The Effect of Intratumor Heterogeneity in Pancreatic Ductal Adenocarcinoma Progression and Treatment.

BACKGROUND AND OBJECTIVES: Pancreatic cancer is one of the most lethal malignancies. Even though many substantial improvements in the survival rates for other major cancer forms were made, pancreatic cancer survival rates have remained relatively unchanged since the 1960s. Even more, no standard classification system for pancreatic cancer is based on cellular biomarkers. This review will discuss and provide updates about the role of stem cells in the progression of PC, the genetic changes associated with it, and the promising biomarkers for diagnosis. MATERIALS AND METHODS: The search process used PubMed, Cochrane Library, and Scopus databases to identify the relevant and related articles. Articles had to be published in English to be considered. RESULTS: The increasing number of studies in recent years has revealed that the diversity of cancer-associated fibroblasts is far greater than previously acknowledged, which highlights the need for further research to better understand the various cancer-associated fibroblast subpopulations. Despite the huge diversity in pancreatic cancer, some common features can be noted to be shared among patients. Mutations involving CDKN2, P53, and K-RAS can be seen in a big number of patients, for example. Similarly, some patterns of genes and biomarkers expression and the level of their expression can help in predicting cancer behavior such as metastasis and drug resistance. The current trend in cancer research, especially with the advancement in technology, is to sequence everything in hopes of finding disease-related mutations. CONCLUSION: Optimizing pancreatic cancer treatment requires clear classification, understanding CAF roles, and exploring stroma reshaping approaches.

Predictors of early and late postoperative seizures in meningioma patients: a systematic review and meta-analysis.

Meningioma is the most common type of primary brain tumor which presents with a variety of neurological manifestations. Surgical resection tends to be the preferred treatment. The occurrence of seizures after resection is common, which occur either early, within seven days of operation, or late. Our meta-analysis investigated the possible predictors of early and late postoperative seizures. We assessed the relevant observational studies on predictors of postoperative seizures published in PubMed, Scopus, and Web of Science from January 2000 to September 2022, and those that met inclusion criteria were included. We calculated the association between potential predicting factors and postoperative seizures, odds ratios (ORs) with 95% confidence intervals (CIs) applying either random or fixed-effect models. The early and late postoperative seizures were evaluated individually. Thirteen observational studies involving 4176 patients were included. Seizures occurred in 250 (6%) and 584 (14%) patients, respectively, in the early and late postoperative phases. Shared predictors for early and late seizures included tumors involving the motor cortex (OR = 2.7; 95% CI: 1.67-4.38, OR = 2.46; 95% CI: 1.68-3.61), postoperative neurological deficit (OR = 4.68; 95% CI: 2.67-8.22, OR = 2.01; 95% CI: 1.39-2.92), and preoperative seizures (OR = 2.52; 95% CI: 1.82-3.49, OR = 4.35; 95% CI: 3.29-5.75). Peritumoral edema (OR = 1.99; 95% CI: 1.49-2.64) was a significant factor only among late postoperative seizure patients while surgical complications (OR = 3.77; 95% CI: 2.39-5.93) was a significant factor solely for early postoperative seizures. Meningioma patients commonly experience early and late postoperative seizures. Identifying predictors of postoperative seizures is essential to diagnose and manage them effectively.

Knowledge of cancer symptoms and risk factors: A cross-sectional study from a developing country.

The delayed presentation of cancer patients to healthcare facilities for diagnosis is a pressing issue, as late-stage cancer cases are often more challenging to treat effectively. In low-resource settings, such as those with limited access to healthcare facilities, the impact of inadequate awareness of cancer signs and symptoms can be particularly severe. Therefore, this study aimed to evaluate public knowledge of cancer signs and symptoms and risk factors in the context of Jordan. This cross-sectional study was conducted among participants from all settings. Data was obtained from an Arabic version of the cancer awareness measure (CAM), which was answered online. It described demographic data and knowledge of cancer prevalence, age-related risk, signs, symptoms, and risk factors in recall and recognition-type questions. Participants (n = 1998) completed the questionnaire with a Median age of 35 and an interquartile range of 24. About half (n = 1070) thought that cancer is unrelated to age. Most participants identified breast cancer as the most common cancer among women (81%). Awareness of cancer signs/symptoms significantly differed in the level of knowledge in favor of females. The symptom "unexplained weight loss" was most commonly recognized (66.3%) and "persistent difficulty swallowing" the least (42.6%). As for risk factors, "smoking" was the most identified (76.9%) and "eating less than 5 portions of fruits and vegetables a day" was the least (19%), and "doing <30 minutes of moderate physical activity 5 times a week" as a close second least (19.95%). Females identified "smoking," "passive smoking," "HPV infection," and "having a close relative with cancer" as risk factors significantly more than males. Those with good economic status were more aware that smoking is a cancer risk factor by 1.51 times compared to those with poor economic status. To enhance early diagnosis and presentation in Jordan, there is a need for increased public awareness of the signs, symptoms, and risk factors of cancer. One effective strategy to achieve this goal is to conduct targeted public campaigns that cater to different population groups, such as the youth, to improve their understanding and ensure that the message resonates.

Etrolizumab as an induction and maintenance therapy for ulcerative colitis: A systematic review and meta-analysis of randomized controlled trials.

Background and Aim: Etrolizumab is a gut-targeted anti-ß7 integrin monoclonal antibody. However, the evidence of etrolizumab efficacy and safety in ulcerative colitis remains inconclusive. Therefore, we aim to evaluate the safety and efficacy of etrolizumab as an induction and maintenance therapy for active moderate to severe ulcerative colitis. Methods: We synthesized randomized controlled studies (RCTs) from MEDLINE, Scopus, EMBASE, PubMed, Web of Science, and Cochrane Library until April 2023. The risk ratio (RR) for dichotomous outcomes with the corresponding 95% confidence interval (CI) was used. The study protocol was registered in PROSPERO with ID: CRD42023437040. Results: Five RCTs with 1849 participants were included. The etrolizumab group had a significant clinical response (RR: 1.28 with 95% CI [1.08, 1.51], P = 0.005), clinical remission rates during the induction phase (RR: 2.47 with 95% CI [1.48, 4.11], P = 0.0005), compared with the placebo group in ulcerative colitis; however, there was no statistically significant difference between the two groups, regarding the corticosteroids-free remission rate (RR: 1.92 with 95% CI [0.94, 3.92], P = 0.07). Moreover, endoscopic improvement, endoscopic remission, and histologic remission rates were observed more in the etrolizumab group during both the induction and maintenance phases. For safety outcomes, etrolizumab was significantly safer, but any adverse event was higher in the etrolizumab group than in the placebo. Conclusion: Etrolizumab shows its effectiveness as both an induction and maintenance therapy for moderate or severe UC. The findings demonstrate its positive impact on clinical, endoscopic, and histologic remission rates. Regarding safety, other than any side effects, etrolizumab showed a good safety than a placebo.

Rethinking BMI and Obesity Management: The Transformative Role of Artificial Intelligence.

The body mass index (BMI) is a longstanding, simple, and cost-effective tool for classifying individuals by weight, useful for rapidly screening populations for obesity-related health risks. However, its failure to account for muscle mass, bone density, and fat distribution can lead to misclassifications. This editorial explores the transformative potential of artificial intelligence (AI) in redefining or potentially replacing BMI as a tool for enhancing weight management strategies. Furthermore, it illustrates how AI can offer personalized health assessments, predictive analytics, and tailored interventions, overcoming BMI's shortcomings. By analyzing genetic, lifestyle, and medical data, AI enables a more nuanced approach to weight management, signifying a shift toward precision or personalized medicine. AI-driven virtual assistants enhance weight management by offering continuous support, motivation, and reminders, while AI algorithms analyze medical imaging for precise body composition assessment. AI also aids in early metabolic disorder detection and fosters community support among individuals with similar health goals. However, ethical concerns, data privacy, and algorithm biases require careful attention. Collaboration among healthcare professionals, researchers, and tech developers is vital for maximizing AI's positive impact on public health.

The efficacy and safety of botulinum toxin epicardial fat injection to prevent postoperative atrial fibrillation in patients undergoing cardiac surgery: a meta-analysis of randomized controlled trials.

Background: Postoperative atrial fibrillation (POAF) is prevalent in about 30% to 60% of patients undergoing cardiac surgery, leading to worse outcomes. Botulinum toxin type A (BTX) epicardial injection has been proposed to prevent POAF by impairing cholinergic signaling. Methods: A systematic review and meta-analysis synthesized randomized controlled trials, which were retrieved by searching PubMed, EMBASE, Web of Science, SCOPUS, and Cochrane through November 23, 2022. RevMan version 5.4 was used to pool dichotomous outcomes using risk ratio (RR) and continuous outcomes using mean differences (MD) presented with the corresponding confidence interval (CI). Results: Three randomized controlled trials with 509 patients (308 in the BTX group and 205 in the placebo group) were included in the analysis. There was no difference between BTX and placebo regarding POAF incidence (RR 0.81 with 95% CI [0.65, 1.00], P = 0.05), postoperative hospital length of stay in days (MD -0.03 with 95% CI [-0.54, 0.49], P = 0.91), all-cause mortality (RR 1.64 with 95% CI [0.22, 12.17], P = 0.63), any adverse event (RR 1.03 with 95% CI [0.94, 1.12], P = 0.51), or any serious adverse event (RR 0.89 with 95% CI [0.68, 1.15], P = 0.36). Conclusion: There was no difference between the epicardial fat injection of BTX versus placebo for preventing POAF.

Inpatient outcomes of transcatheter aortic valve replacement based on class of obesity.

Transcatheter aortic valve replacement (TAVR) is a transformative option for severe aortic stenosis, especially in elderly patients. obesity's impact on TAVR outcomes is limited. Using the National Inpatient Sample from 2016 to 2020, We analyzed 217,300 TAVR hospitalizations across BMI groups. No difference in in-hospital mortality was observed, class III obesity experienced longer hospital stays (adjusted ß: 0.43 days, P < 0.05), higher costs (adjusted ß: $3,126, P < 0.05), increased heart failure exacerbation (adjusted odds ratio [aOR]: 2.68, 95% confidence interval [CI]: [1.03-7.01], p < 0.05), vascular access complications (aOR: 1.29, 95% CI: [1.07-1.52], P < 0.05), and post-operative pulmonary complications (Pneumonia (aOR: 1.42, 95% CI: [1.16-1.74], p < 0.05), acute hypoxic respiratory failure (aOR: 1.99, 95% CI: [1.67-2.36], p < 0.05), and non-invasive ventilation (aOR: 1.62, 95% CI: [1.07-2.44], p < 0.05). Complete heart block and permanent pacemaker requirement were higher in both class II and class III ((aOR: 1.30, 95% CI: [1.11-1.51], P < 0.05), (aOR:1.25, 95% CI: [1.06-1.46], P < 0.05) and ((aOR: 1.18, 95% CI: [1.00-1.40], P < 0.05), (aOR:1.22, 95% CI: [1.02-1.45], P < 0.05)) respectively. Understanding these links is crucial for optimizing TAVR care in obesity, ensuring enhanced outcomes, and procedural safety.

Cross-sectional insights into exercise physiology knowledge among medical students in Jordan.

Objectives: Exercise physiology is a branch of physiology that studies how physical activity and exercise alter the structure and function of living organisms. Knowledge of exercise physiology is crucial to improve athletic performance, improve people's ability to cope with extreme circumstances and approach chronic diseases. This research aimed to evaluate the knowledge of future healthcare professionals, namely, the medical students in Jordan regarding exercise physiology. Methods: Responses were collected from 524 undergraduate medical students enrolled in clinical clerkship. An online survey that evaluated participants' basic understanding of various physiological concepts related to physical exercises, such as respiratory exchange ratio, physical fitness, V̇O2 max and exercise at high altitudes was employed in the study. Results: 63.2% of participants had a poor level of exercise physiology knowledge. Misconceptions regarding V̇O2 max definition (93.3%), application (46.4%), significance (35.6%) and related physiological factors (48.7%) were observed. Students had misconceptions about physical fitness evaluation questions (52.5%, 39%, and 41.8%, respectively). Student proportions of 37%, 41%, 80.3% and 73.1% showed misconceptions about muscle groups and energy systems during training, training prescription variables, respiratory exchange ratio, and high-altitude performance, respectively. Significant differences in knowledge levels were found based on respondent characteristics (p < 0.05). Conclusions: Knowledge of exercise physiology is more than desirable for medical professionals. Therefore, efforts must be made to increase awareness and improve knowledge about basic physiological fundamentals related to exercise physiology among medical students in Jordan, as they represent the backbone of healthcare professionals of the future who will deal with medical conditions related to physical activity and exercise.

Safety and Efficacy of Cangrelor in Acute Coronary Syndromes: A Systematic Review and Network Meta-Analysis.

INTRODUCTION: Cangrelor is a potent intravenous non-thienopyridine P2Y12 inhibitor. We conducted a network meta-analysis to study the efficacy and safety of cangrelor as compared with the oral P2Y12 inhibition, clopidogrel, or placebo in acute coronary syndromes. METHODS: This meta-analysis followed the Cochrane collaboration guidelines and the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) protocols. Outcomes of interest included all-cause mortality, myocardial infarction, stent thrombosis, target vessel revascularization, major bleeding, minor bleeding, and the need for blood transfusion. RESULTS: The analysis was comprised of 6 studies including 26,444 patients treated with cangrelor, clopidogrel, or placebo. There were no statistically significant differences in the incidence of all-cause mortality, myocardial infarction, stent thrombosis, target vessel revascularization, or major bleeding. Cangrelor was associated with a higher risk of minor bleeding than clopidogrel or placebo, with no difference in requiring blood transfusion. CONCLUSION: Cangrelor has comparable outcomes to clopidogrel in patients with acute coronary syndromes and can be used as a reliable alternative in this population.

Istaroxime for Patients with Acute Heart Failure: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Istaroxime, an intravenous inotropic agent with a dual mechanism-increasing both cardiomyocyte contractility and relaxation-is a novel treatment for acute heart failure (AHF), the leading cause of morbidity and mortality in heart failure. We conducted a systematic review and meta-analysis that synthesized randomized controlled trials (RCTs), which were retrieved by systematically searching PubMed, Web of Science, SCOPUS, and Cochrane until 24 April 2023. We used a fixed-effect or random-effect model-according to heterogeneity-to pool dichotomous data using the risk ratio (RR) and continuous data using the mean difference (MD), with a 95% confidence interval (CI). We included three RCTs with a total of 300 patients. Istaroxime was significantly associated with an increased left ventricular ejection fraction (mL) (MD: 1.06, 95% CI: 0.29, 1.82; p = 0.007), stroke volume index (MD: 3.04, 95% CI: 2.41, 3.67; p = 0.00001), and cardiac index (L/min/m2) (MD: 0.18, 95% CI: 0.11, 025; p = 0.00001). Also, istaroxime was significantly associated with a decreased E/A ratio (MD: -0.39, 95% CI: -0.58, -0.19; p = 0.0001) and pulmonary artery systolic pressure (mmHg) (MD: 2.30, 95% CI: 3.20, 1.40; p = 0.00001). Istaroxime was significantly associated with increased systolic blood pressure (mmHg) (MD: 5.32, 95% CI: 2.28, 8.37; p = 0.0006) and decreased heart rate (bpm) (MD: -3.05, 95% CI: -5.27, -0.82; p = 0.007). Since istaroxime improved hemodynamic and echocardiographic parameters, it constitutes a promising strategy for AHF management. However, the current literature is limited to a small number of RCTs, warranting further large-scale phase III trials before clinical endorsement.

The Safety and Efficacy of Quadruple Ultra-Low-Dose Combination (Quadpill) for Hypertension Treatment: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

BACKGROUND AND OBJECTIVE: Quadpill, a single pill containing a quadruple combination of quarter doses of four antihypertensive agents, has been investigated for hypertension treatment. This meta-analysis aims to evaluate the safety and efficacy of quadpill for hypertension management. METHODS: We conducted a systematic review and meta-analysis synthesizing randomized controlled trials evaluating quadpill versus monotherapy or placebo in patients with hypertension, which were retrieved by systematically searching PubMed, EMBASE, Web of Science, SCOPUS, and Cochrane through 17 February, 2023. Continuous and dichotomous outcomes were pooled using mean difference (MD) and risk ratio (RR) along with confidence interval (CI), using Revman Version 5.4 software. Our protocol has been published in PROSPERO with ID: CRD42023406527. RESULTS: Four randomized controlled trials with a total of 779 patients were included in our analysis. Quadpill was effective in controlling systolic blood pressure in the short term [4-6 weeks] (RR: - 13.00 with 95% CI [- 17.22, - 8.78], p = 0.00001) and in the long term [12 weeks] (RR: - 6.18 with 95% CI [- 9.35, - 3.01], p = 0.0001). Quadpill was also effective in controlling automated diastolic blood pressure in the short term [4-6 weeks] (MD: - 8.15 with 95% CI [- 9.42, - 6.89], p = 0.00001) and in the long term [12 weeks] (MD: - 6.35 with 95% CI [- 10.37, - 2.33], p = 0.002). Moreover, patients in the quadpill group significantly achieved target blood pressure <140/90 (RR: 1.77 with 95% CI [1.26, 2.51], p = 0.001) compared with the control group. CONCLUSIONS: The quadruple ultra-low-dose combination of antihypertensive drugs (quadpill) was effective and safe for hypertension treatment. However, further large-scale, multicenter, randomized controlled trials are still warranted before endorsement in clinical practice.

Melatonin as a potential treatment for septic cardiomyopathy.

Septic cardiomyopathy (SCM) is a common complication of sepsis contributing to high mortality rates. Its pathophysiology involves complex factors, including inflammatory cytokines, mitochondrial dysfunction, oxidative stress, and immune dysregulation. Despite extensive research, no effective pharmacological agent has been established for sepsis-induced cardiomyopathy. Melatonin, a hormone with diverse functions in the body, has emerged as a potential agent for SCM through its anti-oxidant, anti-inflammatory, anti-apoptotic, and cardioprotective roles. Through various molecular levels of its mechanism of action, it counterattacks the adverse event of sepsis. Experimental studies have mentioned that melatonin protects against many cardiovascular diseases and exerts preventive effects on SCM. Moreover, melatonin has been investigated in combination with other drugs such as antibiotics, resveratrol, and anti-oxidants showing synergistic effects in reducing inflammation, anti-oxidant, and improving cardiac function. While preclinical studies have demonstrated positive results, clinical trials are required to establish the optimal dosage, route of administration, and treatment duration for melatonin in SCM. Its safety profile, low toxicity, and natural occurrence in the human body provide a favorable basis for its clinical use. This review aims to provide an overview of the current evidence of the use of melatonin in sepsis-induced cardiomyopathy (SICM). Melatonin appears to be promising as a possible treatment for sepsis-induced cardiomyopathy and demands further investigation.

The effect of bedtime versus morning dosing of antihypertensive drugs on the cardiovascular outcomes: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND AND OBJECTIVE: Antihypertensive drugs are one of the most effective strategies to prevent disability and mortality; however, there have been contradictory findings about the best dosing time for antihypertensive drugs. Therefore, we aim to evaluate the effect of bedtime versus morning dosing of antihypertensive drugs on cardiovascular outcomes. METHODS: We synthesized randomized controlled studies (RCTs) from the Web of Science, SCOPUS, EMBASE, PubMed, and CENTRAL until 13 October 2022. The risk ratio (RR) for dichotomous outcomes with the corresponding 95% confidence interval (CI) was used. The study protocol was registered in PROSPERO with ID: CRD42022368612. RESULTS: Five RCTs with 59 200 participants were included. Bedtime dosing was significantly associated with less incidence of myocardial infarction (MI) [RR: 0.80 with 95% CI (0.70-0.91), P = 0.0007] compared with morning dosing; however, there was no statistically significant difference between bedtime and morning dosing, regarding all-cause mortality [RR: 0.77 with 95% CI (0.51-1.16), P = 0.21], cardiovascular mortality [RR: 0.65 with 95% CI (0.35-1.21), P = 0.17], major adverse cardiac events (MACE) [RR: 0.79 with 95% CI (0.56-1.10), P = 0.16], heart failure [RR: 0.68 with 95% CI (0.42-1.09), P = 0.11], cerebrovascular accidents [RR: 0.80 with 95% CI (0.53-1.22), P = 0.30], coronary revascularization [RR: 0.79 with 95% CI (0.50-1.24), P = 0.30}, and angina [RR: 0.91 with 95% CI (0.55-1.50), P = 0.70]. CONCLUSION: Evidence about the comparative efficacy of bedtime versus morning dosing of antihypertensives is still uncertain. However, bedtime dosing significantly reduced MI, which warrants more robust RCTs to validate.

The impact of abdominal compression devices on colonoscopy outcomes: a systematic review and meta-analysis of randomized controlled trials.

OBJECTIVE: Colonoscopy is the gold standard method for colorectal cancer screening. Looping occurs in 91% of cases undergoing colonoscopy and can cause patient discomfort, prolonged cecal intubation time (CIT), and colon perforation. This meta-analysis investigates the impact of abdominal compression devices (ACD) on colonoscopy outcomes. METHODS: A systematic review and meta-analysis synthesizing randomized controlled trials (RCTs), retrieved by systematically searching: PubMed, EMBASE, WOS, SCOPUS, and Cochrane through February 2nd, 2023. Continuous and dichotomous outcomes were pooled using mean difference (MD) and risk ratio (RR) along with confidence interval (CI) using Revman. Our review protocol was prospectively published on PROSPERO with ID: CRD42023397344. RESULTS: We included eight RCTs with a total of 1,889 patients. ACD was effective to decrease CIT (MD: -2.15 with a 95% CI [-3.49, -0.80], p = .002), postural change (RR: 0.57 with 95% CI [0.49, 0.66], p = .00001), and VAS pain score (MD: -1.49 with 95% CI [-1.81, -1.17], p = .0001). However, there was no difference between ACD and control groups regarding manual compression (RR: 0.65 with 95% CI [0.42, 1.00], p = .05), complete colonoscopy rate (CCR) (RR: 1.01 with 95% CI [0.99, 1.04], p = .31), and cecal intubation length (CIL) (MD: -2.25 with 95% CI [-7.64, 3.14], p = .41). CONCLUSION: ACD during colonoscopy may enhance patient comfort by reducing CIT, pain, and postural changes. Nevertheless, additional RCTs are necessary to validate these results and determine the most suitable approach to utilize ACD for colonoscopy.

Sex Difference in Clinical and Management Outcomes in Patients With Takotsubo Syndrome: A Systematic Review and Meta-Analysis.

Takotsubo syndrome (TTS) is being increasingly recognized globally with a female sex predilection. However, sex-related differences in clinical outcomes are yet to be identified. Therefore, we aim to investigate the sex differences in clinical outcomes in patients with TTS. We included cohort studies retrieved from the Web of Science, SCOPUS, EMBASE, PubMed, and Cochrane until September 14, 2022. The risk ratio (RR) for dichotomous outcomes with the corresponding 95% confidence interval (CI) was used. The study protocol was registered in PROSPERO with ID: CRD42022363349. Thirteen retrospective cohort studies, with a total of 104,410 patients were included. Men had a higher risk of in-hospital mortality (RR: 2.42 with 95% CI [1.53, 3.83], P = 0.0002), long-term mortality (RR: 1.59 with 95% CI [1.40, 1.80], P = 0.00001), cardiogenic shock (RR: 1.65 with 95% CI [1.52, 1.79], P = 0.00001), arrhythmia (RR: 1.70 with 95% CI [1.56, 1.86], P = 0.00001), and acute kidney injury (RR: 1.71 with 95% CI [1.50, 1.96]. P = 0.00001), as compared with women. However, no significant difference was observed in stroke (RR: 1.22 with 95% CI [0.78, 1.89], P = 0.39), left ventricular thrombus (RR: 0.96 with 95% CI [0.40, 2.33], P = 0.93), and TTS recurrence (RR: 1.11 with 95% CI [0.68, 1.82], P = 0.67) between men and women. Despite women having a higher incidence of TTS, men have higher morbidity and mortality rates. Hence, further studies are necessary to identify the pathophysiological factors of this sex difference in clinical outcomes, including hormonal and psychological variables.