Cutaneous Abnormalities in Patients of Chronic Kidney Disease and In Dialysis Dependent End Stage Renal Disease

Research Article

Cutaneous Abnormalities in Patients of Chronic Kidney Disease and In Dialysis Dependent End Stage Renal Disease

  • Mamun Mostafi *
  • Mohammad Enamul Haque
  • Amir Mohammad Kaiser
  • Masrura Jabin
  • Tania Hoque

*Corresponding Author: Mamun Mostafi, Gonoshasthaya Somaj Vittik Medical College and Nagar Hospital, Dhaka, Bangladesh.

Citation: Mamun Mostafi, Mohammad E. Haque, Amir M. Kaiser, Masrura Jabin, Tania Hoque (2023), Cutaneous Abnormalities in Patients of Chronic Kidney Disease and In Dialysis Dependent End Stage Renal Disease, International Journal of Clinical Nephrology. 5(4); DOI:10.31579/2834-5142/070

Copyright: © 2023, Mamun Mostafi. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Received: 07 November 2023 | Accepted: 14 November 2023 | Published: 21 November 2023

Keywords: adult polycystic kidney disease; hearing impairment; intestinal dialysis

Abstract

Background: Cutaneous manifestations occurring in patients with chronic kidney disease (CKD) are polymorphic and diverse. Comparison between cutaneous abnormalities of CKD patients with or without dialysis has never been explored in Bangladeshi population.

Objective: The aim of this study was to assess the prevalence and characteristics/patterns of different cutaneous manifestations in patients of CKD with or without dialysis.

Patients and methods:  This cross-sectional observational study was done at the Department of Nephrology, Gonoshasthaya Somaj Vittik Medical College and Nagar Hospital, Dhaka, Bangladesh from April, 2019 to March, 2020. Total 150 Patients of CKD stage III – V with or without dialysis were included in the study. Detailed general and systemic examination was performed. e-GFR was calculated by Cockcoft-Gault (CG) formula. And according to the e-GFR, patients were grouped into different stages of CKD. Skin manifestations were evaluated by a qualified skin specialist in the department of Dermatology. Detailed biochemical parameters were assessed. Scraping for fungus and potassium hydroxide mount were done wherever clinically indicated. Data were expressed as mean ± SD, minimum-maximum, and number (percent), unpaired student’s’ test and Chi-square test. Statistical analysis was done by using Statistical Package for Social Science (SPSS) software for Windows Version-14.

Results: Among the 150 study subject 11 (8.73%) were in stage-3, 20(15.87%) in stage-4, 38(30.16%) in stage-5(stable) and 57(45.24%) in stage-5 on dialysis. 99 patients (66%) were male and 51(34%) female. 85 (67.5%) male and 41 (32.5%) female showed cutaneous abnormality. A total of 126 patients (84%) had at least one skin problem; pallor was the most common (72%), while xerosis (68.8%), pruritus (65.3%), pigmentation (33.3%) and half-and-half nail (38.7%) were other common problems. Purpura and fungal infection was 16.66% and 16% respectively. Half and half nails were the most common nail abnormality seen in this study. Pigmentation, purpura, ulcerative stomatitis, bacterial infections were significantly higher in dialysis group and found statistically significant. Pruritus was associated with higher serum calcium, phosphorous and calcium-phosphate product values. There was a significant association between pruritus and xerosis (p .001).

Conclusion: Dermatological manifestations are very common among CKD patients with or without dialysis. Most common manifestations were pallor, xerosis, and pruritus. Pigmentation, purpura, bacterial infections are the most frequent skin abnormalities observed in hemodialysis patients. Serum calcium-phosphate product has a direct relation with pruritus. 

Introduction

Chronic kidney disease (CKD) is growing as a global public health problem. There is a rising incidence and prevalence of kidney failure, with poor outcomes and high cost which is causing a burden to the nations.

 Many studies showed high prevalence of cutaneous abnormalities are associated with chronic kidney disease (CKD) patients and range from the universal xerosis and pruritus to uncommon conditions like purpuric skin changes, acquired perforating dermatosis, and nail changes (1). 

Skin manifestation may be the first important sign of CKD. Persistent cutaneous complaints such as xerosis and intractable pruritus may allow searching for underlying renal dysfunction. 

The dermatological findings may even proceed any clinical or biochemical evidence of CKD and such cutaneous changes are overlooked during routine clinical practice. 

Physician must be aware of such cutaneous manifestation to properly diagnose, reassure, & educate patients & to offer appropriate therapy. Some manifestation might require only simple treatment & dermatological consultation could offer great relief to these patients.

A prompt diagnosis & efficient treatment of these problems can help a lot in relieving patient's discomfort & improving the overall outcome of management and vastly reduce the morbidity and improve the quality of life. So patients with CKD should undergo regular examination for cutaneous manifestation, so that necessary treatment can be given to reduce the morbidity. 

To the best of our knowledge, comparison between CKD patients with cutaneous abnormalities with or without dialysis has never been explored in Bangladeshi population. For this we have enrolled 150 CKD patients to find out the status and pattern of cutaneous abnormalities.

Patients and Methods:

This was a cross-sectional observational study was done at the Department of Nephrology, Gonoshasthaya Somaj Vittik Medical College and Nagar Hospital, Dhaka, Bangladesh. The study time was April, 2019 to March, 2020. Total 150 Patients of Chronic kidney disease (CKD) were included in the study. All patients were adult (>18 years) from both sexes and were suffering from CKD stage III-V, with or without dialysis. Patients with features of acute kidney injury, patients with renal transplant and patients with previous skin diseases were excluded.

Detailed general and systemic examination was performed. Demographic, clinical and medico legal data were collected from patient's case record format. e-GFR was calculated by Cockcoft-Gault (CG) formula. And according to the e-GFR, patients were grouped into different stages of CKD according to K/DOQI 2012 guidelines. Skin manifestations were evaluated by a qualified skin specialist in the department. 

Complete blood count, routine urine examination, biochemical tests( serum glucose for fasting and 2hrs after breakfast, serum urea, serum creatinine, serum calcium, serum inorganic phosphate were done recorded in the data collection sheet. Urinary total protein (UTP) and serum fasting lipid profile were also estimate for these patients. Scraping for fungus and potassium hydroxide mount were done wherever clinically indicated.

Data were expressed mean ± SD, minimum-maximum, and number (percent) as appropriate. Unpaired Student’s ‘t’. test, Chi-square test (with fisher exact modification) were perform to calculate statistical difference and/or association between groups where applicable. Statistical analysis was done by using Statistical Package for Social Science (SPSS) software for Windows Version-14. 

Observation and Results:

Among the 150 study subject 11 (8.73%) were in stage-3, 20(15.87%) in stage-4, 38(30.16%) in stage-5(stable) and 57(45.24%) in stage-5 on dialysis. 126 (84%) patients (Group-A) had cutaneous abnormalities and 24 (16%) patients (Group-B) had no cutaneous abnormalities. 99 patients (66%) were male and 51(34%) female. 85 (67.5%) male and 41 (32.5%) female showed cutaneous abnormality. This distribution did not show any statistical significant association (p=0.387). Mean (±SD) age (yrs.) of the total study subject was 44.6 ± 12.3. 

The mean (±SD)) haemoglobin of patient with Group-A were 7.82±1.42 g/dl and Group B 8.57±1.59g/dl. Mean haemoglobin between the two groups showed statistical significant difference (p=0.021). 

The mean (±SD) UTP of patient with group-A were 2.02±1.03g/d and group B 1.53±1.08g/d. Proteinuria between the two groups showed statistical significant difference (p=0.038). The mean (±SD) serum creatinine and the mean (±SD) lipid profile of patient with group-A and group-B were evaluated and the two groups did not show statistical significant difference.

Among the study patients the main cause of CKD was glomerulonephritis 68 (45.33%) then diabetes 47(31.33%). The other causes were hypertension 16 (10.66%), Obstructive uropathy 10(6.66%), ADPKD 05 (3.3%), Chronic pyelonephritis 01(0.66%). In 3 patients, we could not found any cause of CKD.

The most prevalent skin manifestation was pallor, which was seen in 108 patients (72%).Other skin manifestations included xerosis 103(68.6%), pruritus 98(65.3%), hyperpigmentation 50(33.3%), purpura 25(16.6%) (Table I). Fungal infection was the leading cutaneous infection 24(16%) followed by bacterial 15(10%). Half and half nails were the most common nail abnormality seen in this study (Table I).

Types of Cutaneous abnormality presentFrequency% among total patient
Pallor108   72%  
Pigmentation5033.33%
Xerosis  10368.66%
Pruritus9865.33%
Purpura/Ecchymosis2516.66%
Dermatitis over the A-V fistula010.66%
Bacterial infection 15 10%  
Viral infection08 5.33%
Fungal infection2416%
Parasitic infestation04 2.66%
Xerostomia10 6.66%
Ulcerative stomatitis16 10.66%
Half-and- half nail58 38.66%
Onycolysis085.33%
Onycomycosis117.33%
Mess line042.66%
Koilonychia117.33%
Clubbing042.66%

Table-I: Cutaneous abnormalities present the study subjects (n=150)

**Some participants have more than one finding.

Among the 68 patients with dialysis, 57 (83.8%) had cutaneous manifestation and, 69 82.1%) in non-dialysis group (n=84). CKD with dialysis and without dialysis had hyperpigmentation 30 (52.6%) and 20(29%) (p-0.007) and purpura 20 (35.1%) and 5 (7.2%) (p=.0001), ulcerative stomatitis12 (21.1%) and 4 (5.8%) (p=0.015), bacterial infection11 (19.3%) and 4 (5.8%) (p=.027), respectively. Hyper pigmentation, purpura, ulcerative stomatitis and bacterial infection were statistically significant higher in dialysis group (Table II). Other cutaneous manifestation among the study groups did not show any significant difference.

Types of Cutaneous

abnormality present

Frequency

Dialysis

(n=57)

No. (%)

Non-Dialysis

(n=69)

No. (%)

P value
Pallor108   49(86.0)  59(85)0.942
Pigmentation5030(52.6)20(29.0)0.007
Xerosis  10346 (80.7)57(82.6)0.783
Pruritus9837 (64.9)51 (73.9)0.273
Purpura/Ecchymosis2520(35.1)5(7.2)0.001

Dermatitis over the 

A-V fistula

 

01

 

01 (1.75%)

 

-

 

0.452

Bacterial infection 15 11 (19.3)4(5.8)0.027
Viral infection08 5(8.8)3 (4.3)0.466
Fungal infection2413(22.5)11(15.9)0.329
Parasitic infestation04 2(3.5)2(2.9)1.000
Xerostomia10 5(8.8)5(7.2)0.753
Ulcerative stomatitis16 12(21.1)4(5.8)0.015
Half-and- half nail58 31(54.4)27 (39.1)0.087
Onycolysis084(7.0)4 (5.8)1.000
Onycomycosis114(7.0)7(5.8)1.000
Mess line042 (3.5)2 (2.9)1.000
Koilonychia115 (8.8)6 (817)0.988
Clubbing043(5.3)1(1.4)0.328

Table- II: Cutaneous abnormalities in pre-dialysis and dialysis patients

In group-A the mean (±SD) calcium was 1.87±024mmol/L and group B 1.77±0.20 mmol/L. Mean calcium between the two groups showed statistical significant difference (p=0017) (Table III). In the mean (±SD) inorganic Phosphate in group A was 1.74±0.29mmol/L and group-B 1.61±0.16mmol/L. 

Mean Phosphate between the two groups r showed statistical significant difference (p=0.002) (Table III).  In group-A the mean (±SD) calcium phosphate product was 3.24±0.62 mmol/L and group B 2.84±0.37mmo1/L. Mean calcium phosphate product between the two groups showed statistical significant difference (p<0>

ParametersStudy group (n150)P value

Pruritus Group-A

(n=98)

Non- pruritus Group-B (n=52)

 

Calcium1.87±0.24  1.77±0.200.017
Phosphate1.74±0.291.61±0.16  0.002
Calcium phosphate product3.24±0.622.84±0.37<0>

 

Table-III: Calcium, phosphate and Calcium phosphate product  in subject with or without Pruritus

Out of 150 study subjects present with xerosis and 98 with pruritus. Among them 79 had both xerosis and pruritus. Only 19 study subjects had pruritus without xerosis. On the other hand, 24 had xerosis without pruritus and had no xerosis as well as pruritus. There was a significant association between pruritus and xerosis (p= <0>

PruritusXerosisTotalP value

Present

(n=103)

Absent

(n=47)

Present791998 
Absent282852<0>
Total10347150 

Table- IV: Pruritus and xerosis in study subjects (n=150)

Discussion

Cutaneous manifestations are very common in patients with chronic kidney disease. [2, 3] Found prevalence of kidney disease in 100% and 79% patients respectively. [4, 5] also found prevalence of kidney disease in 100% and 88% patients respectively. [6] Has performed a study among patients receiving hemodialysis and cutaneous disorders were found in 82% patients. In our study population 84% had some form cutaneous complain while, only 16% was free from all skin disorder. These findings of the study accords with previous study. 

Among those had cutaneous complains,8.73%(n=11)were in stage-3 CKD, 15.87%(n=20)were in stage-4 CKD, 30.16%(n=38)were in stage-5 CKD on medical treatment, 45.24%(n=57)were in stage-5 CKD on MHD.

 In our study, 99 (66%) patients were male and 51 (34%) were female. Among the male patients, 85 (65.5%) and among the female 41 (32.5%) showed cutaneous abnormalities. So there is no significant statistical difference between male and female (p=0.387) in development of cutaneous abnormalities.

Patient with cutaneous abnormality had higher UTP and we found high proteinuria was associated with development of cutaneous abnormality in this study (p=0.038).  During evaluation of lipid profile among study groups, we did not find lipid level had no association with development of cutaneous abnormality.  In a study by (7) the main causes of CKD in 150 study patients were due to diabetes (54, 36%); then glomerulonephritis (38, 25%); hypertension/renovascular disease (26, 17%); reflux or other structural malformations (8, 5%); polycystic kidney disease (7, 5%); cancer, trauma, and nephrotoxic agents (9, 6%); or unknown causes (8, 5%).

In current study, the main cause was glomerulonephritis (45.33%, n =68), then diabetes (31.33%, n =47). The other causes are hypertension (10.66%, n =16), obstructive uropathy (6.66%, n=10), ADPKD (3.33%, n=5), chronic pyelonephritis (.66%, n =1). In 3 patients, we could not found any cause of CKD.

Among the cutaneous findings, Pallor of the skin was most common. [8] Observed pallor only 45.45%, but (4) observed pallor as high as 91.5% .In a previous study, (5) also observed pallor 82%. It was observed in 72% and was the most common skin manifestation among CKD patients in this study. Pallor is due to anemia. Mean hemoglobin was 7.82±1.42 in 91.5% of study patients. Anemia in CKD results from decreased erythropoiesis, reduced red cell life span and blood loss during dialysis and degree of anemia governs the quality of life [9]. In present study 85.5% CKD without MHD and 86% with MHD were pallor. Pallor was found slight increase in frequency in dialysis patients though statistically insignificant. Similar study done by (4) found 94.3% CKD without MHD and 89.6% with MHD were pallor. (8) Also found pallor more common in patients on MHD. Pallor more in MHD group, probably more blood loss during dialysis in these group. 

Xerosis was a leading disorder reported in 46- 90% CKD [10, 11, 12]. Xerosis was the most common cutaneous abnormality (79%) in study done by [6] in dialysis patients. [8, 5] also observed xerosis 66.7% and 61% respectively. It was observed in 68.66% and was the second common skin manifestation among CKD patients in this study, predominantly over the lower back and extremities, which accord with previous finding. [4] Found 80% CKD without MHD and 72.9% with MHD had xerosis. In present study, we also found 82.6% CKD without MHD and 80.7% with MHD had xerosis.

A reduction in the size and functional abnormality of eccrine sweat glands, suggesting compromised eccrine secretion leading to epithelial dehydration [13] may contribute to the development of xerosis. Other factors considered in the pathogenesis of xerosis such as caloric and protein malnutrition are more prevalent in this subcontinent scenario as compared to the west [2].

 In addition, the tropical climate with greater sun exposure and resultant chronic dehydration may be fenny contributory [14].

Pruritus is a frequent symptom of CKD and could be severe and intractable with decreased quality of life [15, 16]. It is not present in acute renal failure and does not necessarily subside with dialysis although it improves with kidney transplantation [17]. There is wide variation (15-90%) in its prevalence reported by various worker (18). In a study by [6] found the prevalence of pruritus to be 53%. [5] Also found 53% of patients complained of pruritus. In this study, 65.3% of patients complained of pruritus, a finding similar to previous studies. It was found in 46.7% CKD without MHD (19) and 41.9% to 67% with MHD (20, 21). In present study we also found pruritus in 73.9% CKD patients without MHD and 64.9% CKD patients with MHD respectively. In similar study by [4] found pruritus was present in 57.1% and 62.5% CKD without and with MHD respectively. 

The cause of pruritus in CKD is multifactorial and may or may not improve with dialysis [22, 16]. There are a significant number of proposed etiologies for pruritus in CKD including: skin changes related to xerosis, urochrome deposition, uremic toxemia, calcium and phosphate dysregulation, mast cell proliferation with a concomitant increase in histamine levels, dialysis component allergic reactions, and hypovitaminosis D [23].

Parathyroid hormone and divalent ions (e.g. calcium phosphate and magnesium ions) have also been implicated in the pathogenesis of uremic pruritus, as itching frequently accompanies severe secondary hyperparathyroidism and an elevated calcium phosphate product (10). In the present study, those patients had pruritus, Calcium, Inorganic phosphate and calcium phosphate product were significantly higher than non-pruritus. There was a significant association between pruritus and xerosis(p .001). 

Parathyroid hormone could not evaluated as costly and routinely not done.

Pigmentary changes can occasionally be conspicuous enough to point towards the diagnosis of kidney disease on first presentation [24]. 

 

Diffuse hyperpigmentation has been reported in 36.7%by Thomas et al and in 37% by [5].

Diffuse hyperpigmentation on sun-exposed areas were seen in 33.3% in this hemodialysis and consistent with previous studies.[6] Observed, two types of pigmentary changes; hyperpigmentation (seen in 43% of patients) and a yellowish tinge to the skin (10%) with prominent hyperpigmentation over the sun exposed areas of CKD patients on MHD. Diffuse hyperpigmentation has been reported in 36.7% CKD without MHD [19].In this study hyperpigmentation was found in 29% CKD without MHD and 52.6% patients on MHD, which are significant higher in dialysis group and found statistically significant(p=.007). Such pigmentation is more marked in the sun exposed parts of the body in the subcontinent population could be due to tropical climate and excessive sun exposure in these patients [24].

The incidence is higher with longer duration of dialysis and attributed to the deposition of melanin in the basal layer and superficial dermis due to failure of kidney to excrete β melanocytic hormone that is poorly dialyzable [25]. 

Purpura and ecchymosis are spontaneous cutaneous bleeding affecting 9-20% of (26, 6). [8] Found purpura in 10(10.1%) patients, among whom 7 were on MHD. In this study, it was seen in 25 (16.6%) patients, among whom 20 (35.1%) were on maintenance hemodialysis and 5(7.2%) were without MHD which are significant higher in dialysis group and found statistically highly significant (p=.001). This is consistent with the previous report. Defects in primary haemostasis-like increased vascular fragility, abnormal platelet function, and use of heparin during dialysis are the main causes of abnormal bleeding in these patients [2].

Mucosal changes in the oral cavity have been reported in up to 90% patients with CKD [28]. Xerostomia was seen in 6.66% of the patients, which could be attributed to mouth breathing and dehydration and similar to previous finding (5.05%) by [8] Ulcerative stomatitis, seen in 16(10.66%), significantly higher in dialysis group. [6] Reported ulcerative stomatitis 29% in dialysis group. This could be attributed to the poor oral hygiene [28] and reported to occur with high blood urea [28] as oral mucosal changes are predisposed by bad oral hygiene and superimposed bacterial infection, awareness of oral hygiene in CKD must be encourage. [6] Found sixty-seven skin infections (13 bacterial, 42 fungal and 12 viral), distributed amongst 40 patients. Bacterial infections seen in 13 patients, were common in diabetics. The fungal infections were distributed among 30 patients (30%). Pityriasis versicolor was seen in 15 patients (15%). The viral infections included warts (8%), herpes simplex (3%) and herpes zoster (1%). (29) Have reported the incidence of fungal infection in patients undergoing hemodialysis to be 67%. In the present study bacterial infection, fungal infection and viral infection, parasitic infection were found in 15(10%), 24(16%) and 8 (5.3%), 4(2.66%) respectively. Bacterial infections seen in 15 patients, more marked in dialysis group and were common in diabetics. However among fungal infection pityriasis versicolor was seen in 18 patients; accords with that found in previous study. Patients with chronic kidney disease (CKD) have impaired cellular immunity due to a decreased T lymphocyte cell count; (30) this could explain the high prevalence of infection in these patients.

APD has been reported to occur in 4.5-17% of patients on hemodialysis. [31, 12]. These changes were significantly more prevalent in diabetic patients. In the previous study done by [5] kyrle disease was found in 3%. But it was not found in this study.

 Arteriovenous shunt dermatitis may be seen in 8% of patients on long-term hemodialysis [32]. It was seen only 01 (0.66%) patient in this study. Dermatologic conditions such as uremic frost, erythema papulatum uremicum, uremic roseola, and uremic erysipeloid now seldom occur in patients with CKD. 

Certain specific disorders associated with CKD such as calciphylaxis and nephrogenic fibrosing dermopathy resemble scleromyxedema [6] were not seen in this study, and this could be attributed to shorter duration of dialysis in our patients. 

Previous studies have found a prevalence of half and half nails were 16-50.6%. [10, 2, 6]. Although half and half nails are not always seen in renal failure, they occur in as many as 40% of the patients on dialysis. [2] reported that the nail changes increased in prevalence with respect to time of dialysis and was significantly more pronounced in patients receiving haemodialysis Half and half nails were the most common nail abnormality seen in 58 (38.66%) of this study and more commonly seen in haemodialysis patients 31(54.4%). The pathogenesis of half and half nails has been attributed to increased levels of melanocyte stimulating hormone (MSH) [33]. 

Pathophysiology for this phenomenon is related to the proximal half of the nail appearing white because oedema associated with dilated capillary network and the other half of the nail bed appearing normal [21, 33]. 

Other nail changes observed included onycomycosis 11(7.33%), Onycolysis 8(5.33%), koilonychia 11(5.05%), Mee's line 4(2.66%), and Clubbing 4(2.66%) and no significant difference in dialysis and non-dialysis group.

Conclusions

The dermatological disorder was present in majority CKD patients without and with dialysis and pallor, xerosis and pigmentation were predominant changes. Pigmentation and purpura were significantly higher in MHD patients. There was a significant association between pruritus and xerosis. Dermatological evaluation prompt diagnosis and efficient treatment of these problems can help a lot in relieving patient's discomfort and improving the overall outcome of management and great relief could be offered to the patient if a dermatological consultation was sought.

Study limitations

This was a single center study with small sample size. A multicenter study with large sample can represent the overall cutaneous manifestations in CKD.

Ethical issue:

Approval to perform the study was taken from Institution Review Board (IRB), Gonoshasthaya Somaj Vittik Medical College and Nagar Hospital, Dhaka. All participating individual were thoroughly briefed about nature, purpose implications of the study as well as entire spectrum of benefit and risks. Informed written consent was taken from each study subjects.

References

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Thank you very much for publishing my Research Article titled “Comparing Treatment Outcome Of Allergic Rhinitis Patients After Using Fluticasone Nasal Spray And Nasal Douching" in the Journal of Clinical Otorhinolaryngology. As Medical Professionals we are immensely benefited from study of various informative Articles and Papers published in this high quality Journal. I look forward to enriching my knowledge by regular study of the Journal and contribute my future work in the field of ENT through the Journal for use by the medical fraternity. The support from the Editorial office was excellent and very prompt. I also welcome the comments received from the readers of my Research Article.

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Dr Suramya Dhamija

Dear Erica Kelsey, Editorial Coordinator of Cancer Research and Cellular Therapeutics Our team is very satisfied with the processing of our paper by your journal. That was fast, efficient, rigorous, but without unnecessary complications. We appreciated the very short time between the submission of the paper and its publication on line on your site.

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Bruno Chauffert

I am very glad to say that the peer review process is very successful and fast and support from the Editorial Office. Therefore, I would like to continue our scientific relationship for a long time. And I especially thank you for your kindly attention towards my article. Have a good day!

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Baheci Selen

"We recently published an article entitled “Influence of beta-Cyclodextrins upon the Degradation of Carbofuran Derivatives under Alkaline Conditions" in the Journal of “Pesticides and Biofertilizers” to show that the cyclodextrins protect the carbamates increasing their half-life time in the presence of basic conditions This will be very helpful to understand carbofuran behaviour in the analytical, agro-environmental and food areas. We greatly appreciated the interaction with the editor and the editorial team; we were particularly well accompanied during the course of the revision process, since all various steps towards publication were short and without delay".

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Jesus Simal-Gandara

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

My Testimonial Covering as fellowing: Lin-Show Chin. 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.

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Lin-Show Chin

My experience publishing in Psychology and Mental Health Care was exceptional. The peer review process was rigorous and constructive, with reviewers providing valuable insights that helped enhance the quality of our work. The editorial team was highly supportive and responsive, making the submission process smooth and efficient. The journal's commitment to high standards and academic rigor makes it a respected platform for quality research. I am grateful for the opportunity to publish in such a reputable journal.

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Sonila Qirko

My experience publishing in International Journal of Clinical Case Reports and Reviews was exceptional. I Come forth to Provide a Testimonial Covering the Peer Review Process and the editorial office for the Professional and Impartial Evaluation of the Manuscript.

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Luiz Sellmann