Clinicopathological analysis of BRAF and non-BRAF MAPK pathway-altered gliomas in paediatric and adult patients: a single-institution study of 40 patients.

AIMS: Mitogen-activated protein kinase (MAPK) pathway alteration is a major oncogenic driver in paediatric low-grade gliomas (LGG) and some adult gliomas, encompassing BRAF (most common) and non-BRAF alterations. The aim was to determine the frequency, molecular spectrum and clinicopathological features of MAPK-altered gliomas in paediatric and adult patients at our neuropathology site in Kuwait. METHODS: We retrospectively searched the data of molecularly sequenced gliomas between 2018 and 2023 for MAPK alterations, revised the pathology in view of the 2021 WHO classification and evaluated the clinicopathological data for possible correlations. RESULTS: Of 272 gliomas, 40 (15%) harboured a MAPK pathway alteration in 19 paediatric (median 9.6 years; 1.2-17.6) and 21 adult patients (median 37 years; 18.9-89.2), comprising 42% and 9% of paediatric and adult cases, respectively. Pilocytic astrocytoma and glioblastoma were the most frequent diagnoses in children (47%) and adults (43%), respectively. BRAF V600E (n=17, 43%) showed a wide distribution across age groups, locations and pathological diagnoses while KIAA1549::BRAF fusion (n=8, 20%) was spatially and histologically restricted to cerebellar paediatric LGGs. Non-V600E variants and BRAF amplifications accompanied other molecular aberrations in high-grade tumours. Non-BRAF MAPK alterations (n=8) included mutations and gene fusions involving FGFR1, NTRK2, NF1, ROS1 and MYB. Fusions included KANK1::NTRK2, GOPC::ROS1 (both infant hemispheric gliomas), FGFR1::TACC1 (diffuse LGG), MYB::QKI (angiocentric glioma) and BCR::NTRK2 (glioblastoma). Paradoxical H3 K27M/MAPK co-mutations were observed in two LGGs. CONCLUSION: The study provided insights into MAPK-altered gliomas in Kuwait highlighting the differences among paediatric and adult patients and providing a framework for planning therapeutic polices.

Adherence to the Mediterranean diet is associated with a reduced DAS28 index among patients with rheumatoid arthritis: Case study from KRRD.

BACKGROUND: Rheumatoid arthritis (RA) is a chronic, autoimmune disease that mostly affects the synovial joints. It has been hypothesized that dietary and other environmental and lifestyle factors contribute to the development of RA and its severity. OBJECTIVE: The present study aims to measure the effect of the Mediterranean diet (MedDiet) on the disease activity scores (DAS28) among patients with RA. METHODS: Adult patients who satisfied the American College of Rheumatology (ACR) classification criteria for RA from major hospitals in Kuwait were evaluated. A cross-sectional study conducted on 754 RA patients visits aged (21-79) years. Patients were evaluated using the DAS28. Patients' levels of adherence to the MedDiet are assessed using a validated 14-item Questionnaire (paper or web-based). The data was analyzed using both multivariate and univariate statistics. Multivariate logistic regression was used to analyze the statistical relationship between MedDiet and RA disease activity. RESULTS: The finding suggests that a MedDiet can have a positive impact on DAS28 among patients with RA. In the DAS28 cohort (DAS28 < 3.2, DAS28 ≥ 3.2), several Mediterranean survey components showed statistically significant differences. Patients with a Mediterranean score ≤ 5 was more likely to have hazard effects for DAS28 than those with a Mediterranean score of ≥10 (HR = 0.17, CI [0.08-0.37], p < .001). The finding shows that, Mediterranean levels ≤5, on biologics treatment, CRP, and patient global assessment were significantly associated with overall survival. Additionally, the MedDiet was found to be a significant predictor of DAS28 in the random forest decision tree plot, along with tender, RF, and creatinine. MedDiet patients had a lower DAS28 score than others. CONCLUSION: The findings suggest that optimal drug treatment and a restrictive diet can help to improve DAS28 score for patients with RA. More patients in the cohort DAS28 <3.2 used olive oil, servings of vegetables, fruits, and legumes. In contrast, more patients in the cohort DAS28 ≥ 3.2 consumed red meat, butter, sweetened or soft drinks, cakes, cookies, or biscuits, and tomato sauce.

Prevalence of Latent Tuberculosis Infection Among Rheumatology Patients and Management Practices in the United Arab Emirates: A Single-Center Retrospective Cohort Study.

Introduction Prior to immunosuppression, rheumatology patients are routinely screened for latent tuberculosis (TB) infection using interferon-gamma release assays (IGRAs). Variability in the management of latent and indeterminate IGRA results across institutions limited long-term outcome data. A retrospective study was conducted at Tawam Hospital, United Arab Emirates, to investigate the incidence and management protocols associated with positive and indeterminate IGRA results, as well as TB infection, among patients with rheumatic conditions. Methods A single-center retrospective observational study was performed at Tawam Hospital, Abu Dhabi, UAE. Ethical approval for this study was obtained from the Tawam Human Research Ethics Committee. Laboratory records and the hospital's electronic medical system were used to obtain information about IGRA results over a 12-year period (April 2010-April 2022). The hospital's electronic medical system was used to obtain patient information and subsequent management approaches of positive and indeterminate IGRAs. Moreover, long-term follow-up data were collected to determine the risk of TB reactivation in the cohort. Results We found a total of 1,012 positive and 223 indeterminate IGRA test results within the 12-year period. Within the rheumatology department, 123 positive and 39 indeterminate IGRA results were identified. In the indeterminate IGRA group, the majority were women (n = 24, 61.5%) and UAE nationals (n = 22, 56.4%), and their mean age was 38.6 years. Systemic lupus erythematosus was the most prevalent rheumatologic condition (n = 21, 53.8%). Thirteen (33.3%) were on disease-modifying anti-rheumatic drugs (DMARDs) and 26 (66.7%) were on corticosteroids during IGRA testing. A total of eight patients (20.5%) received anti-TB medications. In the positive IGRA group, the mean age was 55.7 years and the female-to-male ratio was 3:1. The most common rheumatologic condition was rheumatoid arthritis (n = 69, 56%). Sixty-five (52.8%) patients were on conventional DMARDs, 43 (34.9%) were on corticosteroids during IGRA testing, and 74 (60%) received anti-TB medications. Two cases (1.6%) of active TB infections were detected among patients with positive IGRA tests, both of whom were receiving anti-tumor necrosis factor alpha inhibitor treatment in combination with methotrexate. No cases of active TB infection were observed in the indeterminate IGRA group. Conclusion Long-term data on the risk of TB activation in positive and indeterminate IGRA results for rheumatological conditions are low. It is recommended to reassess the choice of using anti-TNF-α, with a positive IGRA result if no other feasible alternatives can be offered. Our findings stress the importance of age, underlying diseases, and immunosuppressive treatments in interpreting IGRA results and guiding patient management. A large multicenter study is needed to understand the differences and outcomes of such patients in TB endemic and nonendemic geographical areas.

In-hospital Mortality Rates in SARS-CoV-2 Patients Treated with Enoxaparin and Heparin.

OBJECTIVES: This study aimed to investigate in-hospital mortality rates in patients with coronavirus disease (COVID-19) according to enoxaparin and heparin use. METHODS: This retrospective cohort study included 962 patients admitted to two hospitals in Kuwait with a confirmed diagnosis of COVID-19. Cumulative all-cause mortality rate was the primary outcome. RESULTS: A total of 302 patients (males, 196 [64.9%]; mean age, 57.2 ± 14.6 years; mean body mass index, 29.8 ± 6.5 kg/m2) received anticoagulation therapy. Patients receiving anticoagulation treatment tended to have pneumonia (n = 275 [91.1%]) or acute respiratory distress syndrome (n = 106 [35.1%]), and high D-dimer levels (median [interquartile range]: 608 [523;707] ng/mL). The mortality rate in this group was high (n = 63 [20.9%]). Multivariable logistic regression, the Cox proportional hazards, and Kaplan-Meier models revealed that the use of therapeutic anticoagulation agents affected the risk of all-cause cumulative mortality. CONCLUSION: Age, hypertension, pneumonia, therapeutic anticoagulation, and methylprednisolone use were found to be strong predictors of in-hospital mortality. In elderly hypertensive COVID-19 patients on therapeutic anticoagulation were found to have 2.3 times higher risk of in-hospital mortality. All cause in-hospital mortality rate in the therapeutic anticoagulation group was up to 21%.

Correction to: Exploring the impact of air pollution on COVID-19 admitted cases: Evidence from vector error correction model (VECM) approach in explaining the relationship between air pollutants towards COVID-19 cases in Kuwait.

[This corrects the article DOI: 10.1007/s42081-022-00165-z.].

In-hospital mortality in SARS-CoV-2 stratified by the use of corticosteroid.

Objective: To investigate COVID-19 related mоrtаlity according to the use of corticosteroid therapy. Design: Retrospective cohort study. Setting: Two tertiary hospitals in Kuwait. Participants: Overall, 962 patients with confirmed SARS-CoV-2 infection, were stratified according to whether they were treated with corticosteroids (dexamethasone or methylprednisolone). The mean age of the patients was 50.2 ± 15.9 years and 344/962 (35.9%) were female. Main outcome measures: In-hospital mortality and cumulative all-cause mortality. Results: Compared to non-corticosteroid therapy patients, corticosteroid therapy patients had a higher prevalence of hypertension, diabetes mellitus, cardiovascular disease, chronic lung disease, and chronic kidney disease; a longer hospital stay (median [IQR]: 17.0 [5.0-57.3] days vs 14.0 [2.0-50.2] days); and a higher in-hospital mortality (51/199 [25.6%] vs 36/763 [4.7%]). Logistic regression analysis showed a higher in-hospital mortality in the corticosteroid group (adjusted odds ratio [aOR]: 4.57, 95% confidence interval [CI]: 2.64-8.02, p < 0.001). Cox proportional hazards regression showed that corticosteroid use was a significant predictor of mortality (hazard ratio [HR]: 3.96, p < 0.001). Conclusions: In-hospital mortality in patients with SARS-CoV-2 on corticosteroid therapy was 4.6 times higher than in those without corticosteroid therapy.

Exploring the impact of air pollution on COVID-19 admitted cases: Evidence from vector error correction model (VECM) approach in explaining the relationship between air pollutants towards COVID-19 cases in Kuwait.

In urban areas, air pollution is one of the most serious global environmental issues. Using time-series approaches, this study looked into the validity of the relationship between air pollution and COVID-19 hospitalization. This time series research was carried out in the state of Kuwait; stationarity test, cointegration test, Granger causality and stability test, and test on multivariate time-series using the Vector Error Correction Model (VECM) technique. The findings reveal that the concentration rate of air pollutants ( O 3 , SO 2 , NO 2 , CO , and PM 10 ) has an effect on COVID-19 admitted cases via Granger-cause. The Granger causation test shows that the concentration rate of air pollutants ( O 3 , PM 10 , NO 2 , temperature and wind speed) influences and predicts the COVID-19 admitted cases. The findings suggest that sulfur dioxide ( SO 2 ), NO 2 , temperature, and wind speed induce an increase in COVID-19 admitted cases in the short term according to VECM analysis. The evidence of a positive long-run association between COVID-19 admitted cases and environmental air pollution might be shown in the cointegration test and the VECM. There is an affirmation that the usage of air pollutants ( O 3 , SO 2 , NO 2 , CO , and PM 10 ) has a significant impact on COVID-19-admitted cases' prediction and its explained about 24% of increasing COVID-19 admitted cases in Kuwait.

In-hospital mortality in SARS-CoV-2 stratified by gamma-glutamyl transferase levels.

BACKGROUND: This study investigates in-hospital mortality amongst patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its relation to serum levels of gamma-glutamyl transferase (GGT). METHODS: Patients were stratified according to serum levels of gamma-glutamyl transferase (GGT) (GGT<50 IU/L or GGT≥50 IU/L). RESULTS: A total of 802 participants were considered, amongst whom 486 had GGT<50 IU/L and a mean age of 48.1 (16.5) years, whilst 316 had GGT≥50 IU/L and a mean age of 53.8 (14.7) years. The chief sources of SARS-CoV-2 transmission were contact (366, 45.7%) and community (320, 40%). Most patients with GGT≥50 IU/L had either pneumonia (247, 78.2%) or acute respiratory distress syndrome (ARDS) (85, 26.9%), whilst those with GGT<50 IU/L had hypertension (141, 29%) or diabetes mellitus (DM) (147, 30.2%). Mortality was higher amongst patients with GGT≥50 IU/L (54, 17.1%) than amongst those with GGT<50 IU/L (29, 5.9%). More patients with GGT≥50 required high (83, 27.6%) or low (104, 34.6%) levels of oxygen, whereas most of those with GGT<50 had no requirement of oxygen (306, 71.2%). Multivariable logistic regression analysis indicated that GGT≥50 IU/L (odds ratio [OR]: 2.02, 95% confidence interval [CI]: 1.20-3.45, p=0.009), age (OR: 1.05, 95% CI: 1.03-1.07, p<0.001), hypertension (OR: 2.06, 95% CI: 1.19-3.63, p=0.011), methylprednisolone (OR: 2.96, 95% CI: 1.74-5.01, p<0.001) and fever (OR: 2.03, 95% CI: 1.15-3.68, p=0.016) were significant predictors of all-cause cumulative mortality. A Cox proportional hazards regression model (B = -0.68, SE =0.24, HR =0.51, p = 0.004) showed that patients with GGT<50 IU/L had a 0.51-times lower risk of all-cause cumulative mortality than patients with GGT≥50 IU/L. CONCLUSION: Higher levels of serum GGT were found to be an independent predictor of in-hospital mortality.

Risk Factors for Mortality in Patients with COVID-19: The Kuwait Experience.

OBJECTIVES: To describe the baseline characteristics and to evaluate the risk factors for in-hospital mortality in patients admitted to hospitals with coronavirus disease (COVID-19) in Kuwait. SUBJECTS AND METHODS: This retrospective cohort study analyzed data of patients admitted to two hospitals in Kuwait with COVID-19. The outcome was assessed by using multivariable analysis of factors affecting survival and mortality. RESULTS: In 962 patients, the case fatality ratio was 9.04%. The mean age of nonsurvivors was 63.5 ± 14.8 years, and most deaths occurred in males (80.5%). For the whole sample, the source of transmission was significantly related to mortality and the median duration of in-hospital stay was 15 days (interquartile range: 2-52 days). In patients with high oxygen requirements, the case fatality rate was 96.6%. Multivariable analysis identified age, hypertension, cardiovascular disease (CVD), and dyspnea on presentation as independent risk factors for COVID-19 mortality. CONCLUSIONS: The mortality rate was higher in older patients with comorbidities such as hypertension and CVD. Early recognition of high-risk patients may help to improve care and reduce mortality.

Outcomes of tocilizumab therapy in severe or critical COVID-19 patients: A retrospective cohort, single-centre study.

OBJECTIVES: To assess the effectiveness and safety of tocilizumab, a humanised anti-interleukin-6 receptor antibody, in the treatment of critical or severe coronavirus disease 2019 (COVID-19) patients. METHODS: This was a retrospective cohort study of severe or critical COVID-19 patients (≥18 years) admitted to one hospital in Kuwait. Fifty-one patients received intravenous tocilizumab, while 78 patients received the standard of care at the same hospital. Both groups were compared for clinical improvement and in-hospital mortality. RESULTS: The tocilizumab (TCZ) group had a significantly lower 28-day in-hospital mortality rate than the standard-of care-group (21.6% vs. 42.3% respectively; p = 0.015). Fifty-five per cent of patients in the TCZ group clinically improved vs. 11.5% in the standard-of-care group (p < 0.001). Using Cox-proportional regression analysis, TCZ treatment was associated with a reduced risk of mortality (adjusted hazard ratio 0.25; 95% CI: 0.11-0.61) and increased likelihood of clinical improvement (adjusted hazard ratio 4.94; 95% CI: 2.03-12.0), compared to the standard of care. The median C-reactive protein, D-dimer, procalcitonin, lactate dehydrogenase and ferritin levels in the tocilizumab group decreased significantly over the 14 days of follow-up. Secondary infections occurred in 19.6% of the TCZ group, and in 20.5% of the standard-of-care group, with no statistical significance (p = 0.900). CONCLUSION: Tocilizumab was significantly associated with better survival and greater clinical improvement in severe or critical COVID-19 patients.

Handling missing data in a rheumatoid arthritis registry using random forest approach.

Missing data in clinical epidemiological research violate the intention-to-treat principle, reduce the power of statistical analysis, and can introduce bias if the cause of missing data is related to a patient's response to treatment. Multiple imputation provides a solution to predict the values of missing data. The main objective of this study is to estimate and impute missing values in patient records. The data from the Kuwait Registry for Rheumatic Diseases was used to deal with missing values among patient records. A number of methods were implemented to deal with missing data; however, choosing the best imputation method was judged by the lowest root mean square error (RMSE). Among 1735 rheumatoid arthritis patients, we found missing values vary from 5% to 65.5% of the total observations. The results show that sequential random forest method can estimate these missing values with a high level of accuracy. The RMSE varied between 2.5 and 5.0. missForest had the lowest imputation error for both continuous and categorical variables under each missing data rate (10%, 20%, and 30%) and had the smallest prediction error difference when the models used the imputed laboratory values.

Ferritin level: A predictor of severity and mortality in hospitalized COVID-19 patients.

INTRODUCTION: This study aims to investigate in-hоsрitаl mоrtаlity in severe асute resрirаtоry syndrоme соrоnаvirus 2 Ñ€Ð°tients strаtified by serum ferritin levels. METHODS: Patients were stratified based on ferritin levels (ferritin levels ≤ 1000 or >1000). RESULTS: Approximately 89% (118) of the patients with ferritin levels > 1000 had pneumonia, and 51% (67) had hypertension. Fever (97, 73.5%) and shortness of breath (80, 61%) were two major symptoms among the patients in this group. Logistic regression analysis indicated that ferritin level (odds ratio [OR] = 0.36, 95% confidence interval [CI] = 0.21-0.62; p < .001), male sex (OR = 2.63, 95% CI = 1.43-5.06; p = .003), hypertension (OR = 4.16, 95% CI = 2.42-7.36; p < .001) and pneumonia (OR = 8.48, 95% CI = 3.02-35.45; p < .001) had significance in predicting in-hospital mortality. Additionally, the Cox proportional hazards analysis and Kaplan-Meier survival probability plot showed a higher mortality rate among patients with ferritin levels > 1000. CONCLUSION: In this study, higher levels of serum ferritin were found to be an independent predictor of in-hоsрitаl mоrtаlity.

Don't close the book on tocilizumab for the treatment of severe COVID-19 pneumonia-the jury is still out: The Kuwait experience.

PURPOSE: This cross-sectional observational study aims to report preliminary data from the first experience using tocilizumab for patients with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection in three of Kuwait's largest public hospitals City. PATIENTS AND METHODS: This chart review study examined the benefits of tocilizumab treatment among 127 patients diagnosed with severe coronavirus disease of 2019 (COVID-19) pneumonia. RESULTS: 90 of 127 patients (71%) survived. Mortality was highest in the elderly with multiple medical conditions. CONCLUSION: Despite the small sample size and retrospective nature of the work, our findings are consistent with recent studies suggesting tocilizumab administration in patients presenting with severe COVID pneumonia with associated hyperinflammatory features conferred mortality benefit.

Handling Complex Missing Data Using Random Forest Approach for an Air Quality Monitoring Dataset: A Case Study of Kuwait Environmental Data (2012 to 2018).

In environmental research, missing data are often a challenge for statistical modeling. This paper addressed some advanced techniques to deal with missing values in a data set measuring air quality using a multiple imputation (MI) approach. MCAR, MAR, and NMAR missing data techniques are applied to the data set. Five missing data levels are considered: 5%, 10%, 20%, 30%, and 40%. The imputation method used in this paper is an iterative imputation method, missForest, which is related to the random forest approach. Air quality data sets were gathered from five monitoring stations in Kuwait, aggregated to a daily basis. Logarithm transformation was carried out for all pollutant data, in order to normalize their distributions and to minimize skewness. We found high levels of missing values for NO2 (18.4%), CO (18.5%), PM10 (57.4%), SO2 (19.0%), and O3 (18.2%) data. Climatological data (i.e., air temperature, relative humidity, wind direction, and wind speed) were used as control variables for better estimation. The results show that the MAR technique had the lowest RMSE and MAE. We conclude that MI using the missForest approach has a high level of accuracy in estimating missing values. MissForest had the lowest imputation error (RMSE and MAE) among the other imputation methods and, thus, can be considered to be appropriate for analyzing air quality data.

Influence of Ambient Air Pollution on Rheumatoid Arthritis Disease Activity Score Index.

Rheumatoid arthritis (RA) is a chronic autoimmune of an unknown etiology. Air pollution has been proposed as one of the possible risk factors associated with disease activity, although has not been extensively studied. In this study, we measured the relationship between exposure to air pollutants and RA activity. Data on RA patients were extracted from the Kuwait Registry for Rheumatic Diseases (KRRD). Disease activity was measured using disease activity score with 28 examined joints (DAS-28) and the Clinical Disease Activity Index (CDAI) during their hospital visits from 2013 to 2017. Air pollution was assessed using air pollution components (PM 10 , NO 2 , SO 2 , O 3 , and CO). Air pollution data were obtained from Kuwait Environmental Public Authority (K-EPA) from six different air quality-monitoring stations during the same period. Multiple imputations by the chained equations (MICE) algorithm were applied to estimate missing air pollution data. Patients data were linked with air pollution data according to date and patient governorate address. Descriptive statistics, correlation analysis, and linear regression techniques were employed using STATA software. In total, 1651 RA patients with 9875 follow-up visits were studied. We detected an increased risk of RA using DAS-28 in participants exposed to SO 2 and NO 2 with ß = 0 . 003 (95% CI: 0.0004-0.005, p < 0 . 01 ) and ß = 0 . 003 (95% CI: 0.002-0.005, p < 0 . 01 ), respectively, but not to PM 10 , O 3 , and CO concentrations. Conclusively, we observed a strong association between air pollution with RA disease activity. This study suggests air pollution as a risk factor for RA and recommends further measures to be taken by the authorities to control this health problem.