Safety, Tolerability, and Neurohormonal Changes of the Combination Captopril Plus Losartan in the Early Postinfarction Period: A Pilot Study

Suppression of formation of angiotensin II (A-II) is thought to be a major contributor to the hemodynamic response to angiotensin-converting enzyme inhibition (ACE-in) therapy. However, angiotensin II (A-II) plasma levels may rebound during ACE-in treatment. The study sought to verify the feasibility, safety, and tolerability of the combination of captopril (75 mg/d) plus losartan (25 mg/d). We also wished to establish whether the combination was able to avoid the increase of angiotensin II resulting from losartan treatment in early postinfarction phases of reperfused anterior acute myocardial infarction (AMI). Forty-four patients, hospitalized for suspected anterior AMI within 4 hours from the onset of symptoms, suitable for thrombolysis (first episode), Killip class I-II and reperfused, receiving 75 mg/d of captopril within 3 days from admission, and with systolic blood pressure (BP) >120 mmHg were randomized (single-blind) into two groups: Group A included 22 patients (6 women and 16 men) and received captopril 75 mg/d and placebo. Group B included 22 patients (5 women and 17 men) and received captopril 75 mg/d within 3 days from admission plus losartan 12.5 mg, as the first dose, and 25 mg/d (BP >110 mmHg) successively. Norepinephrine (NE) and A-II levels were measured on the 3rd and 10th days after admission. The two groups were similar with regard to age, sex, creatinine kinase peak, ejection fraction, end-systolic volume, and risk factors. Group B (captopril plus losartan) showed a significant reduction of BP, from 124 ± 8.5 mmHg to 108 ± 6.4 mmHg, P < 0.001, at 10 days after admission. In group A, BP was 122 ± 9 mmHg, and 10 days after admission BP was 118 ± 11 mmHg. NE and A-II values did not show significant differences in basal samples. At 10 days after admission values were NE 298 + 90 versus 272 ± 86 pg/mL and A-II 6.07 ± 2.97 versus 5.29 ± 2.05 pg/mL for the two groups. Our data suggest, for the first time, that the combination of captopril plus losartan is feasible and does not produce serious side effects. When losartan was added to ACE-in treatment, there was no significant increase in A-II.     

Vascular endothelial growth factor, left ventricular dysfunction and mortality in hemodialysis patients

OBJECTIVES: Vascular endothelial growth factor induces nitric oxide-dependent angiogenic effects and participates in the inflammatory response. This cytokine is over-expressed in the myocardium in experimental models of pressure overload and renal mass ablation, and vascular endothelial growth factor is increased in end-stage renal disease. We investigated the relationship between vascular endothelial growth factor, left ventricular function (by midwall fractional shortening) and mortality in a prospective cohort study in 228 hemodialysis patients. RESULTS: Serum vascular endothelial growth factor concentration was associated directly with interleukin-6 and tumor necrosis factor-alpha (P < 0.01) and inversely with albumin (P = 0.007) but was independent of the endogenous inhibitor of nitric oxide synthesis, asymmetric dimethylarginine. Vascular endothelial growth factor was inversely related with midwall fractional shortening (P = 0.002) and predicted mortality (P = 0.02). In multivariate analyses testing the involvement of this angiogenic cytokine in left ventricular dysfunction and death, these links remained substantially unmodified after adjustment for Framingham risk factors, risk factors peculiar to end-stage renal disease (Hb, Ca, P) and previous cardiovascular complications. However, these links became weaker and not significant when biomarkers of inflammation and asymmetric dimethylarginine were sequentially introduced into the multivariate models. In crude and adjusted analyses, left ventricular function was lowest in patients who displayed both high vascular endothelial growth factor and high asymmetric dimethylarginine, intermediate in patients with either high vascular endothelial growth factor or high asymmetric dimethylarginine and highest in those with low asymmetric dimethylarginine and low vascular endothelial growth factor (P = 0.001). CONCLUSION: Vascular endothelial growth factor is associated with left ventricular systolic dysfunction and mortality in hemodialysis patients. Vascular endothelial growth factor appears to be in the pathway whereby inflammation and nitric oxide inhibition lead to cardiomyopathy and death in hemodialysis patients.     

Comparative analysis of the incidence of surgical site infections in patients with liver resection for colorectal hepatic metastases after neoadjuvant chemotherapy

Background

The aim of this study was to identify the incidence of surgical site infections (SSIs) and postoperative complications, as defined by the Clavien–Dindo classification, after hepatic resection for metastatic colorectal cancer in patients with and without associated neoadjuvant chemotherapy.

Methods

A total of 181 patients were studied retrospectively. Patients were divided into two groups: the first group comprised patients with associated neoadjuvant chemotherapeutic treatment for liver metastases with a latency time <8 wk and the second group comprised patients without associated neoadjuvant chemotherapy.

Results

Variables of duration of liver surgery, length of total hospital stay, and length of postoperative hospital stay seem to be correlated with SSIs and postoperative complications, P < 0.005 and P < 0.0001, respectively. Duration of surgery is a risk factor for SSIs, with an odds ratio of 1.15, and for complications according to the Clavien–Dindo classification, with an odds ratio of 1.35.

Conclusions

Neoadjuvant chemotherapy was not a significant risk factor for SSIs, whereas the total length of hospital stay, length of postoperative hospital stay, and duration of surgery were independent predictors of SSIs and complications according to the Clavien–Dindo classification.     

Predicting severity of pathological scarring due to burn injuries: a clinical decision making tool using Bayesian networks

It is important for clinicians to understand which are the clinical signs, the patient characteristics and the procedures that are related with the occurrence of hypertrophic burn scars in order to carry out a possible prognostic assessment. Providing clinicians with an easy‐to‐ use tool for predicting the risk of pathological scars. A total of 703 patients with 2440 anatomical burn sites who were admitted to the Department of Plastic and Reconstructive Surgery, Burn Center of the Traumatological Hospital in Torino between January 1994 and May 2006 were included in the analysis. A Bayesian network (BN) model was implemented. The probability of developing a hypertrophic scar was evaluated on a number of scenarios. The error rate of the BN model was assessed internally and it was equal to 24·83%. While classical statistical method as logistic models can infer only which variables are related to the final outcome, the BN approach displays a set of relationships between the final outcome (scar type) and the explanatory covariates (patient's age and gender, burn surface area, full‐thickness burn surface area, burn anatomical area and wound‐healing time; burn treatment options such as advanced dressings, type of surgical approach, number of surgical procedures, type of skin graft, excision and coverage timing). A web‐based interface to handle the BN model was developed on the website www.pubchild.org (burns header). Clinicians who registered at the website could submit their data in order to get from the BN model the predicted probability of observing a pathological scar type.     

Clinical and functional outcomes of internal fixation with intertrochanteric antegrade nail in older patients with proximal extracapsular femoral fractures

Purpose

The intertrochanteric Trigen Intertan^® nail (Smith & Nephew, Memphis, TN) is a popular fixation device for proximal extracapsular femoral fractures (PEFFs). We evaluated clinical and functional outcomes in patients with PEFFs treated with Trigen Intertan^® nail.

Methods

In a single-site, prospective observational study, clinical and functional parameters were recorded for all patients admitted to the Emergency Department with PEFFs from June 2008 through June 2011. Patients with severe cognitive impairment, severe disability, neoplastic pathological fractures, or suffering from terminal illnesses were not eligible for the study. Fractures were classified according to the AO/OTA classification system. Preoperative physical fitness was assessed via the American Association of Anaesthetists (ASA) score. The Barthel index was used to quantify the level of physical function before fracture and at follow-up.

Results

One-hundred thirty-five patients with PEFFs were eligible for inclusion during the 3-year survey (mean age 83.2 ± 9.5 years; 82 % females). Fracture type distribution was as follows: A1.1 = 18 %, A1.2 = 7 %, A1.3 = 5 %, A2.1 = 44 %, A2.2 = 21 %, A2.3 = 5 %. All patients were treated with Trigen Intertan^® nail. Two patients experienced a fracture of the femoral shaft during the insertion of a long nail for an A2.3 fracture. Weight-bearing was allowed between the third and tenth postoperative day depending on pain tolerance and general conditions. No loss of reduction, collapse of the femoral neck, nonunion or fixation failure were observed. Two patients died within 10 days postoperatively, and nine within 6 months after surgery. Functional status 1 month after surgery was lower than pre-fractural levels, and improved over follow-up. At 6 months, functional status was comparable to the pre-fractural level.

Conclusions

Trigen Intertan^® produces highly satisfactory clinical and functional results in older patients with PEFFs. Complete functional recovery is obtained on average 6 months after surgery.     

Electrolyte abnormalities in cystic fibrosis: systematic review of the literature

Background

Cystic fibrosis per se can sometimes lead to hyponatremia, hypokalemia, hypochloremia or hyperbicarbonatemia. This tendency was first documented 60 years ago and has subsequently been confirmed in single case reports or small case series, most of which were retrospective. However, this issue has not been addressed analytically. We have therefore systematically reviewed and analyzed the available literature on this subject.

Methods

This was a systematic review of the literature.

Results

The reports included in this review cover 172 subacute and 90 chronic cases of electrolyte imbalances in patients with cystic fibrosis. The male:female ratio was 1.57. Electrolyte abnormalities were mostly associated with clinically inapparent fluid volume depletion, mainly affected patients aged ≤2.5 years, frequently tended to recur and often were found before the diagnosis of cystic fibrosis was established. Subacute presentation often included an history of heat exposure, vomiting, excessive sweating and pulmonary infection. History of chronic presentation, in contrast, was often inconspicuous. The tendency to hypochloremia, hypokalemia and metabolic alkalosis was similar between subacute and chronic patients, with hyponatremia being more pronounced (P?<?0.02) in subacute compared to chronic presentations. Subacute cases were treated parenterally; chronic ones were usually managed with oral salt supplementation. Retention of urea and creatinine was documented in 38 % of subacute cases.

Conclusions

The findings of our review suggest that physicians should be aware that electrolyte abnormalities can occur both as a presenting and a recurring feature of cystic fibrosis.     

Current status of COVID-19 treatment: An opinion review

The pandemic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has garnered the attention of scientists worldwide in the search for an effective treatment while also focusing on vaccine development. Several drugs have been used for the management of coronavirus disease 2019 (COVID-19), which has affected many hospitals and health centers worldwide. Statistically significant results are lacking on the effectiveness of the experimented drugs in reducing COVID-19 morbidity or mortality, as there are very few published randomized clinical trials. Despite this, the literature offers some material for study and reflection. This opinion review attempts to address three burning questions on COVID-19 treatment options. (1) What kind of studies are currently published or ongoing in the treatment of patients with COVID-19? (2) What drugs are currently described in the literature as options of treatment for patients affected by the infection? And (3) Are there specific clinical manifestations related to COVID-19 that can be treated with a customized and targeted therapy? By answering these questions, we wish to create a summary of current COVID-19 treatments and the anti-COVID-19 treatments proposed in the recent clinical trials developed in the last 3 mo, and to describe examples of clinical manifestations of the SARS-CoV-2 infection with a cause-related treatment.