RESUMO
BACKGROUND: Great saphenous vein (GSV) antireflux procedures have evolved during the past few decades to reduce elevated venous pressure. Untreated reflux in the below knee (BK) GSV (BK-GSV) can lead to persistent venous hypertension and deterioration of the venous circulation. The purpose of the present systematic review was to study the influence of BK-GSV intervention on venous disease progression. METHODS: A search was conducted, adhering to the PRISMA (preferred reporting items for systematic reviews and meta-analyses) guidelines. The PubMed and Embase databases were searched and cross-referenced. Studies were included if they had met the inclusion criterion of BK-GSV disease as a primary or secondary outcome. Two of the authors independently determined the eligibility and extracted the relevant data. RevMan, version 5.3 (Cochrane Training, London, UK), and SPSS (IBM Corp, Armonk, NY) were used for statistical computation. RESULTS: Fifteen studies that had assessed BK-GSV reflux recurrence after ablative intervention were included in our analysis. Of the 15 studies, 6 had assessed patients after above knee (AK) high ligation and stripping (HLS), 7 after AK endovenous laser ablation (AK-EVLA), and 2 after AK- and BK-EVLA (AK+BK EVLA). In total, 525 limbs had undergone HLS, 696 AK-EVLA, and 147 AK+BK EVLA. AK+BK EVLA was associated with significantly lower odds of BK-GSV reflux recurrence compared with AK-EVLA only (odds ratio [OR], 0.1857; 95% confidence interval [CI], 0.076-0.4734; P < .0001). Although the odds of recurrent BK-GSV reflux appeared to be greater for patients who had undergone AK-HLS compared with AK+BK HLS, the difference was not statistically significant (OR, 0.62; CI, 0.27-1.43; P = .69). Finally, no statistically significant difference was observed in BK-GSV reflux recurrence between patients receiving AK-EVLA and those receiving AK-HLS (OR, 0.85; 95% CI, 0.52-1.39; P = .31). CONCLUSIONS: Axial hydrostatic reflux from the groin to ankle is best controlled with AK+BK-GSV ablation. However, GSV ablation can result in saphenous nerve injury. For C4 to C6 disease, more aggressive treatment of the AK+BK-GSV is justified if the duplex ultrasound findings demonstrate groin to ankle reflux. Thermal ablation of the BK-GSV has a lower incidence of saphenous nerve injury than does BK saphenous stripping. More randomized controlled trials are needed to answer questions involving disease recurrence and the best techniques to mitigate these recurrences.
Assuntos
Técnicas de Ablação , Procedimentos Endovasculares/métodos , Veia Safena , Insuficiência Venosa/cirurgia , Progressão da Doença , Humanos , JoelhoRESUMO
Background: No previous studies have determined the incidence of acute kidney injury (AKI) in trauma patients treated with vancomycin + meropenem (VM) versus vancomycin + cefepime (VC). The purpose of this study was to fill this gap. Methods: A series of 99 patients admitted to an American College of Surgeons-verified level 1 trauma center over a two-year period who received VC or VM for >48 hours were reviewed retrospectively. Exclusion criteria were existing renal dysfunction or on renal replacement therapy. The primary outcome was AKI as defined by a rise in serum creatinine (SCr) to 1.5 times baseline. Multi-variable analysis was performed to control for factors associated with AKI (age, obesity, gender, length of stay [LOS], nephrotoxic agent(s), and baseline SCr), with significance defined as p < 0.05. Results: The study population was 50 ± 19 years old, 76% male, with a median LOS of 21 [range 15-39] days, and baseline SCr of 0.9 ± 0.2 mg/dL. Antibiotics, diabetes mellitus, and Injury Severity Score were independent predictors of AKI (odds ratio [OR] 4.4; 95% confidence interval [CI] 1.4-12; OR 9.3; 95% CI 1-27; OR 1.2; 95% CI 1.023-1.985, respectively). The incidence of AKI was higher with VM than VC (10/26 [38%] versus 14/73 [19.1%]; p = 0.049). Conclusions: The renal toxicity of vancomycin is potentiated by meropenem relative to cefepime in trauma patients. We recommend caution when initiating vancomycin combination therapy, particularly with meropenem.
Assuntos
Injúria Renal Aguda , Vancomicina , Injúria Renal Aguda/induzido quimicamente , Injúria Renal Aguda/epidemiologia , Adulto , Idoso , Antibacterianos/efeitos adversos , Cefepima/efeitos adversos , Quimioterapia Combinada , Feminino , Humanos , Masculino , Meropeném/efeitos adversos , Pessoa de Meia-Idade , Combinação Piperacilina e Tazobactam , Estudos Retrospectivos , Vancomicina/efeitos adversosRESUMO
UNLABELLED: Kaposi's sarcoma-associated herpesvirus (KSHV) is the causative agent of three human malignancies. KSHV ORF36 encodes a serine/threonine viral protein kinase, which is conserved throughout all herpesviruses. Although several studies have identified the viral and cellular substrates of conserved herpesvirus protein kinases (CHPKs), the precise functions of KSHV ORF36 during lytic replication remain elusive. Here, we report that ORF36 interacts with another lytic protein, ORF45, in a manner dependent on ORF36 kinase activity. We mapped the regions of ORF36 and ORF45 involved in the binding. Their association appears to be mediated by electrostatic interactions, since deletion of either the highly basic N terminus of ORF36 or an acidic patch of ORF45 abolished the binding. In addition, the dephosphorylation of ORF45 protein dramatically reduced its association with ORF36. Importantly, ORF45 enhances both the stability and kinase activity of ORF36. Consistent with previous studies of CHPK homologs, we detected ORF36 protein in extracellular virions. To investigate the roles of ORF36 in the context of KSHV lytic replication, we used bacterial artificial chromosome mutagenesis to engineer both ORF36-null and kinase-dead mutants. We found that ORF36-null/mutant virions are moderately defective in viral particle production and are further deficient in primary infection. In summary, our results uncover a functionally important interaction between ORF36 and ORF45 and indicate a significant role of ORF36 in the production of infectious progeny virions. IMPORTANCE: Kaposi's sarcoma-associated herpesvirus (KSHV) is a human tumor virus with a significant public health burden. KSHV ORF36 encodes a serine/threonine viral protein kinase, whose functions throughout the viral life cycle have not been elucidated. Here, we report that ORF36 interacts with another KSHV protein, ORF45. We mapped the regions of ORF36 and ORF45 involved in their association and further characterized the consequences of this interaction. We engineered ORF36 mutant viruses in order to investigate the functional roles of ORF36 in the context of KSHV lytic replication, and we confirmed that ORF36 is a component of KSHV virions. Moreover, we found that ORF36 mutants are defective in virion production and primary infection. In summary, we discovered and characterized a functionally important interaction between KSHV ORF36 and ORF45, and our results suggest a significant role of ORF36 in the production of infectious progeny virions, a process critical for KSHV pathogenesis.