Comparison of outcomes between minimally invasive and median sternotomy for double and triple valve surgery: A meta-analysis

Background

Limited data exists demonstrating the efficacy of minimally invasive surgery (MIS) compared to median sternotomy (MS) for multiple valvular disease (MVD). This systematic review and meta-analysis aims to compare operative and peri-operative outcomes of MIS vs MS in MVD.

Methods

PubMed, Ovid, and Embase were searched from inception until August 2019 for randomized and observational studies comparing MIS and MS in patients with MVD. Clinical outcomes of intra- and postoperative times, reoperation for bleeding and surgical site infection were evaluated.

Results

Five observational studies comparing 340 MIS vs 414 MS patients were eligible for qualitative and quantitative review. The quality of evidence assessed using the Newcastle-Ottawa scale was good for all included studies. Meta-analysis demonstrated increased cardiopulmonary bypass time for MIS patients (weighted mean difference [WMD], 0.487; 95% confidence interval [CI], 0.365-0.608; P < .0001). Similarly, aortic cross-clamp time was longer in patients undergoing MIS (WMD, 0.632; 95% CI, 0.509-0.755; P < .0001). No differences were found in operative mortality, reoperation for bleeding, surgical site infection, or hospital stay.

Conclusions

MIS for MVD have similar short-term outcomes compared to MS. This adds value to the use of minimally invasive methods for multivalvular surgery, despite conferring longer operative times. However, the paucity in literature and learning curve associated with MIS warrants further evidence, ideally randomized control trials, to support these findings.

     

Association Between Patient and Physician Sex and Physician-Estimated Stroke and Bleeding Risks in Atrial Fibrillation

Background

Physicians treating nonvalvular atrial fibrillation (AF) assess stroke and bleeding risks when deciding on anticoagulation. The agreement between empirical and physician-estimated risks is unclear. Furthermore, the association between patient and physician sex and anticoagulation decision-making is uncertain.

Phase I trial of doxorubicin-containing low temperature sensitive liposomes in spontaneous canine tumors.

PURPOSE: To determine the maximum tolerated dose, dose-limiting toxicities, and pharmacokinetic characteristics of doxorubicin encapsulated in a low temperature sensitive liposome (LTSL) when given concurrently with local hyperthermia to canine solid tumors. EXPERIMENTAL DESIGN: Privately owned dogs with solid tumors (carcinomas or sarcomas) were treated. The tumors did not involve bone and were located at sites amenable to local hyperthermia. LTSL-doxorubicin was given (0.7-1.0 mg/kg i.v.) over 30 minutes during local tumor hyperthermia in a standard phase I dose escalation study. Three treatments, given 3 weeks apart, were scheduled. Toxicity was monitored for an additional month. Pharmacokinetics were evaluated during the first treatment cycle. RESULTS: Twenty-one patients were enrolled: 18 with sarcomas and 3 with carcinomas. Grade 4 neutropenia and acute death secondary to liver failure, possibly drug related, were the dose-limiting toxicities. The maximum tolerated dose was 0.93 mg/kg. Other toxicities, with the possible exception of renal damage, were consistent with those observed following free doxorubicin administration. Of the 20 dogs that received > or = 2 doses of LTSL-doxorubicin, 12 had stable disease, and 6 had a partial response to treatment. Pharmacokinetic variables were more similar to those of free doxorubicin than the marketed liposomal product. Tumor drug concentrations at a dose of 1.0 mg/kg averaged 9.12 +/- 6.17 ng/mg tissue. CONCLUSION: LTSL-doxorubicin offers a novel approach to improving drug delivery to solid tumors. It was well tolerated and resulted in favorable response profiles in these patients. Additional evaluation in human patients is warranted.     

192Ir low dose rate brachytherapy for boosting locally advanced prostate cancers after external beam radiotherapy: a phase II trial.

BACKGROUND AND PURPOSE: To evaluate on 201 locally advanced prostatic cancers prospectively treated in a phase II trial, the efficacy of a combination of external beam radiotherapy (39.6 Gy) and (192)Ir low dose rate brachytherapy (Bt) (40-45 Gy). PATIENTS AND METHODS: Sixty-four patients were included in the intermediate prognosis group with only one of the following adverse factors (PSA > 10 ng/ml, Gleason score > or = 7 or clinical stage > or =T2b) and 137 in the unfavourable group when at least two of these factors were present. RESULTS: The actuarial 4 years biochemical no evidence of disease is 82.8% for the entire population. It is, respectively, 97 and 76% in the intermediate and unfavourable prognosis groups (P < 0.0001). Grade > or =3 late urinary complications occurred in 13 patients (6.5%). Eight patients (4%) presented late grade 2 rectal complications but no grades 3-5 was observed. CONCLUSIONS: Even if an alpha/beta of 1.5-3 Gy theoretically favours the use of a high dose rate mode of irradiation, the early results presented here are as good as those reported for similar groups of patients with high dose rate treatments. Late toxicity is identical but our urinary toxicity is within the less favourable and rectal toxicity within the most favourable results. We can postulate that while inducing very high hyperdosage regions (V150) mainly focused on the peripheral zone, most of the Bt techniques consist of a more ablative treatment. Many of the radiobiological studies on Bt did not in fact take into account the heterogeneity of irradiation inside the CTV. This study highlights the need to explore pulsed dose rate therapies, permanent implant and new available radioisotopes such as (169)Ytterbium that will offer the safety of low and lower dose rates. The actual late toxicity of the different Bt techniques is not yet inexistent indeed.     

The molecular and clinical impact of hepatocyte growth factor, its receptor, activators, and inhibitors in wound healing

Wound healing involves a number of cellular and molecular events, many of which are controlled by soluble growth factors. In the process of healing, hepatocyte growth factor, a cytokine known to act as mitogen, motogen, and morphogen, has been postulated to play multiple roles during several stages of this complex biological process. Produced primarily by stromal fibroblasts, hepatocyte growth factor regulates angiogenesis, vascular permeability, cell migration, matrix deposition and degradation, and other biological processes. The current article discusses recent progress in understanding the multiple roles played by this growth factor in tissue repair.     

Etanercept decreases tumor necrosis factor-α activity in chronic wound fluid

High levels of tumor necrosis factor-alpha (TNF-alpha), a pro-inflammatory cytokine, are present in the wound fluid of chronic nonhealing wounds. This leads to increased inflammation, cytokine expression, and ultimately results in impaired wound healing and tissue destruction. Etanercept is a recombinant fusion protein that consists of the soluble TNF receptor (p75) linked to the Fc portion of human IgG1. It is an effective inhibitor of TNF-alpha and has been shown to provide rapid and sustained improvement in rheumatoid arthritis by acting as a soluble receptor binding TNF-alpha and preventing its proinflammatory activities. Therefore, the aim of this study was to determine whether Etanercept could inhibit TNF-alpha activity in chronic wound fluid. Wound fluid was collected from the venous leg ulcers of 16 different patients. The effect of Etanercept on TNF-alpha activity was evaluated using both a TNF-alpha bioassay and an enzyme-linked immunoassay. Etanercept was found to reduce the cytotoxic effect of chronic wound fluid on L929 fibroblasts by approximately 30% and neutralized TNF-alpha binding in the enzyme-linked immunoassay by up to 80%. Direct application of Etanercept to chronic wounds may therefore reduce the inflammatory activity of TNF-alpha, which could reduce the chronicity of venous leg ulcers and thus aid in the healing of these wounds.     

Serum monitoring of antipsychotic drug levels during concomitant administration of sertraline and antipsychotic medication.

OBJECTIVE: To assess whether pharmacokinetic drug interactions occur when sertraline is added to antipsychotic medications. METHOD: Forty-eight patients with remitted DSM-IV schizophrenia and comorbid major depression were randomized to placebo for 6 weeks or sertraline 50 mg for 4 weeks followed by sertraline 50 mg to 100 mg for 2 weeks for nonresponders. Treatment with the patients' usual antipsychotic continued. Weekly clinical outcome assessments occurred for 6 weeks, and serum samples for drug monitoring were collected at Weeks 1, 5, and 6. Serum concentrations of sertraline and antipsychotics were measured with standard assays. RESULTS: In both placebo- and sertraline-treated groups, most patients displayed minor fluctuations in antipsychotic serum levels over 6 weeks. There was no clinical evidence of drug interactions in the sertraline-treated group. CONCLUSIONS: Clinically significant adverse effects did not occur despite variable antipsychotic serum levels with or without sertraline. Concern about pharmacokinetic interactions should not deter the use of sertraline for depression in individuals with schizophrenia.