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On Sep 2018




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On Sep 2018




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"Journal of Clinical and Diagnostic Research is at present a well-known Indian originated scientific journal which started with a humble beginning. I have been associated with this journal since many years. I appreciate the Editor, Dr. Hemant Jain, for his constant effort in bringing up this journal to the present status right from the scratch. The journal is multidisciplinary. It encourages in publishing the scientific articles from postgraduates and also the beginners who start their career. At the same time the journal also caters for the high quality articles from specialty and super-specialty researchers. Hence it provides a platform for the scientist and researchers to publish. The other aspect of it is, the readers get the information regarding the most recent developments in science which can be used for teaching, research, treating patients and to some extent take preventive measures against certain diseases. The journal is contributing immensely to the society at national and international level."



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On Aug 2018




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Dr. Arundhathi. S
MBBS, MD (Pathology),
Sanjay Gandhi institute of trauma and orthopedics,
Bengaluru.
On Aug 2018




Dr. Mamta Gupta,
"It gives me great pleasure to be associated with JCDR, since last 2-3 years. Since then I have authored, co-authored and reviewed about 25 articles in JCDR. I thank JCDR for giving me an opportunity to improve my own skills as an author and a reviewer.
It 's a multispecialty journal, publishing high quality articles. It gives a platform to the authors to publish their research work which can be available for everyone across the globe to read. The best thing about JCDR is that the full articles of all medical specialties are available as pdf/html for reading free of cost or without institutional subscription, which is not there for other journals. For those who have problem in writing manuscript or do statistical work, JCDR comes for their rescue.
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Reviewing articles is no less a pain staking process and requires in depth perception, knowledge about the topic for review. It requires time and concentration, yet I enjoy doing it. The JCDR website especially for the reviewers is quite user friendly. My suggestions for improving the journal is, more strict review process, so that only high quality articles are published. I find a a good number of articles in Obst. Gynae, hence, a new journal for this specialty titled JCDR-OG can be started. May be a bimonthly or quarterly publication to begin with. Only selected articles should find a place in it.
An yearly reward for the best article authored can also incentivize the authors. Though the process of finding the best article will be not be very easy. I do not know how reviewing process can be improved. If an article is being reviewed by two reviewers, then opinion of one can be communicated to the other or the final opinion of the editor can be communicated to the reviewer if requested for. This will help one’s reviewing skills.
My best wishes to Dr. Hemant Jain and all the editorial staff of JCDR for their untiring efforts to bring out this journal. I strongly recommend medical fraternity to publish their valuable research work in this esteemed journal, JCDR".



Dr. Mamta Gupta
Consultant
(Ex HOD Obs &Gynae, Hindu Rao Hospital and associated NDMC Medical College, Delhi)
Aug 2018




Dr. Rajendra Kumar Ghritlaharey

"I wish to thank Dr. Hemant Jain, Editor-in-Chief Journal of Clinical and Diagnostic Research (JCDR), for asking me to write up few words.
Writing is the representation of language in a textual medium i e; into the words and sentences on paper. Quality medical manuscript writing in particular, demands not only a high-quality research, but also requires accurate and concise communication of findings and conclusions, with adherence to particular journal guidelines. In medical field whether working in teaching, private, or in corporate institution, everyone wants to excel in his / her own field and get recognised by making manuscripts publication.


Authors are the souls of any journal, and deserve much respect. To publish a journal manuscripts are needed from authors. Authors have a great responsibility for producing facts of their work in terms of number and results truthfully and an individual honesty is expected from authors in this regards. Both ways its true "No authors-No manuscripts-No journals" and "No journals–No manuscripts–No authors". Reviewing a manuscript is also a very responsible and important task of any peer-reviewed journal and to be taken seriously. It needs knowledge on the subject, sincerity, honesty and determination. Although the process of reviewing a manuscript is a time consuming task butit is expected to give one's best remarks within the time frame of the journal.
Salient features of the JCDR: It is a biomedical, multidisciplinary (including all medical and dental specialities), e-journal, with wide scope and extensive author support. At the same time, a free text of manuscript is available in HTML and PDF format. There is fast growing authorship and readership with JCDR as this can be judged by the number of articles published in it i e; in Feb 2007 of its first issue, it contained 5 articles only, and now in its recent volume published in April 2011, it contained 67 manuscripts. This e-journal is fulfilling the commitments and objectives sincerely, (as stated by Editor-in-chief in his preface to first edition) i e; to encourage physicians through the internet, especially from the developing countries who witness a spectrum of disease and acquire a wealth of knowledge to publish their experiences to benefit the medical community in patients care. I also feel that many of us have work of substance, newer ideas, adequate clinical materials but poor in medical writing and hesitation to submit the work and need help. JCDR provides authors help in this regards.
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In the era of fast growing newer technologies, and in computer and internet friendly environment the manuscripts preparation, submission, review, revision, etc and all can be done and checked with a click from all corer of the world, at any time. Of course there is always a scope for improvement in every field and none is perfect. To progress, one needs to identify the areas of one's weakness and to strengthen them.
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Every one of us: authors, reviewers, editors, and publisher are responsible for enhancing the stature of the journal. I wish for a great success for JCDR."



Thanking you
With sincere regards
Dr. Rajendra Kumar Ghritlaharey, M.S., M. Ch., FAIS
Associate Professor,
Department of Paediatric Surgery, Gandhi Medical College & Associated
Kamla Nehru & Hamidia Hospitals Bhopal, Madhya Pradesh 462 001 (India)
E-mail: drrajendrak1@rediffmail.com
On May 11,2011




Dr. Shankar P.R.

"On looking back through my Gmail archives after being requested by the journal to write a short editorial about my experiences of publishing with the Journal of Clinical and Diagnostic Research (JCDR), I came across an e-mail from Dr. Hemant Jain, Editor, in March 2007, which introduced the new electronic journal. The main features of the journal which were outlined in the e-mail were extensive author support, cash rewards, the peer review process, and other salient features of the journal.
Over a span of over four years, we (I and my colleagues) have published around 25 articles in the journal. In this editorial, I plan to briefly discuss my experiences of publishing with JCDR and the strengths of the journal and to finally address the areas for improvement.
My experiences of publishing with JCDR: Overall, my experiences of publishing withJCDR have been positive. The best point about the journal is that it responds to queries from the author. This may seem to be simple and not too much to ask for, but unfortunately, many journals in the subcontinent and from many developing countries do not respond or they respond with a long delay to the queries from the authors 1. The reasons could be many, including lack of optimal secretarial and other support. Another problem with many journals is the slowness of the review process. Editorial processing and peer review can take anywhere between a year to two years with some journals. Also, some journals do not keep the contributors informed about the progress of the review process. Due to the long review process, the articles can lose their relevance and topicality. A major benefit with JCDR is the timeliness and promptness of its response. In Dr Jain's e-mail which was sent to me in 2007, before the introduction of the Pre-publishing system, he had stated that he had received my submission and that he would get back to me within seven days and he did!
Most of the manuscripts are published within 3 to 4 months of their submission if they are found to be suitable after the review process. JCDR is published bimonthly and the accepted articles were usually published in the next issue. Recently, due to the increased volume of the submissions, the review process has become slower and it ?? Section can take from 4 to 6 months for the articles to be reviewed. The journal has an extensive author support system and it has recently introduced a paid expedited review process. The journal also mentions the average time for processing the manuscript under different submission systems - regular submission and expedited review.
Strengths of the journal: The journal has an online first facility in which the accepted manuscripts may be published on the website before being included in a regular issue of the journal. This cuts down the time between their acceptance and the publication. The journal is indexed in many databases, though not in PubMed. The editorial board should now take steps to index the journal in PubMed. The journal has a system of notifying readers through e-mail when a new issue is released. Also, the articles are available in both the HTML and the PDF formats. I especially like the new and colorful page format of the journal. Also, the access statistics of the articles are available. The prepublication and the manuscript tracking system are also helpful for the authors.
Areas for improvement: In certain cases, I felt that the peer review process of the manuscripts was not up to international standards and that it should be strengthened. Also, the number of manuscripts in an issue is high and it may be difficult for readers to go through all of them. The journal can consider tightening of the peer review process and increasing the quality standards for the acceptance of the manuscripts. I faced occasional problems with the online manuscript submission (Pre-publishing) system, which have to be addressed.
Overall, the publishing process with JCDR has been smooth, quick and relatively hassle free and I can recommend other authors to consider the journal as an outlet for their work."



Dr. P. Ravi Shankar
KIST Medical College, P.O. Box 14142, Kathmandu, Nepal.
E-mail: ravi.dr.shankar@gmail.com
On April 2011
Anuradha

Dear team JCDR, I would like to thank you for the very professional and polite service provided by everyone at JCDR. While i have been in the field of writing and editing for sometime, this has been my first attempt in publishing a scientific paper.Thank you for hand-holding me through the process.


Dr. Anuradha
E-mail: anuradha2nittur@gmail.com
On Jan 2020

Important Notice

Case Series
Year : 2023 | Month : January | Volume : 17 | Issue : 1 | Page : SR01 - SR03 Full Version

Effects of Perinatally Acquired Cytomegalovirus Infection on Growth Hormone Axis


Published: January 1, 2023 | DOI: https://doi.org/10.7860/JCDR/2023/58814.17200
Sayan Chatterjee, Shreya Ray Chaudhuri, Subhasish Bhattacharya

1. Assistant Professor, Department of Paediatrics, Chittaranjan Seva Sadan, Kolkata, West Bengal, India. 2. Postgraduate Trainee, Department of Paediatrics, Chittaranjan Seva Sadan, Kolkata, West Bengal, India. 3. Professor, Department of Paediatrics, Chittaranjan Seva Sadan, Kolkata, West Bengal, India.

Correspondence Address :
Dr. Sayan Chatterjee,
97/B, Block-D, Bangur Avenue, Kolkata, West Bengal, India.
E-mail: sayanchat_82@yahoo.co.in

Abstract

Cytomegalovirus (CMV) is one of the most common causes of perinatally acquired infection worldwide. It affects almost every organ system with varied type of clinical manifestation. In this case series, effect of perinatally acquired cytomegalovirus infection was studied on relatively unexplored area i.e, on growth hormone axis. Effect of standard antiviral treatment was also studied in these children. Five children were diagnosed to have perinatally acquired cytomegalovirus infection and it was found that all of these children were suffering from growth hormone deficiency (as evidenced by low insulin-like growth factor 1 and insulin-like growth factor binding protein 3 level as well). Some of the children were also found to have other endocrine manifestations like hypothyroidism and hypoglycaemia. They were treated with intravenous Ganciclovir followed by oral Valganciclovir and most of them responded well.

Keywords

Endocrine manifestation, Hepatosplenomegaly, Insulin growth factor

Cytomegalovirus (CMV) is one of the most important agents causing perinatal infection. Most commonly, symptomatic CMV infection is acquired congenitally through transplacental transmission or perinatally during birth or through breast milk (1). CMV infection can also occur later in life, but mostly they remain asymptomatic (in 90% cases) in normal individual (2). The manifestation of congenital CMV infection is manifold, and it affects almost every system of our body. The most common features in a case of congenital CMV are hepatosplenomegaly, direct hyperbilirubinaemia, petechial haemorrhage, microcephaly, Intrauterine Growth Restriction (IUGR) (3). This case series highlighted a relatively unexplored area of possible association of the disease and suppression of the growth hormone axis, as manifested by reduced serum Insulin like Growth Factor 1 (IGF 1) and Insulin-like Growth Factor Binding Protein 3 (IGFBP 3) (4), and by little to no response of growth hormone level to various challenge tests. All of these five cases presented within the first 4 months of their chronological age, with different clinical pictures and various endocrine manifestations. But one thing was common in them, that is, suppression of the growth hormone axis.

Case Report

Case 1

A 3-months-old (chronological age) male child was admitted in the hospital with complaints of not gaining weight along with huge hepatosplenomegaly. Previously the child was admitted in Neonatal Intensive Care Unit (NICU) because of prematurity (33 weeks), low birth weight (1.8 kg), perinatal asphyxia {Hypoxic-Ischaemic Encephalopathy (HIE) stage 2},, sepsis, shock, and had required ventilator support (Table/Fig 1). Magnetic Resonance Imaging (MRI) brain had been done which revealed bilateral haemorrhagic infarct in temporoparietal region. During discharge from NICU at 17th day of life child had a weight of 2 kg and length of 45 cm. At that time child did not have hepatosplenomegaly.

On admission, the child had a weight of 2.7 kg and a length of 56 cm, conjugated hyperbilirubinaemia, anaemia, and had recurrent episodes of hypoglycaemia in absence of sepsis. Blood sample for hormonal assay were collected during two different occasions of hypoglycaemia revealed low insulin (0.16 μU/mL), borderline cortisol (5.1 μg/dL), and low growth hormone (0.7 ng/mL) levels. Serum IGF1 and IGFBP3 values were also significantly low (Table/Fig 1). Child also tested positive for CMV Immunoglobulin M (IgM), and he had a urinary CMV Deoxyribonucleic Acid (DNA) Polymerase Chain Reaction (PCR) of around 18000 copies/mL. The mother was diagnosed with hypothyroidism during 1st trimester, and the child was also diagnosed to have secondary hypothyroidism for which he was started on levothyroxin supplements. MRI was repeated, which showed sequelae of congenital infection, but there was no definite involvement of sella or parasellar structures. Retinal examination was normal.

The patient was started on hormone replacement therapy with hydrocortisone and thyroxin. The child was also treated with Inj. Ganciclovir for 4 weeks followed by oral Valganciclovir for next 4 months. Subsequently there was a gradual improvement of the general condition of the patient along with complete resolution of hypoglycaemia. His growth parameters were followed at 6th, 9th and 12th month (chronological age) and his weight and height were 4.2 kg and 61 cm, 5.8 kg and 67 cm, 7.1 kg and 71 cm, respectively.

Case 2

A 3-month-old male child presented to emergency with three episodes of generalised tonic clonic seizure within last 24 hours. The child was delivered vaginally at term with a birth weight of 2.8 kg and had uneventful neonatal period (Table/Fig 1). Management was done as per protocol and he was found to have low serum calcium level, which was subsequently corrected by calcium and vitamin D3 supplementation (child also had low vitamin D3, and borderline elevated alkaline phosphatase). The child had a weight of 5.2 kg and length of 60 cm at the time of admission. There was hepatosplenomegaly, and both CMV IgM and Urinary CMV DNA PCR (7.24 lakh copies/mL) were positive. Retinal examination was normal. Accordingly, the child was started on Inj. Ganciclovir for three weeks, later to be replaced by oral Valganciclovir for next three months. Serum IGF1 and IGF-BP3 were also low (Table/Fig 1), and growth hormone level after clonidine challenge test was 0.9 ng/mL. The child had a weight of 9.2 kg at one year of age and sizes of liver and spleen were reduced almost to normal.

Case 3

A 4-month old male child presented with severe anaemia, jaundice, and hepatosplenomegaly. The child was delivered vaginally at term with a birth weight of 2.65 kg and neonatal period was uneventful (Table/Fig 1). Investigations revealed autoimmune haemolytic anaemia (high reticulocyte count and positive direct coombs test). He also had three episodes of convulsion during hospital stay. His nutritional status was normal at the time of admission (weight was 4.9 kg and length was 61 cm). The mother was diagnosed with hypothyroidism during first trimester, and the child’s thyroid profile revealed central hypothyroidism, with low levels of FT4 and TSH (0.21 μIU/mL). The child also tested positive for CMV IgM and had a high urinary CMV DNA load (15 lakh copies). Clonidine stimulation test was done to assess growth hormone levels, which were found to be consistently low. Serum IGF1 and IGFBP3 were also low (Table/Fig 1). Retinal examination was normal.

The child was put on Ganciclovir initially for three weeks followed by oral Valganciclovir for next four months. His liver function returned to normal by six months of age. Child had maintained normal growth parameters throughout the period (weight was 8.9 kg and length was 72 cm at one year of age). Hepatosplenomagaly also regressed considerably at one year of age. Also, during this one year of follow-up, he maintained a normal haemoglobin level.

Case 4

A 2-month-old male child presented with fever for four days along with watering of eyes. Examination revealed significant pallor and huge hepatosplenomegaly. Mother had a history of fever with rash in first trimester. The child was delivered at term by caesarean section with a birth weight of 3.1 kg (Table/Fig 1). At the time of admission, the child had a weight of 4.8 kg and a length of 58 cm. Investigations revealed positive CMV IgM (Table/Fig 1), and urinary CMV DNA PCR showed 22000 copies. Serum IGF1 (<15 ng/mL) and IGF-BP3 (<0.5 μg/mL) were also low (Table/Fig 1). Clonidine stimulation test also showed low level of growth hormone. Retinal examination was normal. The child was treated with Inj. Ganciclovir for four weeks in view of recurrent blood transfusion within a short span. Initially, the child responded well, fever subsided, and the blood transfusion requirement went down, size of the liver and spleen also started to reduce. The child was discharged in stable condition with oral Valganciclovir for the next four months. But after about three months, the child was readmitted with features suggestive of Haemophagocytic Lymphohistiocytosis (HLH) including fever >5 days, splenomegaly, pancytopenia (haemoglobin was 5.4 gm/dL, total leucocyte count 1800/cumm with 10% neutrophil, platelet 60000), high ferritin, high triglyceride, low fibrinogen. Genomic sequencing was done and it showed the familial form of HLH. The child was started on steroid and other drugs as per protocol, but he succumbed at the age of 9 months.

Case 5

A 4-month-old male child presented with complain of not gaining weight and length. There was history of gross weight loss and intermittent low-grade fever over last two months. The child was delivered at home and as per parents, he was born with average weight. There was no documentation about his nutritional status in his 1st 4 months. On examination, all the anthropometric indices were well below 3Z Score as per World Health Organisation (WHO) growth chart, and there was moderate hepatosplenomegaly. The child also experienced a few episodes of hypoglycaemia during the hospital stay. All episodes were asymptomatic and managed by allowing breast feeding. Investigations revealed presence of anaemia, and blood culture showed growth of Staphylococcus aureus.

He was started on F-75 starter diet along with appropriate antibiotics (vancomycin and amikacin for 14 days) and supportive treatment (vitamin A, D, K, B-complex including folic acid, potassium, magnesium sulphate as per management protocol of severe acute malnutrition). Chest X-ray showed few patchy infiltrates, and gastric lavage revealed very high load of Mycobacterium tuberculosis, for which the baby was started on antitubercular drug. The mother was also tested positive for tuberculosis. CMV IgM was positive and subsequently, urinary PCR showed around 20,000 CMV DNA copies/mL. Serum IGF1 and IGF-BP3 were found to be low (Table/Fig 1). Blood sample for growth hormone obtained during hypoglycaemic episodes also found to be low. Retinal examination was normal. The child was also started on Ganciclovir for three weeks and then shifted to oral Valganciclovir. During the hospital stay, he started to gain weight and gradually become free of symptoms. The child was discharged in stable condition, but unfortunately, he was lost to follow-up. All the cases have been briefed together in (Table/Fig 1).

Discussion

In the present case series, it was seen that CMV infection manifested as a myriad of clinical signs and symptoms. The patients were all male children, aged 2-4 months, and only one among the five patients hada history of prior hospital admission, before this diagnosis of CMV infection was made. Rest of the four patients were well from birth till the onset of the present disease. All the children had hepatosplenomegaly and anaemia, while others showed isolated findings like jaundice (cholestatic/haemolytic), microcephaly, classical MRI findings.

However, all these patients were also found to have a depressed growth hormone axis, as evidenced by a low level of serum IGF1 and IGF-BP3, which are independent markers of the level of growth hormone. Growth hormone challenge tests by induced hypoglycaemia (done in two patients) or by clonidine suppression (done in three patients), which revealed persistently low growth hormone levels in all. Some other endocrine manifestations werehypothyroidism in two children, recurrent hypoglycaemia not attributable to other causes in two children, altered vitamin D3-calcium metabolism in one child, and low serum cortisol level in one child.

Cytomegalovirus is known to cause intrauterine growth restriction in neonates (5), hence it can be hypothesised that similar action can also be exerted in the extrauterine life also. However, probably there were only two documentations of panhypopituitarism associated with CMV infection in children of similar age group (6),(7) and some in immunocompromised adults (8). Chan U et al., described a 2-month-old child with septo-optic dysplasia and acquired CMV infection presented with cholestasis, hepatosplenomegaly, panhypopituitarism and growth retardation. After treatment with Ganciclovir and hormone replacement therapy, there is improvement in cholestasis and growth rate (6). Hara K et al., described a term infant with congenital CMV infection presented with recurrent hypoglycaemia and panhypopituitarism. This child also responded well with Ganciclovir and hormone replacement therapy (7).

As for the other endocrine manifestations, there are sporadic reports of each being associated with congenital CMV (9),(10),(11), but the data is inadequate to draw any conclusion. Tuli G et al., described two newborns with congenital hypothyroidism with congenital CMV infection (9). Jayamanne MDCJP et al., described a newborn with congenital CMV infection with recurrent hypoglycaemic episodes (10). Dinleyici EC et al., described two infants with CMV-associated adrenal insufficiency in childhood. Both of them responded well to appropriate adrenal substitution therapy and Ganciclovir (11).

Question remains as to whether these cases were congenital CMV infection or acquired. None of the children except one had any complications in the neonatal period, and the earliest age of presentation (except in one) was two months. CMV IgM may remain elevated for several months, thereby rendering the exact localisation of the time of infection difficult (12). However, high values of CMV DNA copies isolated from urine via PCR is much stronger evidence of current infection, and may point more towards an acquired infection rather than a congenital one (13),(14). However, another contradictory factor is that the features like hepatosplenomegaly, anaemia is more common in congenital infections, as are the chances of long-term sequelae.

Conclusion

To conclude, it can be stated that all the five infants with CMV infection discussed, showed growth hormone suppression, of which three had visible growth restriction. Once treatment with Ganciclovir was started, most patients responded well, while one required hormone replacement therapy. Whether this hormonal manifestation is caused by the CMV itself, or there are other confounding factors can only be concluded by further research into the pathophysiology of the disease. So, whenever any symptomatic CMV infection was found, possible suppression of growth hormone axis should be kept in mind and appropriate decision to be taken regarding treatment.

References

1.
Pass RF, Anderson B. Mother-to-child transmission of cytomegalovirus and prevention of congenital infection. J Pediatric Infect Dis Soc. 2014;3(Suppl 1):S2- S6. Doi: 10.1093/jpids/piu069. PMID: 25232473; PMCID: PMC4164178. [crossref] [PubMed]
2.
Ronchi A, Zeray F, Lee LE, Owen KE, Shoup AG, Garcia F, et al. Evaluation of clinically asymptomatic high-risk infants with congenital cytomegalovirus infection. J Perinatol. 2020;40(1):89-96. https://doi.org/10.1038/s41372-019-0501-z. [crossref] [PubMed]
3.
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DOI and Others

DOI: 10.7860/JCDR/2023/58814.17200

Date of Submission: Jul 05, 2022
Date of Peer Review: Aug 30, 2022
Date of Acceptance: Sep 23, 2022
Date of Publishing: Jan 01, 2023

AUTHOR DECLARATION:
• Financial or Other Competing Interests: None
• Was informed consent obtained from the subjects involved in the study? Yes
• For any images presented appropriate consent has been obtained from the subjects. Yes

PLAGIARISM CHECKING METHODS:
• Plagiarism X-checker: Jul 06, 2022
• Manual Googling: Sep 16, 2022
• iThenticate Software: Sep 22, 2022 (5%)

ETYMOLOGY: Author Origin

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