The potential impact of renin-angiotensin system inhibitors on cancer survival and recurrence: A systemic review and meta-analysis.

Renin-angiotensin-system inhibitors (RASi), specifically angiotensin-converting enzyme inhibitors (ACEi) and angiotensin II receptor blockers (ARBs), are widely used anti-hypertensives. Their impact on the prognostic outcomes among cancer patients has been subject to scrutiny and debate. The aim of this study is to evaluate the effect of RASi on survival in cancer patients. We systematically searched PubMed, Web of Science, Embase and Cochrane Library for relevant studies published until April 1st, 2022. All the studies, interventional or observational, which examined effects of ARBs and ACEi on cancer prognosis compared to a control group and reported the survival outcomes and Hazards Ratios were included in the analysis. From each study, pooled hazard ratios (HR) with corresponding 95% confidence intervals (95% CI) were identified and collected. Subgroup analysis was conducted to investigate heterogeneity. Sixty-one studies were included in this meta-analysis. Data of 343,283 participants were used in the study. It was found that RASi improved overall survival (OS) (HR=0.88; 95% CI: 0.82-0.93; P<0.0001), progression free survival (PFS) (HR=0.72; 95% CI: 0.65-0.79; P<0.00001), disease specific survival (DSS) (HR=0.86; 95% CI: 0.71-1.04; P=0.03), and recurrence free survival (RFS) (HR=0.74; 95% CI: 0.58-0.93; P=0.01) in cancer patients. The effect of RASi on OS varied depending on the type of cancer or type of RASi (ACEi or ARBs), according to subgroup analysis. The usage of RAS inhibitors has a positive impact on survival outcomes and recurrence among cancer patients.

True brachial artery aneurysm: A systematic review.

Objective: To identify and critically appraise literature on true brachial artery aneurysm, exploring its demographic characteristics, aetiologies, clinical manifestations and different methods of repair along with complication rates to determine future treatment strategies. METHODS: The systematic review was conducted at Liaquat National Hospital, Karachi, from September 30, 2021, to November 30, 2022, in line with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Literature was searched on MEDLINE, EMBASE and Cochrane databases for relevant studies in English language or with English translation published till May 31, 2022. The key words used for the search were "brachial artery aneurysm". Data was noted on a proforma and was subjected to descriptive analysis. RESULTS: Of 113 articles, 6 (5.3%) were retrospective studies, 7 (6.1%) were case series and 100 (88.4%) were case reports. The total number of patients involved was 157 with mean age 43.1±23.4 years (range: 2 months to 84 years). The gender was mentioned for 152(96.8%) patients; 111(73%) males and 41(27%) females. The mean diameter of true brachial artery aneurysm was 36.2 ±17.5mm and 106(67.5%) patients presented with localised swelling, 65(41.4%) with pain, 41(26.1%) with distal ischaemic symptoms, and 28(17.8%) with median nerve compression. True brachial artery aneurysms were more common in renal failure patients having a history of arteriovenous fistula creation in the affected limb and were on immunosuppressant drugs due to renal transplant 81(51.5%). Less common causes included primary/idiopathic 27(17.1%), trauma 13(8.2%), connective tissue disorders 8(5%) and vasculitis 7(4.5%). The treatment of choice was aneurysmectomy in 142(90.4%) cases, with revascularisation of limb primarily with reversed great saphenous vein graft 79(50.3 %), followed by end-to-end anastomosis of brachial artery 17(10.8%) and synthetic grafting 17(10.8%). Endovascular intervention was performed in 6(3.8%) cases to exclude true brachial artery aneurysm, and to re-establish adequate blood flow to the associated limb. Conclusion: True brachial artery aneurysm, although a rarity, may lead to significant neurological and vascular problems if ignored. Arteriovenous fistula and immunosuppression are identified as two significant risk factors in the development of true brachial artery aneurysm. Therefore, an effective long-term follow up in renal failure patients is recommended to prevent its complications. Open surgical repair has been the most preferred mode of treatment, but further significant studies are needed to explore and compare different modes of surgical intervention, like open versus endovascular, to plan future treatment strategies.

Hyperhomocysteinemia in a Patient With Subdural Hematoma and Subarachnoid Hemorrhage Secondary to a Traumatic Brain Injury.

Traumatic brain injury (TBI) is a significant global health issue, contributing substantially to mortality and disability. Serum biomarkers, such as homocysteine (Hcy), play a critical role in the prognosis of brain injuries, with hyperhomocysteinemia (HHcy) potentially leading to neurological disorders. We present the case of a 64-year-old patient admitted to the emergency department following a road traffic accident (RTA). Magnetic resonance imaging (MRI) revealed parietal subdural hematoma (SDH), right frontal contusion, and left subarachnoid hemorrhage (SAH). The patient underwent a craniotomy to address SAH and SDH. Initial Hcy levels were markedly elevated compared to post-operative levels. Hcy represents a rapid, non-invasive, and cost-effective diagnostic tool for assessing brain injury severity and guiding medical intervention. Early detection of HHcy could potentially mitigate vascular and neurological complications, thereby improving patient outcomes.

Short-course versus prolonged-course antibiotic regimens for ventilator-associated pneumonia: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Current guidelines recommend short-duration antibiotic therapy for non-fermenting gram-negative bacilli (NF-GNB) ventilator-associated pneumonia (VAP) which may be associated with a higher recurrence of pneumonia. In this meta-analysis, we aimed to compare short- versus prolonged-course antibiotic regimens for VAP. METHODS: We searched several databases for randomized controlled trials (RCTs) that compared the effectiveness of a short- versus long-course of antibiotic treatment in patients with VAP. Data analysis was performed using RevMan 5.4. RESULTS: Our pooled analysis consisted of six RCTs. For 28-day mortality, no significant difference was found between the prolonged course and the short course. Administration of a short course of antibiotics increased the risk of recurrence of pneumonia in patients with VAP due to NF-GNB (RR 1.73; 95% CI: 1.17-2.54). Secondary outcomes, such as clinical resolution, duration of ICU stay, and duration of mechanical ventilation, revealed no significant difference between the two regimens. The quality of evidence was low for most outcomes. CONCLUSIONS: Low-quality evidence suggests that a short course of antibiotics is associated with a higher recurrence of pneumonia in NF-GNB VAP with no difference in mortality as compared to a prolonged course. For definitive conclusions, large-scale and blinded RCTs are required.

Supratotal Resection: An Emerging Concept of Glioblastoma Multiforme Surgery-Systematic Review And Meta-Analysis.

BACKGROUND: The severe neurologic tumor known as glioblastoma (GBM), also referred to as a grade IV astrocytoma, is rapidly progressive and debilitating. Supratotal resection (SpTR) is an emerging concept within glioma surgery, which aims to achieve a more extensive resection of the tumor than is possible with conventional techniques. METHODS: We performed a language-independent search of PubMed, Scopus, and Cochrane CENTRAL to identify all available literature up to August 2022 of patients undergoing SpTR assessing survival outcomes in comparison to other surgical modalities. RESULTS: After screening for exclusion, a total of 13 studies, all retrospective in design, were identified and included in our meta-analysis. SpTR was associated with significantly increased overall survival (hazard ratio 0.77, 95% CI 0.71-0.84; P < 0.01, I2 = 96%) and progression-free survival (hazard ratio 0.2, 95% CI 0.07-0.56; P = 0.002, I2 = 88%). CONCLUSION: SpTR is associated with greater overall survival and PFS when compared with other glioblastoma surgeries like GTR or SubTR.

Effectiveness of endovascular repair versus open surgery for the treatment of thoracoabdominal aneurysm: A systematic review and meta analysis.

Background: Thoracoabdominal aortic aneurysms (TAAAs) are associated with significant comorbidities. The aim of our study is to compare the outcomes of open repair versus endovascular repair of TAAAs. Methods: A thorough literature search was conducted on MEDLINE, Embase, and Cochrane Central databases. The analysis included observational studies comparing the outcomes of surgical vs endovascular aneurysm repair (EVAR) of TAAA. Mortality, spinal cord ischemia (SCI), renal failure, stroke, paraplegia, and respiratory and cardiac problems were all included in the studies. The results were provided as relative risks (RRs) with 95% confidence intervals (CIs). These were then aggregated using an inverse variance weighted random-effects model, and the pooled analysis was displayed using forest plots. Results: This meta-analysis compromising of twelve studies revealed significant results, favoring endovascular repair versus open surgery for all-cause mortality (HR = 1.91; 95% CI: 1.68-2.18; P < 0.00001), SCI (HR = 1.62; 95% CI: 1.18-2.21; P = 0.003), respiratory complications (HR = 2.22; 95% CI: 1.78-2.77; P < 0.00001), and cardiac complications (HR = 1.66; 95% CI: 1.38-2.00; P < 0.00001). Upon subgroup analysis based on propensity matched, results were consistent and significant for the outcomes of all-cause mortality, cardiac complications, and respiratory complications. For the propensity unmatched subgroup, the incidence of all-cause mortality, SCI, respiratory complications, and cardiac complications were lower among endovascular repair cohort. Conclusion: Current evidence supports the use of endovascular repair over open surgery. However, there is a need to conduct dedicated randomized controlled trials to effectively compare and determine the benefits and risk of both strategies.

Renal Effects of High-Dose Versus Low-Dose Lisinopril in Patients With Diabetic Nephropathy.

Background The present study was conducted to assess the renal effects of high dose versus low dose lisinopril in patients with diabetic nephropathy. Methodology A prospective observational study was conducted at the Khyber Teaching Hospital, Peshawar, Khyber Pakhtunkhwa, Pakistan, between July 1, 2019, to January 1, 2020. Patients were divided into two groups. Group A patients were administered a low dose (5 mg per day) of Lisinopril and group B were administered a higher dose of therapy (20 mg/day) for three months. At the end of the study, baseline renal functions, electrolytes, and status of microalbuminuria were compared with follow-up values. The primary outcome was to assess the change in microalbuminuria levels in patients at baseline, one month, and three months of therapy. Results A total of 72 patients were included in group A (low dose) and 72 patients were enrolled in group B (high dose). The mean ages of group A and group B were 56.3 ± 12.9 years and 53.48 ± 12.2 years, respectively. The majority of the patients in the groups were male. At baseline, the mean microalbuminuria levels in the two groups were not significantly different however, at three months post treatment, the levels were significantly much lower in high dose patients as compared to patients who were on low dose lisinopril (146.06 ± 23.89 vs. 184.69 ± 26.27; p < 0.0001). The three-month urea levels were significantly lower in group A as compared to group B (38.91 ± 7.07 vs. 43.26 ± 3.02; p = 0.008). Three-month creatinine and potassium levels were not significantly different between the groups (p = 0.7 and 0.12, respectively).  Conclusion Our study revealed that even though group B (high dose lisinopril) had significantly reduced microalbuminuria, the urea levels were found to be higher in this cohort of patients as compared to group A patients on low-dose lisinopril. Moreover, the majority of the patients in group B reported significant improvements in blood pressure control as compared to group A, which indicated that a high dose of lisinopril is more effective in patients with diabetic nephropathy than a low dose of lisinopril. The levels of creatinine after three months of treatment did not differ significantly. Further randomized trials are warranted in order to ascertain the effectiveness of high dose of lisinopril in patients with diabetic nephropathy.

Effect of novel glucose lowering agents on non-alcoholic fatty liver disease: A systematic review and meta-analysis.

BACKGROUND: The efficacy of novel glucose-lowering drugs in treating non-alcoholic fatty liver disease (NAFLD) in patients with and without type-2 diabetic patients (T2DM) remains unclear. AIM: To conduct a meta-analysis to evaluate the efficacy of 3 novel glucose-lowering drug classes, namely glucagon-like peptide-1 receptor agonists (GLP-1RA), sodium-glucose co-transporter 2 (SGLT2) inhibitors, and dipeptidyl-peptidase-4 (DPP4) inhibitors on hepatic parameters: Aspartate Aminotransferase (AST), Alanine Aminotransferase (ALT), Gamma-Glutamyl Transferase (GGT), Bilirubin, and FIB-4 (Fibrosis). METHODS: MEDLINE was searched from inception through October 2021 for randomized placebo or active glucose-lowering drug-controlled trials. A random-effects model was used to pool the results. A p-value of less than or equal to 0.05 was considered significant. Results were presented as weighted mean differences (WMD) and corresponding 95% confidence intervals (CIs). RESULTS: Our pooled analysis consisted of 40 studies. A significant reduction was seen in AST with SGLT2 inhibitors (WMD = -2.31 IU/L, 95%CI: -3.16 to -1.47 IU/L, P < 0.00001) and GLP-1RA (WMD = -3.29 IU/L, 95%CI: -5.98 to -0.61 IU/L, P = 0.02). Similarly, significant reduction was seen in ALT with SGLT2 inhibitors (WMD = -5.93 IU/L, 95%CI: -7.70 to -4.16 IU/L, P < 0.00001) and GLP-1RAs (WMD = -9.92 IU/L, 95%CI: -19.89 to 0.05 IU/L, P = 0.05). In contrast, DPP-4 inhibitors showed no significant reduction in AST (WMD = -3.20 IU/L, 95%CI: -11.13 to 4.73 IU/L, P = 0.43) or ALT (WMD = -4.81 IU/L, 95%CI: -15.83 to 6.21 IU/L, P = 0.39). A significant reduction in GGT was seen with SGLT2 inhibitors (WMD = -6.49 IU/L, 95%CI: -11.09 to -1.89 IU/L, P = 0.006) and GLP-1RAs (WMD = -12.38 IU/L, 95%CI: -15.69 to -9.07 IU/L, P < 0.00001). However, significant results were not observed with DPP-4 inhibitors (WMD = -0.92 IU/L, 95%CI: -5.80 to 3.96 IU/L, P = 0.71). There was a statistically significant reduction in FIB-4 index with SGLT2 inhibitors (WMD = -0.21, 95%CI: -0.40 to -0.03, P = 0.02) and GLP-1 RA (WMD = -0.15, 95%CI: -0.29 to 0.00, P = 0.05). Lastly, SGLT2 inhibitors led to a significant change in bilirubin levels (WMD = 2.03, 95%CI: 0.76 to 3.30, P = 0.002) while the change in bilirubin was not significant with GLP-1 agonists (WMD = -0.21, 95%CI: -1.09 to 0.66, P = 0.63) and DPP-4 inhibitors (WMD = 0.14, 95%CI: -1.55 to 1.83, P = 0.87). CONCLUSION: SGLT2 inhibitors and GLP-1 agonists have a beneficial effect on hepatic parameters in patients with NAFLD. However, further research is needed to evaluate the effect of DPP-4 inhibitors on hepatic function properly.