Determinants of Weight Loss prior to Diagnosis in Inflammatory Bowel Disease: A Retrospective Observational Study

Aims. To identify prevalence, severity, and environmental determinants of weight loss in inflammatory bowel disease (IBD) patients just prior to time of formal diagnosis. Methodology. IBD patients attending outpatient clinic were questioned about weight loss prior to diagnosis and other environmental and demographic variables. The percentage BMI loss was calculated for each subject and factors associated with weight loss were determined. Results. Four hundred and ninety-four subjects were recruited (237 cases of Crohn’s disease (CD) and 257 cases of ulcerative colitis (UC)). Overall, 57% of subjects with CD and 51% of subjects with UC experienced significant weight loss prior to diagnosis (>5% BMI loss). Younger age at diagnosis and history of previous IBD surgery were significantly associated with both lower BMI at diagnosis and increased weight loss prior to diagnosis. In CD patients, increasing age at diagnosis was inversely associated with weight loss prior to diagnosis. Ileal disease was a risk factor of weight loss, whereas prior appendectomy was associated with reduced risk of weight loss. Conclusions. Weight loss is a significant problem for many IBD patients at presentation, especially in younger age and CD with ileal involvement. Appendectomy is associated with diminished weight loss

Integration of measurable residual disease by WT1 gene expression and flow cytometry identifies pediatric patients with high risk of relapse in acute myeloid leukemia

BackgroundMolecular testing plays a pivotal role in monitoring measurable residual disease (MRD) in acute myeloid leukemia (AML), aiding in the refinement of risk stratification and treatment guidance. Wilms tumor gene 1 (WT1) is frequently upregulated in pediatric AML and serves as a potential molecular marker for MRD. This study aimed to evaluate WT1 predictive value as an MRD marker and its impact on disease prognosis.MethodsQuantification of WT1 expression levels was analyzed using the standardized European Leukemia Network real-time quantitative polymerase chain reaction assay (qRT-PCR) among a cohort of 146 pediatric AML patients. Post-induction I and intensification I, MRD response by WT1 was assessed. Patients achieving a ≥2 log reduction in WT1MRD were categorized as good responders, while those failing to reach this threshold were classified as poor responders.ResultsAt diagnosis, WT1 overexpression was observed in 112 out of 146 (76.7%) patients. Significantly high levels were found in patients with M4- FAB subtype (p=0.018) and core binding fusion transcript (CBF) (RUNX1::RUNX1T1, p=0.018, CBFB::MYH11, p=0.016). Following induction treatment, good responders exhibited a reduced risk of relapse (2-year cumulative incidence of relapse [CIR] 7.9% vs 33.2%, p=0.008). Conversely, poor responders’ post-intensification I showed significantly lower overall survival (OS) (51% vs 93.2%, p<0.001), event-free survival (EFS) (33.3% vs 82.6%, p<0.001), and higher CIR (66.6% vs 10.6%, p<0.001) at 24 months compared to good responders. Even after adjusting for potential confounders, it remained an independent adverse prognostic factor for OS (p=0.04) and EFS (p=0.008). High concordance rates between WT1-based MRD response and molecular MRD were observed in CBF patients. Furthermore, failure to achieve either a 3-log reduction by RT-PCR or a 2-log reduction by WT1 indicated a high risk of relapse. Combining MFC-based and WT1-based MRD results among the intermediate-risk group identified patients with unfavorable prognosis (positive predictive value [PPV] 100%, negative predictive value [NPV] 85%, and accuracy 87.5%).ConclusionWT1MRD response post-intensification I serves as an independent prognostic factor for survival in pediatric AML. Integration of WT1 and MFC-based MRD results enhances the reliability of MRD-based prognostic stratification, particularly in patients lacking specific leukemic markers, thereby influencing treatment strategies

One year cardiac follow up of young world cup football team compared to nonathletes

Introduction: Sudden cardiac death among professional young athletes has become a significant concern mainly attributed to structural heart changes and ECG abnormalities. Objectives: We aimed primarily to compare echocardiographic and electrocardiographic changes in young professional athletes versus a control group of sedentary lifestyled nonathletic individuals of the same age group. Secondly, we aimed to follow up echocardiographic and electrocardiographic changes in young professional athletes after one year. Methods: We conducted the study from May 2008 to May 2009 by clinical examination, transthoraxic echocardiography and 12 lead ECG. Our study group was the national football team candidates for the youth world cup occurring in Cairo 2009. This study group was compared to a control group of randomly picked nonathletic third year medical students after exclusion of anyone with a known medical illness. The study group was classified into Athletes I representing athletes at the beginning of the study and Athletes II representing athletes after one year follow up. Results: The Study group comprised 34 males, mean age 18.82 ± 1.56 years while the Control group comprised 28 males, age mean 19.64 ± 2.31 years. There was not a significant difference between the two groups regarding number, age, height or weight (P > 0.05). Athletes I vs control: Clinical parameters showed significantly lower Systolic Blood Pressure SBP (athletes 117.79 ± 6.536, control 126.43 ± 17.043, P = 0.008) and Heart Rate HR (athletes 68.88 ± 5.044, control 77.43 ± 6.033, P = 0.001). ECG parameters showed a significantly longer RR interval (athletes 0.88 ± 0.065, control 0.76 ± 0.078, P = 0.001), while Corrected QTc interval was not significantly different (athletes 0.41 ± 0.029, control 0.42 ± 0.022, P > 0.05). Echo parameters showed a significant increase in Ejection fraction EF (athletes 60.94 ± 3.084 vs control 54.14 ± 13.063, P = 0.005) and Left atrial dimension LA (athletes 3.28 ± 0.392 vs control 2.58 ± 1.321, P = 0.005). On the other hand Septal wall in diastole SWD, Right ventricle dimension RV, Left ventricular end systolic dimension LVESD, Left Ventricular End Diastolic Dimension LVEDD, Aortic Root AO, and Posterior wall in diastole PWD were not significantly different (P > 0.05). Athletes II vs control: QTc became significantly longer (athletes 0.43 ± 0.028 vs control 0.42 ± 0.022, P = 0.05). SWD was significantly thicker (athletes 1.21 ± 0.23 vs control 1.07 ± 0.17, P = 0.04). SBP, HR remained significantly lower and RR, EF, LA remained significantly greater (P  0.05). Athletes I vs athletes II: ECG parameters showed a significant increase in QTc (0.41 ± 0.029 vs 0.43 ± 0.028, P = 0.005) and RR interval (0.81 ± 0.167 vs 0.88 ± 0.065, P = 0.046). Echo parameters showed a significant increase in SWD (1.21 ± 0.232 vs 0.93 ± 0.124, P  0.05). Conclusions: Professional football playing in young males results in significant changes compared to their control of sedentary nonathletic medical students of similar age. Clinical parameters showed a significant decrease in systolic blood pressure SBP and heart rate HR, ECG parameters showed significant increase in RR interval and QTc interval, and Echocardiographic parameters showed a significant increase in Left atrium diameter LA, Septal wall in diastole SWD, and ejection fraction EF. One year of professional football playing in young males causes a continuing significant increase in ECG parameters QTc, RR interval, and echocardiographic parameters SWD, LA, Right ventricle dimension RV, Posterior wall in diastole PWD and decrease in Left ventricular end systolic diameter LVESD compared to themselves one year earlier. The international concern of Sudden cardiac death among professional young athletes may be attributed to Structural heart changes and ECG abnormalities acquired with professional training

Long-term effect of mass chemotherapy of Schistosoma mansoni on infection rate and diagnosis accuracy

Objectives: To assess the performance of microscopic stool examination, which is used widely for the diagnosis and assessment of infection rates of Schistosoma mansoni in Egypt, for the evaluation of chemotherapy efficacy after a decade of regular mass treatment. Methods: A total of 651 individuals from Lower Egypt (55 children and 596 adults) were examined for S. mansoni ova by microscopic stool examination (MSE) alone (n = 166; 111 adults and 55 children), rectal biopsy (RB) alone (n = 32 adults), or both MSE and RB (n = 453 adults). Results: Infection detection rates were significantly lower in the MSE alone group (9%; 15/166) compared to the RB alone group (40.6%; 13/32) and to the RB+MSE group (37.7%; 171/453). Out of all positive cases in the MSE+RB group, only 23/171 patients (13.5%) were positive by stool examination, of whom 21 were also positive by RB, in contrast to 169/171 patients (86.5%) positive by RB in the same group. It was noted that adding MSE to RB did not increase the prevalence compared to RB alone: 37.3% in the MSE+RB group vs. 40.6% in the RB only group. Using the summation of both MSE and RB tests as the gold standard, the sensitivity of MSE was significantly lower than that of RB: 13.5% vs. 98.8%. Conclusions: The implementation of mass treatment programmes has resulted in a new era of light infection, for which conventional parasitological methods for the diagnosis and monitoring of infection can miss many patients

DataSheet_1_Integration of measurable residual disease by WT1 gene expression and flow cytometry identifies pediatric patients with high risk of relapse in acute myeloid leukemia.docx

BackgroundMolecular testing plays a pivotal role in monitoring measurable residual disease (MRD) in acute myeloid leukemia (AML), aiding in the refinement of risk stratification and treatment guidance. Wilms tumor gene 1 (WT1) is frequently upregulated in pediatric AML and serves as a potential molecular marker for MRD. This study aimed to evaluate WT1 predictive value as an MRD marker and its impact on disease prognosis.MethodsQuantification of WT1 expression levels was analyzed using the standardized European Leukemia Network real-time quantitative polymerase chain reaction assay (qRT-PCR) among a cohort of 146 pediatric AML patients. Post-induction I and intensification I, MRD response by WT1 was assessed. Patients achieving a ≥2 log reduction in WT1MRD were categorized as good responders, while those failing to reach this threshold were classified as poor responders.ResultsAt diagnosis, WT1 overexpression was observed in 112 out of 146 (76.7%) patients. Significantly high levels were found in patients with M4- FAB subtype (p=0.018) and core binding fusion transcript (CBF) (RUNX1::RUNX1T1, p=0.018, CBFB::MYH11, p=0.016). Following induction treatment, good responders exhibited a reduced risk of relapse (2-year cumulative incidence of relapse [CIR] 7.9% vs 33.2%, p=0.008). Conversely, poor responders’ post-intensification I showed significantly lower overall survival (OS) (51% vs 93.2%, pConclusionWT1MRD response post-intensification I serves as an independent prognostic factor for survival in pediatric AML. Integration of WT1 and MFC-based MRD results enhances the reliability of MRD-based prognostic stratification, particularly in patients lacking specific leukemic markers, thereby influencing treatment strategies.</p

Global economic burden of unmet surgical need for appendicitis

Background There is a substantial gap in provision of adequate surgical care in many low- and middle-income countries. This study aimed to identify the economic burden of unmet surgical need for the common condition of appendicitis. Methods Data on the incidence of appendicitis from 170 countries and two different approaches were used to estimate numbers of patients who do not receive surgery: as a fixed proportion of the total unmet surgical need per country (approach 1); and based on country income status (approach 2). Indirect costs with current levels of access and local quality, and those if quality were at the standards of high-income countries, were estimated. A human capital approach was applied, focusing on the economic burden resulting from premature death and absenteeism. Results Excess mortality was 4185 per 100 000 cases of appendicitis using approach 1 and 3448 per 100 000 using approach 2. The economic burden of continuing current levels of access and local quality was US $92 492 million using approach 1 and$73 141 million using approach 2. The economic burden of not providing surgical care to the standards of high-income countries was $95 004 million using approach 1 and$75 666 million using approach 2. The largest share of these costs resulted from premature death (97.7 per cent) and lack of access (97.0 per cent) in contrast to lack of quality. Conclusion For a comparatively non-complex emergency condition such as appendicitis, increasing access to care should be prioritized. Although improving quality of care should not be neglected, increasing provision of care at current standards could reduce societal costs substantially

Global economic burden of unmet surgical need for appendicitis

Background There is a substantial gap in provision of adequate surgical care in many low- and middle-income countries. This study aimed to identify the economic burden of unmet surgical need for the common condition of appendicitis. Methods Data on the incidence of appendicitis from 170 countries and two different approaches were used to estimate numbers of patients who do not receive surgery: as a fixed proportion of the total unmet surgical need per country (approach 1); and based on country income status (approach 2). Indirect costs with current levels of access and local quality, and those if quality were at the standards of high-income countries, were estimated. A human capital approach was applied, focusing on the economic burden resulting from premature death and absenteeism. Results Excess mortality was 4185 per 100 000 cases of appendicitis using approach 1 and 3448 per 100 000 using approach 2. The economic burden of continuing current levels of access and local quality was US $92 492 million using approach 1 and$73 141 million using approach 2. The economic burden of not providing surgical care to the standards of high-income countries was $95 004 million using approach 1 and$75 666 million using approach 2. The largest share of these costs resulted from premature death (97.7 per cent) and lack of access (97.0 per cent) in contrast to lack of quality. Conclusion For a comparatively non-complex emergency condition such as appendicitis, increasing access to care should be prioritized. Although improving quality of care should not be neglected, increasing provision of care at current standards could reduce societal costs substantially

Global variation in postoperative mortality and complications after cancer surgery: a multicentre, prospective cohort study in 82 countries

© 2021 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 licenseBackground: 80% of individuals with cancer will require a surgical procedure, yet little comparative data exist on early outcomes in low-income and middle-income countries (LMICs). We compared postoperative outcomes in breast, colorectal, and gastric cancer surgery in hospitals worldwide, focusing on the effect of disease stage and complications on postoperative mortality. Methods: This was a multicentre, international prospective cohort study of consecutive adult patients undergoing surgery for primary breast, colorectal, or gastric cancer requiring a skin incision done under general or neuraxial anaesthesia. The primary outcome was death or major complication within 30 days of surgery. Multilevel logistic regression determined relationships within three-level nested models of patients within hospitals and countries. Hospital-level infrastructure effects were explored with three-way mediation analyses. This study was registered with ClinicalTrials.gov, NCT03471494. Findings: Between April 1, 2018, and Jan 31, 2019, we enrolled 15 958 patients from 428 hospitals in 82 countries (high income 9106 patients, 31 countries; upper-middle income 2721 patients, 23 countries; or lower-middle income 4131 patients, 28 countries). Patients in LMICs presented with more advanced disease compared with patients in high-income countries. 30-day mortality was higher for gastric cancer in low-income or lower-middle-income countries (adjusted odds ratio 3·72, 95% CI 1·70–8·16) and for colorectal cancer in low-income or lower-middle-income countries (4·59, 2·39–8·80) and upper-middle-income countries (2·06, 1·11–3·83). No difference in 30-day mortality was seen in breast cancer. The proportion of patients who died after a major complication was greatest in low-income or lower-middle-income countries (6·15, 3·26–11·59) and upper-middle-income countries (3·89, 2·08–7·29). Postoperative death after complications was partly explained by patient factors (60%) and partly by hospital or country (40%). The absence of consistently available postoperative care facilities was associated with seven to 10 more deaths per 100 major complications in LMICs. Cancer stage alone explained little of the early variation in mortality or postoperative complications. Interpretation: Higher levels of mortality after cancer surgery in LMICs was not fully explained by later presentation of disease. The capacity to rescue patients from surgical complications is a tangible opportunity for meaningful intervention. Early death after cancer surgery might be reduced by policies focusing on strengthening perioperative care systems to detect and intervene in common complications. Funding: National Institute for Health Research Global Health Research Unit

Effects of hospital facilities on patient outcomes after cancer surgery: an international, prospective, observational study

© 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 licenseBackground: Early death after cancer surgery is higher in low-income and middle-income countries (LMICs) compared with in high-income countries, yet the impact of facility characteristics on early postoperative outcomes is unknown. The aim of this study was to examine the association between hospital infrastructure, resource availability, and processes on early outcomes after cancer surgery worldwide. Methods: A multimethods analysis was performed as part of the GlobalSurg 3 study—a multicentre, international, prospective cohort study of patients who had surgery for breast, colorectal, or gastric cancer. The primary outcomes were 30-day mortality and 30-day major complication rates. Potentially beneficial hospital facilities were identified by variable selection to select those associated with 30-day mortality. Adjusted outcomes were determined using generalised estimating equations to account for patient characteristics and country-income group, with population stratification by hospital. Findings: Between April 1, 2018, and April 23, 2019, facility-level data were collected for 9685 patients across 238 hospitals in 66 countries (91 hospitals in 20 high-income countries; 57 hospitals in 19 upper-middle-income countries; and 90 hospitals in 27 low-income to lower-middle-income countries). The availability of five hospital facilities was inversely associated with mortality: ultrasound, CT scanner, critical care unit, opioid analgesia, and oncologist. After adjustment for case-mix and country income group, hospitals with three or fewer of these facilities (62 hospitals, 1294 patients) had higher mortality compared with those with four or five (adjusted odds ratio [OR] 3·85 [95% CI 2·58–5·75]; p<0·0001), with excess mortality predominantly explained by a limited capacity to rescue following the development of major complications (63·0% vs 82·7%; OR 0·35 [0·23–0·53]; p<0·0001). Across LMICs, improvements in hospital facilities would prevent one to three deaths for every 100 patients undergoing surgery for cancer. Interpretation: Hospitals with higher levels of infrastructure and resources have better outcomes after cancer surgery, independent of country income. Without urgent strengthening of hospital infrastructure and resources, the reductions in cancer-associated mortality associated with improved access will not be realised. Funding: National Institute for Health and Care Research