Early Reconstruction with Locoregional-Free Flaps in Post-COVID-19 Rhino-orbital-cerebral Mucormycosis Craniofacial Deformities: A Single-Center Clinical Experience from India.

Aim of the Study Mucormycosis is a rare invasive and fatal fungal infection and its resurgence in coronavirus disease 2019 (COVID-19) patients has been a matter of grave concern. It is essentially a medical disease, but surgical debridement of necrotic tissues is of paramount importance leading to severe craniofacial deformities. In this case series, we present our experience with the feasibility of early reconstruction after surgical debridement. Case Series As a Dedicated COVID Center (DCH), the institute received the largest population of COVID-19 mucormycosis patients from the entire eastern region of the country between May 2021 and August 2021. More than 5,000 COVID-19 were admitted out of which 218 patients were diagnosed with mucormycosis. Nine patients, seven males and two females, with a mean age of 39 years with craniofacial mucormycosis underwent debridement and early reconstructions (2-4 weeks from first debridement and start of antifungal therapy) with free and pedicled flaps. All flaps survived and showed no evidence of recurrence. The average time of the early reconstruction after surgical debridement was 1.7 weeks once the course of systemic amphotericin B was received. Conclusion After aggressive surgical resection and a short course of antifungal therapy, early reconstruction can be done safely based on clinical criteria, as long as there is no evidence of hyphae invasion on wound edges in the intraoperative pathology examination.

Serial cytoreductive surgery and survival outcomes in recurrent adult-type ovarian granulosa cell tumors.

BACKGROUND: Few studies have evaluated the role of cytoreductive surgery in patients with recurrent adult granulosa cell tumors of the ovary. Despite a multitude of treatment modalities in the recurrent setting, the optimal management strategy is not known. Cytoreductive surgery offers an attractive option for disease confined to the abdomen/pelvis. However, few studies have evaluated the role of surgery compared with systemic therapy alone following the first recurrence and subsequent disease progressions. OBJECTIVE: This study aimed to determine the impact of secondary, tertiary, and quaternary cytoreductive surgery on survival outcomes in recurrent adult granulosa cell tumors of the ovary. STUDY DESIGN: This is a multicenter, retrospective cohort study evaluating patients with recurrent adult granulosa cell tumors of the ovary enrolled in the MD Anderson Rare Gynecologic Malignancy Registry from 1970 to 2022. Study inclusion criteria consisted of histology-proven recurrent disease, at least 1 documented recurrence, and treatment/treatment planning at the MD Anderson Cancer Center or Lyndon B. Johnson General Hospital. The primary exposure was cytoreductive surgery, and the outcomes of interest were progression-free survival and overall survival. Survival analyses were restricted to eligible patients with resectable disease without medical barriers to surgery at each progression episode. Demographic and clinicopathologic characteristics were summarized using descriptive statistics. Progression-free survival (after first, second, and third progression) and overall survival were estimated with methods of Kaplan and Meier, and were modeled via Cox proportional hazards regression. Multivariable analyses were performed for progression-free survival after first progression and overall survival. RESULTS: Among the 369 patients with adult granulosa cell tumors of the ovary in the registry, 149 patients met the study inclusion criteria. Secondary cytoreductive surgery was associated with a significant improvement in progression-free survival on univariable (hazard ratio, 0.37; 95% confidence interval, 0.17-0.81, P=.01) and multivariable analyses (hazard ratio, 0.42; 95% confidence interval, 0.19-0.92; P=.03). Those who underwent secondary cytoreductive surgery had a significantly improved median overall survival compared with those who did not undergo cytoreductive surgery (181.92 vs 61.56 months, respectively; P=.002). Overall survival benefit remained statistically significant on multivariable analysis (hazard ratio, 0.28; 95% confidence interval, 0.11-0.67; P=.004). Tertiary cytoreductive surgery was similarly associated with a significant improvement in progression-free survival (hazard ratio, 0.43; 95% confidence interval, 0.26-0.70; P=.001). Despite a similar trend, quaternary cytoreductive surgery was not associated with a significant improvement in progression-free survival (hazard ratio, 0.74; 95% confidence interval, 0.42-1.26; P=.27). CONCLUSION: Among those with resectable disease and no medical contraindications to surgery, cytoreductive surgery may have a beneficial impact on progression-free survival and overall survival in patients with recurrent adult granulosa cell tumors of the ovary.

Leveraging Large Language Models (LLM) for the Plastic Surgery Resident Training: Do They Have a Role?

Introduction Large language models (LLMs) are designed for recognizing, summarizing, translating, predicting, and generating text-based content from knowledge gained from extensive data sets. ChatGPT4 (Generative Pre-trained Transformer 4) (OpenAI, San Francisco, California, United States) is a transformer-based LLM model pretrained on public data as well as data obtained from third-party sources using deep learning techniques of fine tuning and reinforcement learning from human feedback to predict the next text. We wanted to explore the role of LLM as a teaching assistant (TA) in plastic surgery. Material and Methods TA roles were first identified in available literature, and based on the roles, a list of suitable tasks was created where LLM could be used to perform the task. Prompts designed to be fed in to the LLM (specifically ChatGPT) to generate appropriate output, were then created and fed to the ChatGPT model. The outputs generated were scored by evaluators and compared for interobserver agreement. Results A final set of eight TA roles were identified where a LLM could be utilized to generate content. These contents were scored for usefulness and accuracy. These were scored independently by the eight study authors in a scoring sheet created for the study. Interobserver agreements for content accuracy, usefulness, and clarity were 100% for content generated for the following: interactive case studies (generation), simulation of preoperative consultations, and generation of ethical considerations. Discussion LLMs in general and ChatGPT (on which this study is based) in specific, can generate answers to questions and prompts based on huge amount of text fed into the model for training the underlying language model. The answers generated have been found to be accurate, readable, and even indistinguishable from human-generated text. This capability of automated content synthesis can be exploited to generate summaries to text, answer short and long answers, and generate case scenarios. We could identify a few such scenarios where the LLM could in general be utilized to play the role of a TA and aid plastic surgery residents in particular. In addition, these models could also be used by students to obtain feedback and gain reflection which itself stimulates critical thinking. Conclusion Incorporating LLMs into the educational arsenal of plastic surgery residency programs can provide a dynamic, interactive, and individualized learning experience for residents and prove to be worthy TAs of future.

Comparative Tumor Microenvironment Analysis of Primary and Recurrent Ovarian Granulosa Cell Tumors.

Adult-type granulosa cell tumors (aGCT) are rare ovarian sex cord tumors with few effective treatments for recurrent disease. The objective of this study was to characterize the tumor microenvironment (TME) of primary and recurrent aGCTs and to identify correlates of disease recurrence. Total RNA sequencing (RNA-seq) was performed on 24 pathologically confirmed, cryopreserved aGCT samples, including 8 primary and 16 recurrent tumors. After read alignment and quality-control filtering, DESeq2 was used to identify differentially expressed genes (DEG) between primary and recurrent tumors. Functional enrichment pathway analysis and gene set enrichment analysis was performed using "clusterProfiler" and "GSVA" R packages. TME composition was investigated through the analysis and integration of multiple published RNA-seq deconvolution algorithms. TME analysis results were externally validated using data from independent previously published RNA-seq datasets. A total of 31 DEGs were identified between primary and recurrent aGCTs. These included genes with known function in hormone signaling such as LHCGR and INSL3 (more abundant in primary tumors) and CYP19A1 (more abundant in recurrent tumors). Gene set enrichment analysis revealed that primarily immune-related and hormone-regulated gene sets expression was increased in recurrent tumors. Integrative TME analysis demonstrated statistically significant depletion of cancer-associated fibroblasts in recurrent tumors. This finding was confirmed in multiple independent datasets. IMPLICATIONS: Recurrent aGCTs exhibit alterations in hormone pathway gene expression as well as decreased infiltration of cancer-associated fibroblasts, suggesting dual roles for hormonal signaling and TME remodeling underpinning disease relapse.

Important signs to check posterior capsule integrity.

For beginner surgeons, it is difficult to recognize the posterior capsule during cataract surgery. In the case of brown cataracts with a thin posterior capsule and in cataracts with asteroid hyalosis, it is difficult to identify the capsule before intraocular lens (IOL) implantation even for expert surgeons. Here we illustrate five important signs, which can be practiced in routine cases to make sure the posterior capsule is intact, before IOL implantation.

Histone deacetylase 1, Sirtuin 1, and Sirtuin 3 single-nucleotide polymorphisms and the risk of endometriosis in South Indian women.

The aim of the study was to investigate the association between Histone deacetylase 1 (HDAC1), Sirtuin1 (SIRT1), and Sirtuin3 (SIRT3) single-nucleotide polymorphisms (SNPs) and risk of endometriosis in South Indian women. A total of 300 subjects were recruited in this case-control study comprising 150 affected women and 150 women with no evidence of disease. All the subjects were of South Indian origin. The genotyping of HDAC1, SIRT1, and SIRT3 SNPs (rs1741981T/C, rs144124002A/G, and rs536715G/A) was carried out on DNA from subjects by PCR-RFLP and sequencing analysis. The genotype (p = .00782) and allele (p = .02561) frequencies of the HDAC1 rs1741981 polymorphism showed significant difference between cases and controls. In contrast, SIRT1 (rs144124002) and SIRT3 (rs536715) SNPs did not show significant association with the disease. The HDAC1 polymorphism may constitute a heritable risk factor for endometriosis in South Indian women. To date, there is no reported study on the association of polymorphisms in HDAC1, SIRT1, and SIRT3 with endometriosis risk. Impact StatementWhat is already known on this subject? Endometriosis is a benign gynaecological disease characterised by the implantation of functional endometrial tissue at ectopic positions, associated with an increased risk of malignant transformation. Epigenetic mechanisms are essential for normal development and maintenance of tissue-specific gene expression patterns. Histone modification, including deacetylation of lysine residues by HDACs, is a key epigenetic mechanism of gene expression regulation in endometriosis, therefore genetic variation in HDACs causing epigenetic control defects might lead to disease susceptibility.What do the results of this study add? Our study shows that the HDAC1 SNP is significantly associated with endometriosis in South Indian women, whereas the SNPs of SIRT1 and SIRT3 could not show any association with the disease.What are the implications of these findings for clinical practice and/or further research? The polymorphism of HDAC1 rs1741981 could be used as an important marker of genetic susceptibility to endometriosis development. Analysis of this SNP might help to identify patients at high risk for disease outcome.

Facilitating Safe Discharge Through Predicting Disease Progression in Moderate Coronavirus Disease 2019 (COVID-19): A Prospective Cohort Study to Develop and Validate a Clinical Prediction Model in Resource-Limited Settings.

BACKGROUND: In locations where few people have received coronavirus disease 2019 (COVID-19) vaccines, health systems remain vulnerable to surges in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections. Tools to identify patients suitable for community-based management are urgently needed. METHODS: We prospectively recruited adults presenting to 2 hospitals in India with moderate symptoms of laboratory-confirmed COVID-19 to develop and validate a clinical prediction model to rule out progression to supplemental oxygen requirement. The primary outcome was defined as any of the following: SpO2 < 94%; respiratory rate > 30 BPM; SpO2/FiO2 < 400; or death. We specified a priori that each model would contain three clinical parameters (age, sex, and SpO2) and 1 of 7 shortlisted biochemical biomarkers measurable using commercially available rapid tests (C-reactive protein [CRP], D-dimer, interleukin 6 [IL-6], neutrophil-to-lymphocyte ratio [NLR], procalcitonin [PCT], soluble triggering receptor expressed on myeloid cell-1 [sTREM-1], or soluble urokinase plasminogen activator receptor [suPAR]), to ensure the models would be suitable for resource-limited settings. We evaluated discrimination, calibration, and clinical utility of the models in a held-out temporal external validation cohort. RESULTS: In total, 426 participants were recruited, of whom 89 (21.0%) met the primary outcome; 257 participants comprised the development cohort, and 166 comprised the validation cohort. The 3 models containing NLR, suPAR, or IL-6 demonstrated promising discrimination (c-statistics: 0.72-0.74) and calibration (calibration slopes: 1.01-1.05) in the validation cohort and provided greater utility than a model containing the clinical parameters alone. CONCLUSIONS: We present 3 clinical prediction models that could help clinicians identify patients with moderate COVID-19 suitable for community-based management. The models are readily implementable and of particular relevance for locations with limited resources.

Clinical profile and management of sixth nerve palsy in pediatric patients (0-15 years) in Southern India - A hospital-based study.

PURPOSE: This study was done to evaluate the clinical profile in pediatric patients (0-16 years) presenting with acute onset esotropia due to sixth nerve palsy and its management options in a tertiary care set up of Southern India. METHODS: A total of 12 patients presenting to our OPD with acute onset esotropia due to sixth nerve palsies were included in this retrospective study. All patients were observed for 6 months and managed with prism and/or patching while waiting for spontaneous resolution and later managed surgically. Neuroimaging was done in all cases. RESULTS: The mean deviation of esotropia at presentation was 30.17 ± 5.7 Prism Diopter (range 12-50 Prism Diopter 95% CI, SD 10.11). Mean age of the patients during presentation was 8.6 ± 2.4 years (range: 1-15 years, SD 4.27). Among the common causes of sixth nerve palsy in our study population were trauma and idiopathic intracranial hypertension followed by tumor and miscellaneous causes. Only three patients underwent surgical correction of residual deviation after a waiting period of 6 months for self-resolution. Spontaneous resolution was observed in 41.6% patients, and surgical correction (unilateral resection-recession) was done in 25% of the patients with good surgical outcome. CONCLUSION: At 1-year follow up, the motor outcome was satisfactory except for one patient who had diffuse pontine glioma and had worsening neurological symptoms on follow-up.

A study of referral pattern to pediatric ophthalmology department in a tertiary eye-care center of South-India.

PURPOSE: The study was aimed at finding out the present pattern of referrals to the Pediatric Ophthalmology outpatient department (OPD) in a tertiary eye care hospital and thus identify the discrepancy of referral, if any, which would help to modify and enhance the practice guidelines. METHODS: The study was conducted by retrospectively collecting data from all referral letters that were already uploaded in the Electronic Medical Report (EMR) against all patients from June 2019 to December 2019. All pediatric patients in the age group of 0-16 years were included in the study. The practicing field of referring clinicians was noted along with the maximum information that could be collected from the referral letter and were thus assessed for the quality, accuracy, and timely referral. RESULTS: Out of 77 referrals received in the study period, six referral letters neither had any mention of the designation of the referring clinician nor any specific diagnosis or details. Thus, only 71 patients were included for further study. The referring clinicians were mainly ophthalmologists, pediatricians, general practitioners (GPs), and others (cardiologists, neurologists). Maximum patients were referred by ophthalmologists (76%) but visual acuity was noted only for 30% of these patients. Almost half of the referral diagnosis was accurate. Pediatrician referrals were found to be more detailed and précised. CONCLUSION: There is a need for a standardized hospital-specific format of referrals and basic training to primary care providers on some simple tests (Lights reflex tests) for identifying the "red flags" in pediatric eye examination and thus enhancing the quality and timely referral per se.

DNMT1 and DNMT3B gene variants and their association with endometriosis in South Indian women.

BACKGROUND: Endometriosis is a multifactorial estrogen dependent gynecological disease characterized by implantation of functional endometrial tissue at ectopic positions. Though this disease is benign, it is associated with an increased risk of malignant transformation. Epigenetic disruptions like aberrant DNA methylation, resulting changes in gene expression capacity, are important in tumor progression and malignant cellular transformation. Therefore, variation in genes involved in DNA methylation might lead to disease susceptibility. PURPOSE: To investigate the association between DNA methyl transferases (DNMT1 and DNMT3B) single nucleotide polymorphisms (SNPs) and the risk of endometriosis in South Indian women. METHODS: In the present study, we examined the genotypic and allele distribution of DNMT1 (rs10423341C/A, rs2228611G/Aandrs4804490C/A) and DNMT3B (rs1569686G/T) among the endometriosis patients (n = 150) and controls (n = 150). The genotypes were analyzed by polymerase chain reaction (PCR) and sequencing methods. Haplotype frequencies for multiple loci and the standardized disequilibrium coefficient (D') for pairwise linkage disequilibrium (LD) were surveyed by Haploview Software. RESULT: Significant increase in the frequencies of DNMT1 rs10423341 (P = 0.04601), rs2228611 (P = 0.00175) and DNMT3B rs1569686 (P = 0.033) genotypes and alleles was observed in patients compared to controls. In addition, the frequency of A/A/C (P = 0.0065) haplotype was significantly high in patients. But the DNMT1 (rs4804490) SNP did not show significant association with the disease. CONCLUSION: The DNMT1 and DNMT3B polymorphism may constitute an inheritable risk factor for endometriosis in South Indian women. To the best of our knowledge there is no reported study on the association of polymorphisms in DNMT1 and DNMT3B with endometriosis risk.

Perfect anterior capsulorhexis using a dented cystitome.

We describe a novel intraoperative technique of measuring and creating an adequate size continuous curvilinear capsulorhexis (CCC) in phacoemulsification, using a dented cystitome as the ruler. A pair of curved tenotomy scissors is used to create a dent on the cystitome at a distance of 2.5 mm length (i.e., half of the desired approximate capsulorhexis diameter). The dented cystitome is used as a guide for making a CCC of approximately 5 mm diameter, which is considered adequate for phacoemulsification. This method of measuring the capsulorhexis helps in achieving a well centered and stable intraocular lens with a 360° overlap of the optic edge by the anterior capsular rim in the postoperative period. Using a dented cystitome for capsulorhexis mandates reliable and consistent results in the hands of the novice as well as the experienced surgeons.

Polymorphous Adenocarcinoma: A Rare Case Report with Unique Radiographic Appearance on CBCT.

BACKGROUND: Polymorphous low-grade adenocarcinoma (PLGA) is a slow growing malignant tumor of minor salivary glands and is generally of indolent nature. However, according to the most recent WHO Classification of Salivary Gland Tumors (2017), the cancer is classified as Polymorphous AdenoCarcinoma (PAC). PAC presents as a less aggressive tumor, though it could on rare occasions demonstrate distant metastasis. Case Presentation. A 47-year-old man who was referred by a private practitioner for a CBCT scan in reference to a proliferative soft-tissue growth in the hard palate. The growth was mild and tender and there was Grade III mobility in relation to all the maxillary teeth. Panoramic radiograph taken previously had revealed evidence of alveolar bone loss in relation to the maxillary teeth and was inconclusive of any other findings. The CBCT scan revealed evidence of moth-eaten appearance of maxilla with destruction of medial and lateral walls and floor of maxillary sinus. There was also evidence of involvement of right eustachian tube, ethmoidal wall, and nasopalatine canal. An intraosseous malignancy of the palate was suspected, and a total maxillectomy was performed. The tissue sample was sent for histopathological assessment wherein changes diagnostic for polymorphous low-grade adenocarcinoma of the palate were observed. CONCLUSION: PAC is a distinct, yet commonly occurring, minor salivary gland tumor with varied clinical and histologic appearance. This case report highlights the importance of CBCT in diagnosing the intraosseous involvement of such tumors which can help shed some light in enhancing our knowledge about the minor salivary gland malignancies like PAC.

Imaging Techniques: Options for the Diagnosis and Monitoring of Treatment of Enthesitis in Psoriatic Arthritis.

Psoriatic arthritis (PsA) affects up to 30% of patients with psoriasis and may include musculoskeletal manifestations such as enthesitis. Enthesitis is associated with joint damage, and early detection and treatment are essential to management of the disease. Traditionally assessed by clinical examination and conventional radiography, entheseal inflammation can now be more accurately assessed earlier in the disease using techniques such as ultrasound, magnetic resonance imaging, computed tomography, and molecular imaging. However, there is little consensus on the optimum definition for diagnosing enthesitis in PsA or on the ideal scoring system for measuring response to treatment. This review aims to summarize the benefits and limitations of different imaging modalities in the assessment of enthesitis. It also proposes that adoption of standardized definitions and validation of scoring systems and imaging techniques in clinical trials will allow the efficacy of new treatment options to be assessed more accurately.

E3 ubiquitin ligase RNF123 targets lamin B1 and lamin-binding proteins.

Lamins are key nuclear proteins which are important for maintaining nuclear structure and function. Mutations in lamins cause a spectrum of genetic diseases termed as laminopathies. RING finger containing E3 ubiquitin ligase, RNF123, is transcriptionally upregulated in cells expressing rod domain lamin A mutations. However, the functional relevance of RNF123 in laminopathic cells is not clear. Using a mass spectrometry-based approach, we identified lamins and lamin-binding proteins retinoblastoma protein (pRb), lamina-associated polypeptide 2α (LAP2α), and emerin as RNF123-interacting proteins. We determined that RNF123 mediated the ubiquitination of these proteins and caused the proteasomal degradation of pRb, LAP2α, and lamin B1. Furthermore, these proteins were also targeted for proteasomal degradation in cells expressing lamin A rod domain mutants G232E, Q294P, and R386K. Overexpression of RNF123 resulted in delayed transit through the S-phase which was alleviated by coexpression of pRb or LAP2α. Our findings imply that RNF123-mediated ubiquitination of lamin-binding proteins may contribute to disease-causing mechanisms in laminopathies by depletion of key nuclear proteins and defects in cell cycle kinetics.

Ultrasound characterization of cutaneous ulcers in systemic sclerosis.

Skin ulcers in scleroderma (SSc) patients are considered a major challenge, both in clinical assessment and treatment decisions. The objective of our study is to assess ultrasonographic (US) morphology of skin ulcers in SSc patients and evaluate if US will be of value in enhancing our clinical information and influence our management plans. We examined a convenience sample of 21 skin ulcers reported in 10 SSc patients by US. We used a previously published US definition of normal skin and developed a preliminary US definition of skin ulcer. Skin ulcers were evaluated by gray scale (GS) and power Doppler (PD) and separated into ulcer and non-ulcer lesions; pain and ulcer measures were obtained using visual analogue scales (VAS). Lesions were characterized and ulcers were clinically and sonographically measured. Ten patients presenting with 21 skin lesions were examined by US. Applying our US definition of skin ulcer, all ulcers were available to measure by ultrasound. Eight lesions were sonographically defined as ulcers, and 13 lesions as non-ulcer lesions. Three ulcers had high PD signals suggestive of infection requiring antibiotic treatment and were monitored for 2 weeks showing a decrease of the pain, VAS, and PD signals. Five lesions showed subclinical calcinosis. This is the first study to show the promising role of US in defining skin ulcers of SSc patients. US may support the assessment of morphology and extent of skin ulcers in SSc and can be a helpful tool for detecting underlying pathology.

A novel screening tool (Karanth's test) for vitamin B12 deficiency: a pilot study.

BACKGROUND: No practical tests are currently available for screening vitamin B12 deficiency because the available techniques are invasive, expensive, and require a particular level of infrastructure and service that is not available in all places such as rural areas. Thus, we have examined the efficacy of a novel method (Karanth's test) for identifying people with vitamin B12 deficiency as part of a pilot study. METHODS: An observer-blind study was conducted on 83 consenting patients from a tertiary teaching hospital whose blood was drawn for estimation of serum vitamin B12 over a 2-month period. All of these patients completed the study. In the Karanth's test, the skin color tone is measured at the interphalangeal joint and the phalanx using the Von Luschan skin tone chart. The test result is obtained from differences in the values obtained. This test was performed on the day blood was drawn to measure the serum vitamin B12 levels in the study patients and on every day until discharge for patients tested to be deficient. RESULTS: Of the 83 patient subjects, 20 showed deficient vitamin B12 levels in the blood test. The Karanth's test readings were significantly different for patients with normal and deficient levels of vitamin B12 (95 % CI, 0.838-2.153). ROC curve analysis suggested that a difference greater than 1.5 should be considered positive. The sensitivity and specificity of the test were determined to be 80 and 84.1 %, respectively. Patients were grouped further according to the Fitzpatrick scale. There were no type I, II or III patients and insufficient IV cases to determine sensitivity and specificity. Sensitivity and specificity were determined to be 57.1 and 94.6 % in type V and 92 and 63.6 % in type VI, respectively. We found that 87 % of our patients who tested positive had normal values on discharge. CONCLUSION: The Karanth's test is a useful screen for a vitamin B12 deficiency and warrants further evaluation in a larger study population.

Comprehensive appraisal of magnetic resonance imaging findings in sustained rheumatoid arthritis remission: a substudy.

OBJECTIVE: To evaluate the effect of sustained American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) Boolean remission on residual joint inflammation assessed by magnetic resonance imaging (MRI) and to secondarily evaluate other clinical definitions of remission, within an early seropositive rheumatoid arthritis (RA) cohort. METHODS: A subcohort of 118 RA patients was enrolled from patients who completed the 2-year, double-blind randomized Treatment of Early Aggressive Rheumatoid Arthritis (TEAR) trial. Patients received a single contrast-enhanced 1.5T MRI of their most involved wrist. Two readers scored MRIs for synovitis, osteitis, tenosynovitis, and erosions. Clinical assessments were performed every 3 months during the trial and at time of MRI. RESULTS: The subcohort was 92% seropositive with mean age 51 years, duration 4.1 months, and Disease Activity Score in 28 joints using the erythrocyte sedimentation rate 5.8 at TEAR entry. Total MRI inflammatory scores (tenosynovitis + synovitis + osteitis) were lower among patients in clinical remission. Lower MRI scores were correlated with longer duration of Clinical Disease Activity Index (CDAI) remission (ρ = 0.22, P = 0.03). At the time of MRI, 89 patients had no wrist pain/tenderness/swelling; however, all 118 patients had MRI evidence of residual joint inflammation after 2 years. No statistically significant differences in damage or MRI inflammatory scores were observed across treatment groups. CONCLUSION: This is the first detailed appraisal describing the relationship between clinical remission cut points and MRI inflammatory scores within an RA randomized controlled trial. The most stringent remission criteria (2011 ACR/EULAR and CDAI) best differentiate the total MRI inflammatory scores. These results document that 2 years of triple therapy or tumor necrosis factor plus methotrexate treatment in early RA does not eliminate MRI evidence of joint inflammation.

Older age at rheumatoid arthritis onset and comorbidities correlate with less Health Assessment Questionnaire-Disability Index and Clinical Disease Activity Index response to etanercept in the RADIUS 2 registry.

BACKGROUND: Controversy exists in understanding the effects of age at onset and comorbidities in predicting rheumatoid arthritis (RA) response to biologic therapy. OBJECTIVE: The objective of this study was to investigate the influence of age at onset and number of comorbidities on Health Assessment Questionnaire-Disability Index (HAQ-DI) and Clinical Disease Activity Index (CDAI) responses in active RA patients after 6 months of treatment with etanercept. METHODS: One thousand eight hundred ninety-nine RA patients were assessed after 6 months of etanercept therapy. Patients met the following inclusion criteria: initiated etanercept, continued therapy for at least 6 months, and were not in CDAI low disease activity (LDA) at baseline (CDAI ≤10.0). Changes in HAQ-DI and CDAI scores over 6 months were analyzed across age of onset quintiles. Multivariate regression models evaluated the independent association between both age at onset and number of comorbidities with change in HAQ-DI/CDAI scores or achieving LDA, while accounting for other covariates. RESULTS: Significant improvements in HAQ-DI and CDAI scores were observed in all age-onset groups, although HAQ-DI improvements were less in older-onset patients. Results of multiple linear regression demonstrated that younger age at onset, higher baseline HAQ-DI/CDAI score, rheumatoid factor positivity, shorter disease duration, and fewer comorbidities at baseline were independently associated with improvement in both HAQ-DI and CDAI scores. Similarly, achieving CDAI LDA after 6 or more months of etanercept was associated with younger age at onset, higher baseline CDAI, shorter disease duration, and fewer comorbidities. CONCLUSIONS: These patients with older-onset RA and more comorbidities clinically improved with etanercept, but had lower odds of achieving CDAI LDA. Age of onset and number of comorbidities may be important in determining RA tumor necrosis factor inhibitor response.