A Complicated case of Sjogren’s Syndrome (SS), Rheumatoid arthritis, Pyoderma Gangrenosum, Quadriparesis, Recurrent Infections & Ischaemic Stroke, SIADH-an update with Review of Literature of Neurological Manifestations in Autoimmune Disease-A Case R

Case report | DOI: https://doi.org/10.31579/2642-973X/064

A Complicated case of Sjogren’s Syndrome (SS), Rheumatoid arthritis, Pyoderma Gangrenosum, Quadriparesis, Recurrent Infections & Ischaemic Stroke, SIADH-an update with Review of Literature of Neurological Manifestations in Autoimmune Disease-A Case R

  • Kulvinder Kochar Kaur 1*
  • Gautam Nand Allahbadia 2
  • Mandeep Singh 3

1 Obstt&Gynae, specialistreproductive endocrinology&Infertility specialist, Centre for Human Reproduction, India

2 Obstt&Gynae Rotunda-A Centre for Human Reproduction, India

3 Neurology Consultant Neurologist Department Swami Satyanand Hospital, Punjab

*Corresponding Author: Kulvinder Kochar Kaur, Obstt&Gynae, specialistreproductive endocrinology&Infertility specialist, Centre for Human Reproduction, India.

Citation: Kulvinder Kochar Kaur, Gautam Nand Allahbadia, Mandeep Singh, (2023), A complicated case of Sjogren’s syndrome (SS), Rheumatoid arthritis, Pyoderma gangrenosum, Quadriparesis, recurrent infections & Ischaemic Stroke, SIADH-an update with review of literature of neurological manifestations in autoimmune disease-A Case Report, J. Brain and Neurological Disorders, 6(5): DOI:10.31579/2642-973X/064

Copyright: © 2023, Kulvinder Kochar Kaur. 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: 15 June 2023 | Accepted: 26 June 2023 | Published: 03 July 2023

Keywords: sjogren’s s syndrome (ss); rheumatoid arthritis; pyoderma gangrenosum; recurrent ischaemic stroke; quadriparesis; t2dm

Abstract

Autoimmune diseases are well known to be associated with  neurological manifestations, usually they are not v complicated.Here we report a  patient whose initial  presentation was in the  form of Rheumatoid arthritis whose robustness escalated gradually for which methotrexate  20mg/day , prednisolone-5mg/day, hydroxychloroquinone -400mg5mg/day was started .Over time in view of severe anaemia methotrexate was omitted and 3 units bloodtransfused  Gradually she developed TB as well .8 yrs subsequently she generated quadriparesis secondary  to recurrent Ischaemic Stroke as,besides pulmonary tuberculosis/herpes zoster subsequent to first dose of rituximab 1000mg iv infusion on day1 following which inview of CD19 zero she never got the second dose till now -9 mths after 1st dose.She had further formed another conditions where  involvementofof  both innate along  with adaptive immune  system occur that is pyoderma gangrenosum for which heavy dosage of corticosteroids were given this was followed by drug induced hyperglycaemia one mth later hence steroids were stopped.Despite all attempts at therapy  and now on this admission  Sjogren’s s syndrome(SS) wasdiagnosed  with Ro52  3+,and SSA 2+.On admission she generated SIADH for which tolvaptan was started.Her right limb power has returned but left is still weak ,so she is unable to move.

1.Introduction

1.1Sjogren’s syndrome (SS)

Sjogren’s syndrome (SS) constitutes an autoimmune disease whose presentation   is in the form of lymphocytic along with plasmacytic infiltration into exocrine glands [1]. The central nervous system (CNS) is implicated in equivalent to 6% of SS patients as well as neurologic symptoms takes place prior to systemic symptoms in greater than 50%of cases [2]. Canonically, CNS implication present in the form of   multiple sclerosis (MS)-like injuries in the brain, longitudinally   extensive transverse myelitis (LETM), cranial neuropathies, vasculitis, aseptic meningitis, encephalitis, in addition to cerebellar ataxia [3,4]. Noticeably,   whereas  patients might  meet criteria for SS, it is necessary to test for aquaporin-4 IgG as well as myelin oligodendrocyte glycoprotein (MOG) IgG since CNS  implication in  SS is usually correlated with simultaneous neuromyelitis optica spectrum disorder (NMOSD) [3,4].The confirmation  for treatment of CNS disease in SS is restricted along with requires   monitoring   disease robustness in the  form defined by the EULAR (European League Against Rheumatism) Sjogren’s syndrome disease activity index (ESSDAI) [5,6]. Classicalfirst-line therapy for robust inflammatory manifestation includes high dose  intravenous methylprednisolone, 1000 mg daily for 3–5 days, followed by   a course of oral prednisone, 0.5–1 mg/kg/day tapered over weeks to months [2-7]. Plasmapheresis (PLEX) combined with steroids might offer a strategy with effectiveness   for LETM in addition to further   mirrors rational empiric therapy given NMO overlap potential [8]. The 2020 EULAR SS guideline recommends cyclophosphamide as well as  PLEX +rituximab as second-line and third-line therapy, respectively, for robust CNS implication however but breakthrough disease is frequent (level IV)[7]. Noticeably, however, for MS-like manifestation, MS disease- manipulating immunotherapy is required to be utilized (level V) [6].

1.1A   Diagnostic Biomarkers in Sjogren’s syndrome

Autoantibodies to the autoantigens Ro/SSA as well as La/SSB are the most significant     biomarkers isolated till   date along with have been integrated into the classification    criteria for primary Sjogren’s syndrome [5-9]. Subsequent to all these years of scientific   evaluation, anti-Ro/SSA in addition to anti-La/SSB are still today significant  for the disease   classification like they work in the form of diagnostic markers   for Sjogren’s syndrome. Ro/SSA as well as La/SSB actually are constituted of three cellular proteins Ro52, Ro60, along with La48 – dependent on their molecular weight, which was discovered in the late 1960s along with early 1970s[10,11]. Based   on the testing method utilized, the   selection criteria for primary Sjogren’s syndrome, in addition to the patient cohorts, the prevalences of seropositivity are about 70% for Ro52, 40% for Ro60, as well 50%for La48 [12]. The Ro as well as La proteins were first identified in addition to properties studied for their partition in ribonucleoprotein (RNP) complexes with human Y RNAs, which pointed to implication in cellular post-transcriptional controlling. More particular    functions were subsequently    attributed, with Ro52 (alias TRIM21) revealed to be a ubiquitin E3 ligase, as well as Ro60 in addition to   La48 have both been illustrated to be RNA-binding   proteins [13]. A data-guided study of international patient cohorts (5) has demonstrated that anti-Ro/SSA is the second-best anticipator of Sjogren’s syndrome subsequent to focus score, when the most recent criteria for Sjogren’ ssyndrome are employed. Anti-nuclear antibodies (ANA) [14]. along with rheumatoid factor (RF) [15]. are further paradigms frequently determined in Sjogren’s syndrome in the form of clinical along with diagnostic gadgets   however have only partly made a position inthe classification criterion.

Muscarinic type 3 receptor(M3R) portray one of the new promising biomarkers with direct biological as well as functional links to exocrine liberation. It is thought that antibodies towards M3R might probably hamper   saliva liberation [16]. Certain workers have   displayeda 60–80% concordance of anti-M3R with Sjogren’s syndrome [17]. but the usage has been inhibited by replication issues and anti-M3R is thereby   not widely utilized in the form of a biomarker [18]. in clinical   settings. Calprotectin is a complicated  marker of the S100A8 and S100A9  proteins observed with enrichment in neutrophils. In the presence of calcium (Ca2+), calprotectin possesses inflammatory in addition to antimicrobial activities. Salivary, however not blood, calprotectin has been illustrated to possess robust association with clinical signs of Sjogren’s syndrome [19]. Serum calprotectin    has more recently been illustrated to be a marker for carotid atherosclerosis in primary Sjogren’s syndrome [20]. Reactions to   rituximab treatment was further evaluated in a multicentre, randomized, double-blind, placebo-controlled trial known as ‘Tolerance and Efficacy of Rituximab in   Primary Sjogren’s Syndrome’ (TEARS) [21]. Patients with primary Sjogren’s syndrome were examined with Salivary gland ultrasonography (SGUS) prior to the first placebo/rituximab infusion along with 6 months subsequently. At every examination, SGUS of the parotid as well as submandibular glands was performed    the paradigms echo structure (score 0–4), size of each as well as the   gland, along with vascularization dependent   on the resistive index   of the transverse facial artery of the parotid gland, were   recorded prior to as well as subsequent to lemon juice stimulation. Parotid    parenchyma echostructure improved in 50% of their   rituximab-treated patients in contrast to 7% of the    placebo-treated patients (P = 0.03). Submandibular     gland echostructure also improved in a larger percentage of rituximab-treated patients, although not statistically   significantly. The size of the glands along with the   resistive index was unaltered. For diagnostic reasons, recent studies imply  that simplified strategy for SGUS evaluation of    the major salivary glands might  be enough.

1.1A   Sjogren’s s syndrome (SS)and weakness of limbs

 Sjogren’s s syndrome (SS) has been detailed in the form of an inflammatory disease of salivary in addition to lacrimal glands having the properties of the canonical sicca symptoms presenting with dry mouth in addition to eyes along with lymphocytic infiltration   of glandular tissue [22]. Extra glandular presentations are frequent as well as inclusive of inflammation of joints, skin, Kidney, heart, lung as well as Intestines [23]. Inflammation of the nervous system display another complication   of SS. Peripheral nervous implication mainly manifests in the form of sensory neuropathy in addition to a broad range of sensory modes as well as organization designs [24]. Motor dysfunction secondary to neuropathy has not been encountered till now  in patients with SS[24,25]. Nevertheless, this kind of robust complication of SS with fulminant generation of weakness of limbs however good reactions to immunosuppressive treatment was detailed in various case reports [26,27]. In view of the prevalence of peripheral neuropathy correlated with SS escalates with age [28]. Miscalculation of paralysis in the  form of a  neurological complication of SS  is of  extensive risk. Patients whose   manifestation is in the form of weakness of limbs as the chief complaint of polyneuropathy are basically given treatment in a neurological unit where SS in the form of an etiologic cause might not be evaluated routinely. In view of diagnosis of SS is    in general made in immunological departments, Rheumatologists have greater familiarity with this autoimmune disease in contrast to neurologists.

Seeliger et al. for definition of this   condition in detail, evaluated the clinical features of SS patients with neuropathy in addition to motor impairment for promoting diagnostic strategies as well as treatment suitability.  They evaluated 184 patients with neuropathy correlated with weakness of limbs who went through all diagnosis procedures   inclusive of all investigations for SS.44 patients with Sjogren’s s syndrome (American College of

Rheumatology/European League Against Rheumatism(ACR-EULAR) classification criteria for primary Sjogren’s syndrome are the end result of an international collaboration and have been derived using awell-established and confirmed methodology) in addition to robust neuropathy were isolated. As per their outcomes SS was observed at a median age of 63 yrs as well as gender organization illustrated  a ratio that was balanced with a female : male ratio of1:1.AntiSSA(Ro) antibodies were determined in   48% whereas seronegative patients had a diagnosis of SS made dependent on sialadenitis  on minor salivary glands biopsy with a focal score of≥ 1. Maximum number of patients(93%) got a diagnosis of SS made  subsequent to appearance of neurological symptoms. There was symmetrical involvement of limbs in 84% patients(57% tetraparesiss,27%paraparesis).No influence on  sensory function was found in11% of patients pointing that Sjogren’s syndrome correlated neuropathy possess the  capacity of  presenting in the  form of a pure motor syndrome. Electrophysiological determination did not display pathognomic observations(23

2. Rheumatoid arthritis (RA)

Rheumatoid arthritis (RA) mirrors an inflammatory condition possessing the properties of joint   deformation, synovitis, as well as erosive arthritis [1]. In RA, activated monocytes in addition to lymphocytes infiltrate the joints, skin, eyes, lung, along with blood vessels, inclusive of the nervous system as well [30]. Compressive myelopathy is the most frequent CNS    presentation whereas leptomeningitis, encephalitis, as well as    CNS vasculitis can further   take placealthough such brain implication in RA is rare [31]. Less than half of   patients with CNS disease have active synovitis and 34% of patients had no   history of RA prior to diagnosis [32]. The most frequent brain MRI observation is   nodular patchy or lepto-meningeal thickening as well as enhancement, and biopsy is the gold standard for diagnosis [1-33]. Given that CNS disease in RA is germane occasionally, for therapy effectiveness is restricted to case series in addition to expert opinion [5-34]. Acute compressive myelopathy   is maximumfrequently treated with surgical intervention along with IV steroids [5]. The advocated acute therapy for CNS vasculitis is high-dose IV steroids in addition to cyclophosphamide [5-35]. For RA- correlated leptomeningitis, steroids are the maximum frequent treatment   to start with, but roughly 50% of patients will not   respond to steroids alone [5-37]. Case studies validate   the use of either     cyclophosphamide or rituximab [36]. Anti-TNF agents should not be utilized as they may be inefficacious and escalate CNS disease activity [33]. Conclusive   outcomes are absent with regards to the effectiveness of methotrexate for implication of CNS of RA [1]. According to thought of sustenance therapy, it is significant to   notice that the recurrence of RA meningitis occurs occasionally [36]. In addition to disease manipulating therapy, there is confirmation that the transitory neurological deficiencies inRA meningoencephalitis should be treated with antiepileptic drugs (AEDs). Even episodes that are not clearly electroclinical seizures seem to respond toAED’s [33-37].

3.Case Report

A47 year old lady was admitted  with in ICU of GBP hospital with history of  8yrs of  joints pains and escalated blood  urea, fever x2days 1month back, sudden onset of rt hemiparesis subsequent   to high grade fever-subsided with  medicines ,2 days later developed sudden altered sensorium in the  form of diminished   responsiveness ,faecal as well asurine incontinence, altered sensorium on 8/9/22with the diagnosis of old case of Rheumatoid  Arthritis(RA) / Sjogren’s s syndrome(SS) / type2Diabetes  mellitus(T2DM) / recurrent Ischaemic Stroke/quadriparesis/ pulmonary Tuberculosis/herpes zoster/Bed sores GrII/SIADH. Prior to that in october21she had Pyoderma gangrenosum generated  on both ankles for which  high steroids given=>hyperglcaemia She was medicated as per that.Onaug2022 she fell semi-conscious at night for which she was shifted to Holy Family emergency .Was diagnosed as brain Stroke as well as pulmonary tuberculosis in left lung subsequent to CT Scan, MRI as well as   Contrast MRI- following21 days ICUstty she was shifted  to GBP hospital with multiple bed sores, feeding tube along with urinary catheter where she stayed in ICU x10 days followed by transferred to ward. Even here subsequent to Doppler Echo, brain MRI, concluded vasculitis and decided to give rituximab Previous history of 8yrs back was -  initiation of methotrexate 20mg/day , prednisolone-5mg/day, hydroxy chloroquine one -400mg5mg/day-initially 200mg followed by  bd  since 2013 was done -,where prednisolone-5mg/day, and hydroxychloroquine one were omitted in view of patient’s consumption of nonsteroidal anti inflammatory drugs (NSAIDS) off and on for pain, had history of  generation of generalized weakness, body aches and pain, easy fatiguability, which was insidious  in onset as well as  gradually progressive -6mths prior to that she had developed  robust an aemia. hence methotrexate was omitted and 3 units blood transfusion was done. -7mths back she formed skin lesions in both ankles    which was diagnosed as pyoderma gangrenosum for which heavy dosage of corticosteroids were, given this was followed by drug induced hyper glycaemia one mth later hence steroids were stopped Now she had presented with quadriparesis with altered sensorium On General Physical Examination (GPE)- spontaneous eye opening, poorly responding to commands, reduced verbal output

BP-140/90mmHg, p-96/min, RR-14/min 

P+I-, C-, Cl-LN-PE-

CVS-S1, S2were+nt, Chest occasional crepts

                   Rt                              Lt

Tone- UL-Rt-increased--   Lt-decreased

           LL Rt-increased    Lt-decreased

Power - UL- 1/5                    0/5

            LL   0/5                    0/5

PlantarsRt- increased Lt-increased     

    NR-            KS-

             4/9/22             14/9/22

  CBC-Hb-9.3                     9.6

          TLC-14100            4900

         DLC-94/5              77/16

       Plt-6.6l                      1.6l

OT/PT-U/ml     51/70           27/55

SB        -0.5 mg/ml        0.4 mg/ml       

Alp-343 U/ml                      289 U/ml

TP/Alb-5.4/2.4           5.1/2.5

INR/APTT- 1.0

Cr/urea- 0.4/42 mg/ml    0.3/21 mg/ml       

Na/K-127/4.2mEq/L            128/3.5 mEq/L             

AntiCCP-106.21(increased)

APCAProfile- -ve

AntiSSA-++

RO-+++

Rest ANA profile- -ve

CRP-+VE

ESR-65

25/8

Bal-GeneXpert

MTB -detected

Rif-not detected

24/8

cerebrospinal fluid (CSF) -Cells-1

                                         Prot-45

                                       Sugar-69

 GeneXpert- MTB -not detected

                    Fungal c/s—ve

                   OCB- --ve

SPEP-nor,  Tridot-  -ve ferrinin-1252

c/s-enterobacter aerogenosa-amika,lfx,meso,mox,diptaz

HbA1c-8

Carotid doppler 

Her ANI profile was as follow

1st MRI REPORT-21/8/22

 

Repeat MRI-ON 28/9/22

Hence both MRI revealed narrowing of middle cerebral artery – with involvement of RtM1- M2segment of RtMCA, M1 segment of left MCA as well as bilateral vertebral arteries 

NECT- 28-7-22revealed numerous acute infarcts in posterior limb of right internal capsule, bilateral basal ganglia, right ventricular area explaining quadriparesis

 Initially for DM glypen 80mg od-from aug 20th was on & insulin 10unitbd- dose was altered to 10-8-8 wi 10 lentus at night-which was omitted on   discharge when was shifted to metformin 500mg bd

Her altered sensorium was secondary to hyponatraemia, which was corrected with intravenous (iv) saline

It was planned to start intravenous (iv)rituximab 1000mg intravenous infusion on day1 and day15

Nevertheless, she developed fever and on evaluation it was herpes zoster as well as   pulmonary tuberculosis confirmed by GeneXpert for which ATT was initiated with acyclovir, however she had abnormalities of LFT hence dose altered to Inj streptomycin 750mg ðionamide. In the mean time she developed SIADH for which tolvaptan 15mg of oral powder was given. Since fever was troubling off & on she was stable she was discharged on following treatment on 22/9/22with the final diagnosis of Rheumatoid Arthritis (RA) / Sjogren’s s syndrome (SS) / type2Diabetes   mellitus(T2DM) / recurrent Ischaemic Stroke/quadriparesis/ pulmonary tuberculosis/herpes zoster/Bed sores GrII/SIADH, asked to report weekly on the following medicines and start rituximab once temperature settled.

Telmasartan 40 mgod, amlong5mg od, Inj lentus insulin 10 U s/c, clexane 0.4 U s/c, Levofloxacin 750mg od, Inj streptomycin 750mg, ethionamide-250mg od, methyl lobal -1500mgod, tolvaptan-15mg od, ecosprin 75mg od,HCQ-200mg od.1st dose of iv rituximab 1000mg iv infusion administration was given finally on 17-11-22 on subsiding of fever in addition to herpes zoster. It was planned to be given at 10 drops/min over24hrs however as she developed sweating and restlessness Subsequently although 2nd dose was planned on day15it has not been given till now in view of considerable anorexia and her CD 19 has been 0 for over 3 mths. At present her right side function has returned but left side is still weak &has started feeding without a pipe now

4. Discussion

Here we present a case of Rheumatoid Arthritis, Sjogren’s s syndrome which was not diagnosed till the development of recurrent Ischaemic Stroke as well as quadriparesis that too only in GBPH as had been suggested by Seeligeretal.[29]. Despite, a known   diabetic that had got controlled with  medication, she developed  pyoderma gangrenosum for which heavy dosage of corticosteroids , subsequent  to which she generated    drug induced hyperglycaemia one mth later hence steroids were stopped, with her HbA1c rising to 8 .Ours is a complex case who had manifestations of  numerous autoimmune diseases like RA, SS, DM, pyoderma gangrenosum  which resulted   in robust joint   pains requiring HCQ, methotrexate ,although we feel she should have  received high   dose   intravenous methylprednisolone, 1000 mg daily for 3–5 days followed by bya course of oral prednisone, 0.5–1 mg/kg/day tapered over weeks to months, rather than toxic methotrexate  which led to development of robust anaemia. Gradually over time her condition became inimical with her generating numerous infections like TB, herpes zoster in addition to recurrent Ischaemic Strokes however not till 2022 despite   Rheumatologists treating her for8 yrs  Sjogren’s s syndrome was not suspected although they had a debate on ruling out APLA syndrome or RF with Sjogren’s s syndrome(SS)  in 2020 in view of  repeated leptomening it is with blood in CSF & so   rituximab infusion was considered in 2020 however postponed   in view of expenditure  involved. It is our feeling that as recommended by 2020 EULAR SS guideline cyclophosphamide which is the first line drug advocated instead of rituximab that is 3rd line drug subsequent to cyclophosphamide, Plasmapheresis (PLEX) combined with steroids followed by rituximab 1000mg as a third line therapy was needed. She developed herpes zoster in addition to pulmonary tuberculosis following rituximab, besides CSF culture grew enterobacter aerogenosa-sensitive to amika, lfx, meso, mox, diptaz, for which she is getting Levofloxacin 750mg od till now & due toliver toxicity canonical ATT was shifted to streptomycin 750mg ,ethionamide-250mg now and though her right limb function has recovered ,she still has lt weakness with CD 19 count not escalating(still o) and she needed tube feeding till now .Hence one has to keep in mind once there is aberrant  behave our of RF, one should keep in mind correlated SS. Furthermore, in view of syndrome of inappropriate antidiuretic hormone secretion (SIADH) production, tolvaptan-15mg od was initiated &further continued with caution not to be given unsupervised. Considering that use of tolvaptan is debatable might be it could have been avoided. Our patient still cannot get up on her own and move around with the expenditure mammoth yet no clear solution in sight . 

References

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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