Publications by authors named "Shefali Sharma"

58 Publications

Complex Regional Pain Syndrome.

Mediterr J Rheumatol 2021 Jun 30;32(2):174-175. Epub 2021 Jun 30.

Clinical Immunology and Rheumatology Unit, Post Graduate Institute of Medical Education and Research, Chandigarh, India.

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http://dx.doi.org/10.31138/mjr.32.2.174DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8369268PMC
June 2021

Comparison of two dose escalation strategies of methotrexate in active rheumatoid arthritis: a multicentre, parallel group, randomised controlled trial.

Ann Rheum Dis 2021 Jun 10. Epub 2021 Jun 10.

Division of Clinical Immunology and Rheumatology, Department of Internal Medicine, Post Graduate Institute of Medical Education and Research, Chandigarh, India.

Objectives: There are no head-to-head trials of different dose escalation strategies of methotrexate (MTX) in RA. We compared the efficacy, safety and tolerability of 'usual' (5 mg every 4 weeks) versus 'fast' (5 mg every 2 weeks) escalation of oral MTX.

Methods: This multicentre, open-label (assessor blinded) RCT included patients 18-55 years of age having active RA with disease duration <5 years, and not on DMARDs. Patients were randomized 1:1 into usual or fast escalation groups, both groups starting MTX at 15 mg/week till a maximum of 25 mg/week. Primary outcome was EULAR good response at 16 weeks, secondary outcomes were ΔDAS28 and adverse effects (AE). Analyses were intention-to-treat.

Results: 178 patients with mean DAS28-CRP of 5.4(1.1) were randomized to usual (n=89) or fast escalation groups (n=89). At 16 weeks, there was no difference in good EULAR response in the usual (28.1%) or fast escalation (22.5%) groups (p=0.8). There was no difference in mean ΔDAS28-CRP at 8 weeks (-0.9, -0.8, p=0.72) or 16 weeks (-1.3, -1.3, p=0.98). Even at 24 weeks (extended follow-up), responses were similar. There were no inter-group differences in ΔHAQ, or MTX-polyglutamates 1-3 levels at 8 or 16 weeks. Gastrointestinal AE were higher in the fast escalation group over initial 8 weeks (27%, 40%, p=0.048), but not over 16 weeks. There was no difference in cytopenias, transaminitis, or drug discontinuation/dose reduction between the groups. No serious AE were seen.

Conclusion: A faster MTX escalation strategy in RA was not more efficacious over 16-24 weeks, and did not significantly increase AE, except higher gastrointestinal AE initially.

Trial Registration Number: CTRI/2018/12/016549.
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http://dx.doi.org/10.1136/annrheumdis-2021-220512DOI Listing
June 2021

Vaginal Hysterectomy Rates Before and After Implementation of a Multiple-Tier Intervention.

Obstet Gynecol 2021 04;137(4):641-647

Department of Obstetrics and Gynecology, Cooper University Healthcare, Camden, New Jersey; Spectrum Health Medical Group, Urogynecology & Reconstructive Pelvic Surgery, Grand Rapids, Michigan; and Cooper Research Institute, Cooper University Healthcare, and Cooper Medical School of Rowan University, Camden, New Jersey.

Objective: To assess a multiple-tier intervention to increase vaginal hysterectomy rates.

Methods: We performed a cohort study assessing hysterectomy performance before and after implementation of a multiple-tier intervention to increase vaginal hysterectomy rates at a single tertiary care medical center. This intervention involved resident and attending education and simulation, professional development, design of a clinical pathway to assist in hysterectomy decision making, and development of a surgical mentorship program.

Results: Data from 698 hysterectomies (253 preintervention and 445 postintervention) were included. The preintervention time period extended from January 1, 2016, to December 31, 2017 (24 months), and the postintervention period from January 1, 2018, to February 28, 2020 (26 months). The intervention was implemented over the month of December 2017 but was not complete until January 1, 2018. The preintervention and postintervention cohorts were similar in most demographic and clinical aspects. Postintervention, the proportion of vaginal hysterectomies was higher (26.5% vs 5.5%, odds ratio 6.2, 95% CI 3.52-11.35), including in those performed for reasons other than prolapse (6.8% vs 0%, P<.001). Logistic regression revealed that prolapse, uterine weight less than 250 g, and surgery during the postintervention cohort were significantly associated with vaginal hysterectomy. Operative complications did not differ significantly by hysterectomy type.

Conclusion: Implementation of a multiple-tier intervention was associated with an increase in vaginal hysterectomies.
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http://dx.doi.org/10.1097/AOG.0000000000004318DOI Listing
April 2021

Primary Tuberculous Myositis-Report of a Case and Systematic Review of Literature in the Last 25 Years.

J Clin Rheumatol 2020 Dec 14. Epub 2020 Dec 14.

From the Department of Internal Medicine, Postgraduate Institute of Medical Education and Research.

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http://dx.doi.org/10.1097/RHU.0000000000001668DOI Listing
December 2020

Lenabasum for Systemic Sclerosis-Are Cannabinoids the Missing Link? Comment on the Article by Spiera et al.

Arthritis Rheumatol 2021 04 18;73(4):715-716. Epub 2021 Feb 18.

Post Graduate Institute of Medical Education and Research, Chandigarh, India.

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http://dx.doi.org/10.1002/art.41578DOI Listing
April 2021

Efficacy of a step-down regimen of oral prednisolone in axial spondyloarthritis: result of a double-blind randomized controlled trial (COBRA-AS Study).

Rheumatology (Oxford) 2021 04;60(4):1932-1941

Division of Rheumatology and Clinical Immunology, Department of Internal Medicine, Postgraduate Institute of Medical Education and Research, Chandigarh, India.

Objectives: To evaluate the efficacy and safety of a step-down regimen of oral prednisolone over 24 weeks in patients of axial SpA (axSpA).

Methods: This proof-of-concept double-blind randomized controlled trial enrolled patients with active axSpA (BASDAI ≥4) having predominantly axial disease (≤1 active joint currently) and inadequate response to NSAIDs. They were randomized to receive either oral prednisolone (n = 32) or placebo (n = 33) at a dose of 60, 40, 30, 20, 15 and 10 mg daily for 1 week each, following which they received 5 mg prednisolone (or placebo) daily for 18 weeks. The primary endpoint was a 50% improvement in the BASDAI (BASDAI50) at week 24. Analysis was intention to treat.

Results: A BASDAI50 was achieved by 12 of 32 patients (37.5%) in the prednisolone arm and 3 of 33 patients (9.1%) in the placebo arm at 24 weeks [difference 28.4% (95% CI 7.9, 46.7)]. However, there was no difference in achieving a 20 or 40% improvement in the Assessment of SpondyloArthritis international Society response between the groups. Although there was a significant intergroup difference in adjusted ΔBASDAI and ΔAnkylosing Spondylitis Disease Activity Score with CRP at 24 weeks, there was no difference at 12 weeks. There was also no significant difference in ΔBASFI, ΔBAS-G or ΔBASMI at 12 or 24 weeks. No serious adverse events were noted. There was significant weight gain in the first 12 weeks in the prednisolone group vs placebo [0.9 (s.d. 0.4) kg], but not at 24 weeks.

Conclusions: In this small study, oral prednisolone was efficacious in axSpA in achieving the primary outcome, but many crucial secondary outcomes such as functional improvement were not met. Its impact on bone loss was not studied.Trial registration: CTRI/2018/01/011342.
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http://dx.doi.org/10.1093/rheumatology/keaa685DOI Listing
April 2021

Tocilizumab in COVID-19: finding the optimal route and dose.

Lancet Rheumatol 2020 Dec 17;2(12):e738-e739. Epub 2020 Sep 17.

Division of Clinical Immunology and Rheumatology, Department of Internal Medicine, Postgraduate Institute of Medical Education and Research, Chandigarh 160012, India.

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http://dx.doi.org/10.1016/S2665-9913(20)30334-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7498201PMC
December 2020

A Randomized Controlled Trial of a Multimedia Patient Education Tool for Stress Versus Urgency Urinary Incontinence.

Female Pelvic Med Reconstr Surg 2021 07;27(7):403-408

From the Division of Female Pelvic Medicine and Reconstructive Surgery, Cooper University Hospital, Camden, NJ.

Objective: The aim of this study was to determine whether there was a difference in patient education when comparing traditional conversation-based patient counseling with multimedia-based patient counseling about stress and urgency urinary incontinence.

Methods: Patients seeking treatment for urinary incontinence were randomized to traditional, conversation-based counseling from a physician regarding stress and urgency urinary incontinence (control group) or view a video (multimedia) as their counseling (treatment group). A vignette-based assessment of the patient's knowledge of stress and urgency urinary incontinence was administered as a pretest, immediate posttest, and 6- to 8-week delayed posttest. The Incontinence Impact Questionnaire, short form, was used to assess quality of life and was administered at the initial visit and at the 6- to 8-week follow-up call. Patient satisfaction was recorded at the end of the initial visit using a continuous visual analog scale, and health literacy was evaluated using the Rapid Estimate of Adult Literacy in Medicine-Short Form or Short Assessment of Health Literacy-Spanish.

Results: In the 98 participants, immediate posttest scores trended toward significance between the control and treatment groups (P = 0.086). This trend was lost at the delayed posttest (P = 0.122). Both methods of education showed a significant difference between pretest, immediate posttest, and delayed posttest (P < 0.001). There were no demographic differences between groups.

Conclusions: Multimedia-based patient education represents an effective method of providing patient education regarding urinary incontinence because those who received video education showed comparable comprehension of this topic when compared with standard physician counseling. Video education can feasibly be used as an alternative to, or in conjunction with, current patient education practices in a urogynecology setting.
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http://dx.doi.org/10.1097/SPV.0000000000000946DOI Listing
July 2021

Rare cause of red eye in scleroderma.

BMJ Case Rep 2020 Aug 24;13(8). Epub 2020 Aug 24.

Clinical Immunology and Rheumatology, Department of Internal Medicine, Post Graduate Institute of Medical Education and Research, Chandigarh, India

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http://dx.doi.org/10.1136/bcr-2020-236042DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7449542PMC
August 2020

Ovarian dysfunction with moderate-dose intravenous cyclophosphamide (modified NIH regimen) and mycophenolate mofetil in young adults with severe lupus: a prospective cohort study.

Arthritis Res Ther 2020 08 14;22(1):189. Epub 2020 Aug 14.

Clinical Immunology and Rheumatology Division, Department of Internal Medicine, Postgraduate Institute of Medical Education and Research, Chandigarh, India.

Background: Ovarian toxicity is a dreaded complication of cyclophosphamide (CYC). With the use of lower cumulative doses of intravenous CYC (modified NIH regimens) and availability of better markers of ovarian toxicity, the incidence of ovarian dysfunction needs reassessment. Lupus disease activity, by itself, is also believed to affect ovarian function negatively.

Methods: This single-centre prospective cohort study recruited 50 female patients of severe lupus aged 18-40 years. Twenty-five patients each received induction with either monthly intravenous CYC (0.5-0.75 g/m) for 6-9 months or daily oral mycophenolate mofetil (MMF). Details of menstrual irregularities; serum levels of FSH, LH, estradiol, AMH, and inhibin B; and sonographic assessment of ovarian volume and antral follicular count were done at baseline and 6 months after treatment. Amenorrhoeic patients were re-evaluated at 1 year.

Results: Mean (SD) age of subjects in the CYC and MMF groups was 31.4 (6.3) and 28.4 (4.4) years, respectively. Mean (SD) SLEDAI at the initiation of therapy was 7.2 (2.5) in the CYC group and 5.8 (3.4) in the MMF group. The mean cumulative dose of CYC used was 4.6 (1.8) g. Three patients in the CYC group (versus none in MMF) had amenorrhoea at 6 months-two of these regained menses within 6 months, while only one (4%) developed sustained amenorrhoea (lasting more than 12 months) at 41 years of age, likely menopause. Serum FSH levels increased (p = 0.03), while AMH (p = 0.002) and inhibin B (p < 0.001) levels decreased significantly with 6 months of CYC therapy. Ovarian volume also reduced significantly (p = 0.005) with 6 months of CYC therapy, while antral follicular count reduced numerically (p = 0.32). Levels of AMH, inhibin-B, estradiol, ovarian volume, and antral follicular count after 6 months therapy were significantly lesser in the CYC group compared to the MMF group, despite being similar before the start of therapy.

Conclusions: Ovarian dysfunction with monthly intravenous CYC (modified NIH regimen) was predominantly subclinical, with a negative effect on ovarian reserve. No premature ovarian failure was noted at 1 year. No ovarian dysfunction occurred in the MMF group, despite having patients with severe background lupus. Use of intravenous CYC for induction may thus not be restricted in young lupus females with incomplete families for fear of gonadotoxicity, especially in life- or organ-threatening situations, where the benefits outweigh this subclinical risk.
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http://dx.doi.org/10.1186/s13075-020-02292-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7429750PMC
August 2020

Prevalence of antiphospholipid antibodies in patients with overt myocardial dysfunction in systemic lupus erythematosus. A case-control study.

Lupus 2020 Oct 4;29(12):1503-1508. Epub 2020 Aug 4.

Department of Internal Medicine, PGIMER, Chandigarh, India.

Background: Small case-series have reported overt myocardial dysfunction to be associated with positive antiphospholipid antibodies in patients of systemic lupus erythematosus (SLE). However, there is no case-control study that has examined this association.

Methods: This case-control study recruited patients of SLE (fulfilling SLICC criteria) with overt myocardial dysfunction as cases and those without this as controls. Overt myocardial dysfunction was defined by echocardiography as global left ventricular dysfunction and reduced ejection fraction (<50%). Those patients with a prior diagnosis of anti-phospholipid antibody syndrome, coronary artery disease, rheumatic heart disease or severe pulmonary artery hypertension were excluded. Antibodies tested included lupus anticoagulant, anticardiolipin antibodies (IgM and IgG) and anti-beta 2 glycoprotein 1 antibodies (IgM and IgG). Patients with positive tests underwent repeat testing for persistent positivity after 12 weeks.

Results: This study included 51 patients (21 cases and 30 controls) having a mean (SD) age of 33 (13.3) years, and disease duration (median, IQR) of 28 months (12-38 months). The mean ejection fraction of cases was 31.7 (9.3)% while that of controls was 55.7 (1.7)% (p = 0.03). The frequency (percentage) of positive antiphospholipid antibodies was not significantly different between cases and controls (43%, 40%, p = 0.8). The frequency (percentage) of anti-cardiolipin antibody was also not significant between the groups (38%, 37%, p = 0.57). Serositis and leucopenia were more prevalent in SLE patients with myocardial dysfunction (p = 0.005).

Conclusion: This study did not find any significant association of anti-phospholipid antibodies with overt myocardial dysfunction in patients of SLE.
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http://dx.doi.org/10.1177/0961203320947784DOI Listing
October 2020

Rational use of tocilizumab in COVID-19.

Ann Rheum Dis 2020 Jul 31. Epub 2020 Jul 31.

Division of Clinical Immunology and Rheumatology, Department of Internal Medicine, Post Graduate Institute of Medical Education and Research, Chandigarh, Chandigarh, India

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http://dx.doi.org/10.1136/annrheumdis-2020-218519DOI Listing
July 2020

Acute myocardial dysfunction in lupus: outcomes in Asian Indians.

Clin Rheumatol 2020 Dec 22;39(12):3661-3667. Epub 2020 May 22.

Department of Internal Medicine, Post Graduate Institute of Medical Education and Research, Chandigarh, 160012, India.

Background: Acute myocardial dysfunction is an uncommon but potentially fatal complication in systemic lupus erythematosus (SLE). We describe the outcome in a small series of Asian Indian patients and examine associated factors.

Methods: SLE patients who fulfilled the 2012 SLICC criteria and developed new-onset myocardial dysfunction were included in this retrospective case series. Acute myocardial dysfunction was defined as global hypokinesia and left ventricular ejection fraction (LVEF)<50% on echocardiography (with or without symptoms) in patients with SLE. Survival was assessed using Kaplan-Meier survival analysis and Cox regression.

Results: This study included 37 patients with mean age 28.2 ± 11.2 years and median (range) LVEF of 35% (18-48%) at presentation. A majority had active disease, with SLEDAI-2k ≥ 5 in 26 (of 28). All patients received oral corticosteroids and a majority received additional immunosuppression, including pulse methylprednisolone in 28 and cyclophosphamide in 27. Nine patients died during hospitalisation (25%), a majority due to infections. Death was significantly associated with elevated procalcitonin at presentation (p = 0.05), elevated white cell count (p = 0.02) and low complement C3 (p = 0.03). In those who survived, long-term outcomes were good, with complete myocardial recovery in 14 (64%). A higher ejection fraction at presentation was associated with complete recovery.

Conclusions: In this small series of patients of SLE with acute myocardial dysfunction, we report a significant in-hospital mortality due to infections. Many of the patients who died had elevated procalcitonin at presentation. A diligent search for infection seems prudent in lupus patients who present with acute myocardial dysfunction. Key Points • In patients of SLE with acute myocardial dysfunction who were treated with immunosuppression, there was significant short-term mortality due to infections. • This mortality was associated with elevated procalcitonin at baseline and may suggest some of them had pre-existing hidden sepsis. • A prudent search for infections in these patients before immunosuppression may help to decrease short-term mortality.
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http://dx.doi.org/10.1007/s10067-020-05177-2DOI Listing
December 2020

Efficacy and safety of pirfenidone in systemic sclerosis-related interstitial lung disease-a randomised controlled trial.

Rheumatol Int 2020 May 1;40(5):703-710. Epub 2020 Apr 1.

Post Graduate Institute of Medical Education and Research, Chandigarh, India.

To assess the efficacy and safety of pirfenidone in systemic sclerosis-related interstitial lung disease (SSc-ILD). This was a double-blind, randomised, placebo-controlled, pilot study. Subjects with SSc-ILD and forced vital capacity (FVC) between 50 and 80% of the predicted (%pred) value were randomised in 1:1 ratio to receive either pirfenidone (2400 mg/day) or placebo for 6 months. Primary outcome was the proportion of subjects with either stabilisation or improvement in FVC at 6 months. Secondary outcomes were the absolute change in the %pred FVC, Mahler's dyspnoea index, 6-min walk distance (6MWD), modified Rodnan skin score (MRSS) and serum levels of tumour necrosis factor α (TNF-α) and transforming growth factor β (TGF-β). Thirty-four subjects with median (range) age of 41 (20-63) years (91.2% women) and median (range) %pred FVC of 65 (51-78) were enrolled. Stabilisation/improvement in FVC was seen in 16 (94.1%) and 13 (76.5%) subjects in the pirfenidone and placebo groups, respectively (p = 0.33). The median (range) absolute change in %pred FVC was - 0.55 (- 9 to 7%) and 1.0 (- 42 to 11.5%) in the treatment and control groups, respectively (p = 0.51). The changes in 6MWD, dyspnoea scores, MRSS, and levels of TNF-α and TGF-β were not significantly different between groups. Common adverse events were gastrointestinal disturbances and skin rash. We failed to find a significant beneficial effect of pirfenidone over placebo in improving/stabilising FVC, exercise capacity, symptoms, or skin disease. Study is underpowered to provide conclusive evidence. Larger studies with longer follow-up periods are required.
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http://dx.doi.org/10.1007/s00296-020-04565-wDOI Listing
May 2020

Anti-Jo-1 Syndrome Often Misdiagnosed as Rheumatoid Arthritis (for Many Years): A Single-Center Experience.

J Clin Rheumatol 2021 Jun;27(4):150-155

From the Clinical Immunology and Rheumatology Division, Department of Internal Medicine.

Background: Antisynthetase syndrome is characterized by a triad of myositis, arthritis, and interstitial lung disease. Anti-Jo-1 is the most common associated autoantibody. This study planned to look at the presentation of anti-Jo-1 antisynthetase syndrome in a single Indian center.

Methods And Materials: This was a medical records review single-center study that included patients with anti-Jo-1 antisynthetase syndrome over 10 years.

Results: This study included 27 patients with anti-Jo-1 antisynthetase syndrome, with mean age of 40 ± 9.2 years and female preponderance (female-to-male ratio, 4:1). At presentation, the characteristic triad was present in only 4 patients. A majority presented with the incomplete form, with 2 clinical features (of triad) in 11 and single feature (of triad) being present in 12 patients at initial presentation. Seven presented only with polyarthritis, out of which 6 had been earlier diagnosed as rheumatoid arthritis. Time gap from diagnosis of "rheumatoid arthritis" to antisynthetase syndrome ranged from 3 to 20 years. In patients who had only arthritis in the beginning, there was a significantly longer delay to diagnosis of antisynthetase syndrome, higher frequency of rheumatoid factor, and lower frequency of anti-Ro-52. Overall, outcome was good, with Eastern Cooperative Oncology Group class 1 or 2 in most except 2 patients.

Conclusions: Anti-Jo-1 antisynthetase syndrome commonly presented as incomplete (not a triad) and often only with arthritis. These patients are diagnosed and treated as rheumatoid arthritis for many years, before a diagnosis of antisynthetase syndrome is made. Being aware of this presentation may help in earlier diagnosis by actively searching for subtle clues.
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http://dx.doi.org/10.1097/RHU.0000000000001234DOI Listing
June 2021

Methotrexate in Early Chikungunya Arthritis: A 6 Month Randomized Controlled Open-label Trial.

Curr Rheumatol Rev 2020 ;16(4):319-323

Department of Internal Medicine, Postgraduate Institute of Medical Education and Research, Chandigarh, India.

Objective: Evidence for treating chikungunya arthritis early in the course of illness is scarce. This study assesses the efficacy of Methotrexate in early Chikungunya arthritis.

Methods: It is a randomized controlled open-label assessor-blinded trial with a crossover design. Sixty patients with persistent post chikungunya arthritis with at least 3 or more tender or swollen joints (28 joint count) were recruited. MTX arm was given oral Methotrexate and NSAID arm was given NSAIDs (Naproxen 1 gm/day or Etoricoxib 120 mg/day). Patients were followed at 1, 2, 4 and 6 months. After 2 months patients in NSAID arm who have not achieved remission were given MTX. The primary endpoint was remission (no tender or swollen joints by 28 joint count) at 6 months. Secondary endpoints were change in CDAI, Indian HAQ, total steroid use, total NSAID use, and serious adverse effects. Intention to treat analysis was used.

Results: TJC, SJC, CDAI and HAQ were matched between two at baseline. Remission was achieved by 28 patients (93%, CI- 78%-98%) in the NSAID arm and 26 patients (86%, CI-70%- 94%) in MTX arm (p=0.18). There was no significant difference in steroid need, change in HAQ, CDAI, TJC or SJC. Those who have not achieved remission had higher disease activity at baseline.

Conclusion: A protocol-based approach with steroid and NSAIDs helped to achieve remission in most patients with early subacute phase of post-Chikungunya arthritis and the effect was comparable to that of early initiation of methotrexate.
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http://dx.doi.org/10.2174/1573397115666190925154140DOI Listing
January 2020

Effect of mycophenolate mofetil (MMF) on systemic sclerosis-related interstitial lung disease with mildly impaired lung function: a double-blind, placebo-controlled, randomized trial.

Rheumatol Int 2020 Feb 7;40(2):207-216. Epub 2019 Dec 7.

Department of Internal Medicine, Post Graduate Institute of Medical Education and Research (PGIMER), Sector 12, Chandigarh, 160012, India.

The efficacy and safety of mycophenolate mofetil (MMF) has been studied in patients with systemic sclerosis (SSc)-related interstitial lung disease (ILD) with moderate-severe impairment. There is no study on its use in patients with mildly impaired lung function. The objective of this study is to determine the efficacy and safety of MMF for treating mild SSc-ILD (forced vital capacity (FVC) ≥ 70% predicted). This was a double-blind, randomized, placebo-controlled pilot trial. The subjects with SSc-ILD with FVC ≥ 70% were randomized to receive either MMF (2 g/day) or placebo for 6 months. FVC, diffusing capacity of lungs for carbon monoxide (DLCO), modified Rodnan skin score (mRSS), Short Form-36 (SF36v2), Mahler's Dyspnoea Index (MDI), and 6-min walk distance (6MWD) were recorded at baseline and at 6 months. Forty-one subjects were included in the study (MMF: 20, placebo: 21). FVC decreased by a median of 2.7% (range - 21 to 9) in MMF arm and increased by 1% (range - 6 to 10) in placebo arm (p = 0.131). SF36v2 scores improved in both the groups. Median change in MDI (3 vs 3), DLCO (1% vs 1.5%), and 6MWD (0 m vs 0 m) was similar between the study groups. MMF was effective in improving mRSS (- 5 vs - 1, p = 0.045) compared to placebo. Adverse events occurred with similar frequency in both the study groups. In this pilot study, MMF did not result in significant improvement in lung function in SSc-ILD with minimally impaired lung function, but was effective in reducing the skin tightness. Larger studies are needed to confirm these findings. This study was registered at ClinicalTrials.gov (NCT02896205).
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http://dx.doi.org/10.1007/s00296-019-04481-8DOI Listing
February 2020

Nodal Eosinophilic Granulomatosis With Polyangiitis (EGPA).

J Clin Rheumatol 2020 Oct;26(7):e259-e260

Clinical Immunology and Rheumatology Services, Department of Internal Medicine, All India Institute of Medical Sciences, New Delhi, India.

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http://dx.doi.org/10.1097/RHU.0000000000001110DOI Listing
October 2020

Esophageal manometry, esophagogastroduodenoscopy, and duodenal mucosal histopathology in systemic sclerosis.

JGH Open 2019 Jun 20;3(3):206-209. Epub 2019 Mar 20.

Department of Gastroenterology Postgraduate Institute of Medical Education and Research Chandigarh India.

Background And Aim: Systemic sclerosis (SSc) is known to involve the gastrointestinal (GI) tract, resulting in dysmotility, gastroesophageal reflux disease, and mucosal changes causing significant morbidity. The study aimed to assess esophageal motility and duodenal mucosal changes in SSc.

Methods: This is a prospective, cross-sectional, single-center study of 23 patients with SSc diagnosed on the basis of standard criteria. Clinical details including the GI symptoms were recorded. All of them underwent esophagogastroduodenoscopy with duodenal biopsy, and 21 underwent esophageal manometry.

Results: Regurgitation, heartburn, and dysphagia were seen in 19 (82%), 16 (69%), and 10 (43%) patients, respectively. On endoscopy, 19 patients (83%) showed changes of reflux esophagitis (4 had grade C esophagitis), and 3 had esophageal candidiasis. Of the 21 patients who underwent esophageal manometry, 13 (62%) had absent peristalsis, 6 (28%) had ineffective peristalsis, and 10 (48%) had hypotensive lower esophageal sphincter (LES). Duodenal biopsy showed partial villous atrophy in 9 (39%) patients, increased intraepithelial lymphocytes in 18 (78%), and excess of mononuclear inflammatory cells in lamina propria in 21 (91%). Partial villous atrophy was seen more commonly in those with abnormal esophageal peristalsis and a hypotensive LES.

Conclusion: Most of the patients with SSc had esophageal dysmotility in the form of absent peristalsis, ineffective esophageal peristalsis, and hypotensive LES. Histology of descending duodenum demonstrated partial villous atrophy and chronic inflammatory infiltrates in most of the patients with SSc.
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http://dx.doi.org/10.1002/jgh3.12138DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6586572PMC
June 2019

Assessment of gastric emptying half time as a quantitative measure of gastrointestinal dysmotility in systemic sclerosis.

Rheumatology (Oxford) 2019 11;58(11):2064-2065

Department of Gastroenterology, Postgraduate Institute of Medical Education and Research, Chandigarh, India.

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http://dx.doi.org/10.1093/rheumatology/kez247DOI Listing
November 2019

Urinary incontinence and quality of life in endometrial cancer patients after robotic-assisted laparoscopic hysterectomy with lymph node dissection.

J Obstet Gynaecol 2019 Oct 10;39(7):986-990. Epub 2019 Jun 10.

Department of Female Pelvic Medicine & Reconstructive Surgery, University of Louisville , Lousiville , KY , USA.

To determine the long-term effects of lymph node dissection on lower urinary tract symptoms in patients treated for endometrial cancer. We conducted a retrospective cohort study of 74 patients with International Federation of Gynaecology and Obstetrics (FIGO) Stage I endometrial cancer who underwent surgical intervention with and without lymph node dissection, and evaluated them with the Urinary Distress Inventory-6 (UDI-6) and Incontinence Impact Questionnaire-7 (IIQ-7). Patients who underwent lymph node dissection reported higher but not statistically different rates of bother by lower urinary tract symptoms compared to those without lymph node dissection. The scores for the lymph node dissection group and the control group were a mean IIQ-7 score of 14.9 ± 23 and 10.5 ± 22.9 (=.419) and a mean UDI-6 score of 30.0 ± 25.3 and 20.7 ± 22.9 (=.104), respectively. Lymph node dissection at the time of robotic-assisted surgery did not have a significant effect on lower urinary tract symptoms nor did it affect patient responses on quality of life questionnaires. IMPACT STATEMENT The aetiology of urinary incontinence is multifactorial and there has been debate on how a patient's surgical history affects their risk of developing urinary incontinence. Prior studies have highlighted the relationship between hysterectomy and urinary incontinence (Milsom et al. 1993 ). Additional research has also been done to elucidate the prevalence of pelvic floor disorders in patients who have been surgically treated for endometrial cancer (Erekson et al. 2009 ; Nosti et al. 2012 ). There is limited information on how robotic-assisted lymphadenectomy during surgical staging for endometrial cancer affects patients' urinary function and their quality of life. In this manuscript, we demonstrate that patients who underwent robotic-assisted total laparoscopic hysterectomy (TLH) with lymphadenectomy neither had significant difference in lower urinary tract symptoms nor on quality of life questionnaires as compared to those who did not undergo lymphadenectomy. Worsening of quality of life in regards to urinary incontinence should not be considered a factor of long term surgical morbidity associated with lymph node dissection. There is a need for further studies that focus on the prevalence of pelvic floor disorders in patients after undergoing surgical staging for endometrial cancer and potential interventions that may address these issues.
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http://dx.doi.org/10.1080/01443615.2019.1584887DOI Listing
October 2019

Calcinosis Cutis at an Unusual Location.

J Clin Rheumatol 2020 Sep;26(6):e200

From the Clinical Immunology and Rheumatology Services, Department of Internal Medicine, Postgraduate Institute of Medical Education and Research, Chandigarh, India.

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http://dx.doi.org/10.1097/RHU.0000000000001069DOI Listing
September 2020

Keloidal Morphea: Clinical Picture.

J Clin Rheumatol 2020 Sep;26(6):e178-e179

From the Clinical Immunology and Rheumatology Services, Department of Internal Medicine, Postgraduate Institute of Medical Education and Research, Chandigarh, India.

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http://dx.doi.org/10.1097/RHU.0000000000001053DOI Listing
September 2020

Differentiating disease activity from damage in systemic sclerosis: it's still early days!

Ann Rheum Dis 2020 08 22;79(8):e98. Epub 2019 May 22.

Clinical Immunology and Rheumatology, Department of Internal Medicine, Post Graduate Institute of Medical Education and Research, Chandigarh, Indiaa

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http://dx.doi.org/10.1136/annrheumdis-2019-215588DOI Listing
August 2020

Diablo ubiquitination analysis by sandwich immunoassay.

J Pharm Biomed Anal 2019 Sep 3;173:40-46. Epub 2019 May 3.

BERG LLC, 500 Old Connecticut Path, Framingham, MA, 01701, United States.

Ubiquitin plays an essential role in modulating protein function, and deregulation of the ubiquitin system leads to the development of a variety of human diseases. E3 Ubiquitin ligases that mediate ubiquitination and degradation of caspases prevent apoptosis, and as such belong to the family of inhibitors of apoptosis proteins (IAPs). Diablo is a substrate of IAPs but also a negative regulator of IAPs in apoptotic pathway as it blocks the interaction between IAPs and caspases. In efforts to identify IAP inhibitors, we developed sandwich immunoassays in conjunction with an electrochemical luminescence (ECL) platform for quantitation of total Diablo, ubiquitinated Diablo, and ubiquitinated Diablo with K48-specific linkage. The assay panel detects Diablo ubiquitination level changes in the presence of IAP inhibitor or proteasome inhibitor, demonstrating its potential as a cost-efficient high-throughput method for drug discovery involving IAP ubiquitination cascade. The ECL based sandwich assay panel performance was subsequently evaluated for precision, linearity, and limit of quantification.
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http://dx.doi.org/10.1016/j.jpba.2019.05.005DOI Listing
September 2019

Evolutionary Consequences of Sex-Specific Selection in Variable Environments: Four Simple Models Reveal Diverse Evolutionary Outcomes.

Am Nat 2019 01 15;193(1):93-105. Epub 2018 Nov 15.

The evolutionary trajectories of species with separate sexes depend on the effects of genetic variation on female and male traits as well as the direction and alignment of selection between the sexes. Classical theory has shown that evolution is equally responsive to selection on females and males, with natural selection increasing the product of the average relative fitness of each sex over time. This simple rule underlies several important predictions regarding the maintenance of genetic variation, the genetic basis of adaptation, and the dynamics of "sexually antagonistic" alleles. Nevertheless, theories of sex-specific selection overwhelmingly focus on evolution in constant environments, and it remains unclear whether they apply under changing conditions. We derived four simple models of sex-specific selection in variable environments and explored how conditions of population subdivision, the timing of dispersal, sex differences in dispersal, and the nature of environmental change mediate the evolutionary dynamics of sex-specific adaptation. We find that these dynamics are acutely sensitive to ecological, demographic, and life-history attributes that vary widely among species, with classical predictions breaking down in contexts of environmental heterogeneity. The evolutionary rules governing sex-specific adaptation may therefore differ between species, suggesting new avenues for research on the evolution of sexual dimorphism.
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http://dx.doi.org/10.1086/700720DOI Listing
January 2019

Will SPAR be useful in the usual patients with scleroderma?

Ann Rheum Dis 2019 11 7;78(11):e125. Epub 2018 Sep 7.

Internal Medicine, Clinical Immunology and Rheumatology Services, Chandigarh, India.

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http://dx.doi.org/10.1136/annrheumdis-2018-214256DOI Listing
November 2019

Characteristics and Treatment of Chronic Chikungunya Virus: Comment on the Article by Chang et al.

Arthritis Rheumatol 2018 11 27;70(11):1890-1891. Epub 2018 Aug 27.

Postgraduate Institute of Medical Education and Research, Chandigarh, India.

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http://dx.doi.org/10.1002/art.40673DOI Listing
November 2018
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