Clinical profiling, treatment characteristics and outcome in Behcet's Disease (BD)-A retrospective cohort study from Karnataka Rheumatology Association (KRA).

BACKGROUND: Behcet's disease (BD) has a heterogeneous and unpredictable phenotype that differs in various geographical areas. OBJECTIVE: To describe the clinical phenotype & outcome of Behcet's disease(BD) from Karnataka, India and compare them with large cohorts from endemic regions. METHODS: Databases of practising rheumatologists from Karnataka were reviewed to retrieve clinical characteristics, course of illness, prescribing information and outcome at last follow-up of patients clinically diagnosed as BD. The classification criteria, namely revised International criteria for Behcet's disease (rICBD) and International study group (ISG) criteria were applied. Outcome was defined as complete or partial remission, persistent disease or relapse. RESULTS: We included 72 patients, equal gender distribution and mean age 37.4 ± 12.8 years from 8 rheumatology centres. Commonest presentations were recurrent oral aphthosis 58(80.6%), genital ulcers 36(50%) and ocular manifestations 40(55.6%). Three-quarters [51/72(70.8%)] fulfilled rICBD criteria whereas only half [36/72(50%)] fulfilled ISG criteria. Apart from glucocorticoids [53/72(73.6%)], frequently prescribed therapies were colchicine 39(54.2%) and azathioprine 35(48.6%). Eleven-patients received biologics(anti-TNF-α) and JAK inhibitors to treat severe organ involvement. HLA-B*51 and pathergy tests were positive in 27/45(60%) and 12/34(35.3%) patients respectively. Outcomes were documented in 94.4%(68/72) patients at median follow-up of 24 (12;36) months. Majority [46/68(67.6%)] had complete remission, 17/68(25%) had partial remission, 4/68(5.9%) had persistent while 1/68(1.5%) had relapsing course. CONCLUSION: Majority of BD patients had orogenital aphthosis and ocular manifestations and an excellent response to treatment. Key Points • In our region, Behçet's Disease primarily manifests with recurrent oral aphthae and ocular involvement, with comparatively lower incidence of severe genital ulcers and neurological involvement than in endemic regions. • Apart from glucocorticoids, colchicine and azathioprine are the most commonly used agents. Biologics and JAK inhibitors are prescribed infrequently, primarily in cases of severe organ involvement. • A significant proportion of patients achieved either complete or partial remission during follow-up, with no observed mortality suggesting a milder disease course and better outcome compared to endemic regions. • Gender, HLA-B*51 status, and pathergy response did not exert any significant influence on the clinical profile or outcome in BD patients in Karnataka.

Acute transitory head mislocalization - a novel syndrome of pathological embodiment in a patient with traumatic brain injury - a case study.

Feeling of body ownership is a complex process with different brain mechanisms involved in integrating the varied and multiple representations of the body . The ability to discriminate between one's own and others' body parts can be lost after brain damage. We report a unique case study of a patient with head injury who experienced a phenomenon where he felt that his head was positioned with another person standing next to him. We describe this as a form of pathological embodiment and call it the "head mislocalization" phenomenon. We report his clinical findings and using the methods of lesion mapping and lesion network mapping postulate the neural mechanisms for this symptom.

Assessing frailty in older Indian patients before cancer treatment: Comparative analysis of three scales and their implications for overall survival.

INTRODUCTION: Frailty, characterized by ageing-related vulnerability, influences outcomes in older adults. Our study aimed to investigate the relationship between frailty and clinical outcomes in older Indian patients with cancer. MATERIALS AND METHODS: Our observational single-centre study, conducted at Tata Memorial Hospital from February 2020 to July 2022, enrolled participants aged 60 years and above with cancer. Frailty was assessed using the Clinical Frailty Scale (CFS), G8, and Vulnerable Elders Survey (VES)-13. The primary objective was to explore the correlation between baseline frailty and overall survival. Statistical analyses include Kaplan-Meier, Cox proportional hazards, and Harrell's C test. RESULTS: A total of 1,177 patients (median age 68, 76.9% male) were evaluated in the geriatric oncology clinic. Common malignancies included lung (40.0%), gastrointestinal (35.8%), urological (11.9%), and head and neck (9.0%), with 56.5% having metastatic disease. Using CFS, G8, and VES-13 scales, 28.5%, 86.4%, and 38.0% were identified as frail, respectively. Median follow-up was 11.6 months, with 43.3% deaths. Patients fit on CFS (CFS 1-2) had a median survival of 28.02 months, pre-frail (CFS 3-4) 13.24 months, and frail (CFS ≥5) 7.79 months (p < 0.001). Abnormal G8 (≤14) and VES-13 (≥3) were associated with significantly lower median survival (p < 0.001). Multivariate analysis confirmed CFS's predictive power for mortality (p < 0.001), with hazard ratios [HRs] for pre-frail at 1.61(95% confidence interval [CI] 1.25 to 2.06) and frail at 2.31 (95%CI 1.74 to 3.05). G8 ≤ 14 had HR 2.00 (95%CI 1.42 to 2.83), and abnormal VES-13 had HR 1.36 (95%CI 1.11-1.67). In the likelihood ratio test, CFS significantly improved the model fit (p < 0.001). Harrell's C index for survival prediction was 0.62 for CFS, 0.54 for G8, and 0.58 for VES-13. DISCUSSION: In conclusion, our study highlights varying frailty prevalence and prognostic implications in older Indian patients with cancer, emphasizing the need for personalized care in oncology for this aging population. We would recommend using CFS as a tool to screen for frailty for older Indian patients with cancer.

Self-motion induced environmental kinetopsia and pop-out illusion - Insight from a single case phenomenology.

Stable visual perception, while we are moving, depends on complex interactions between multiple brain regions. We report a patient with damage to the right occipital and temporal lobes who presented with a visual disturbance of inward movement of roadside buildings towards the centre of his visual field, that occurred only when he moved forward on his motorbike. We describe this phenomenon as "self-motion induced environmental kinetopsia". Additionally, he was identified to have another illusion, in which objects displayed on the screen, appeared to pop out of the background. Here, we describe the clinical phenomena and the behavioural tasks specifically designed to document and measure this altered visual experience. Using the methods of lesion mapping and lesion network mapping we were able to demonstrate disrupted functional connectivity in the areas that process flow-parsing such as V3A and V6 that may underpin self-motion induced environmental kinetopsia. Moreover, we suggest that altered connectivity to the regions that process environmental frames of reference such as retrosplenial cortex (RSC) might explain the pop-out illusion. Our case adds novel and convergent lesion-based evidence to the role of these brain regions in visual processing.

Performance of potentially inappropriate medications assessment tools in older Indian patients with cancer.

BACKGROUND: Polypharmacy and potentially inappropriate medication (PIM) use are common problems in older adults. Safe prescription practices are a necessity. The tools employed for the identification of PIM sometimes do not concur with each other. METHODS: A retrospective analysis of patients ≥60 years who visited the Geriatric Oncology Clinic of the Tata Memorial Hospital, Mumbai, India from 2018 to 2021 was performed. Beer's-2015, STOPP/START criteria v2, PRISCUS-2010, Fit fOR The Aged (FORTA)-2018, and the EU(7)-PIM list-2015 were the tools used to assess PIM. Every patient was assigned a standardized PIM value (SPV) for each scale, which represented the ratio of the number of PIMs identified by a given scale to the total number of medications taken. The median SPV of all five tools was considered the reference standard for each patient. Bland-Altman plots were utilized to determine agreement between each scale and the reference. Association between baseline variables and PIM use was determined using multiple logistic regression analysis. RESULTS: Of the 467 patients included in this analysis, there were 372 (79.66%) males and 95 (20.34%) females with an average age of 70 ± 5.91 years. The EU(7)-PIM list was found to have the highest level of agreement given by a bias estimate of 0.010, the lowest compared to any other scale. The 95% CI of the bias was in the narrow range of -0.001 to 0.022, demonstrating the precision of the estimate. In comparison, the bias (95%) CI of Beer's criteria, STOPP/START criteria, PRISCUS list, and FORTA list were -0.039 (-0.053 to -0.025), 0.076 (0.060 to 0.092), 0.035 (0.021 to 0.049), and -0.148 (-0.165 to -0.130), respectively. Patients on polypharmacy had significantly higher PIM use compared to those without (OR = 1.47 (1.33-1.63), p = <0.001). CONCLUSIONS: The EU(7)-PIM list was found to have the least bias and hence can be considered the most reliable among all other tools studied.

Comparison of Risk Factors During First and Second Wave of COVID-19 in Patients with Autoimmune Rheumatic Diseases (AIRD): Results from KRACC Subset.

Background: The differential influence and outcome of various risk factors on occurrence of COVID-19 among patients with autoimmune rheumatic diseases (AIRD) during different COVID-19 peaks is underreported. Aim: To assess the impact and outcome of conventional risk factors, immunosuppressants, and comorbidities on the risk of COVID-19 among AIRD patients during the first two COVID-19 peaks. Design: Prospective, non-interventional longitudinal cohort study. Methods: This is a subset of the KRA COVID19 cohort undertaken during the initial wave of COVID-19 (W1) (Apr-Dec2021); and the 2nd-wave (W2) (Jan-Aug2021). Data collected included description of AIRD subsets, treatment characteristics, comorbidities, and COVID-19 occurrence. Risk factors associated with mortality were analysed. The incidence rate was compared with that of the general population in the same geographic region. Results: AIRD patients (n=2969) had a higher incidence of COVID-19 in the W2 (7.1%) than in the W1 (1.7%) as compared to the general population (Government bulletin). Age (p<0.01) and duration of AIRD (p<0.001) influenced COVID-19 occurrence in W2 while major disease subsets and immunosuppressants including glucocorticoids did not. The W2 had lower HCQ usage (Adjusted Odds Ratio [AOR]-0.81) and comorbidities like hypertension (AOR -0.54) and pre-existing lung disease (AOR -0.38;0.19-0.75) compared to W1. Older age (1.11) and coexistent diabetes mellitus (AOR 6.74) were independent risk factors associated with mortality in W2. Conclusions: We report 1.7 times higher occurrence, and no influence of major disease subsets or immunosuppressants including glucocorticoids on COVID-19. Age and diabetes were independent risk factors for mortality.

The current status of geriatric oncology in India.

Geriatric oncology in India is relatively new. The number of older persons with cancer is increasing exponentially; at our institution, 34% of patients registered are 60 years and over. Apart from the Tata Memorial Hospital in Mumbai, there are currently no other Indian centers that have a dedicated geriatric oncology unit. Geriatric assessments (GAs) are done sporadically, and older patients with cancer are usually assessed and treated based on clinical judgement. Challenges to increasing the uptake of GA include a lack of training/time/interest or knowledge of the importance of the GA. Other challenges include a lack of trained personnel with expertise in geriatric oncology, and a paucity of research studies that seek to advance the outcomes in older Indian patients with cancer. We anticipate that over the next 10 years, along with the inevitable increase in the number of older persons with cancer in India, there will be a commensurate increase in the number of skilled personnel to care for them. Key goals for the future include increased research output, increased number of dedicated geriatric oncology units across the country, India-specific geriatric oncology guidelines, geriatric oncology training programs, and a focus on collaborative work across India and with global partners. In this narrative review, we provide a broad overview of the status of geriatric oncology in India, along with a description of the work done at our center. We hope to spark interest and provide inspiration to readers to consider developing geriatric oncology services in other settings.

Occurrence and outcome of COVID-19 in AIRD patients on concomitant treatment with Tofacitinib- results from KRA COVID COHORT (KRACC) subset.

INTRODUCTION: We assessed the risk factors and outcome of COVID-19 in patients with autoimmune rheumatic diseases(AIRD) who contracted infection while on background treatment with tofacitinib. METHODS: This is a non-interventional, cross-sectional, questionnaire based telephonic study which included consecutive AIRD patients on tofacitinib co-treatment. Data related to the AIRD subset, disease modifying anti rheumatic drugs(DMARDs) including glucocorticoids and comorbidities, was collected from 7 rheumatology centers across Karnataka during the second wave of COVID-19 pandemic. The information about COVID-19 occurrence and COVID-19 vaccination was recorded. RESULTS: During the study period (Jun-July 2021), 335 AIRD patients (80.6% female) on treatment with tofacitinib were included. The mean duration of tofacitinib use was 3.4+/-3.1months. Thirty-six(10.75%) patients developed COVID-19. Diabetes mellitus (p = 0.04 (OR 2.60 (1.13-5.99)) was identified as a risk factor for COVID-19 in our cohort. Almost half of our cohort was COVID-19 vaccinated with at least one dose, with resultant decline in incidence of COVID-19(OR 0.15 (0.06-0.39) among the vaccinated. Recovery amongst COVID-19 infection group was 91.2%. CONCLUSIONS: The subset of AIRD patients who were on treatment with tofacitinib were found to have a higher rate of COVID-19 infection as compared to our KRACC cohort. Pre-existing comorbidity of diabetes mellitus was the significant risk factor in our cohort. This subset of the KRACC cohort shows RA patients had a lesser infection and PsA patients had a higher infection.

Validation of the Onco-MPI in predicting short-term mortality in older Indian patients with cancer.

INTRODUCTION: The number of older patients with cancer is increasing exponentially worldwide, and a similar trend has also been noted in India. The Multidimensional Prognostic Index (MPI) strongly correlates the presence of individual comorbidities with mortality, and the Onco-MPI prognosticates patients accurately for overall mortality. However, limited studies have evaluated this index in patient populations beyond Italy. We evaluated the performance of the Onco-MPI index in predicting mortality in older Indian patients with cancer. MATERIALS AND METHODS: This observational study was conducted between October 2019 and November 2021 in the Geriatric Oncology Clinic at Tata Memorial Hospital in Mumbai, India. The data of patients aged ≥60 years with solid tumors who underwent a comprehensive geriatric assessment was analysed. The study's primary aim was to calculate the Onco-MPI for patients in the study and correlate it with one-year mortality. RESULTS: A total of 576 patients aged ≥60 years were included in the study. The median age (range) of the population was 68 (60-90) years, and 429 (74.5%) were male. After a median follow-up of 19.2 months, 366 (63.7%) patients had died. The proportion of patients classified as low risk (0-0.46), moderate risk (0.47-0.63) and high risk (0.64-1.0) were 38% (219 patients), 37% (211 patients) and 25% (145 patients), respectively. There was a significant difference in one-year mortality rates between the low-risk patients compared to medium and high-risk patients (40.6% vs 53.1% vs 71.7%; p < 0.001). DISCUSSION: The current study validates the Onco-MPI as a predictive tool for estimating short-term mortality in older Indian patients with cancer. Further prospective studies need to build on this index to obtain a score with greater discrimination in the Indian population.

Safety, immunogenecity and effectiveness of ChAdOx1 nCoV-19 vaccine during the second wave of pandemic in India: a real-world study.

OBJECTIVES: This real-world study was conducted to assess the adverse effects following immunization (AEFI) and immunogenicity of ChAdO×1 nCoV-19 vaccine in terms of neutralising antibody titers and to study the effects of covariates such as age, sex, comorbidities and prior COVID status on these outcomes. Also, the effectiveness of the vaccine based on interval between the two doses was also investigated. METHODS: A total of 512 participants (M/F=274/238) aged 35(18-87) years comprising a mixed population of healthcare workers, other frontline workers and general public were enrolled between March and May 2021. Records for adverse events if any were collected telephonically by following up with participants up to 6 months post first dose and graded as per Common Terminology Criteria for Adverse Events (CTCAE) version 5. Blood samples for measuring antibody titers against the receptor binding domain (RBD) were collected serially using a convenient sampling strategy up to 6 months after the first dose. Data on breakthrough COVID infection was collected telephonically till December 2021. RESULTS: Incidence of local reactions was higher after first dose at 33.4 % (171/512) compared to those after second dose at 12.9 % (66/512). Commonest side effect observed was injection site pain after the first (87.1 %; 149/171) and second (87.9 %; 56/66) dose respectively. Among systemic reactions, fever was the most common manifestation followed by myalgia and headache. Female sex (p<0⸱001) and age less than 60 years (p<0⸱001) had significantly higher predilection for systemic toxicities. Age ≤60 years (p=0.024) and prior-COVID (p<0.001) were found to be significantly associated with higher antibody titers, however, no association was found between these variables and breakthrough COVID infection. Longer spacing between the doses (≥6 weeks) was found to offer better protection against breakthrough infection compared to a spacing of 4 weeks. All breakthroughs were mild-moderate in severity, not requiring hospitalization. CONCLUSIONS: The ChAdOx1 nCov-19 vaccine is apparently safe and effective against SARS-CoV-2 virus infection. Prior COVID infection and younger age group achieve higher antibody titers, but no additional protection. Delaying the second dose up to at least 6 weeks is more effective compared to shorter spacing between doses.

A Practical Ambulatory Approach to Atrioventricular Block Secondary to Lyme Carditis.

Lyme carditis (LC) is a potentially reversible cause of complete atrioventricular (AV) dissociation that rarely requires a permanent pacemaker. The time to resolution is variable, sometimes requiring weeks, making a temporary permanent pacemaker (TPPM) a suitable bridge to recovery. We report on a 31-year-old man with serology-confirmed Lyme disease with complete heart block during the peak of the coronavirus disease 2019 pandemic. A TPPM was implanted and the patient was discharged the following day with regular follow-up in the ambulatory setting. Once 1:1 AV conduction was reestablished, the TPPM was removed. Our case demonstrates that the use of a TPPM for AV-dissociation secondary to LC is a safe and feasible strategy in select individuals which can minimize patient morbidity as well as hospital length of stay and overall health care costs.

Risk factors associated with COVID-19 in systemic lupus erythematosus: Results from a longitudinal prospective cohort.

INTRODUCTION: Patients with SLE (systemic lupus erythematosus) have a higher risk of infection due to dysregulated immune system as well as long-term use of immunosuppressants (IS). This could influence the risk of COVID-19 and its outcome. METHODS: We conducted a longitudinal prospective study across 15 rheumatology centres during the first wave of the pandemic to understand the risk factors contributing to COVID-19 in SLE patients. During the 6 months follow-up, those who tested positive for COVID-19, their clinical course and outcome information were recorded. RESULTS: Through the study period (April-December 2020), 36/1379 lupus patients (2.9%) developed COVID-19. On analysing the COVID-19 positive versus negative cohort during the study period, male gender (adjusted RR 3.72, 95% C.I. 1.85,7.51) and diabetes (adjusted RR 2.94, 95% C.I. 1.28, 6.79) emerged as the strongest risk factors for COVID-19, in the adjusted analysis. There was no significant influence of organ involvement, hydroxychloroquine, glucocorticoid dosage (prednisolone< 7.5 mg or ≥ 7.5 mg/day) or IS on the risk of COVID-19. There was only one death (1/36) among the lupus patients due to COVID-19. CONCLUSION: Traditional risk factors rather than lupus disease process or IS influenced the risk of COVID-19 in our cohort.

Comparative Evaluation of Solubility of Gutta-Percha in Three Different Solvents: A Cone-Beam Computed Tomography (CBCT) Study.

Background Gutta-percha is the most frequently used filling material for root canal obturation. This thermoplastic material fulfills the primary requisites for root canal filling, one of which is easily removable material in cases of endodontic retreatment. The most commonly used solvents were chloroform, xylene, and orange oil due to their effectiveness in dissolving and removing maximum gutta-percha in a minimum time. Aims The aim is to evaluate and compare the solubility of gutta-percha in three different organic solvents, i.e., orange oil, xylene, and chloroform. Methods and material Forty extracted mandibular second premolars with a single canal were selected. The sample was categorized into control, orange oil, xylene, and chloroform. Access cavity preparations with cleaning and shaping were performed by k files and rotary files, followed by obturation. Two drops of assigned solvent were placed on the orifices of the obturated canal, and corona-gutta-percha ha was removed by gates glidden drills. Cone-beam computed tomography (CBCT) images were taken before and after the gutta-percha removal, and the solvents' efficacy was assessed. Statistical analysis The statistical test applied for the analysis was one-way analysis of variance (ANOVA). The confidence interval and p-value were set for this test at 95% and < 0.05, respectively. Results Gutta-percha Removal was found to be maximum with orange oil (Group II) followed by xylene (Group III) >Chloroform (Group IV) >Control Group. The Statistical Analysis by ANOVA revealed a significant difference between the four groups with a p-value of less than 0.05. Furthermore, the pair-wise comparison revealed that the amount of gutta-percha removal with orange oil significantly differs from xylene and chloroform, with a significance level of less than 0.021,001. However, there was no difference observed between control and chloroform. Conclusions Within the limitations of this in vitro study, it can be concluded that the maximum amount of gutta-percha removal was found in the orange oil group. The amount of gutta-percha removal with orange oil significantly differs from xylene and chloroform, with a significance level of less than 0.02,001. Hence there was no difference observed between Control and Chloroform groups.

Revisiting the Conundrum: A Case Report on Trauma Whipple's Pancreaticoduodenectomy.

Despite its rarity, pancreatic trauma is a serious condition because of its retroperitoneal location, association with other organ injuries, and complex bilio-vascular anatomy. Even less common are isolated pancreatic injuries. In grade four injuries, there is a debate over resectional vs. non-resectional management and appropriate treatment is particularly difficult. Here we discuss a patient with grade four pancreatic injury with pancreatic ascites presenting four days after the incident and traumatic pancreatitis. She underwent pylorus-preserving pancreatoduodenectomy and recovered well with acceptable morbidity.

Role of ADME gene polymorphisms on imatinib disposition: results from a population pharmacokinetic study in chronic myeloid leukaemia.

PURPOSE: Imatinib is a substrate of CYP3A4, ABCB1 and ABCG2, and is known to have wide variability in pharmacokinetics (PK). At the same time, a clear relationship between drug levels and response also exists for imatinib in chronic myeloid leukaemia (CML). Therefore, pharmacogenetic-based dosing of imatinib is an attractive proposition. This study aims to characterize the population pharmacokinetics of imatinib in order to identify significant covariates including pharmacogenetic variants. METHODS: Forty-nine patients with CML were enrolled in the study after being on imatinib for at least 4 consecutive weeks. Steady-state pharmacokinetic sampling was performed either in a sparse (4 samples each, n = 44) or intensive manner (9 samples each, n = 5). An additional pharmacogenetic sample was also collected from all patients. Plasma imatinib levels were estimated using a validated HPLC method. Pharmacogenetic variants were identified using the PharmacoScan array platform. Population pharmacokinetic analysis was carried out using NONMEM v7.2. Seven SNPs within CYP3A4, ABCB1 and ABCG2 genes were evaluated for covariate effect on the clearance of imatinib. RESULTS: Imatinib PK was well characterized using a one-compartment model with zero-order absorption. The clearance and volume of distribution were found to be 10.2 L/h and 389 L respectively. Only SNP rs1128503 of the ABCB1 gene had a small but insignificant effect on imatinib clearance, with a 25% reduction in clearance observed in patients carrying the polymorphism. Twenty-three out of forty-nine patients (47%) carried the polymorphic allele, of whom 17 were heterozygous and six were homozygous. CONCLUSION: Our study conclusively proves that genetic polymorphisms in the CYP3A4 and ABC family of transporters do not have any role in the personalized dosing of imatinib in CML.