Celiac Disease Among Gastrointestinal Patients Attending a Gastro-Intestinal Endoscopy Unit: Prevalence, Symptoms, Signs, and Association with age and Gender

Research Article | DOI: https://doi.org/10.31579/2767-7370/049

Celiac Disease Among Gastrointestinal Patients Attending a Gastro-Intestinal Endoscopy Unit: Prevalence, Symptoms, Signs, and Association with age and Gender

  • Muhamed Ahmed Al-Haimi 1
  • Samah Mohsen Askar Al-Harthi 2
  • Hassan Abdulwahab Al-Shamahy 3*

 1 Department of Medicine-Gastroenterology Division, Faculty of Medicine and Health Sciences, Sana’a University, Republic of Yemen.

2 Department of Medicine, Faculty of Medicine, Dahmar University, Republic of Yemen.

3 Medical Microbiology department, Faculty of Medicine, Genius University for Sciences & Technology, Dhamar city, Republic of Yemen. 

*Corresponding Author: Hassan Abdulwahab Al-Shamahy, Medical Microbiology department, Faculty of Medicine, Genius University for Sciences & Technology, Dhamar city, Republic of Yemen.

Citation: Muhamed Ahmed Al-Haimi, Samah Mohsen Askar Al-Harthi, Hassan Abdulwahab Al-Shamahy (2023), Celiac Disease Among Gastrointestinal Patients Attending a Gastro-Intestinal Endoscopy Unit: Prevalence, Symptoms, Signs, and Association with age and Gender, J New Medical Innovations and Research, 4(2); DOI:10.31579/2767-7370/049

Copyright: © 2023, Hassan Abdulwahab Al-Shamahy. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Received: 13 March 2023 | Accepted: 21 March 2023 | Published: 28 March 2023

Keywords: celiac disease (cd); prevalence; signs; symptoms; upper gastrointestinal endoscopy; yemen

Abstract

Background and objectives:

Celiac disease is a multisystem autoimmune disease that is triggered in genetically susceptible individuals by eating products containing gluten. It affects approximately 1% of the population worldwide, although a significant proportion of patients remain undiagnosed. The prevalence of celiac disease has not been well established in Yemen, either in the general population or in symptomatic patients. Therefore, the current study aimed to assess the prevalence of disease in asymptomatic patients undergoing upper GI endoscopy to investigate associated symptoms and signs; and whether CD prevalence differs significantly between different ages and genders in a tertiary hospital in Sana'a.

Methods: A cross-sectional study based on the results of esophagogastroduodenoscopy (EGD) and serological markers; total IgA anti-tissue transglutaminase (tTG), and total anti-endomysial IgA (EMA), for 111 patients with gastrointestinal symptoms who were all patients who attended endoscopy units in the research period in the Police Hospital. Data were collected by means of a pre-designed questionnaire then the results were analyzed.

Results: The patients were 49 males and 62 females, with a mean age equal to 27.6 ± 12.5 years (range, 4–64 years). The prevalence of CD among gastrointestinal patients was 16.2%. There was an association of CD with females (rate 19.4%, OR = 1.7, p = 0.31) but not statistically significant, and its prevalence among age groups was approximately equal except for 0% prevalence in >60 years of age. Looking at clinical signs and symptoms comparing the positive and negative CD group, there was a significant association between celiac disease and steatorrhea, weight loss, aphthous stomatitis, anemia, hair loss, dry skin, pruritus, depression, peripheral neuropathy, and amenorrhea, sterility, sterility, menopause, angular chilosis and dermatitis.

Conclusion: A high rate of CD was identified among gastrointestinal symptoms patients undergoing upper gastrointestinal endoscopy, arriving at the tertiary hospital in Sana’a, Yemen, and this demonstrates the importance of general practitioners in identifying patients with CD, especially in the absence of a medical facility for CD, and this was facilitated through the serological markers test. Our findings also indicate that celiac disease is more common in females, children and younger people, and there was an association between CD and the non-gastrointestinal classic symptoms of this disease as hair loss, dry skin, itching, depression, and peripheral neuropathy which can be used for clinical diagnosis.

Introduction

Internationally, celiac disease (CD) have an effect on between 1 in 100 and 1 in 170 people [1,2]. However, rates vary between different regions of the world from 1 in 300 to 1 in 40 [2]. It was also found that 1 out of every 105 blood donors carries IgA TG [3] in their blood. Because of the variable signs and symptoms, it is believed that about 85% of sufferers go undiagnosed [4]. It was also found that the percentage of people with a clinically diagnosed disease (symptoms trigger a diagnostic test) is 0.05-0.27% in most studies [1-4]. CD consequences from a reaction with gluten, which is a group of different proteins found in wheat and other grains such as barley and rye. Moderate amounts of oats, free from pollution with further gluten-containing grains, are regularly tolerated. The incidence of harms may depend on the type of oats. CD appears in people with a genetic predisposition. When exposed to gluten, the abnormal immune response may result in the production of many different auto-antibodies that can involve a number of distinct organs. In the small intestine, this causes an inflammatory reaction and may lead to villous atrophy. This affects the absorption of nutrients, often leading to anemia [1-4]. In the diagnosis of CD by histopathology; upper endoscopy is performed with a biopsy of the duodenum (beyond the duodenal bulb) or the jejunum to obtain multiple (four to eight) samples of the duodenum. It is known that not all areas may be affected equally; for example, if biopsies are taken from healthy intestinal tissue, the result will be a false negative [5]. Even in the same bioptic fragment, the presence of different degrees of damage may appear [6]. Most people with celiac disease emerge from a normal-looking small intestine on endoscopy before biopsies are examined in the lab. However, five findings at endoscopy have been associated with high specificity for celiac disease: 1- scalloping of small bowel folds (pictured), 2- paucity of folds, 3-mosaic pattern of the mucosa, 4- Submucosal vascular protrusion, 5- and nodular pattern of mucosa [7].  The gold standards in diagnosing CD are bowel biopsy and positive serological markers as tTG IgA and EMA IgA. European guidelines recommend that in adolescents and children with symptoms compatible with celiac disease, the diagnosis can be made without the need for an intestinal biopsy if tTG antibody titers are 10 times the upper limit of normal [8]. CD is a persistent autoimmune disease that primarily affects the small intestine, so classic symptoms include digestive problems such as chronic diarrhea, flatulence, loss of appetite, mala-absorption and failure of children to grow normally. This begins regularly between six months and two years of age. Non-classical symptoms are more common, especially in people older than 2 years. There may be moderate or absent gastrointestinal symptoms, a large number of symptoms related to any part of the body, or no visible symptoms. It is also associated with autoimmune diseases, such as type 1 diabetes, Hashimoto's, and thyroiditis [1,11]. There are limited studies in CD in Yemen [12,13] as well as studies in gastroenterology and/or autoimmune diseases are still limited in Yemen and only a few studies have been conducted on autoimmune diseases, and gastrointestinal diseases among adults and children [14-26]. Therefore, the current study aimed to assess the prevalence of disease in symptomatic patients undergoing upper gastrointestinal endoscopy to investigate associated symptoms and signs; and whether prevalence of CD varies greatly between different ages and genders in a tertiary hospital in Sana'a. 

Materials and Methods

Study design and setting: This cross sectional study was conducted at the unit of endoscopy in the Police Hospital (PH) in Sana'a, Yemen.

Study population: The population of this study were all patients whom referred to endoscopy unit.

Inclusion criteria: All patients referred to the endoscopy unit at the time of the study with gastrointestinal symptoms with different ages and genders, willing to participate, not previously diagnosed as CD.

Inclusion criteria: Patients with chronic liver diseases, irritable bowel disease, and acute viral gastroenteritis.

Data collection and laboratory diagnosis: 111 symptomatic patients undergoing endoscopy were enrolled in this study. Among them, 49 (44.1%) males and 62 (55.9%) females attended pediatric clinics, internal medicine clinics, and gastroenterology units and referred to endoscopy unit in KUH from April 2020 to January 2021. Data were collected by predesigned questionnaire including demographic data, history and physical examination results, (symptoms and signs). CD cases diagnosis were based on the results of esophagogastroduodenoscopy (EGD), serological markers; total IgA anti-tissue transglutaminase (tTG), and total IgA anti-endomysial (EMA) IgA. By enzyme-linked immunosorbent assay (ELISA), positive ATtg IgA and EMA IgA criteria greater than 10 times the upper limit of normal (ULN) in children or less than 10 times the ULN but confirmed by small bowel biopsy, were the criteria used to measure the prevalence of celiac disease. Hemoglobin levels (to define anemia based on a hemoglobin concentration less than 11 g/dL) were also included. The subjects were divided into categories based on gender and age. Clinical signs, symptoms and other diseases associated with celiac disease were also collected and analyzed.

Data Analysis: The whole data were analyzed by IBM SPSS Statistics 22. Ink (International Business Machines Corporation, New York, USA). The outcomes for variables were given in the form of rates (%). Chi Square was used for categorical variables that measured association among categorical variables. P-values less than 0.05 were considered significant. Odds of celiac disease (odds ratio, OR) were also analyzed by sex, age groups, symptoms and signs, with 95% CI, X2 and p to test for significance of association with the above factors.

Results

The study included 49 males (44.1%) and 62 females (55.9%). Considering ages, mean ± SD = 27.6 ± 12.5 years and range = 4–64 years; Most of the patients were in the age group 20-40 years (58.6%), followed by 4-19 years (20.7%), then 41-60 years (18%), while only 3 (2.7%) were over 60 years old (Table 1). Looking at the signs of serology; AtTG was positive in 18 (16.2%) patients, and EMA was positive in 23 (20.7%) patients. With histological findings, IEI was positive in 78 (70.3%), while only 18 (16.2%) were positive for villous atrophy. When sensitivity and specificity of the methods used for diagnosis were considered by comparing villous atrophy as a standard test for CD diagnosis, the AtTG test was 100% sensitive and specific to diagnostic CD, for EMA sensitivity was 94.4% and specificity 93.5%, while less sensitivity occurred for IEI (88.8%) and very low specificity (34.1%) for IEI occurred (Table 2).

CharactersNumber%P
Gender
Male4944.1<0>
Female6255.9
Age groups
4-19 years2320.7<0>
20-40 years6558.6
41-60 years2018
>60 years32.7
Total111100Mean ±SD =27.6±12.5 years
   Range= 4-64years

Table 1: Age and gender distribution of patients referred for upper gastrointestinal endoscopy with intestinal symptoms in the police hospital endoscopy unit, Sana'a, Yemen

*significance level less than 0.05 (P).

ResultsSerologyHistologyPrevalence of CD

AtTG

No (%)

EMA

No (%)

IEI

No (%)

Villus atrophy

No (%)

Positive18 (16.2)23 (20.7)78 (70.3)18 (16.2)18 (16.2)
Negative93 (83.7)88 (79.2)33 (29.7)93 (83.7)93 (83.7)
sensitivity10094.488.8Reference 
Specificity10093.534.1 

Table 2: The positive rate of Celiac disease markers among patients referred for upper gastrointestinal endoscopy with intestinal symptoms

Table 3 shows the association of positive celiac disease with different sex and age groups for patients who completed UG endoscopy. There was a slightly higher rate of CD among females (19.4%) with an OR equal to 1.7 while in males it was 12.2%; and the differences were not statistically significant. The highest incidence of CD was in the 41-60 year group (20% with OR = 1.4), followed by the 2-19 year group (17.7%) and the 20-40 year group (15.4%), while all cases in the >60 year group were negative for CD, while the differences were not statistically significant for all ages results.

Characters celiac disease n=18ORCI 95%X2p
No%
Gender
Malen=49612.20.20.2-1.61.00.31
Femalen=621219.41.70.59-4.91.00.31
Age groups
2-19 yearsn=23417.41.10.3-370.020.86
20-40 yearsn=651015.40.80.3-2.30.070.77
41-60 yearsn=204201.40.4-4.70.250.61
>60 yearsn=300.00.0undefined0.590.43
Totaln=1111816.2    

Table 3: The association of positive celiac diseases with different sex and age groups of patients completed UG endoscopy

OR=Odds ratioCI 95% = 95% confidence limitsX2 = chi squarepp value

Looking at clinical signs and symptoms comparing the positive and negative CD group, there was a significant association between celiac disease and steatorrhea with rate was100% (p<0 OR=20.6,CI OR=15.2, CI=4.1- OR=6.3,CI OR=15.6, CI=4.5 OR=10.1, CI=3.2 OR=17.8, CI=4.5 OR=2.9, CI=1.1- OR=5.1, CI=1.2 p=0.01), OR=6.3,CI p=0.007), OR=18.4, CI=11.7- OR=13, CI=2.2 OR=19.1, CI=4.3>

Symptoms and signsPatients with intestinal symptoms n=111celiac disease n=18ORCI 95%X2p
No%%No
Abdominal pain10897.318100undefined0.590.43
Anorexia8475.718100undefined6.90.008
Flatulence10493.718100undefined1.40.029
Chronic diarrhea10594.618100undefined1.20.26
Steatorrhoea 4742.318100undefined29.2<0>
Abdominal distention101911794.41.80.2-150.310.57
Weight loss5953.21794.420.62.6-16114.7<0>
Nausea –vomiting8072.11794.48.11.1-63.75.30.02
Heart burn9282.91688.91.70.3-8.50.540.45
Aphthus stomatitis3834.21583.315.24.1-57.323<0>
Anemia4742.31477.86.31.9-20.911.1<0>
Hair loss3127.91477.815.64.5-5326.5<0>
Dry skin3228.81372.210.13.2-31.919.7<0>
Arthralgia3329.79502.81.1-8.14.20.03
Itching1210.8844.417.84.5-69.825.2<0>
Depression2825.2844.42.91.1-8.34.20.04
Dermatitis109738.919.14.3-84.723.3<0>
Angular chilosis65.4422.2132.2-77.711.1<0>
Headache1210.8422.230.8-11.42.90.08
Backache1412.6422.22.30.65-8.61.80.17
Peripheral neuropathy98.1422.25.11.2-215.70.01
Amenorrhea87.2422.26.31.4-287.20.007
Infertility43.6316.718.411.7-18810.50.001
Dermatitis herpetiformis10.915.6undefined5.20.02
        
Anxiety21.815.65.40.3-90.71.70.19
Convulsion21.815.65.40.3-90.71.70.19
Total1111001816.2    

Table 4: The association of positive celiac diseases with Clinical signs and symptoms comparing with that negative celiac disease of patients completed UG endoscopy

OR=Odds ratioCI 95% = 95% confidence limitsX2 = chi squarepp value

Discussion

At TG was positive in 18 (16.2%) of our patients, and the production of AtTG could be explained by the sedation being the reaction by which glutamate residues are formed by cleavage of the epsilon-amino group of a glutamine side chain. The transamide process, occurring three times more often than deamidation is the cross-linking of the glutamine residues of the gliadin peptide to the lysine residues of tTG in a reaction catalyzed by transglutaminase. Cross-linking may occur either inside or outside the active site of the enzyme. The latter case produces a permanently covalently bound complex between gliadin and tTg. This results in the formation of new epitopes that are believed to stimulate the primary immune response by which auto-antibodies against tTg are developed [27,28], this interaction confirms the specificity of AtTG in CD diagnosis. In the current study, when the sensitivity and specificity of the methods used for diagnosis were considered by comparing villous atrophy as a standard diagnostic test for CD, the AtTG test was 100% sensitive and specific; and intended for diagnostic CD so that this test could be used as an alternative to an endoscopic procedure. Due to the invasive nature of the endoscopic procedure, patients' reluctance to undergo scope examination and biopsy sampling, as well as the many pitfalls related to histology, a growing interest has emerged in the past decades in non-biopsy diagnosis of CD. This has already been validated in pediatric CD and has been implemented since 2012 ESPHGAN Guidelines, which allowed the diagnosis of CD without biopsies in European symptomatic children who met the three diagnostic criteria: tissue transglutaminase antibodies greater than 10 times the upper limit of normal (ULN).), positive antibody (EMA) and positive HLA-DQ2/DQ8 haplotype [8]. This allowed a significant reduction in the number of endoscopy needed to diagnose CD and especially pediatric CD [29]. Furthermore, the updated 2020 ESPHGAN Guidelines define lighter rules for a non-vital strategy for CD diagnosis, not requiring HLA testing and the presence of symptoms in children with IgA transglutaminase 2 (TG-2) antibody values ​​10 times ULN and positive EMA in a second serum sample [30]. Though the pediatric practice has motivated researchers and clinicians to turn to adult CDs to support the non- biopsy strategy, some have suggested more caution as there can be misdiagnosis with such bases, especially in primary care, and others against the omission of endoscopy and biopsies in duodenum in adult CD as a baseline for histology, comparison with follow-up biopsy in non-responders is needed [31,32]. In addition, while there is a good correlation between serology and mucosal injury at diagnosis, CD-bound antibodies do not accurately detect persistent villous atrophy in CD patients treated with a gluten-free diet [33]. Recently developed investigative tools, such as the HLA-DQ-based tetra-gluten-based blood test, may modify the way that diagnose CD in the near future, imminent verification and scalability. This technology, joint with validation of serology-based diagnostic algorithms, may lead to a change in diagnostic criteria because a small bowel biopsy is no longer necessary while patients continue to follow a gluten-containing diet. These revolutionizes may transform the roles of gastroenterologists, from diagnosis to management and follow-up. If an evidence-based, biopsy-free strategy is developed for diagnosis, the incidence of celiac disease may grow further and motivate interventional studies to prevent celiac disease in at-risk individuals [34]. In Yemen, the prevalence of CD has not been well estimated so far, and only two previous studies discussed were found for CD in adult fertility and CD among gastrointestinal patients [12, 13], and the current work is an attempt to determine the rate of CD among suspected clinically patients. The prevalence of celiac disease among patients with gastrointestinal symptoms undergoing endoscopy in the current study was 16.2%. Compared with our observations, the prevalence of CD in the current study exceeds the rate of CD among suspects GI patients in Al-dossary et al. study (9.2%) [12]. Also, compared to our observations, the prevalence of CD in Yemen exceeds the rate of CD among suspected patients with gastrointestinal symptoms as in Saudi Arabia, South Yorkshire, Amsterdam, the Netherlands and North America among the symptoms representing the gastrointestinal tract; 7.6%, 4.7%, 3.0% and 2.0%, respectively [35-38]. In addition, our result is higher than that presented by Dickey et al. and Hopper et al. [39,40] where the incidence of CD among patients with undiagnosed gastrointestinal symptoms was about 9%. In contrast to our average (16.2%), the prevalence of CD among Iranian patients with irritable bowel syndrome was about 12% and among patients with gastrointestinal symptoms in Italy was about 13% as reported by Shahbazkhani et al.  and Carroccio et al.  respectively [41,42]. Considering gender, there was an association between CD and females at a rate of 19.4% versus 12.2% of males (OR = 1.7, p = 0.31) (Table 3). This result is similar to that previously reported where the incidence of CD was higher in females than males (17.0 vs. 7.8 per 100,000 person-years) in the cohort analysis [43], but this may be for the reason that a higher proportion of men may remain undiagnosed. . A systematic review and meta-analysis also found a slight increase in seropositivity among women participating in screening studies [44] although some studies in adults found that men and women had similar seroprevalence rates [45, 46]. Finally, men may be less likely to undergo duodenal biopsy during upper endoscopy for indications such as diarrhea and weight loss, which may play a role in under-diagnosis [47]. CD can appear at any age, including the elderly [48]. It is known that the CD appeared for the first time in childhood and it thought that it was a disease of children only; However, it may appear at all ages. Considering the age in the current study, there was a higher rate in the 41-60 year age group where the rate was 20% (Table 2). This differs from what was previously reported as the incidence of CD was higher in the younger age group. This rise in CD at an older age can be explained by the fact that such diagnoses point to the late discovery of CD despite the long-suffering. Also, recent prospective cohort studies have found that most patients develop CD before the age of 10 years [49,50]. Looking at clinical signs and symptoms in the current study comparing the positive and negative CD group, there was a significant association between celiac disease and steatorrhea (100%),  weight loss (OR=20.6), aphthous stomatitis (15.2), anemia (OR=6.3), hair loss rate (OR=15.6), dry skin (OR=10.1), pruritus (OR=17.8), depression (OR=2.9), peripheral neuropathy (OR=5.1), amenorrhea (OR=6.3), infertility (OR=18.4), angular chilosis (OR=13), and dermatitis (OR=19.1) (Table 4). These findings are almost similar to those reported in the literature where symptoms of untreated celiac disease include pale, loose, or oily stools (steatorrhea) and weight loss or failure to gain weight. Other common symptoms may be subtle or occur primarily in organs other than the intestine itself [51]. It's also possible to have celiac disease without any classic symptoms at all. This has been shown to comprise at least 43% of presentations in children [52]. Furthermore, many adults with latent disease may only develop fatigue or anemia [53]. Many undiagnosed individuals who consider themselves asymptomatic are in fact not, but are accustomed to living in a chronic health condition. In fact, after initiation of a gluten-free diet and subsequent development becoming apparent, these individuals are often able to recall and retrospectively recognize previous symptoms of their untreated disease that they mistakenly ignored [54]. The incidence of CD is increasing as it spreads throughout the world. There is a trend towards increased diagnosis of atypical presentations, and there is emerging evidence for accurate diagnosis other than biopsy among patients and particularly in children [49].

Conclusion

A high rate of CD was identified among gastrointestinal symptoms patients undergoing upper gastrointestinal endoscopy, arriving at the tertiary hospital in Sana’a, Yemen, and this demonstrates the importance of general practitioners in identifying patients with CD, especially in the absence of a medical facility for CD, and this was facilitated through the serological markers test. Our findings also indicate that celiac disease is more common in females, children and younger people, and there was an association between CD and the non-gastrointestinal classic symptoms of this disease as hair loss, dry skin, itching, depression, and peripheral neuropathy which can be used for clinical diagnosis. However, more studies are needed to support and confirm our findings and conclusions. According to this high prevalence, clinicians should pay more attention to CD when examining huge different symptoms to avoid misdiagnosis or long-term delay diagnosis.

Acknowledgments

The authors acknowledge the Police Hospital for support this research and materials supply.

Authors’ Contributions

All authors contributed to the study design, analysis and manuscript writing.

Ethical Approval

Ethical approval was obtained from the Ethics Committee from the Faculty of Medicine and Health Sciences, Sana’a University, Sana'a, Yemen. 

References

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I would like to express my gratitude towards you process of article review and submission. I found this to be very fair and expedient. Your follow up has been excellent. I have many publications in national and international journal and your process has been one of the best so far. Keep up the great work.

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Douglas Miyazaki

We are grateful for this opportunity to provide a glowing recommendation to the Journal of Psychiatry and Psychotherapy. We found that the editorial team were very supportive, helpful, kept us abreast of timelines and over all very professional in nature. The peer review process was rigorous, efficient and constructive that really enhanced our article submission. The experience with this journal remains one of our best ever and we look forward to providing future submissions in the near future.

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Dr Griffith

I am very pleased to serve as EBM of the journal, I hope many years of my experience in stem cells can help the journal from one way or another. As we know, stem cells hold great potential for regenerative medicine, which are mostly used to promote the repair response of diseased, dysfunctional or injured tissue using stem cells or their derivatives. I think Stem Cell Research and Therapeutics International is a great platform to publish and share the understanding towards the biology and translational or clinical application of stem cells.

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Dr Tong Ming Liu

I would like to give my testimony in the support I have got by the peer review process and to support the editorial office where they were of asset to support young author like me to be encouraged to publish their work in your respected journal and globalize and share knowledge across the globe. I really give my great gratitude to your journal and the peer review including the editorial office.

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Husain Taha Radhi

I am delighted to publish our manuscript entitled "A Perspective on Cocaine Induced Stroke - Its Mechanisms and Management" in the Journal of Neuroscience and Neurological Surgery. The peer review process, support from the editorial office, and quality of the journal are excellent. The manuscripts published are of high quality and of excellent scientific value. I recommend this journal very much to colleagues.

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S Munshi

Dr.Tania Muñoz, My experience as researcher and author of a review article in The Journal Clinical Cardiology and Interventions has been very enriching and stimulating. The editorial team is excellent, performs its work with absolute responsibility and delivery. They are proactive, dynamic and receptive to all proposals. Supporting at all times the vast universe of authors who choose them as an option for publication. The team of review specialists, members of the editorial board, are brilliant professionals, with remarkable performance in medical research and scientific methodology. Together they form a frontline team that consolidates the JCCI as a magnificent option for the publication and review of high-level medical articles and broad collective interest. I am honored to be able to share my review article and open to receive all your comments.

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Tania Munoz

“The peer review process of JPMHC is quick and effective. Authors are benefited by good and professional reviewers with huge experience in the field of psychology and mental health. The support from the editorial office is very professional. People to contact to are friendly and happy to help and assist any query authors might have. Quality of the Journal is scientific and publishes ground-breaking research on mental health that is useful for other professionals in the field”.

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George Varvatsoulias

Dear editorial department: On behalf of our team, I hereby certify the reliability and superiority of the International Journal of Clinical Case Reports and Reviews in the peer review process, editorial support, and journal quality. Firstly, the peer review process of the International Journal of Clinical Case Reports and Reviews is rigorous, fair, transparent, fast, and of high quality. The editorial department invites experts from relevant fields as anonymous reviewers to review all submitted manuscripts. These experts have rich academic backgrounds and experience, and can accurately evaluate the academic quality, originality, and suitability of manuscripts. The editorial department is committed to ensuring the rigor of the peer review process, while also making every effort to ensure a fast review cycle to meet the needs of authors and the academic community. Secondly, the editorial team of the International Journal of Clinical Case Reports and Reviews is composed of a group of senior scholars and professionals with rich experience and professional knowledge in related fields. The editorial department is committed to assisting authors in improving their manuscripts, ensuring their academic accuracy, clarity, and completeness. Editors actively collaborate with authors, providing useful suggestions and feedback to promote the improvement and development of the manuscript. We believe that the support of the editorial department is one of the key factors in ensuring the quality of the journal. Finally, the International Journal of Clinical Case Reports and Reviews is renowned for its high- quality articles and strict academic standards. The editorial department is committed to publishing innovative and academically valuable research results to promote the development and progress of related fields. The International Journal of Clinical Case Reports and Reviews is reasonably priced and ensures excellent service and quality ratio, allowing authors to obtain high-level academic publishing opportunities in an affordable manner. I hereby solemnly declare that the International Journal of Clinical Case Reports and Reviews has a high level of credibility and superiority in terms of peer review process, editorial support, reasonable fees, and journal quality. Sincerely, Rui Tao.

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Rui Tao

Clinical Cardiology and Cardiovascular Interventions I testity the covering of the peer review process, support from the editorial office, and quality of the journal.

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Khurram Arshad

Clinical Cardiology and Cardiovascular Interventions, we deeply appreciate the interest shown in our work and its publication. It has been a true pleasure to collaborate with you. The peer review process, as well as the support provided by the editorial office, have been exceptional, and the quality of the journal is very high, which was a determining factor in our decision to publish with you.

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Gomez Barriga Maria Dolores

The peer reviewers process is quick and effective, the supports from editorial office is excellent, the quality of journal is high. I would like to collabroate with Internatioanl journal of Clinical Case Reports and Reviews journal clinically in the future time.

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Lin Shaw Chin

Clinical Cardiology and Cardiovascular Interventions, I would like to express my sincerest gratitude for the trust placed in our team for the publication in your journal. It has been a true pleasure to collaborate with you on this project. I am pleased to inform you that both the peer review process and the attention from the editorial coordination have been excellent. Your team has worked with dedication and professionalism to ensure that your publication meets the highest standards of quality. We are confident that this collaboration will result in mutual success, and we are eager to see the fruits of this shared effort.

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Maria Dolores Gomez Barriga

Dear Dr. Jessica Magne, Editorial Coordinator 0f Clinical Cardiology and Cardiovascular Interventions, I hope this message finds you well. I want to express my utmost gratitude for your excellent work and for the dedication and speed in the publication process of my article titled "Navigating Innovation: Qualitative Insights on Using Technology for Health Education in Acute Coronary Syndrome Patients." I am very satisfied with the peer review process, the support from the editorial office, and the quality of the journal. I hope we can maintain our scientific relationship in the long term.

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Dr Maria Dolores Gomez Barriga

Dear Monica Gissare, - Editorial Coordinator of Nutrition and Food Processing. ¨My testimony with you is truly professional, with a positive response regarding the follow-up of the article and its review, you took into account my qualities and the importance of the topic¨.

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Dr Maria Regina Penchyna Nieto

Dear Dr. Jessica Magne, Editorial Coordinator 0f Clinical Cardiology and Cardiovascular Interventions, The review process for the article “The Handling of Anti-aggregants and Anticoagulants in the Oncologic Heart Patient Submitted to Surgery” was extremely rigorous and detailed. From the initial submission to the final acceptance, the editorial team at the “Journal of Clinical Cardiology and Cardiovascular Interventions” demonstrated a high level of professionalism and dedication. The reviewers provided constructive and detailed feedback, which was essential for improving the quality of our work. Communication was always clear and efficient, ensuring that all our questions were promptly addressed. The quality of the “Journal of Clinical Cardiology and Cardiovascular Interventions” is undeniable. It is a peer-reviewed, open-access publication dedicated exclusively to disseminating high-quality research in the field of clinical cardiology and cardiovascular interventions. The journal's impact factor is currently under evaluation, and it is indexed in reputable databases, which further reinforces its credibility and relevance in the scientific field. I highly recommend this journal to researchers looking for a reputable platform to publish their studies.

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Dr Marcelo Flavio Gomes Jardim Filho

Dear Editorial Coordinator of the Journal of Nutrition and Food Processing! "I would like to thank the Journal of Nutrition and Food Processing for including and publishing my article. The peer review process was very quick, movement and precise. The Editorial Board has done an extremely conscientious job with much help, valuable comments and advices. I find the journal very valuable from a professional point of view, thank you very much for allowing me to be part of it and I would like to participate in the future!”

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Zsuzsanna Bene

Dealing with The Journal of Neurology and Neurological Surgery was very smooth and comprehensive. The office staff took time to address my needs and the response from editors and the office was prompt and fair. I certainly hope to publish with this journal again.Their professionalism is apparent and more than satisfactory. Susan Weiner

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Dr Susan Weiner