Mohamed Abo Zeid

Background Streptococcus pneumoniae remains a major cause of morbidity and mortality worldwide, particularly among children and older adults. Although 13-valent pneumococcal conjugate vaccine (PCV13) significantly reduced the burden of pneumococcal disease, non-PCV13 serotypes such as 22 F and 33 F continue to cause invasive pneumococcal disease (IPD). PCV15 was developed to address this gap by including serotypes 22 F and 33 F. Methods Following PRISMA guidelines, a comprehensive literature search was conducted across multiple databases through March 2024. Randomized controlled trials (RCTs) comparing PCV15 and PCV13 were included. Primary outcomes included IgG geometric mean concentrations (GMCs) and opsonophagocytic activity geometric mean titers (OPA GMTs) for serotypes 22 F and 33 F. Results Nineteen RCTs (n = 16,046) were included. PCV15 demonstrated significantly higher immunogenicity than PCV13 for serotypes 22 F and 33 F across most age and dose subgroups. For IgG GMCs, pooled mean differences (MDs) for serotype 22 F were 6.34 (95% CI 5.13–7.56; I²=97%) in infants, 10.09 (95% CI 6.06–14.13; I²=92%) in children, and 3.19 (95% CI 2.01–4.36; I²=96%) in adults. For serotype 33 F, MDs were 2.40 (95% CI 1.52–3.28; I²=99%), 4.27 (95% CI 3.74–4.80; I²=0%), and 6.81 (95% CI 5.10–8.52; I²=93%), respectively. OPA GMTs also favored PCV15 for serotype 22 F after both single-dose (MD = 1.55, 95% CI 0.69–2.41; I²=99%) and three-dose schedules (MD = 1.66, 95% CI 1.24–2.08; I²=87%), while for serotype 33 F, superiority was observed only with three doses (MD = 0.98, 95% CI 0.56–1.39; I²=90%). PCV15 was associated with higher rates of injection-site adverse events (RR = 1.08, 95% CI 1.03–1.11), whereas systemic adverse events were comparable between groups (RR = 1.03, 95% CI 1.00–1.06). Meta-regression identified a significant negative association between age and IgG GMC 22 F (β=-0.061, 95% CI -0.096 to -0.025; p ≤ 0.001). Certainty of evidence ranged from low to moderate according to GRADE assessment, primarily limited by inconsistency across studies. Conclusion PCV15 demonstrated significantly higher immunogenicity against serotypes 22 F and 33 F than PCV13 across most age and dose subgroups while maintaining a generally comparable safety profile. These findings support the immunogenic advantage of PCV15 for the additional serotypes included in the vaccine; however, studies evaluating clinical effectiveness are needed to determine whether these immunological differences translate into reductions in pneumococcal disease.

Objectives: Laparoscopic cholecystectomy (LC), though minimally invasive, sometimes leads to significant postoperative pain. Ketamine has shown potential in alleviating it, but small sample sizes and variability in administration protocols limit the generalizability of prior findings. This study evaluated the effectiveness of ketamine in reducing postoperative pain across multiple time points. Methods: A thorough search of multiple databases was conducted, covering publications up to January 2025. Data from eligible randomized controlled trials (RCTs) were extracted and pooled to calculate mean differences (MDs) for postoperative pain scores at 30 minutes, 1, 2, 4, and 12 hours, along with opioid consumption (morphine and tramadol) and adverse events. Results: The analysis included 22 RCTs with 1163 participants. Ketamine significantly reduced postoperative pain compared with placebo ( MD =−0.37, 95% CI: [−0.56 to −0.17], P =0.0002). Subgroup analyses at 30 minutes showed significant pain reduction in bolus + infusion ( MD =−0.70, 95% CI: [−1.33 to −0.07], P =0.03), bolus alone ( MD =−1.28, 95% CI: [−2.29 to −0.27], P =0.01), and propofol-based maintenance ( MD =−0.89, 95% CI: [−1.44 to −0.34], P =0.002). In addition, ketamine significantly reduced morphine ( MD =−0.46, 95% CI: [−0.91 to −0.02], P =0.04) and tramadol consumption ( MD =−1.03, 95% CI: [−1.86 to −0.21], P =0.01). Discussion: Ketamine reduced opioid use and postoperative pain at 30 minutes, with efficacy varying by administration method. Future RCTs should standardize dosage, anesthesia protocols, and pain management strategies to enhance evidence consistency.

Catheter-related bladder discomfort (CRBD) is a common postoperative problem following urinary catheterization. Current pharmacologic options have limited use due to side effects. Lidocaine, with analgesic, anti-inflammatory, and antimuscarinic properties, may provide an effective and safer alternative. This study aims to systematically evaluate (1) the efficacy of intravenous (IV) lidocaine compared with normal saline, (2) the efficacy of intravesical lidocaine compared with normal saline, and (3) postoperative outcomes including opioid requirements, as specified in the PROSPERO registration (CRD420251155678). A systematic search of randomized controlled trials (RCTs) was conducted in accordance with PRISMA guidelines. Studies comparing intravenous or intravesical lidocaine with normal saline for CRBD prevention in adult surgical patients were included. Primary outcomes were CRBD incidence and severity at predefined postoperative time points. Secondary outcomes included opioid consumption when reported. Study quality was assessed using the RoB 2 tool, and the certainty of evidence was evaluated by GRADE and trial sequential analysis (TSA). Five RCTs, including 463 patients, were analyzed. Lidocaine significantly reduced moderate-to-severe CRBD compared with saline at 0 h (RR = 0.42, 95% CI 0.32–0.55), 1 h (RR 0.42, 95% CI 0.28, 0.61), and 2 h (RR 0.33, 95% CI 0.12, 0.90), but not at 6 h (RR 0.30, 95% CI 0.07, 1.22). No significant difference was observed in postoperative opioid consumption (MD − 0.56, 95% CI − 1.14, 0.03). TSA confirmed conclusive results at 0 and 1 h, with high-certainty evidence per GRADE. Both IV and transurethral lidocaine significantly reduce early postoperative CRBD. Lidocaine represents a safe, effective, and easily applicable option for short-term prevention of CRBD.

Objective Our goal is to conduct an investigation into the safety and efficacy of 𝛽3 agonist (Mirabegron) in patients with heart failure (HF) comparing it to placebo. Methods We searched internet databases for eligible randomized controlled trials (RCTs) up to April 1st, 2024. Heart rate, stroke volume, systolic blood pressure, cardiac index, and adverse events were the primary outcomes that were analyzed. Inverse variance was used to compute the risk ratio (RR) and pooled mean differences (MD), along with their 95% CI. Results Four studies were included in our paper with a total of 454 patients. The mirabegron group showed a statistically significant improvement compared to the placebo group in Cardiac index (MD: 0.28, [95% CI: 0.02 , 0.53], P = 0.03), but pooled analysis did not favor either of the two arms in heart rate, ejection fraction, stroke volume and systolic blood pressure (MD: 2.54, [95% CI: -1.05 , 6.13]), (MD: 2.40, [95% CI: -2.51 , 7.3]), (MD: 0.56, [95% CI: -2.45 , 3.56]), and (MD: 0.11, [95% CI:-0.15 , 0.38]) respectively. Furthermore, there were not significant variations between the two groups in adverse events, and serious adverse events (RR: 1.06, [95% CI: 0.87, 1.29]), and (RR: 1.06, [95% CI: 0.70, 1.60], p = 0.80) respectively. Conclusion The Cardiac index was considerably enhanced with Mirabegron, but all other effectiveness and safety outcomes were unchanged. Further RCTs for longer durations and on more diverse populations still need to be conducted.

This systematic review and meta-analysis investigated the efficacy and safety of support rods and bridges in loop stoma formation, a practice frequently employed in colorectal surgery despite the associated complications and controversial efficacy. The aim of this study is to provide evidence-based guidance on their routine use. Adhering to the Cochrane Collaboration’s recommendations, we conducted this systematic review and meta-analysis systematically searching PubMed, Scopus and Web of Science for randomized controlled trials (RCTs) evaluating the efficacy of rods/ bridges in loop ileostomies. Key outcomes assessed included stoma retraction, stoma/skin necrosis, peristomal dermatitis, infection, and mucocutaneous separation. This review included six studies encompassing 1,239 patients (195 ileostomy, 1,044 colostomy). Analysis revealed no statistically significant difference in stoma retraction (RR = 0.70, 95% CI [0.37 to 1.33], P = 0.28). Conversely, for stoma/skin necrosis, four studies were analyzed and showed a statistically significant difference favoring the non-rod/bridge group (RR = 5.04, 95% CI [1.72 to 14.73], P = 0.003). For peristomal dermatitis, three studies revealed a statistically significant difference favoring the non-rod/bridge group (RR = 2.01, 95% CI [1.55 to 2.60], P < 0.00001), with ostomy rod use identified as a significant risk factor (OR 3.42, p < 0.01). Outcomes for infection and mucocutaneous separation showed no significant difference. Based on the our results, routine rod/bridge use does not appear to reduce stoma retraction and may be associated with an increased risk of necrosis and dermatitis. That is why the routine use of rod/bridge does not appear to be justified, but the small number of the included studies limit the generalizability of these results. Trial sequential analysis indicated that future high-quality RCTs with diverse and larger populations and are recommended to obtain more rigorous evidence.

Background: Healive is an inactivated vaccine for hepatitis A virus developed in China and was found to be well-tolerated and highly immunogenic in adults and children. It is our aim this study to compare the safety and immunogenicity of Healive® with Havrix® and live attenuated vaccines in pediatric populations. Methods: A systematic search of PubMed, Scopus, Web of Science, and Embase databases was conducted following PRISMA guidelines. Randomized controlled trials (RCTs) comparing Healive with other vaccines were included. Results: Seven RCTs involving 3664 patients were included. Healive showed comparable efficacy to Havrix regarding seroconversion rates and GMT at one month (SMD = 0.24, 95% CI [-0.11 to 0.59]), but achieved better results at six (SMD = 0.85, 95% CI [0.57 to 1.07]) and seven months (SMD = 0.55, 95% CI [0.41 to 0.70]). When compared to live attenuated vaccines, Healive demonstrated superior GMT at one month (SMD = 0.31, 95% CI [0.07 to 0.56]) and two years (SMD = 0.36, 95% CI [0.06 to 0.67]). Conclusion: Healive appears to be effective and safe for preventing hepatitis A, providing at least five years of protection. This review underscores the importance of ongoing research to optimize hepatitis A vaccination strategies, including standardized assays for antigen content, clarification of protective antibody levels, and large-scale trials in regions of intermediate endemicity.

Background: Chronic spontaneous urticaria (CSU) is a skin condition characterized by itchy hives and/or angioedema, impairing patients’ quality of life even with the current available medications. This study aims to evaluate the efficacy and safety of Ligelizumab, a high-affinity monoclonal anti-IgE antibody, in the treatment of CSU. Methods: We performed a systematic review and meta-analysis in accordance with PRISMA criteria, methodically exploring databases for randomized controlled trials (RCTs) comparing Ligelizumab with placebo in patients with CSU. Studies that reported outcomes like the itch severity score (ISS7), the hives severity score (HSS7), and adverse events were included in our analysis. Results: Four RCTs were included in our analysis with a total of 2,481 patients with CSU. Ligelizumab significantly improved urticaria symptoms as measured by change in ISS7 at week 12 in adults (MD = -3.67, 95% CI: [-4.25 to -3.09], p < 0.00001), change in UAS7 at week 12 in adults (MD = -9.18, 95% CI: [-10.45 to -7.92], p < 0.00001), and change in UAS7 at week 12 in adolescents (MD = -6.48, 95% CI: [-12.84 to -0.12], p = 0.05). Regarding safety outcomes, only Ligelizumab 120mg showed significantly higher upper respiratory tract infection rates (RR = 2.70, 95% CI [1.17 to 6.21], p = 0.02). Conclusion: Our findings suggest that Ligelizumab, at doses 72 and 120 mg, might be able to improve the symptoms of CSU evidenced by the improvements in ISS7 UAS7 and UAS7 response rate and the overall quality of life with an acceptable safety profile with certain concerns regarding Ligelizumab 120 mg causing upper respiratory tract infections. However, the small number of studies included limit the generalizability of our results.

Introduction: To evaluate the efficacy of tranexamic acid (TXA) in blepharoplasty surgery. Methods: A meta-analysis was conducted following PRISMA guidelines. PubMed, Web of Science, Cochrane Library, and Scopus databases were searched for randomized controlled trials (RCTs). Data extraction focused on outcomes, such as ecchymosis scores, time to recovery, intraoperative pain, operative time, and hemostasis quality. The risk of bias was assessed using the ROB 2 tool. RevMan 5.4 software was used for meta-analysis with mean differences (MD) and standardized MD (SMD) calculated for various outcomes. Results: Five RCTs comprising 594 participants (1154 eyes) met the inclusion criteria. Overall, TXA significantly reduced postoperative ecchymosis on postoperative days (POD) 1 and 7 (SMD = – 0.54, 95% CI: [– 0.71 to – 0.38], p < 0.00001) with moderate heterogeneity ( I ² = 50%). TXA significantly shortened patient-reported recovery time (MD = – 0.72 days, 95% CI: [– 1.02 to – 0.42], p < 0.00001) with homogeneity ( I ² = 0%). Also, TXA significantly reduced operative time (MD = – 1.20 minutes, 95% CI: [– 2.39 to – 0.01], p < 0.05). On the other hand there was no significant difference in intraoperative pain scores or surgeon-assessed hemostasis quality for SC TXA; however, IV TXA improved hemostasis assessment (MD = – 0.70, 95% CI: [– 1.02 to – 0.38], p < 0.0001). Conclusion: TXA significantly reduces ecchymosis, expedites recovery, and enhances operative time and hemostasis in blepharoplasty. These findings support TXA’s use as an effective adjunct to improve blepharoplasty recovery, although further studies are warranted to optimize dosing and minimize thromboembolic risks. Level of Evidence I: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

This study aims to evaluate the efficacy and safety of ensifentrine in COPD patients. Following the PRISMA guidelines, we conducted a systematic review and meta-analysis, systematically searching PubMed, Web of Science, Scopus, and Cochrane library up to 12 December 2024, for randomized controlled trials (RCTs) evaluating ensifentrine compared to placebo in COPD patients. Eligibility criteria included studies reporting outcomes such as pulmonary function tests, exacerbation rates, and adverse events. Subgroup analysis was conducted based on the timing of outcome evaluation and the doses administered. Additionally, a meta-regression model was employed to evaluate the possible correlations between the Ensifentrine doses and “Average forced expiratory volume (FEV 1)” results and identify the optimal dose. Trial sequential analysis (TSA) was implemented to ensure the conclusiveness of our results. Furthermore, the GRADE approach was used to assess the certainty of evidence and for quality assessment the RoB-2 tool was used. Four RCTs were included in our analysis with a total of 2370 COPD patients. Compared to placebo, ensifentrine 3 mg significantly improved lung functions as measured by change in average FEV1 (MD = 0.09, 95% CI: [0.07 to 0.12]), change in peak FEV1 (0–3 h) (MD = 0.15, 95% CI: [0.13 to 0.18]), and change in morning trough FEV1 (MD = 0.04, 95% CI: [0.02 to 0.07]). Subgrouping based on the administrated dose found that ensifentrine 3 mg showed higher, yet non-significant results compared to the included doses (0.75, 1.5, and 6 mg) in all pulmonary function tests. Moreover, meta-regression revealed a significant dose–response relationship for average FEV1 up to 3 mg, indicating optimal efficacy at 3-mg dose. Ensifentrine also significantly improved quality of life measures, with no significant increase in adverse events across doses. Ensifentrine has proven to be effective in improving lung functions and respiratory symptoms with an acceptable safety profile, thus suggesting a valuable addition to the management of COPD with consideration of potential adverse effects. Nevertheless, further studies with extended long-term follow-up are essential to fully assess the sustained efficacy and safety of ensifentrine and support its optimal therapeutic integration. Clinical trial number: Not applicable.