UNASSIGNED: Nocturnal blood pressure (BP) is correlated with an increased risk of cardiovascular events and is an important predictor of cardiovascular death in hypertensive patients.
UNASSIGNED: Nocturnal BP control is of great importance for cardiovascular risk reduction. This systematic review and meta-analysis aimed to explore the efficacy of angiotensin receptor blockers (ARBs) for nocturnal BP reduction in patients with mild to moderate hypertension.
UNASSIGNED: PICOS design structure was used to formulate the data extraction. All statistical calculations and analyses were performed with R.
UNASSIGNED: Seventy-seven studies with 13,314 participants were included. The overall analysis indicated that nocturnal BP drop varied considerably among different ARBs. Allisartan (13.04 [95% CI (-18.41, -7.68)] mmHg), olmesartan (11.67 [95% CI (-14.12, -9.21)] mmHg), telmisartan (11.11 [95% CI (-12.12, -10.11)] mmHg) were associated with greater reduction in nocturnal systolic BP. In the aspect of the nocturnal-diurnal BP drop ratio, only allisartan was greater than 1. While, the variation tendency of last 4-6 h ambulatory BP was basically consistent with nocturnal BP. Additionally, allisartan showed improvement effect in the proportion of patients with dipping BP pattern.
UNASSIGNED: This study demonstrates that for patients with mild to moderate hypertension, allisartan, olmesartan and telmisartan have more advantages in nocturnal BP reduction among the ARBs, while allisartan can reduce nighttime BP more than daytime BP and improve the dipping pattern.
This meta-analysis explores the efficacy of Angiotensin II AT1 receptor antagonists (ARBs) on nocturnal blood pressure (BP) reduction in mild to moderate hypertension.The results demonstrate that for patients with mild to moderate hypertension, allisartan, olmesartan and telmisartan have more advantages in nocturnal BP reduction among the ARBs.Allisartan can reduce nighttime BP more effectively than daytime BP, which also improve the dipping pattern.

MET exon14 skipping mutations (METex14s) are rarely reported as a potential resistance mechanism to EGFR tyrosine kinase inhibitors (TKIs). The efficacy of targeted therapy against METex14s emerging after osimertinib resistance is uncertain. Herein, we report a case of EGFR-mutated metastatic lung adenocarcinoma in which METex14 was detected in a re-biopsy upon first-line osimertinib resistance. The patient received capmatinib monotherapy as third-line therapy, which was ineffective, followed by an exceptional response to salvage therapy with afatinib. This report highlights the heterogeneity of EGFR-TKI resistance and that targeting rare resistance mechanisms remains challenging.

For >3 decades now, angiotensin receptor blockers (ARB) have been used in the management of hypertension (HTN) and HTN-related cardiovascular (CV) diseases. Olmesartan medoxomil (OLM) is an angiotensin II type 1 (AT1) receptor antagonist (or blocker) that binds tightly to the AT1 receptor with long-lasting efficacy over the 24-hour period and safety demonstrated in several trials. It is well tolerated and effective in reducing blood pressure (BP) in mono and combination therapy with thiazide diuretics or calcium channel blockers across a wide range of patient subgroups. The effectiveness and safety of OLM-based combination therapies have good and tolerable profiles with high adherence in the fixed single-pill formulation. Consistent antihypertensive efficacy and good tolerability when used as monotherapy or as a combined therapy make OLM a valuable treatment option for adults with HTN. In this review, we discuss the important clinical implications of OLM as an optimal choice as monotherapy and combination therapy in managing patients with HTN.

Despite significant progress in modern medicine and pharmacology, damage to the nervous system with various etiologies still poses a challenge to doctors and scientists. Injuries lead to neuroimmunological changes in the central nervous system (CNS), which may result in both secondary damage and the development of tactile and thermal hypersensitivity. In our review, based on the analysis of many experimental and clinical studies, we indicate that the mechanisms occurring both at the level of the brain after direct damage and at the level of the spinal cord after peripheral nerve damage have a common immunological basis. This suggests that there are opportunities for similar pharmacological therapeutic interventions in the damage of various etiologies. Experimental data indicate that after CNS/PNS damage, the levels of 16 among the 28 CC-family chemokines, i.e., CCL1, CCL2, CCL3, CCL4, CCL5, CCL6, CCL7, CCL8, CCL9, CCL11, CCL12, CCL17, CCL19, CCL20, CCL21, and CCL22, increase in the brain and/or spinal cord and have strong proinflammatory and/or pronociceptive effects. According to the available literature data, further investigation is still needed for understanding the role of the remaining chemokines, especially six of them which were found in humans but not in mice/rats, i.e., CCL13, CCL14, CCL15, CCL16, CCL18, and CCL23. Over the past several years, the results of studies in which available pharmacological tools were used indicated that blocking individual receptors, e.g., CCR1 (J113863 and BX513), CCR2 (RS504393, CCX872, INCB3344, and AZ889), CCR3 (SB328437), CCR4 (C021 and AZD-2098), and CCR5 (maraviroc, AZD-5672, and TAK-220), has beneficial effects after damage to both the CNS and PNS. Recently, experimental data have proved that blockades exerted by double antagonists CCR1/3 (UCB 35625) and CCR2/5 (cenicriviroc) have very good anti-inflammatory and antinociceptive effects. In addition, both single (J113863, RS504393, SB328437, C021, and maraviroc) and dual (cenicriviroc) chemokine receptor antagonists enhanced the analgesic effect of opioid drugs. This review will display the evidence that a multidirectional strategy based on the modulation of neuronal-glial-immune interactions can significantly improve the health of patients after CNS and PNS damage by changing the activity of chemokines belonging to the CC family. Moreover, in the case of pain, the combined administration of such antagonists with opioid drugs could reduce therapeutic doses and minimize the risk of complications.

BACKGROUND: Helicobacter pylori (H. pylori) infects over half the global population, causing gastrointestinal diseases like dyspepsia, gastritis, duodenitis, peptic ulcers, G-MALT lymphoma, and gastric adenocarcinoma. Eradicating H. pylori is crucial for treating and preventing these conditions. While conventional proton pump inhibitor (PPI)-based triple therapy is effective, there\'s growing interest in longer acid suppression therapies. Potassium competitive acid blocker (P-CAB) triple and dual therapy are new regimens for H. pylori eradication. Initially used in Asian populations, vonoprazan (VPZ) has been recently Food and Drug Administration-approved for H. pylori eradication.
OBJECTIVE: To assess the efficacy of regimens containing P-CABs in eradicating H. pylori infection.
METHODS: This study, following PRISMA 2020 guidelines, conducted a systematic review and meta-analysis by searching MEDLINE and Scopus libraries for randomized clinical trials (RCTs) or observational studies with the following command: [(\"Helicobacter pylori\" OR \"H pylori\") AND (\"Treatment\" OR \"Therapy\" OR \"Eradication\") AND (\"Vonaprazan\" OR \"Potassium-Competitive Acid Blocker\" OR \"P-CAB\" OR \"PCAB\" OR \"Revaprazan\" OR \"Linaprazan\" OR \"Soraprazan\" OR \"Tegoprazan\")]. Studies comparing the efficacy of P-CABs-based treatment to classical PPIs in eradicating H. pylori were included. Exclusion criteria included case reports, case series, unpublished trials, or conference abstracts. Data variables encompassed age, diagnosis method, sample sizes, study duration, intervention and control, and H. pylori eradication method were gathered by two independent reviewers. Meta-analysis was performed in R software, and forest plots were generated.
RESULTS: A total of 256 references were initially retrieved through the search command. Ultimately, fifteen studies (7 RCTs, 7 retrospective observational studies, and 1 comparative unique study) were included, comparing P-CAB triple therapy to PPI triple therapy. The intention-to-treat analysis involved 8049 patients, with 4471 in the P-CAB intervention group and 3578 in the PPI control group across these studies. The analysis revealed a significant difference in H. pylori eradication between VPZ triple therapy and PPI triple therapy in both RCTs and observational studies [risk ratio (RR) = 1.17, 95% confidence interval (CI): 1.11-1.22, P < 0.0001] and (RR = 1.13, 95%CI: 1.09-1.17, P < 0.0001], respectively. However, no significant difference was found between tegoprazan (TPZ) triple therapy and PPI triple therapy in both RCTs and observational studies (RR = 1.04, 95%CI: 0.93-1.16, P = 0.5) and (RR = 1.03, 95%CI: 0.97-1.10, P = 0.3), respectively.
CONCLUSIONS: VPZ-based triple therapy outperformed conventional PPI-based triple therapy in eradicating H. pylori, positioning it as a highly effective first-line regimen. Additionally, TPZ-based triple therapy was non-inferior to classical PPI triple therapy.

OBJECTIVE: The European Medicines Agency (EMA) maintains a list of designated medical events (DMEs), events that are inherently serious and are prioritized for signal detection, irrespective of statistical criteria. We have analysed the results of our previously published scoping review to determine whether DME signals differ from those of other adverse events in terms of time to communication and characteristics of supporting reports of suspected adverse drug reactions.
METHODS: For all signals, we obtained the launch year of medicinal products from textbooks or regulatory agencies, extracted the year of the first report in VigiBase and calculated the interval between the first report and communication (time to communication, TTC). We further retrieved the average completeness (via vigiGrade) of the reports in each case series in the years before the communication. We categorised as DME signals those concerning an event in the EMA\'s list. We described the two groups of signals using medians and interquartile ranges (IQR) and compared them using the Brunner-Munzel test, calculating 95% confidence intervals (95% CI) and P values.
RESULTS: Of 4520 signals, 919 concerned DMEs and 3601 concerned non-DMEs. Signals of DMEs were supported by a median of 15 reports (IQR 6-38 reports) with a completeness score of 0.52 (IQR 0.43-0.62) and signals of non-DMEs by 20 reports (IQR 6-84 reports) with a completeness score of 0.46 (IQR 0.38-0.56). The probability that a random DME signal was supported by fewer reports than non-DME signals was 0.56 (95% CI 0.54-0.58, P < 0.001) and that of one having lower average completeness was 0.39 (95% CI 0.36-0.41, P < 0.001). The median TTCs of DME and non-DME signals did not differ (10 years), but the TTC was as low as 2 years when signals (irrespective of classification) were supported by reports whose average completeness was > 0.80.
CONCLUSIONS: Signals of designated medical events were supported by fewer reports and higher completeness scores than signals of other adverse events. Although statistically significant, the differences in effect sizes between the two groups were small. This suggests that listing certain adverse events as DMEs is not having the expected effect of encouraging a focus on reports of the types of suspected adverse reactions that deserve special attention. Further enhancing the completeness of the reports of suspected adverse drug reactions supporting signals of designated medical events might shorten their time to communication and reduce the number of reports required to support them.

BACKGROUND: Dabrafenib and trametinib represent targeted therapy options under investigation for treatment of gliomas harboring BRAF V600 mutations. We systematically reviewed the literature and conducted meta-analyses to assess the efficacy and safety of these agents.
METHODS: PubMed, Embase, and Scopus were searched from inception to September 2023 for studies examining dabrafenib and/or trametinib for gliomas. Outcomes included response rates (ORR, CR, PR), progression rates (PD), 6- and 12-month PFS, adverse events, and dosing modifications. Meta-analyses were conducted using random effect models.
RESULTS: Nine studies met the inclusion criteria. Meta-analysis demonstrated overall response rates (ORR) of 50% (95% confidence interval (CI): 35-65%) for low-grade gliomas (LGG) and 40% (95% CI: 29-51%) for high-grade gliomas (HGG). Pooled ORR was 45% (95% CI: 36-54%) for both glioma grades. The complete response rate was 13% (95% CI: 05-27%) for HGG and 5% (95% CI: 1-10%) for both LGG and HGG. Six-month progression-free survival (PFS) rates reached 87% in LGG and 67% in HGG and a pooled 6-month PFS 78% (95% CI: 58-98%), declining at 12 months to 67% and 44%, respectively, with a pooled 12-month PFS 56% (95% CI: 34-79%). Grade 1-4 adverse events occurred in 100% of LGG and 63% of HGG patients.
CONCLUSIONS: Dabrafenib and trametinib demonstrate promising anti-tumor efficacy in gliomas, particularly low-grade tumors, achieving durable disease stabilization in many patients. However, toxicity significantly limited tolerability. Additional research should further examine efficacy and refine safe administration protocols across glioma subtypes.

Approximately 43 720 new cases of thyroid carcinoma are expected to be diagnosed in 2023 in the US. Five-year relative survival is approximately 98.5%. This review summarizes current evidence regarding pathophysiology, diagnosis, and management of early-stage and advanced thyroid cancer.
Papillary thyroid cancer accounts for approximately 84% of all thyroid cancers. Papillary, follicular (≈4%), and oncocytic (≈2%) forms arise from thyroid follicular cells and are termed well-differentiated thyroid cancer. Aggressive forms of follicular cell-derived thyroid cancer are poorly differentiated thyroid cancer (≈5%) and anaplastic thyroid cancer (≈1%). Medullary thyroid cancer (≈4%) arises from parafollicular C cells. Most cases of well-differentiated thyroid cancer are asymptomatic and detected during physical examination or incidentally found on diagnostic imaging studies. For microcarcinomas (≤1 cm), observation without surgical resection can be considered. For tumors larger than 1 cm with or without lymph node metastases, surgery with or without radioactive iodine is curative in most cases. Surgical resection is the preferred approach for patients with recurrent locoregional disease. For metastatic disease, surgical resection or stereotactic body irradiation is favored over systemic therapy (eg, lenvatinib, dabrafenib). Antiangiogenic multikinase inhibitors (eg, sorafenib, lenvatinib, cabozantinib) are approved for thyroid cancer that does not respond to radioactive iodine, with response rates 12% to 65%. Targeted therapies such as dabrafenib and selpercatinib are directed to genetic mutations (BRAF, RET, NTRK, MEK) that give rise to thyroid cancer and are used in patients with advanced thyroid carcinoma.
Approximately 44 000 new cases of thyroid cancer are diagnosed each year in the US, with a 5-year relative survival of 98.5%. Surgery is curative in most cases of well-differentiated thyroid cancer. Radioactive iodine treatment after surgery improves overall survival in patients at high risk of recurrence. Antiangiogenic multikinase inhibitors and targeted therapies to genetic mutations that give rise to thyroid cancer are increasingly used in the treatment of metastatic disease.

OBJECTIVE: We evaluated the effectiveness and safety of pan-genotypic regimens, glecaprevir/pibrentasvir (GLE/PIB), sofosbuvir/velpatasvir (SOF/VEL), and sofosbuvir/daclatasvir (SOF/DCV) and other direct-acting antivirals (DAA) regimens for the treatment of hepatitis C virus (HCV)-infected adolescents (12-18 years), older children (6-11 years), and young children (3-5 years). The purpose of this systematic review and meta-analysis was to inform the World Health Organization (WHO) guidelines.
METHODS: We included clinical trials and observational studies published up to August 11, 2021, that evaluated DAA regimens in HCV-infected adolescents, older children, and young children. We searched MEDLINE, EMBASE, and CENTRAL databases and key conference abstracts. Sustained virological response 12 weeks after the end of treatment (SVR12), adverse events (AEs), and treatment discontinuation were the outcomes evaluated. Risk of bias was assessed using a modified version of the ROBINS-I tool. Data were pooled using random-effects models, and certainty of the evidence was assessed using the GRADE approach.
RESULTS: A total of 49 studies including 1882 adolescents, 436 older children, and 166 young children were considered. The SVR12 was 100% (95% Confidence Interval: 96-100), 96% (90-100), and 96% (83-100) for GLE/PIB in adolescents, older, and young children, respectively; 95% (90-99), 93% (86-98), and 83% (70-93), for SOF/VEL, respectively; and 100% (97-100) and 100% (94-100) for SOF/DCV in adolescent and older children, respectively. There was a clear trend towards a higher rate of any reported AE from adolescents (50%), older children (53%), to young children (72%). Serious AEs and treatment discontinuations were uncommon in adolescents and older children (<1%) but slightly higher in young children (3%).
CONCLUSIONS: All three pan-genotypic DAA regimens were highly effective and well-tolerated and are now recommended by the WHO for use in adults, adolescents, and children down to 3 years, which will simplify procurement and supply chain management. The evidence was based largely on single-arm non-randomized controlled studies. Moreover, there were also missing data regarding key variables such as route of HCV acquisition, presence or absence of cirrhosis, or HIV co-infection that precluded evaluation of the impact of these factors on outcomes.
UNASSIGNED: CRD42020146752.

Craniopharyngiomas present unique challenges in surgical management due to their proximity to critical neurovascular structures. This systematic review investigates genetic and immunological markers as potential targets for therapy in craniopharyngiomas, assessing their involvement in tumorigenesis, and their influence on prognosis and treatment strategies. The systematic review adhered to PRISMA guidelines, with a thorough literature search conducted on PubMed, Ovid MED-LINE, and Ovid EMBASE. Employing MeSH terms and Boolean operators, the search focused on craniopharyngiomas, targeted or molecular therapy, and clinical outcomes or adverse events. Inclusion criteria encompassed English language studies, clinical trials (randomized or non-randomized), and investigations into adamantinomatous or papillary craniopharyngiomas. Targeted therapies, either standalone or combined with chemotherapy and/or radiotherapy, were examined if they included clinical outcomes or adverse event analysis. Primary outcomes assessed disease response through follow-up MRI scans, categorizing responses as follows: complete response (CR), near-complete response (NCR), partial response, and stable or progressive disease based on lesion regression percentages. Secondary outcomes included treatment type and duration, as well as adverse events. A total of 891 papers were initially identified, of which 26 studies spanning from 2000 to 2023 were finally included in the review. Two tables highlighted adamantinomatous and papillary craniopharyngiomas, encompassing 7 and 19 studies, respectively. For adamantinomatous craniopharyngiomas, Interferon-2α was the predominant targeted therapy (29%), whereas dabrafenib took precedence (70%) for papillary craniopharyngiomas. Treatment durations varied, ranging from 1.7 to 28 months. Positive responses, including CR or NCR, were observed in both types of craniopharyngiomas (29% CR for adamantinomatous; 32% CR for papillary). Adverse events, such as constitutional symptoms and skin changes, were reported, emphasizing the need for vigilant monitoring and personalized management to enhance treatment tolerability. Overall, the data highlighted a diverse landscape of targeted therapies with encouraging responses and manageable adverse events, underscoring the importance of ongoing research and individualized patient care in the exploration of treatment options for craniopharyngiomas. In the realm of targeted therapies for craniopharyngiomas, tocilizumab and dabrafenib emerged as prominent choices for adamantinomatous and papillary cases, respectively. While adverse events were common, their manageable nature underscored the importance of vigilant monitoring and personalized management. Acknowledging limitations, future research should prioritize larger, well-designed clinical trials and standardized treatment protocols to enhance our understanding of the impact of targeted therapies on craniopharyngioma patients.