(4):613–621
SIDS Mortality2
(per 1000 live births)
Reflux Index
Odds Ratio
SIDS Mortality
Odds Ratio3
65. Avoid tobacco smoke exposure
Tobacco smoke is known to lower esophageal sphincter pressure and to
promote GER in adults.
A study in infants found that those with biochemically confirmed perinatal
exposure to tobacco smoke had significantly more frequent and more
proximally migrating reflux events, as measured by esophageal impedance
testing, compared with unexposed infants.
Effects of Smoking Exposure in Infants on Gastroesophageal Reflux as a Function of the Sleep-Wakefulness State. Djeddi D, Stephan-Blanchard E, LékéA, Ammari M, Delanaud S, Lemaire-Hurtel
AS, Bach V, Telliez F J Pediatr. 2018;201:147. Epub 2018 Jul 2.
66. Avoid overfeeding
Because simple reflux is promoted by gastric distention, providing smaller
feedings often reduces the frequency or quantity of reflux.
For infants with suboptimal weight gain, it may be helpful to provide
smaller but more frequent feedings and/or to concentrate the formula.
67. Other modifications
Avoid car seat position
Avoid tight fitting diapers
Extensively hydrolysate formulas are more digestible than non-hydrolyzed
proteins and allow an accelerated gastric emptying.
Treat constipation (Colo-gastric break)
68. Efficacy of Conservative Therapy for Infant Gastroesophageal Reflux
Objective: To determine the efficacy of non-pharmacologic conservative therapy for infant
gastroesophageal reflux disease (GERD).
Study design: Consenting parents of the first 50 screened infants who met
inclusion/exclusion criteria including abnormal (>16/42) scores on the Infant
Gastroesophageal Reflux Questionnaire-Revised (I-GERQ-R; n = 40) were taught
conservative therapy measures: feeding modifications, positioning, and tobacco smoke
avoidance. We compared I-GERQ-R scores and symptom response details before and 2
weeks after.
Results: The median initial and final scores were 23 (16-36) and 18 (7-34; P < .000001).
78% improved ; 59% improved at least the threshold of 5 points; 24% became normal.
Efficacy of conservative therapy as taught in the primary care setting for symptoms suggesting infant gastroesophageal reflux. Orenstein SR, McGowan JD J Pediatr. 2008;152(3):310.
69. Temporal association between reflux-like behaviors and
gastroesophageal reflux in preterm and term infants
Signs commonly ascribed to GER in preterm infants include: feeding
intolerance or aversion, poor weight gain, frequent regurgitation, apnea,
cough, desaturation and bradycardia and behavioral signs.
The temporal association of these perceived signs of GER with either acidic
or nonacidic reflux episodes as measured by MII and pH is not supported,
and the signs will usually improve with time without treatment.
Funderburk A, et al. J Pediatr Gastroenterol Nutr. 2016;62(4):556–561
70. Apnea & GERD
A study of 119 premature infants with a mean gestational age of 28 weeks
used 12-hour cardiorespiratory monitoring to record 6255 acidic GER
episodes.
Apnea ≥15 seconds was associated with only 1 percent of the GER
episodes. There was no difference in the rate of apnea ≥15 seconds before,
during, or after GER episodes.
GER did not prolong apnea duration.
Similar findings were shown in a subsequent study from the same tertiary
center, in which less than 3 percent of all cardiorespiratory events (defined
as apnea ≥10 seconds, bradycardia ≤80 bpm, and oxygen desaturation
≤85%) were preceded by GER.
Characterization of cardiorespiratory events following gastroesophageal reflux in preterm infants. Di Fiore J, Arko M, Herynk B, Martin R, Hibbs AM J Perinatol. 2010 Oct;30(10):683-7. Epub 2010 Mar 11.
Apnea is not prolonged by acid gastroesophageal reflux in preterm infants. Di Fiore JM, Arko M, Whitehouse M, Kimball A, Martin RJ Pediatrics. 2005;116(5):1059.
72. Treating physiologic GER in infants
Once the diagnosis of GER is established
Parental education, reassurance, and anticipatory guidance are recommended
Dietary changes and thickening of formula can be considered
In general, no other intervention is necessary
If symptoms worsen or do not resolve or “warning signs” develop, referral
to a pediatric gastroenterologist is recommended
Vandenplas Y, Rudolph CD, Di Lorenzo C, et al. Pediatric gastroesophageal reflux clinical practice guidelines: joint recommendations of the North American Society for Pediatric Gastroenterology,
Hepatology, and Nutrition (NASPHAN) and the European Society for Pediatric Gastroenterology, Hepatology, and Nutrition (ESPGHAN). J Pediatr Gastroesophageal Nutr. 2009;49(4):548–557
73. Mechanism of action of Histamine Receptor Antagonists
(H2RAs) and Proton Pump Inhibitors (PPIs).
Olbe L, Carlsson E, Lindberg P. A proton-pump inhibitor expedition: the case histories of omeprazole and esomeprazole. Nat Rev Drug Discov. 2003 Feb; 2(2): 132-9.
74. Mechanism of action of Histamine Receptor Antagonists
(H2RAs) and Proton Pump Inhibitors (PPIs).
Olbe L, Carlsson E, Lindberg P. A proton-pump inhibitor expedition: the case histories of omeprazole and esomeprazole. Nat Rev Drug Discov. 2003 Feb; 2(2): 132-9.
75. Medication Dose Age limit
PPI
Omeprazole 0.7-3.3 mg/Kg/d, max20mg/d > 2 years
Lansoprazole 0.7-3.3 mg/Kg/d > 1 year
Esomeprazole <20Kg: 10 mg/d
>20 Kg: 10-20 mg/d
> 1 year
Pantoprazole >15 Kg to <40 Kg: 20 mg/d For erosive esophagitis in children
>5yr
H2RA
Famotidine 1 mg/Kg/d divided in 2-3 doses; max 20mg/d > 1month
Ranitidine 5-10mg/Kg/d divided in 2-3 doses; max300mg/d > 1month
Cimetidine No pediatric indication
Antacids
Calcium carbonate > 2 year
Sucralfate No pediatric indication
Van Pinxteren B, Sigterman KE, Bonis P, et al Cochrane Database Syst Rev 2010;(11):CD002095.
Khan M, Santana J, Donnellan C, et al. Cochrane Database Syst Rev 2007;(2):CD003244.
76. Effect of H2RAs on Healing of Esophagitis
N = 26 children with esophagitis treated with nizatidine 10 mg/kg/d or placebo for 8 weeks
Nizatidine
Placebo
Esophagitis
Healing
15%
69%
“Vomiting” reduced in both treatment arms; significant
improvement in other GERD symptoms only with nizatidine
Simeone D, Caria MC, Miele E, et al. Treatment of childhood peptic esophagitis: a double-blind placebo-controlled trial of nizatidine. J Pediatr Gastroenterol Nutr. 1997;25(1):51–55
77. Effect of Omeprazole on Esophagitis
Hassall E, Israel D, Shepherd R, et al. Omeprazole for treatment of chronic erosive esophagitis in children: a multicenter study of efficacy,
safety, tolerability and dose requirements. International Pediatric Omeprazole Study Group. J Pediatr. 2000;137(6):800–807
N = 65 children
with erosive
esophagitis
% of
Patients
100
80
60
40
20
0
Healed with
3.5 mg/kg/day
95%
72%
44%
Healed with
1.4 mg/kg/day
Healed with
0.7 mg/kg/day
78. Optimal Timing of PPI Dose
Single PPI dose:
Administer half-hour
before breakfast
If second PPI dose:
Administer half-hour
before evening meal
79. Available Prokinetic Agents Are Unproven or
Ineffective
• Cisapride: withdrawn
• Bethanechol: only 1 randomized controlled trial (RCT)
• Erythromycin: no RCT
• Domperidone: available in Canada, no RCT
• Metoclopramide:
– Esophageal pH improvement in 1 of 6 RCT
– Clinical improvement in 1 of 4 RCT
– High incidence (~30% prevalence) of adverse events
Vandenplas Y, Rudolph CD, Di Lorenzo C, et al. Pediatric gastroesophageal reflux clinical practice guidelines: joint recommendations of the North American Society for Pediatric Gastroenterology, Hepatology, and
Nutrition (NASPHAN) and the European Society for Pediatric Gastroenterology, Hepatology, and Nutrition (ESPGHAN). J Pediatr Gastroesophageal Nutr. 2009;49(4):548–557
81. Goals of Pharmacotherapy
1. Control symptoms
2. Promote healing
3. Prevent complications
4. Improve health-related quality of life
5. Avoid adverse effects of treatment
82. Surgical Treatment of Refractory GERD
Fundoplication is an anti-reflux surgery that may benefit children with
confirmed GERD who have failed optimal medical therapy, who are
dependent on medical therapy over a long period, or who have life-
threatening complications of GERD.
Side effects include: bloating syndrome, impaired gastric
accommodation, gastric hypersensitivity, rapid gastric emptying,
retching, or dysphagia
Scoliosis and epilepsy in children with neurologic impairments, decrease
the success rate of anti-reflux therapy.
In this group of children, fundoplication is associated with a 40% surgical
failure rate, 12% to 30% rate of recurrent reflux, 59% experiencing
postoperative complications, and a 1-3% mortality rate.
Hauer JM. JAMA Pediatr 2014;168(2):188.
83. Vomiting and regurgitation
Good feeding
Good weight gain
Happy spitter
No complications
No medical treatment
Vomiting and regurgitation
Poor feeding
Poor weight gain
Irritable and fussy
Complications
Medical/surgical treatment
GER GERD
85. History & PE
Red
Flags
Investigate or refer
Yes
1. Bilious vomiting
2. Hematemesis, hematochezia
3. Consistently forceful vomiting
4. Onset of vomiting after 6 months of life
5. Constipation and/or Diarrhea
6. Abdominal tenderness, distension
7. Poor weight gain or weight loss
87. History & PE
Red
Flags
Investigate or refer
Yes
No
Non-pharmacological
treatment
1. Thickened formula
2. Positioning (left side decubitus with 30
degrees elevation) after meals
3. Reduced feeding volumes
4. Avoid car seats position
5. Avoid Passive smoking
6. Avoid tight diapers
7. Reversed upright position for burping
8. Treat constipation
9. Reassure parents
88. History & PE
Red
Flags
Investigate or refer
Yes
No
Non-pharmacological
treatment
Improved
Continue treatment
No
Consider eHF
If breastfed, maternal
avoidance diet
Yes
89. History & PE
Red
Flags
Investigate or refer
Yes
No
Non-pharmacological
treatment
Improved
Continue treatment
No
Yes
Improved
Continue treatment
Yes
No Consider 2-4 weeks of acid
suppression trial
Consider eHF
If breastfed, maternal
avoidance diet
90. History & PE
Red
Flags
Investigate or refer
Yes
No
Non-pharmacological
treatment
Improved
Continue treatment
No
Yes
Improved
Continue treatment
Yes
No Consider 2-4 weeks of acid
suppression trial
Improved Yes
No
Revisit differential
diagnosis, investigate or
refer
Consider eHF
If breastfed, maternal
avoidance diet
91. Take home message
1. GER is a physiologic process, LESR is a useful process
2. In most cases a history and physical examination, with attention to warning
signals, are sufficient to reliably diagnose GER/GERD
3. Upper GI, endoscopy, pH probe and Multi-channel intraluminal impedance
are used to confirm GERD’s complications, or to R/O other conditions
4. Non-pharmacological management is successful in most cases
5. Medical treatment is prescribed to treat esophagitis
6. More than 95% of All GER will disappear by 12 months of age