Association of Sex Hormones and Androgens with Disease Activity in Premenopausal Females with Rheumatoid Arthritis.

Background: Gonadal sex hormone dysfunction is frequently reported in patients with Rheumatoid arthritis (RA). The relationship of these hormones with disease activity is still not clear and whether the hormone imbalance leads to increased severity of RA is not well studied in this part of the world. The present study aimed to elucidate this fact. Methods: It was a cross-sectional observational study performed in 80 premenopausal females with definite RA at a tertiary care hospital in New Delhi, India over one year. Patients were subjected to investigations as per the protocol and a fasting venous blood sample for hormone levels was collected in the follicular phase of their menstrual cycle. Results: A statistically significant correlation by linear logistic regression analysis was found between disease activity (as measured by DAS28) and serum progesterone, FSH, and prolactin, while serum testosterone and DHEAS showed an inverse relationship with disease activity. Low s. prolactin, and s. FSH as well as high s. testosterone and s. DHEAS were found to be associated with target clinical goals in RA (ie, remission and low disease activity). On multivariate logistic regression analysis, serum prolactin showed a direct association. (p=0.016, OR= 1.009. C.I.= 1.0021.017) and serum testosterone were found to have an inverse relationship (p=0.002, OR= 0.017, C.I.=0.001-0.237) with disease activity in this group of individuals. Conclusion: Serum levels of sex hormones may be helpful in predicting disease activity among patients with RA, and in future, may be used to guide treatment of severe refractory disease, unresponsive to conventional treatment with DMARDs, especially in resource-poor settings.

Curettage versus wide resection followed by arthrodesis/arthroplasty for distal radius Giant cell tumours: A meta-analysis of treatment and reconstruction methods.

Purpose: Primary aim of this review was to compare the two treatment modalities-curettage and wide excision (WE)- of Giant cell tumours of distal radius along with the methods of reconstruction viz. arthrodesis (AD) and arthroplasty (AP), and determine which had a better outcome. Methods: PubMed and Cochrane library databases were systematically searched using a well-defined search strategy by two independent reviewers. Inclusion/exclusion criteria were predetermined using the PICO format. MINORS tool was used to evaluate study quality. Recurrence rate (RR) was the chief oncological determinant whereas range of motion, grip strength, disability of arm, shoulder and hand (DASH) and musculoskeletal tumour society (MSTS) scores and complication rates were the functional outcome measures used. Results: For the first part, a total of 11 articles (284 patients) were analysed. The second half- AP versus AD-included four studies (71 patients). Quantitative analysis revealed a significantly higher RR (Odds ratio (OR) 8.6 [95% CI, 3.4, 21.75]) with curettage. WE, on the other hand, was associated with a higher complication rate (OR 0.3[ 95% CI, 0.14, 0.62]) and lower grip strength (Standard Mean Difference (SMD) 18.08[95% CI, 13.78, 22.37]). Complication rates were also significantly higher with wrist AP (OR 6.36[ 95% CI, 1.72, 23.52]). Remaining functional parameters failed to show any significant difference between either group. Conclusion: WE is the preferred surgical strategy in terms of lower RR and functionally equivalent results. In terms of the choice of reconstruction following WE, there is a trend towards higher patient satisfaction after wrist AD.

Effect of antiretroviral therapy on cardiac risk markers in people living with HIV/AIDS.

Introduction: Chronic HIV infection and antiretroviral therapy (ART) are the major causes of cardiovascular diseases (CVDs) and mortality in HIV patients. This study was conducted to look upon the effect of ART on CVD risk markers in patients on different ART regimens and ART-naïve patients. Methods: It was a cross-sectional, observational study done on 120 HIV-infected patients. CV risk markers were assessed and correlated with disease-specific factors within individual subgroups differentiated as Group A (ART naïve), Group B (first-line ART), and Group C (second-line ART). Carotid intimal medial thickness (CIMT) and high-sensitivity C reactive protein (hsCRP) were done to classify cases as having CVD. Results: CVD risk parameters were found to be significantly higher in cases on ART, as compared to ART-naïve cases. The mean CIMT among cases in Group C, Group B, and Group A was 0.072 ± 0.01 cm, 0.063 ± 0.01 cm, and 0.055 ± 0.01 cm, respectively (P < 0.01). 95%, 65% and 25% cases in Group C, Group B, and Group A, respectively, had high CIMT (>0.06 cm) and were seen to be directly correlated with disease-related factors, i.e., duration of disease and ART, type of ART, and low CD4 cell counts. hsCRP was significantly increased in 65 out of total 120 cases. The mean hsCRP in Group A, Group B, and Group C was 3.69 ± 3.37, 4.21 ± 3.4, and 5.72 ± 3.54 mg/L, respectively (P < 0.01), which corresponds to the high risk of CVD. Conclusion: CVD risk parameters of CIMT and hsCRP are seen to be higher in patients on ART than ART-naive subjects.

Calcaneal osteomyelitis caused by Acremonium sp in an immunocompetent adult - A case report.

Fungal osteomyelitis of calcaneus is rare in immunocompetent adults. A case of fungal osteomyelitis of calcaneus in a 19 year old immunocompetent female without any history of trauma caused by Acremonium sp is presented. The patient was treated with surgical debridement, autogenous iliac crest bone grafting and antifungal chemotherapy for 6 months. At latest follow up after 2 years, patient is asymptomatic and the osteolytic lesion is healed with no signs of recurrence. This case report highlights a rare presentation of chronic painful calcaneal osteomyelitis with an osteolytic lesion.

Massive Gouty Tophi Presenting as Pseudotumor of the Elbow: A Rare Presentation.

Gout is a systemic metabolic disorder characterized by hyperuricemia and deposition of monosodium urate crystals in joints and other extra-articular tissues. Poorly controlled cases progress to chronic gout with tophi, which can sometimes assume massive sizes. We report one such case of a 39-year-old male with poorly controlled polyarticular tophaceous gout presenting with a massive swelling of the left elbow simulating a soft tissue tumor. Subsequent investigations confirmed it to be a massive tophus which was then surgically excised, as the mass was not responding to the medical management. At the latest follow-up after two years, the patient has full function of the elbow and gout is well controlled with medications.

Mazabraud's Syndrome - A Diagnosis Commonly Missed.

INTRODUCTION: Mazabraud's syndrome is a rare benign disorder characterized by the association of single or multiple intramuscular myxomas with monostotic or polyostotic form of fibrous dysplasia. Around 80 cases have been described till date; however, a higher incidence may be expected due to silent nature of the disease and missed diagnosis. The authors report one such case of a missed diagnosis. CASE REPORT: A 39-year-old lady presented with recurrent soft tissue myxomas in thigh. A thorough evaluation with radiographs and magnetic resonance imaging (MRI) and a clinical suspicion of this rare entity helped in making the diagnosis of Mazabraud's syndrome. The patient was treated with wide excision of the recurrent thigh swelling and watchful observation of two other asymptomatic swelling detected on MRI examination. Bisphosphonate therapy was given for fibrous dysplasia. At latest follow-up after 2 years, the patient was asymptomatic with no recurrence. CONCLUSION: The report highlights the importance of a high degree of suspicion of this clinical entity in patients treated for recurrent soft tissue swelling as both myxomas and fibrous dysplasia behave differently than their isolated counterparts.

A case of acute septic arthritis hip caused by Brucella melitensis in an adolescent child.

Brucella is among the most common zoonotic diseases affecting humans. Although musculoskeletal involvement is seen in a large proportion of patients, the disease is often diagnosed late or misdiagnosed due to its subtle nature and rarity, and lack of awareness among clinicians. In this report, a 12-year-old girl was diagnosed with acute septic arthritis of the hip based on clinico-radiological features, and managed with standard treatment, including arthrotomy. However, the child did not respond to the treatment. Based on the histopathology and local endemicity, Brucella was suspected, and confirmed after serological testing. The child subsequently responded to treatment and, at latest follow-up at 1 year, had a full painless range of motion, with no relapse.

Evaluation of Aspartate Aminotransferase-to-Platelet Ratio Index as a Non-Invasive Marker for Liver Cirrhosis.

INTRODUCTION: Liver biopsy is considered as a gold standard for the diagnosis of cirrhosis. Till date there is no non-invasive marker to replace it. AIM: To investigate the effectiveness of Aspartate aminotransferase-to-platelet ratio index (APRI) as a non-invasive marker for liver cirrhosis. MATERIALS AND METHODS: Fifty-one patients with cirrhosis, identified on USG abdomen were included in study. Platelet count and Aspartate aminotransferase (AST) were done using haematology automatic analyser and automatic HITACHI-912 Auto Analyser respectively. APRI was calculated for every patient using the formula {(AST / ULN) x 100}/platelet count (10(9)/L). Predictive accuracy was evaluated with a receiver-operating characteristics (ROC) curve. RESULTS: APRI correctly classified 49 (96.1%) patients of cirrhosis with area under the ROC curve of 0.973 (95% CI) at cut-off 0.65 with negative predictive value (NPV) and Positive predictive value (PPV) of 96% and 96.1% respectively. The sensitivity and specificity of the test was found to be 96% and 96.1% respectively. CONCLUSION: APRI could identify cirrhosis with high degree of accuracy in the studied patients.

Human CDC2-like kinase 1 (CLK1): a novel target for Alzheimer's disease.

The cdc2-like kinases (CLKs) are an evolutionarily conserved group of dual specificity kinases belonging to the CMGC (cyclin-dependent kinases (CDKs), mitogen-activated protein kinases (MAP kinases), glycogen synthase kinases (GSK) and CDK-like kinases). The CLK family consists of four isoforms namely CLK1, CLK2, CLK3 and CLK4. The human CLK1 encoded protein comprises 454 amino acids and the catalytic domain of CLK1 exhibits the typical protein kinase fold. CLK1 has been shown to autophosphorylate on serine, threonine and tyrosine residues and phosphorylate exogenous substrates on serine and threonine residues. CLK1 plays an important role in the regulation of RNA splicing through phosphorylation of members of the serine and arginine-rich (SR) family of splicing factors. CLK1 is involved in the pathophysiology of Alzheimer's disease by phosphorylating the serine residue in SR proteins. Nuclear speckles of the nucleoplasm contain the stored form of SR proteins and are moderately responsible for the choice of splicing sites during pre-mRNA splicing. Hence, the inhibition of CLK1 can be used as a therapeutic strategy for Alzheimer's disease. Many natural and synthetic molecules are reported to possess CLK1 inhibitory activity. Some specific examples are Marine alkaloid Leucettamine B and KH-CB19. Leucettamine B is a potent inhibitor of CLK1 (15 nM), Dyrk1A (40 nM), and Dyrk2 (35 nM) and a moderate inhibitor of CLK3 (4.5 µM) whereas KH-CB19 is a highly specific and potent inhibitor of the CLK1/CLK4. X-ray crystallographic studies have revealed the binding mode of marine sponge metabolite hymenialdisine and a dichloroindolyl enamino nitrile (KH-CB19) to CLK1. This review focuses on the role of CLKs in the pathophysiology of Alzheimer's disease and therapeutic potential of targeting CLK1 in Alzheimer's disease drug discovery and development. In addition, the recent developments in drug discovery efforts targeting human CLK1 are also highlighted.