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.

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.

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.

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.

The efficacy and safety of pre-hospital plasma in patients at risk for hemorrhagic shock: an updated systematic review and meta-analysis of randomized controlled trials.

BACKGROUND AND OBJECTIVE: Plasma is a critical element in hemostatic resuscitation post-injury, and its prompt administration within the prehospital setting may reduce the complications resulting from hemorrhage and shock. Our objective is to assess the efficacy and safety of prehospital plasma infusion in patients susceptible to hemorrhagic shock. METHODS: We conducted our study by aggregating randomized controlled trials (RCTs) sourced from PubMed, EMBASE, Scopus, Web of Science, and Cochrane CENTRAL up to January 29, 2023. Quality assessment was implemented using the Cochrane RoB 2 tool. Our study protocol is registered in PROSPERO under ID: CRD42023397325. RESULTS: Three RCTs with 760 individuals were included. There was no difference between plasma infusion and standard care groups in 24-h mortality (P = 0.11), 30-day mortality (P = 0.12), and multiple organ failure incidences (P = 0.20). Plasma infusion was significantly better in the total 24-h volume of PRBC units (P = 0.03) and INR on arrival (P = 0.009). For all other secondary outcomes evaluated (total 24-h volume of packed FFP units, total 24-h volume of platelets units, massive transfusion, vasopressor need during the first 24 h, any adverse event, acute lung injury, transfusion reaction, and sepsis), no significant differences were observed between the two groups. CONCLUSION: Plasma infusion in trauma patients at risk of hemorrhagic shock does not significantly affect mortality or the incidence of multiple organ failure. However, it may lead to reduced packed red blood cell transfusions and increased INR at hospital arrival.

A case report of lung metastasis in a cervical cancer presenting as a consolidation.

Cervical cancer is a preventable cancer in the United States. We discuss a case of a 43-year-old woman who presented with signs and symptoms of Cerebrovascular accident (CVA) as well as shortness of breath and chest tightness. Upon investigation, it was concluded that she had developed multiple brain infarcts, pulmonary embolism, and deep venous thrombosis in both lower extremities. However, after her pulmonary symptoms worsened, further investigations revealed an uncommon occurrence of infiltrative lung metastasis. This finding was particularly surprising as she had recently been diagnosed with squamous cell carcinoma of the cervix. It is important to note that patients who have not undergone regular cervical cancer screening can remain without symptoms until the disease has reached an advanced stage, as is the case with this patient. Various screening methods, such as Pap smear cytology, human papillomavirus (HPV) DNA testing, and visual inspection tests, are available to detect and prevent cervical cancer.

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.

The effects of transcranial direct current stimulation on cognitive function for mild cognitive impairment: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Transcranial direct current stimulation (tDCS) emerged as a potential modality for enhancing cognitive functions in patients with cognitive decline, including mild cognitive impairment (MCI). Our systematic review and meta-analysis aim to synthesize the available randomized controlled trials (RCTs) on the effects of tDCS on cognitive functions in patients with MCI. METHODS: Our review protocol was registered on PROSPERO with ID: CRD42022360587. We conducted a systematic database search until September 2022. Standardized mean difference (SMD) and pooled effect size (ES) for robust variance estimation (RVE) method were used as effect estimates for our meta-analysis. RESULTS: We included 11 RCTs with a total of 429 participants. The meta-analysis showed that, compared to sham groups, tDCS did not improve global functioning (measured by MOCA) (SMD = 0.02, CI = - 0.30 to 0.35; p = 0.88), memory domain (ES = 0.681, CI = - 2.15 to 3.51, p = 0.576), sustained attention (measured by TMT-A) (SMD = - 0.21, CI = - 0.52 to 0.10, p = 0.19), and executive function (measured by TMT-B) (SMD = - 0.53, CI = - 1.56 to 0.50, p = 0.20). CONCLUSION: Our meta-analysis found no significant effect of tDCS on cognitive functions in MCI patients, including effects on global functioning, memory, sustained attention, and executive function. Therefore, an important change to be tested in future studies is to look for a better combination with tDCS for patients with MCI.

Poly(ADP-ribose) polymerase inhibitors in the treatment landscape of triple-negative breast cancer (TNBC).

OBJECTIVE: Chemotherapy is the mainstay for triple-negative breast cancer (TNBC) patients. Over the years, the use of chemotherapy for these patients has demonstrated many adversities, including toxicity and resistance, which suggested the need to develop novel alternative therapeutic options, such as poly(ADP-ribose) polymerase inhibitors (PARPi). Herein, we provide an overview on PARPi, mechanisms of action and the role of biomarkers in PARPi sensitivity trials, clinical advances in PARPi therapy for TNBC patients based on the most recent studies and findings of clinical trials, and challenges that prevent PARP inhibitors from achieving high efficacy such as resistance and overlapping toxicities with other chemotherapies. DATA SOURCES: Searching for relevant articles was done using PubMed and Cochrane Library databases by using the keywords including TNBC; chemotherapy; PARPi; BRCA; homologous recombination repair (HRR). Studies had to be published in full-text in English in order to be considered. DATA SUMMARY: Although PARPi have been used in the treatment of local/metastatic breast malignancies that are HER2 negative and has a germline BRCA mutation, several questions are still to be answered in order to maximize the clinical benefit of PARP inhibitors in TNBC treatment, such as questions related to the optimal use in the neoadjuvant and metastatic settings as well as the best combinations with various chemotherapies. CONCLUSIONS: PARPi are emerging treatment options for patients with gBRCA1/2 mutations. Determining patients that are most likely to benefit from PARPi and identifying the optimal treatment combinations with high efficacy and fewer side effects are currently ongoing.

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 Efficacy and Safety of Etripamil Nasal Spray for Acute Paroxysmal Supraventricular Tachycardia: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: Paroxysmal supraventricular tachycardia (PSVT) treatment requires medically supervised intervention. Etripamil is a novel short-acting calcium channel blocker. Its intranasal spray formulation has a rapid onset of action and shows promise for the unsupervised treatment of PSVT. OBJECTIVE: We aimed to evaluate the efficacy and safety of etripamil nasal spray for the acute conversion of PSVT. METHODS: A systematic review and meta-analysis synthesizing randomized controlled trials (RCTs), which were retrieved by systematically searching the PubMed, EMBASE, Web of Science, SCOPUS, and Cochrane databases through to 1 December 2022. RevMan version 5.4 software was used to pool dichotomous outcomes using risk ratio (RR) presented with the corresponding confidence interval (CI). RESULTS: Three RCTs with a total of 496 participants were included in our analysis. Etripamil was effective for PSVT conversion at 15 min (RR 1.84, 95% CI 1.37-2.48), 30 min (RR 1.86, 95% CI 1.42-2.44), and 60 min (RR 1.25, 95% CI 1.05-1.50) after drug administration; decreasing medical intervention-seeking (RR 0.58, 95% CI 0.37-0.90); and decreasing emergency room (ER) visits (RR 0.61, 95% CI 0.38-0.97). However, there was no difference at 300 min (RR 1.10, 95% CI 0.97-1.25) and it was associated with higher rates of adverse events (RR 3.17, 95% CI 2.15-4.69). CONCLUSION: Etripamil nasal spray was effective and well tolerated to induce PSVT termination for up to 60 min. Therefore, etripamil nasal spray constitutes a promising strategy for PSVT self-termination without medical supervision; however, further RCTs are required before endorsement in clinical practice.

The Role of Non-coding RNAs in Alzheimer's Disease: Pathogenesis, Novel Biomarkers, and Potential Therapeutic Targets

OBJECTIVE: Long non-coding RNAs (IncRNAs) are regulatory RNA transcripts that have recently been associated with the onset of many neurodegenerative illnesses, including Alzheimer's disease (AD). Several IncRNAs have been found to be associated with AD pathophysiology, each with a distinct mechanism. In this review, we focused on the role of IncRNAs in the pathogenesis of AD and their potential as novel biomarkers and therapeutic targets. METHODS: Searching for relevant articles was done using the PubMed and Cochrane library databases. Studies had to be published in full text in English in order to be considered. RESULTS: Some IncRNAs were found to be upregulated, while others were downregulated. Dysregulation of IncRNAs expression may contribute to AD pathogenesis. Their effects manifest as the synthesis of beta-amyloid (Aß) plaques increases, thereby altering neuronal plasticity, inducing inflammation, and promoting apoptosis. CONCLUSION: Despite the need for more investigations, IncRNAs could potentially increase the sensitivity of early detection of AD. Until now, there has been no effective treatment for AD. Hence, InRNAs are promising molecules and may serve as potential therapeutic targets. Although several dysregulated AD-associated lncRNAs have been discovered, the functional characterization of most lncRNAs is still lacking.

Bell's Palsy and COVID-19 Vaccines: A Systematic Review and Meta-Analysis.

INTRODUCTION: Once the COVID-19 pandemic was declared, the world was waiting for the clue that would be able to cut down the progression of the disease. Vaccines play a crucial role in reducing the disease and saving many people worldwide. However, there are several side effects of these vaccines, like pain, fatigue, fever, and neurological defects like Bell's palsy. In this systematic review, we presented evidence about the occurrence of Bell's palsy followed by COVID-19 vaccination. METHODS: We searched PubMed, SCOPUS, EBSCO, and Web of Science (WOS) from inception till October 2022. The quality assessment was conducted using the Joanna Briggs Institute, National Institute of Health, and Newcastle-Ottawa. The analysis was conducted on SPSS. RESULTS: Thirty-five records were involved in our study. The results of our cases revealed that most of the patients (62.8%) experienced unilateral facial paralysis. Also, the majority of the cases were reported after the first dose, and most cases were after Pfizer, AstraZeneca, and Sputnik V vaccines, respectively. The patients who were treated with corticosteroids, IVIG, and anti-viral drugs, showed marked recovery afterward. CONCLUSION: The rate ratio of Bell's palsy after COVID-19 vaccination was 25.3 per 1,000,000. The ratio was higher after the first dose compared to the second dose and was higher among those who took Oxford/AstraZeneca vaccine compared to other vaccines. However, this condition was reported in a small number of cases among a large number of vaccinated people worldwide. It is important to note that the benefits of getting vaccinated far outweigh any potential risks.

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.

The safety and efficacy of CAR-T cells in the treatment of prostate cancer: review.

OBJECTIVE: A new breakthrough development in cancer treatment is chimeric antigen receptor (CAR)-T cell therapy. In this review, we focussed on its efficacy & safety in prostate cancer, obstacles impeding its clinical use, and some strategies trying to overcome them. METHODS: Searching for relevant articles was done using the PubMed and Cochrane Library databases. Studies had to be published in full-text in English in order to be considered. RESULTS: Many factors can limit optimal CAR-T cell outcomes, including the hostile Prostate microenvironment, age, comorbidities, and tumour grade. The adverse effects of the therapy, particularly the cytokine release syndrome, are a major source of worry after treatment administration. Attempts to alter gamma/delta T-cells and NK cells with CAR, on the other hand, have demonstrated higher effectiveness and safety than conventional CAR-T cells. CONCLUSION: To improve the use of immunotherapies, a greater understanding of the prostate cancer microenvironment is required. Concerning toxicity, more research is needed to find the most specific and highly expressed prostate antigens. Furthermore, discovering predictive biomarkers for toxicities, as well as choosing the correct patient for therapy, might decrease immune-related side effects and achieve a greater response.