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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.
Timely publication of journal: Publication of manuscripts and bringing out the issue in time is one of the positive aspects of JCDR and is possible with strong support team in terms of peer reviewers, proof reading, language check, computer operators, etc. This is one of the great reasons for authors to submit their work with JCDR. Another best part of JCDR is "Online first Publications" facilities available for the authors. This facility not only provides the prompt publications of the manuscripts but at the same time also early availability of the manuscripts for the readers.
Indexation and online availability: Indexation transforms the journal in some sense from its local ownership to the worldwide professional community and to the public.JCDR is indexed with Embase & EMbiology, Google Scholar, Index Copernicus, Chemical Abstracts Service, Journal seek Database, Indian Science Abstracts, to name few of them. Manuscriptspublished in JCDR are available on major search engines ie; google, yahoo, msn.
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.
It is well said that "happy beginning is half done" and it fits perfectly with JCDR. It has grown considerably and I feel it has already grown up from its infancy to adolescence, achieving the status of standard online e-journal form Indian continent since its inception in Feb 2007. This had been made possible due to the efforts and the hard work put in it. The way the JCDR is improving with every new volume, with good quality original manuscripts, makes it a quality journal for readers. I must thank and congratulate Dr Hemant Jain, Editor-in-Chief JCDR and his team for their sincere efforts, dedication, and determination for making JCDR a fast growing journal.
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
Case Series
Full Version
Improvement in Outcomes with a New Bedaquiline-based Regimen in Postoperative Cases of Drug-resistant Tuberculosis of the Spine: A Case Series
Correspondence Address :
Dr. Soutrik Kundu,
Junior Resident, Department of Orthopaedics, TNMC and BYL Nair Charitable Hospital, Mumbai-400008, Maharashtra, India.
E-mail: dr.soutrikkundu@gmail.com
The incidence of drug-resistant strains of Tuberculosis (TB) is rising at an alarming rate. With the emergence of newer drug-resistant strains, managing the disease with existing antitubercular agents is becoming increasingly difficult. Few studies exist regarding the treatment of drug-resistant TB of the spine using a Bedaquiline-based regimen. Therefore, the efficacy of shorter regimens with novel drugs such as Bedaquiline and Delamanid in drug-resistant TB of the spine must be analysed. The present case series highlights the outcomes of a newer Bedaquiline-based antitubercular regimen in postoperative cases of drug-resistant TB of the spine. All three cases discussed in this study-54-year-old female, 12-year-old female, and 19-year-old female patients-had a clinical and radiological diagnosis of TB of the spine with significant neurodeficits. They underwent decompression and instrumentation surgery. Postoperatively, all three were diagnosed with drug-resistant TB and were started on a Bedaquiline-based antitubercular regimen. Subsequently, all the patients showed significant improvement in neurodeficits with no radiological evidence of recurrence. Therefore, Bedaquiline might play an important role in the future management of drug-resistant spinal TB.
Antitubercular agents, Bacterial infection, Koch’s spine, Multidrug resistance
Drug-resistant strains of tuberculosis are emerging as a serious health problem in both developed and developing countries. Spinal TB is a paucibacillary infection that is deep-seated, and the demonstration of Acid-fast Bacilli (AFB) with Ziehl-Neelsen (ZN) staining is possible in only 10-30 percent of cases (1). Drug resistance is suspected in cases showing no clinicoradiological improvement or the appearance of new osteoarticular lesions of TB despite being on Antitubercular Treatment (ATT) for a minimum of five months (1). The prevalence of drug resistance in spinal tuberculosis patients is reported to be 28.6%, out of which 4.6% were MDR TB, 6% were pre-extensively Drug-resistant TB (XDR-TB), and 2.7% were XDR-TB; the rest (15.3%) exhibited monodrug resistance (2).
Drug resistance can manifest in various types. Resistance to any of the single first-line anti-TB drugs is known as monodrug resistance, while resistance to more than one first-line anti-TB drug, other than Isoniazid (INH) and Rifampicin (RIF), is known as polydrug resistance. Rifampicin Resistance (RR) is resistance to RIF detected using phenotypic or genotypic methods, with or without resistance to other anti-TB drugs. Multidrug Resistance (MDR) is resistance to both INH and RIF. XDR is considered when resistance is present to both INH and RIF with resistance to atleast 1 of the 3 second-line injectable drugs (capreomycin, kanamycin, and amikacin) and any Fluoroquinolone (FQ). Recently, a newer term has been introduced as pre-XDR, which is resistance to both INH and RIF with resistance to FQ or 1 of the 3 second-line injectable drugs (2).
There is inadequate data in the literature regarding the treatment of XDR-TB spine; therefore, the efficacy of shorter regimens with novel drugs such as Bedaquiline and Delamanid in drug-resistant TB of the spine needs to be analysed (3). The aim of the present study was to assess the outcome of a newer Bedaquiline-based antitubercular regimen in cases of postoperative drug-resistant TB of the spine and to evaluate the effectiveness of this regimen, the improvement of neurological function postsurgery with Bedaquiline, and radiological improvement postsurgery with this regimen using serial radiographs.
Case 1
A 54-year-old female patient presented at the orthopaedic Outpatient Department (OPD) with complaints of upper back pain and weakness in both lower limbs over the past two weeks. The pain had an insidious onset and gradually progressed. She also experienced paraesthesia, difficulty in passing urine, and recent weight loss. The patient had a history of pulmonary tuberculosis six years prior, which was successfully treated with a six-month regimen of antitubercular drugs, leading to a cure. She did not report any history of fever or other medical illnesses.
Upon examination, the patient exhibited 2/5 power in bilateral hip and knee, and 1/5 power in bilateral ankle and toes. There was an 80% loss of sensation below the level of the xiphisternum. Deep tendon reflexes in the bilateral lower limbs were exaggerated, with well-sustained ankle clonus. Spasticity was observed in both lower limbs, and the plantar response showed an extensor reflex. An X-ray revealed the collapse of the D4 vertebra. Magnetic Resonance Imaging (MRI) indicated D4-D5 Koch’s spine with the collapse of the D4 vertebra and an abscess compressing the cord.
Based on these findings, urgent decompression and instrumentation with interbody fusion were performed, and an intraoperative sample was sent for bacterial, fungal, AFB culture and sensitivity, Mycobacteria Growth Indicator Tube (MGIT), GeneXpert TB, and histopathological examination. The patient was started on a four-drug antitubercular regimen based on the clinical and radiological findings mentioned above. The AFB smear report was negative, the MGIT report was positive for Mycobacterium tuberculosis complex, and GeneXpert showed RIF resistance. Subsequent Line Probe Assay (LPA) showed resistance against both RIF and INH. Full Drug Sensitivity Testing (DST) confirmed resistance to both RIF and INH. Therefore, a Bedaquiline-based regimen was initiated, including Bedaquiline, Levofloxacin, Clofazimine, Pyrazinamide, Ethambutol, and a high dose of INH. Bedaquiline was administered for six months, while Levofloxacin, Clofazimine, Pyrazinamide, Ethambutol, and the high dose of INH were continued for 18 months. The patient is currently under treatment.
Monthly follow-up and routine examinations, including radiographs, Electrocardiography (ECG), and blood parameters, were done. Eight months following the surgery, the patient reported no pain, and X-rays did not show any recurrence of the lesion or abscess. Additionally, weight gain and appetite were restored. The patient exhibited full power (5/5) in bilateral hip and knee, but bilateral ankle, Extensor Hallucis Longus (EHL), and Flexor Hallucis Longus (FHL) had a power of 4/5. Sensation was restored in the bilateral lower limbs, and while deep tendon reflexes were exaggerated, clonus and spasticity were absent. The plantar response was not observed, and bowel and bladder habits remained unaltered. The C-reactive Protein (CRP) and Erythrocyte Sedimentation Rate (ESR) were recorded at 1.2 and 8, respectively.
Case 2
A 12-year-old female patient presented with complaints of back pain and difficulty walking for the past three months. She had a known case of TB spine and had been under a standard antitubercular regimen for the last six months. However, her condition deteriorated, and she became bedridden due to worsened back pain over the last three months.
On examination, she had a power of 3/5 in all muscles of the bilateral lower limb, except the right Extensor Hallucis Longus (EHL), which had a power of 4/5. Bilateral deep tendon reflexes were absent, and plantar reflexes were mute. Sensations in the bilateral lower limbs were intact. Tone and nutrition were normal. There was no bladder or bowel involvement. The X-ray and MRI suggested complete collapse of the D6 vertebral body with marrow oedema at D5 and D7 levels. Abnormal prevertebral and paravertebral collections were seen at D5-7 levels, with a maximum thickness of 1.5 mm. An anterior epidural collection was also noted at this level (Table/Fig 1)a-e.
She underwent decompression and instrumentation with interbody fusion (Table/Fig 2)a,b, and intraoperative specimens were sent for bacterial, fungal, AFB culture and sensitivity, GeneXpert TB, MGIT, and histopathological examination. The AFB smear was negative. The histopathological report suggested chronic inflammatory pathology, possibly TB. On GeneXpert, RIF resistance was detected. Therefore, a Bedaquiline-based regimen was started for six months. Later, LPA suggested resistance to all first and second-line antitubercular agents, and thus XDR-TB was diagnosed. Therefore, Para aminosalicylic Acid (PAS) was added to the previous regimen, replacing levofloxacin. Finally, the DST report showed resistance against all antitubercular agents except Clofazimine and PAS. She had taken Bedaquiline for 6 months, and Clofazimine, Cycloserine, Linezolid, and PAS were given for 12 months. She is currently continuing the above regimen. She was routinely followed-up on a monthly basis for the assessment of neurological recovery and monitoring of blood parameters.
After seven months of surgery, the patient had full neurological recovery. Power in the bilateral lower limb was found to be normal, i.e., 5/5 in the bilateral hip, knee, ankle, and toes. Deep tendon reflexes were found to be normal. Bilateral plantar reflexes showed a flexor response bilaterally. Sensation and tone were also normal bilaterally. The Erythrocyte Sedimentation Rate (ESR) and C-Reactive Protein (CRP) values at the end of five months were 11 and 3.46, respectively, and the patient had gained a significant amount of weight (12 kg).
Case 3
A 19-year-old female patient presented at the orthopaedic OPD with a complaint of low back pain and weakness in both lower limbs for the last 1.5 months. The pain had an insidious onset and was gradually progressive in nature. She had no history of any blunt trauma, falls, or lifting heavy weights. There was no history of tingling, numbness, paraesthesia, or any other joint pain, nor any history of Kochs’ or Koch’s contact, fever, or weight loss.
On examination, power in bilateral hips and knees was 3/5, the right ankle and toes were 2/5, and the left ankle and toes were 0/5. Deep tendon reflexes and the plantar reflex were absent in the bilateral lower limbs. Clonus was absent in both lower limbs. Both lower limbs were flaccid, and there was 20% sensory loss below L2 bilaterally. MRI suggested discitis at the L4-L5 level with destruction of the L4 vertebra and a prevertebral collection (Table/Fig 3)a,b.
She underwent decompression and instrumentation with interbody fusion, and intraoperative specimens (Table/Fig 4)a,b were sent for bacterial, AFB, and fungal culture and sensitivity, GeneXpert TB, MGIT, and histopathological examination. The AFB smear report was negative. The histopathological report suggested chronic inflammatory pathology, possibly Tuberculosis. On GeneXpert, RIF resistance was detected, and she was put on the Bedaquiline-based regimen, which contained Bedaquiline, Levofloxacin, Clofazimine, Pyrazinamide, Ethambutol, and a high dose of INH. Following positivity in MGIT, LPA was done, which showed resistance against both RIF and INH. She continued with the above regimen. Full DST confirmed resistance to both RIF and INH, diagnosing it as MDR TB of the spine. Therefore, she continued with the regimen containing Bedaquiline (for six months) and Levofloxacin, Linezolid, Clofazimine, and Cycloserine for eight months. She is currently continuing this regimen. She was routinely monitored using radiographs, ECG, and blood parameters on monthly follow-up.
She was regularly followed-up, and three months following surgery, she had power in bilateral hips and knees at 5/5 and bilateral ankles and toes at 4/5. Deep tendon reflexes were absent, and plantar reflexes showed a flexor response. Sensation, tone, and nutrition were normal in bilateral lower limbs. X-rays didn’t show any recurrence of the lesion. ESR and CRP were 9 and 4.2, respectively.
Among the three cases discussed above, two of them had MDR-TB, and one had XDR-TB. All three of them showed significant neurological recovery several months after surgery with this new Bedaquiline-containing regimen. According to previous literature, the four main causes of drug resistance (1),(3) are incomplete or inadequate treatment (4), non adherence to ATT (5), genetic predisposition to develop drug resistance (6),(7), and Human Immunodeficiency Virus (HIV) co-infection (8),(9). In the present case series as well, Case-1 and Case-2 were known cases of pulmonary TB and spine TB, respectively, and showed failure of treatment with the traditional ATT regimen.
The treatment of drug-resistant tuberculosis comes at a terrible price. It is expensive, takes a longer time to treat, disrupts lives, and has potentially life-threatening side-effects, including depression or psychosis, hearing loss, hepatitis, and kidney impairment (10). Hence, proper diagnosis and timely management are crucial. Current GeneXpert and LPA techniques provide a quick diagnosis of drug resistance in Tuberculosis. Culture remains the gold standard in the diagnosis and drug susceptibility testing of tuberculosis (11).
In the context of drug-resistant TB, a bedaquiline-based regimen should include bedaquiline and atleast four effective second-line drugs. The choice of drugs should be based on the DST pattern in descending order and should form the Other Background Regimen (OBR), including a Second Line Injectable (Kanamycin/Capreomycin), a fluoroquinolone (Levofloxacin/Moxifloxacin), two bacteriostatic drugs (Ethionamide, Cycloserine, Para aminosalicylic Acid), and other medications such as Linezolid, Clofazimine, high-dose INH, and Pyrazinamide, if sensitive.
The dosages are as follows:
(i) Weeks 0-2: Bedaquiline 400 mg daily + OBR;
(ii) Weeks 3-24: Bedaquiline 200 mg thrice a week (with atleast 48 hours gap between doses) + OBR;
(iii) Week 25 (start of the seventh month) until the end of the treatment: Continue with other second-line anti-TB drugs as per the sensitivity pattern and the National Tuberculosis Education Program (NTEP) recommendations, which were recently updated in June 2023 (12).
Similar treatment regimens were planned for all cases in the present case series after proper testing by LPA and DST patterns for the best outcomes, and all three cases responded well.
Delamanid and Bedaquiline are associated with cardiac side-effects like QT prolongation and hence need to be monitored using Echocardiography (ECG) (13). In the present case series, all three cases were followed-up for varying periods of 5 to 8 months after treatment with proper follow-up reports to check for outcomes and prevent any late side-effects. Although a past study has also suggested the effectiveness of a Bedaquiline-based regimen in treating MDR-TB spinal infection without any severe adverse effects (14).
Very few studies are available worldwide regarding the effectiveness of a Bedaquiline-based regimen in the treatment of drug-resistant tuberculosis. According to a case reported very recently in 2022 by De Vito A et al., a similar outcome was observed in a 21-year-old male patient with MDR TB spine managed with a Bedaquiline-based regimen. A Computed Tomography (CT) scan done 1.5 years after starting therapy confirmed the cure (14). Follow-up radiographs in the present case series for all three cases also showed signs of neurological recovery, with no new lesions or abscesses seen.
The newer Bedaquiline-based regimen is effective in treating drug-resistant tuberculosis of the spine and warrants further study to objectively determine the efficacy of this regimen. With the emergence of newer strains with drug resistance, management with the existing antitubercular agents is becoming difficult. Newer drugs need to be added to the existing armamentarium. Bedaquiline and Delamanid are definitely going to play an important role in the management of drug-resistant spine tuberculosis in the future.
DOI: 10.7860/JCDR/2024/64826.18979
Date of Submission: Apr 17, 2023
Date of Peer Review: Jul 25, 2023
Date of Acceptance: Oct 30, 2023
Date of Publishing: Jan 01, 2024
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: Apr 22, 2023
• Manual Googling: Aug 12, 2023
• iThenticate Software: Oct 25, 2023 (7%)
ETYMOLOGY: Author Origin
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