A semi-quantitative visual lateral flow immunoassay for SARS-CoV-2 antibody detection for the follow-up of immune response to vaccination or recovery.

The lateral flow immunoassay (LFIA) technique is largely employed for the point-of-care detection of antibodies especially for revealing the immune response in serum. Visual LFIAs usually provide the qualitative yes/no detection of antibodies, while quantification requires some equipment, making the assay more expensive and complicated. To achieve visual semi-quantification, the alignment of several lines (made of the same antigen) along a LFIA strip has been proposed. The numbering of the reacting lines has been used to correlate with the quantity of some biomarkers in serum. Here, we designed the first semiquantitative LFIA for detecting antibodies and applied it to classify the immune response to SARS-CoV-2 raised by vaccination or natural infection. We used a recombinant spike receptor-binding domain (RBD) as the specific capture reagent to draw two test lines. The detection reagent was selected among three possible ligands that are able to bind to anti-spike human antibodies: the same RBD, staphylococcal protein A, and anti-human immunoglobulin G antibodies. The most convenient detector, adsorbed on gold nanoparticles, was chosen based on the highest correlation with an antibody titre of 171 human sera, measured by a reference serological method, and was the RBD (Spearman's rho = 0.84). Incorporated into the semiquantitative LFIA, it confirmed the ability to discriminate high- and low-titre samples and to classify them into two classes (Dunn's test, P < 0.05). The proposed approach enabled the semiquantification of the immune response to SARS-CoV-2 by the unaided eye observation, thus overcoming the requirement of costly and complicated equipment, and represents a general strategy for the development of semiquantitative serological LFIAs.

The Amount of Cross-Linker Influences Affinity and Selectivity of NanoMIPs Prepared by Solid-Phase Polymerization Synthesis.

The cross-linker methylene-bis-acrylamide is usually present in nanoMIPs obtained by solid-phase polymerization synthesis at 2 mol% concentration, with very few exceptions. Here, we studied the influence of variable amounts of methylene-bis-acrylamide in the range between 0 (no cross-linker) and 50 mol% concentration on the binding properties of rabbit IgG nanoMIPs. The binding parameters were determined by equilibrium binding experiments and the results show that the degree of cross-linking defines three distinct types of nanoMIPs: (i) those with a low degree of cross-linking, including nanoMIPs without cross-linker (0-05 mol%), showing a low binding affinity, high density of binding sites, and low selectivity; (ii) nanoMIPs with a medium degree of cross-linking (1-18 mol%), showing higher binding affinity, low density of binding sites, and high selectivity; (iii) nanoMIPs with a high degree of cross-linking (32-50 mol%), characterized by non-specific nanopolymer-ligand interactions, with low binding affinity, high density of binding sites, and no selectivity. In conclusion, the results are particularly relevant in the synthesis of high-affinity, high-selectivity nanoMIPs as they demonstrate that a significant gain in affinity and selectivity could be achieved with pre-polymerization mixtures containing quantities of cross-linker up to 10-20 mol%, well higher than those normally used in this technique.

Experimental design for the development of a multiplex antigen lateral flow immunoassay detecting the Southern African Territory (SAT) serotypes of foot-and-mouth disease virus.

Antigenic lateral flow immunoassays (LFIAs) rely on the non-competitive sandwich format, including a detection (labelled) antibody and a capture antibody immobilised onto the analytical membrane. When the same antibody is used for the capture and the detection (single epitope immunoassay), the saturation of analyte epitopes by the probe compromises the capture and lowers the sensitivity. Hence, several factors, including the amount of the probe, the antibody-to-label ratio, and the contact time between the probe and the analyte before reaching the capture antibody, must be adjusted. We explored different designs of experiments (full-factorial, optimal, sub-optimal models) to optimise a multiplex sandwich-type LFIA for the diagnosis and serotyping of two Southern African Territory (SAT) serotypes of the foot-and-mouth disease virus, and to evaluate the reduction of the number of experiments in the development. Both assays employed single epitope sandwich, so most influencing variables on the sensitivity were studied and individuated. We upgraded a previous device increasing the sensitivity by a factor of two and reached the visual limit of detection of 103.7 and 104.0 (TCID/mL) for SAT 1 and SAT 2, respectively. The positioning of the capture region along the LFIA strip was the most influent variable to increase the detectability. Furthermore, we confirmed that the 13-optimal DoE was the most convenient approach for designing the device.

Development and In-House Validation of an Enzyme-Linked Immunosorbent Assay and a Lateral Flow Immunoassay for the Dosage of Tenofovir in Human Saliva.

Highly active antiretroviral therapy (HAART) includes very potent drugs that are often characterized by high toxicity. Tenofovir (TFV) is a widely used drug prescribed mainly for pre-exposure prophylaxis (PreP) and the treatment of human immunodeficiency virus (HIV). The therapeutic range of TFV is narrow, and adverse effects occur with both underdose and overdose. The main factor contributing to therapeutic failure is the improper management of TFV, which may be caused by low compliance or patient variability. An important tool to prevent inappropriate administration is therapeutic drug monitoring (TDM) of compliance-relevant concentrations (ARCs) of TFV. TDM is performed routinely using time-consuming and expensive chromatographic methods coupled with mass spectrometry. Immunoassays, such as enzyme-linked immunosorbent assays (ELISAs) and lateral flow immunoassays (LFIAs), are based on antibody-antigen specific recognition and represent key tools for real-time quantitative and qualitative screening for point-of-care testing (POCT). Since saliva is a non-invasive and non-infectious biological sample, it is well-suited for TDM. However, saliva is expected to have a very low ARC for TFV, so tests with high sensitivity are required. Here, we have developed and validated a highly sensitive ELISA (IC50 1.2 ng/mL, dynamic range 0.4-10 ng/mL) that allows the quantification of TFV in saliva at ARCs and an extremely sensitive LFIA (visual LOD 0.5 ng/mL) that is able to distinguish between optimal and suboptimal ARCs of TFV in untreated saliva.

Development of molecular and antigenic-based rapid tests for the identification of African swine fever virus in different tissues.

African swine fever (ASF) is a severe haemorrhagic infectious disease affecting suids, thus representing a great economic concern. Considering the importance of the early diagnosis, rapid point of care testing (POCT) for ASF is highly demanded. In this work, we developed two strategies for the rapid onsite diagnosis of ASF, based on Lateral Flow Immunoassay (LFIA) and Recombinase Polymerase Amplification (RPA) techniques. The LFIA was a sandwich-type immunoassay exploiting a monoclonal antibody directed towards the p30 protein of the virus (Mab). The Mab was anchored onto the LFIA membrane to capture the ASFV and was also labelled with gold nanoparticles for staining the antibody-p30 complex. However, the use of the same antibody for capturing and as detector ligand showed a significant competitive effect for antigen binding, so required an experimental design to minimize reciprocal interference and maximize the response. The RPA assay, employing primers to the capsid protein p72 gene and an exonuclease III probe, was performed at 39 °C. The limit of detection of the method was assessed using a plasmid encoding the target gene and resulted in 5 copy/µL. The new LFIA and RPA were applied for ASFV detection in the animal tissues usually analysed by conventional assays (i.e., real-time PCR), such as kidney, spleen, and lymph nodes. A simple and universal virus extraction protocol was applied for sample preparation, followed by DNA extraction and purification for the RPA. The LFIA only required the addition of 3% H2O2 to limit matrix interference and prevent false positive results. The two rapid methods (25 min and 15 min were needed to complete the analysis for RPA and LFIA, respectively) showed high diagnostic specificity (100%) and sensitivity (93% and 87% for LFIA and RPA, respectively) for samples with high viral load (Ct < 27). False negative results were observed for samples with low viral load (Ct > 28) and/or also containing specific antibodies to ASFV, which decreased antigen availability and were indicative of a chronic, poorly transmissible infection. The simple and rapid sample preparation and the diagnostic performance of the LFIA suggested its large practical applicability for POC diagnosis of ASF.

Effect of Surfactants on the Binding Properties of a Molecularly Imprinted Polymer.

In molecularly imprinted polymers, non-specific interactions are generally based on weak forces between the polymer surface and the sample matrix. Thus, additives able to interfere with such interactions should be able to significantly reduce any non-specific binding effect. Surfactants represent an interesting class of substances as they are cheap and easily available. Here, we present a study of the effect of three surfactants (the anionic sodium dodecylsulphate, SDS, the cationic cetyltrimethylammonium bromide (CTAB) and the non-ionic polyoxyethylene-(20)-sorbitan monolaurate Tween 20) on the binding affinity of a 2,4,5-trichlorophenoxyacetic acid (2,4,5-T)-imprinted polymer for the template and its analogue 2,4-dichlorophenoxyacetic acid (2,4-D). The experimental results indicate that increasing amounts of surfactant decrease the binding affinity for the ligands strongly for the ionic ones, and more weakly for the non-ionic one. This effect is general, as it occurs for both 2,4,5-T and 2,4-D and for both the imprinted and the not-imprinted polymers. It also proves that the magnitude of this effect mainly depends on the presence or absence of an ionic charge, and that the hydrophobic "tail" of surfactants plays only a minor role.

Investigation of the "Antigen Hook Effect" in Lateral Flow Sandwich Immunoassay: The Case of Lumpy Skin Disease Virus Detection.

Lumpy skin disease (LSD) is an infectious disease affecting bovine with severe symptomatology. The implementation of effective control strategies to prevent infection outbreak requires rapid diagnostic tools. Two monoclonal antibodies (mAbs), targeting different epitopes of the LSDV structural protein p32, and gold nanoparticles (AuNPs) were used to set up a colorimetric sandwich-type lateral flow immunoassay (LFIA). Combinations including one or two mAbs, used either as the capture or detection reagent, were explored to investigate the hook effect due to antigen saturation by the detector antibody. The mAb-AuNP preparations were optimized by a full-factorial design of experiment to achieve maximum sensitivity. Opposite optimal conditions were selected when one Mab was used for capture and detection instead of two mAbs; thus, two rational routes for developing a highly sensitive LFIA according to Mab availability were outlined. The optimal LFIA for LSDV showed a low limit of detection (103.4 TCID50/mL), high inter- and intra-assay repeatability (CV% < 5.3%), and specificity (no cross-reaction towards 12 other viruses was observed), thus proving to be a good candidate as a useful tool for the point-of-need diagnosis of LSD.

Oral neomycin and bacitracin are effective in preventing surgical site infections in elective colorectal surgery: a multicentre, randomized, parallel, single-blinded trial (COLORAL-1).

Several regimens of oral and intravenous antibiotics (OIVA) have been proposed with contradicting results, and the role of mechanical bowel preparation (MBP) is still controversial. This study aims to assess the effectiveness of oral antibiotic prophylaxis in preventing Surgical Site Infections (SSI) in elective colorectal surgery. In a multicentre trial, we randomized patients undergoing elective colorectal resection surgery, comparing the effectiveness of OIVA versus intravenous antibiotics (IVA) regimens to prevent SSI as the primary outcome (NCT04438655). In addition to intravenous Amoxicillin/Clavulanic, patients in the OIVA group received Oral Neomycin and Bacitracin 24 h before surgery. MBP was administered according to local habits which were not changed for the study. The trial was terminated during the COVID-19 pandemic, as many centers failed to participate as well as the pandemic changed the rules for engaging patients. Two-hundred and four patients were enrolled (100 in the OIVA and 104 in the IVA group); 3 SSIs (3.4%) were registered in the OIVA and 14 (14.4%) in the IVA group (p = 0.010). No difference was observed in terms of anastomotic leak. Multivariable analysis indicated that OIVA reduced the rate of SSI (OR 0.21 / 95% CI 0.06-0.78 / p = 0.019), while BMI is a risk factor of SSI (OR 1.15 / 95% CI 1.01-1.30 p = 0.039). Subgroup analysis indicated that 0/22 patients who underwent OIVA/MBP + vs 13/77 IVA/MBP- experienced an SSI (p = 0.037). The early termination of the study prevents any conclusion regarding the interpretation of the data. Nonetheless, Oral Neomycin/Bacitracin and intravenous beta-lactam/beta-lactamases inhibitors seem to reduce SSI after colorectal resections, although not affecting the anastomotic leak in this trial. The role of MBP requires more investigation.

Post-pregnancy recurrent biliary colic with intraoperative diagnosis of limy bile syndrome.

INTRODUCTION: Limy bile syndrome (LBS) is an unusual condition in which gallbladder and/or bile ducts are filled with paste-like radiopaque material with a high calcium carbonate content. It can be rarely associated with PTH disorder and hypercalcemia. PRESENTATION OF CASE: A 35-year-old woman presented with epigastric and right hypochondrium pain since a few hours. Similar attacks occurred in the past months soon after a pregnancy with vaginal delivery. Laboratory findings were not significant. The abdominal ultrasound highlighted a micro-lithiasis of gallbladder without complications. Considering the recurrent biliary attacks, laparoscopic cholecystectomy was performed with intraoperative diagnosis of LBS. A subsequent endocrinological screening highlighted a normocalcemic hyperparathyroidism associated with Vitamin D deficiency, likely related to the recent pregnancy and not to LBS. DISCUSSION: LBS is a rare condition with not clear etiology, frequently associated with cholelithiasis, of which it shares clinical presentation and potential complications. Diagnosis of LBS is based on abdominal X-ray/computed tomography scan, or it could be an intraoperative finding. The gold standard treatment is represented by laparoscopic cholecystectomy. The pregnancy with its related cholestatic phenotype could facilitate the LBS manifestation. An endocrinological screening should be performed to rule out a concomitant calcium metabolism disorder. CONCLUSION: Knowledge of this rare condition could help general surgeons handle it properly.

Tailoring the radiotherapy approach in patients with anal squamous cell carcinoma based on inguinal sentinel lymph node biopsy.

BACKGROUND AND OBJECTIVES: The aim of our study was to analyze the results of selective inguinal node irradiation in patients with anal cancer, based on the biopsy of the inguinal sentinel lymph node (SLN), in terms of local control and prognosis. METHODS: Records of patients with anal squamous cell carcinoma from January 2001 to December 2016 were retrospectively reviewed. Tc99 lymphoscintigraphy was performed in all the clinically inguinal negative patients, followed by radio-guided surgical removal of the inguinal SLN. All patients were treated with combined radiochemotherapy. In patients with negative sentinel nodes, the inguinal area was excluded in the radiotherapy field. RESULTS: A total of 123 patients, 76 females (61.8%), mean age 60.1 ± 12.19 years old, underwent intraoperative lymph node retrieval. The histological analysis showed metastasis in the SLN in 28 patients (22.8%). The mean follow-up was 43.44 ± 31.86 months. No inguinal recurrence was observed in patients with negative inguinal sentinel node(s). A statistically significant difference was observed for overall and disease-free survivals in a patient with positive and negative inguinal sentinel nodes. CONCLUSIONS: In patients with anal canal cancer, the exclusion of the inguinal regions from the radiotherapy field, in patients with negative SLN, does not compromise locoregional control nor prognosis.

Management of Hemorrhoidal Disease in Special Conditions: A Word of Caution.

BACKGROUND: Hemorrhoids are a common disease that is often considered an easy problem to solve. Unfortunately, some particular clinical conditions, including Inflammatory Bowel Diseases (IBD), pregnancy, immunosuppression, coagulopathy, cirrhosis with portal hypertension, and proctitis after radiotherapy, challenge hemorrhoids management and the outcomes. METHODS: Research and online contents related to hemorrhoids' treatment in special conditions are reviewed in order to help colorectal surgeons in daily practice. RESULTS: There are very limited data about the outcomes of hemorrhoids treatment in these subgroups of patients. Patients in pregnancy can be effectively treated with medical therapy, reserving surgical intervention in highly selected and urgent cases. In case of thrombosed haemorrhoids, the excision allows a fast symptoms' resolution, with a low incidence of recurrence and a long remission interval. In case of immunosuppressed patients, there is no consensus for the best treatment, even in most HIV positive patients, a surgical procedure can be safely proposed when indicated. There is no sufficient data in the literature related to transplanted patients. The surgical treatment of hemorrhoids in patients with IBD, especially Crohn's Disease, can be unsafe, although there is a paucity of literature on this topic. In case of previous pelvic radiotherapy, it must always be considered that severe complications, like abscesses and fistulas with subsequent pelvic and retroperitoneal sepsis, can occur after surgical treatment of hemorrhoids, so a conservative treatment is advocated. Moreover, caution is recommended in treating patients with coagulopathy, considering possible complications (mostly bleeding) also after outpatient treatments. In case of portal hypertension and cirrhosis, a 'conservative treatment' is recommended. Bleeding hemorrhoids can be treated with hemorrhoidectomy when they do not respond to other treatments. CONCLUSION: International literature is very scant about the treatment of patients affected by hemorrhoids in particular situations. A word of caution and concern even about the indication for minor outpatient procedures must be expressed in these patients, in order to avoid possible life-threatening complications. The first-line treatment is the conservative medical approach associated with the treatment of the primary disease.

Robotic approach to large tailgut cyst with malignant transformation: A case report.

INTRODUCTION: Tailgut cysts (TGC) are rare congenital retrorectal lesions deriving from vestiges of the hindgut. The risk of malignant transformation is relatively high. Thus early diagnosis and a complete removal of the mass are of paramount importance. We present a case of successful robotic exeresis of a large TGC adenocarcinoma. PRESENTATION OF CASE: A healthy 35-year-old woman was found to have a retrorectal TGC with suspected malignant transformation. The patient underwent complete robotic resection of the mass and pathology confirmed a TGC adenocarcinoma. The patient's post-operative course was unremarkable. At 24 months, the patient has not experienced any recurrence nor complained functional disorders. DISCUSSION: The current case highlights the importance of TGC as a differential diagnosis of presacral masses, underscoring that malignant transformation can occur and may result in mortality and morbidity if radical surgery is not performed. Diagnosing TGC adenocarcinoma can be challenging because of its relatively low incidence. Biopsy is not recommended while magnetic resonance imaging (MRI) is indispensable in the evaluation of this lesion as the presence of intracystic vegetations could indicate a malignant transformation. Surgery is the mainstay of treatment and minimally invasive techniques have the potential to minimize morbidity and enhance recovery. Amongst these, the robotic approach can make the dissection of large lesions easier, reducing their manipulation and preventing nerve injuries. CONCLUSION: Robot-assisted resection of a TGC adenocarcinoma is safe and feasible. This approach can be particularly useful in the pelvis providing acceptable functional and oncological outcomes.

Efficacy of Mesoglycan in Pain Control after Excisional Hemorrhoidectomy: A Pilot Comparative Prospective Multicenter Study.

INTRODUCTION: Various pain management strategies for patients undergoing open excisional hemorrhoidectomy have been proposed, yet postoperative pain remains a frequent complaint. OBJECTIVE: To determine whether mesoglycan (30 mg two vials i.m. once/day for the first 5 days postoperative, followed by 50 mg 1 oral tablet twice/day for 30 days) would reduce the edema of the mucocutaneous bridges and thus improve postoperative pain symptoms. PATIENTS AND METHODS: For this prospective observational multicenter study, 101 patients undergoing excisional diathermy hemorrhoidectomy for III-IV degree hemorrhoidal disease were enrolled at 5 colorectal referral centers. Patients were assigned to receive either mesoglycan (study group SG) or a recommended oral dose of ketorolac tromethamine of 10 mg every 4-6 hours, not exceeding 40 mg per day and not exceeding 5 postoperative days according to the indications for short-term management of moderate/severe acute postoperative pain, plus stool softeners (control group CG). RESULTS: Postoperative thrombosis (SG 1/48 versus CG 5/45) (p < 0.001) and pain after rectal examination (p < 0.001) were significantly reduced at 7-10 days after surgery in the mesoglycan-treated group, permitting a faster return to work (p < 0.001); however, in the same group, the incidence of postoperative bleeding, considered relevant when needing a readmission or an unexpected outpatient visit, was higher, possibly owing to the drug's antithrombotic properties. CONCLUSIONS: The administration of mesoglycan after an open diathermy excisional hemorrhoidectomy can reduce postoperative thrombosis and pain at 7-10 days after surgery, permitting a faster return to normal activities.

Current treatments for anal condylomata acuminata.

INTRODUCTION: Condylomata acuminata are the most common sexually transmitted disease worldwide. They are not usually a serious problem, but it causes emotional distress to patient and physician alike because of its marked tendency to recurrence. The presence of anogenital warts mandates treatment, also for potential degeneration of the lesions. EVIDENCE ACQUISITION: A review of the literature has been performed to analyze proposed treatments for anogenital warts. EVIDENCE SYNTHESIS: Many treatments have been employed. They include cytotoxic agents, immunomodulation and physical ablation. The choice of the appropriate treatment varies depending on the number, size, and location of warts. Complications of various treatments are rare but include permanent depigmentation, itching, pain, scarring, bleeding, anal stenosis or incontinence and sepsis. The therapy of these lesions can sometimes be very painful and expensive, and therapy should not be worse than the disease. CONCLUSIONS: No specific antiviral treatment is currently available, and no consensus has been reached on the appropriate treatment for anogenital warts. No data are available to indicate whether treatment eliminates infectivity, the primary aim of treatment being to remove the lesions. There is a paucity of published randomized trials. Despite the introduction of antiviral treatments such as interferon, immunomodulating agents or imiquimod, surgical destruction or removal remains the treatment of choice.

Feasibility of Protective Ventilation During Elective Supratentorial Neurosurgery: A Randomized, Crossover, Clinical Trial.

BACKGROUND: Traditional ventilation approaches, providing high tidal volumes (Vt), produce excessive alveolar distention and lung injury. Protective ventilation, employing lower Vt and positive end-expiratory pressure (PEEP), is an attractive alternative also for neuroanesthesia, when prolonged mechanical ventilation is needed. Nevertheless, protective ventilation during intracranial surgery may exert dangerous effects on intracranial pressure (ICP). We tested the feasibility of a protective ventilation strategy in neurosurgery. MATERIALS AND METHODS: Our monocentric, double-blind, 1:1 randomized, 2×2 crossover study aimed at studying the effect size and variability of ICP in patients undergoing elective supratentorial brain tumor removal and alternatively ventilated with Vt 9 mL/kg-PEEP 0 mm Hg and Vt 7 mL/kg-PEEP 5 mm Hg. Respiratory rate was adjusted to maintain comparable end-tidal carbon dioxide between ventilation modes. ICP was measured through a subdural catheter inserted before dural opening. RESULTS: Forty patients were enrolled; 8 (15%) were excluded after enrollment. ICP did not differ between traditional and protective ventilation (11.28±5.37, 11 [7 to 14.5] vs. 11.90±5.86, 11 [8 to 15] mm Hg; P=0.541). End-tidal carbon dioxide (28.91±2.28, 29 [28 to 30] vs. 28.00±2.17, 28 [27 to 29] mm Hg; P<0.001). Peak airway pressure (17.25±1.97, 17 [16 to 18.5] vs. 15.81±2.87, 15.5 [14 to 17] mm Hg; P<0.001) and plateau airway pressure (16.06±2.30, 16 [14.5 to 17] vs. 14.19±2.82, 14 [12.5 to 16] mm Hg; P<0.001) were higher during protective ventilation. Blood pressure, heart rate, and body temperature did not differ between ventilation modes. Dural tension was "acceptable for surgery" in all cases. ICP differences between ventilation modes were not affected by ICP values under traditional ventilation (coefficient=0.067; 95% confidence interval, -0.278 to 0.144; P=0.523). CONCLUSIONS: Protective ventilation is a feasible alternative to traditional ventilation during elective neurosurgery.

Additive Effect on Survival of Anaesthetic Cardiac Protection and Remote Ischemic Preconditioning in Cardiac Surgery: A Bayesian Network Meta-Analysis of Randomized Trials.

INTRODUCTION: Cardioprotective properties of volatile agents and of remote ischemic preconditioning have survival effects in patients undergoing cardiac surgery. We performed a Bayesian network meta-analysis to confirm the beneficial effects of these strategies on survival in cardiac surgery, to evaluate which is the best strategy and if these strategies have additive or competitive effects. METHODS: Pertinent studies were independently searched in BioMedCentral, MEDLINE/PubMed, Embase, and the Cochrane Central Register (updated November 2013). A Bayesian network meta-analysis was performed. Four groups of patients were compared: total intravenous anesthesia (with or without remote ischemic preconditioning) and an anesthesia plan including volatile agents (with or without remote ischemic preconditioning). Mortality was the main investigated outcome. RESULTS: We identified 55 randomized trials published between 1991 and 2013 and including 6,921 patients undergoing cardiac surgery. The use of volatile agents (posterior mean of odds ratio = 0.50, 95% CrI 0.28-0.91) and the combination of volatile agents with remote preconditioning (posterior mean of odds ratio = 0.15, 95% CrI 0.04-0.55) were associated with a reduction in mortality when compared to total intravenous anesthesia. Posterior distribution of the probability of each treatment to be the best one, showed that the association of volatile anesthetic and remote ischemic preconditioning is the best treatment to improve short- and long-term survival after cardiac surgery, suggesting an additive effect of these two strategies. CONCLUSIONS: In patients undergoing cardiac surgery, the use of volatile anesthetics and the combination of volatile agents with remote preconditioning reduce mortality when compared to TIVA and have additive effects. It is necessary to confirm these results with large, multicenter, randomized, double-blinded trials comparing these different strategies in cardiac and non-cardiac surgery, to establish which volatile agent is more protective than the others and how to best apply remote ischemic preconditioning.

Dexmedetomidine vs midazolam as preanesthetic medication in children: a meta-analysis of randomized controlled trials.

INTRODUCTION: The preoperative period is a stressing occurrence for most people undergoing surgery, in particular children. Approximately 50-75% of children undergoing surgery develop anxiety which is associated with distress on emergence from anesthesia and with later postoperative behavioral problems. Premedication, commonly performed with benzodiazepines, reduces preoperative anxiety, facilitates separation from parents, and promotes acceptance of mask induction. Dexmedetomidine is a highly selective α2 -agonist with sedative and analgesic properties. A meta-analysis of all randomized controlled trials (RCTs) on dexmedetomidine versus midazolam was performed to evaluate its efficacy in improving perioperative sedation and analgesia, and in reducing postoperative agitation when used as a preanesthetic medication in children. METHODS: Studies were independently searched in PubMed, BioMedCentral, Embase, and the Cochrane Central Register of clinical trials and updated on August 15th, 2014. Primary outcomes were represented by improved sedation at separation from parents, at induction of anesthesia, and reduction in postoperative agitation. Secondary outcomes were reduction in rescue analgesic drugs, and duration of surgery and anesthesia. Inclusion criteria were random allocation to treatment and comparison between dexmedetomidine and midazolam. Exclusion criteria were adult studies, duplicate publications, intravenous administration, and no data on main outcomes. RESULTS: Data from 1033 children in 13 randomized trials were analyzed. Overall, in the dexmedetomidine group there was a higher incidence of satisfactory sedation at separation from parents (314 of 424 [74%] in the dexmedetomidine group vs 196 of 391 [50%] in the midazolam group, RR = 1.30 [1.05-1.62], P = 0.02), a reduced incidence of postoperative agitation (14 of 140 [10%] vs 56 of 141 [40%], RR = 0.31 [0.13-0.73], P = 0.008), and a significant reduction in the rescue doses of analgesic drugs (49 of 241 [20%] vs 95 of 243 [39%], RR = 0.52 [0.39-0.70], P < 0.001). There was no evidence of a higher incidence of satisfactory sedation at anesthesia induction or any reduction of duration of surgery and anesthesia. CONCLUSIONS: Dexmedetomidine is effective in decreasing anxiety upon separation from parents, decreasing postoperative agitation, and providing more effective postoperative analgesia when compared with midazolam.

A survey on the use of intra-aortic balloon pump in cardiac surgery.

Intra-aortic balloon pump (IABP) is an established tool in the management of cardiac dysfunction in cardiac surgery. The best timing for IABP weaning is unknown and varies greatly among cardiac centers. The authors investigated the differences in IABP management among 66 cardiac surgery centers performing 40,675 cardiac surgery procedures in the 12-month study period. The centers were contacted through email, telephone, or in person interview. IABP management was very heterogeneous in this survey: In 43% centers it was routinely removed on the first postoperative day, and in 34% on the second postoperative day. In 50% centers, it was routinely removed after extubation of the patients whereas in 15% centers it was removed while the patients were sedated and mechanically ventilated. In 66% centers, patients were routinely receiving pharmacological inotropic support at the time of removal of IABP. The practice of decreasing IABP support was also heterogeneous: 57% centers weaned by reducing the ratio of beat assistance whereas 34% centers weaned by reducing balloon volume. We conclude that the management of IABP is heterogeneous and there is a need for large prospective studies on the management of IABP in cardiac surgery.

Volatile agents for cardiac protection in noncardiac surgery: a randomized controlled study.

OBJECTIVE: Volatile anesthetics reduce the risk of myocardial infarction and mortality in coronary artery surgery. Recently, the American College of Cardiology/American Heart Association Guidelines suggested the use of volatile anesthetic agents for the maintenance of general anesthesia during noncardiac surgery in patients at risk for perioperative myocardial ischemia, but no randomized experience to document the cardioprotective effects of these agents exists in this setting. Therefore, the authors performed a prospective, randomized, controlled trial to compare the effects of sevoflurane versus total intravenous anesthesia, in terms of postoperative cardiac troponin I release in patients undergoing noncardiac surgery. DESIGN: A randomized, controlled trial. SETTING: A teaching hospital. PARTICIPANTS: Eighty-eight consecutive patients undergoing noncardiac surgery. INTERVENTIONS: Patients were allocated randomly to receive either volatile anesthetic (44 patients) as the main anesthetic agent or total intravenous anesthesia (TIVA) (44 patients). MEASUREMENTS: Postoperative cardiac troponin I release was measured as a marker of myocardial necrosis. Patients with detectable postoperative troponin I in the sevoflurane group (12/44, 27.3%) were similar to those in the propofol group (9/44, 20.5%; p = 0.6). There was no significant reduction of postoperative median peak cTnI release (0.16 ± 0.71 ng/mL in the sevoflurane group compared with the TIVA group, 0.03 ± 0.08 ng/mL; p = 0.4). Three patients died at the 1-year follow-up for noncardiac causes (2 in the TIVA group). CONCLUSIONS: In the authors' experience, patients undergoing noncardiac surgery did not benefit from anesthesia based on halogenated anesthetics. Further studies are necessary to evaluate the cardioprotective effects of volatile agents in noncardiac surgery.

Esmolol reduces perioperative ischemia in noncardiac surgery: a meta-analysis of randomized controlled studies.

OBJECTIVE: Literature increasingly has suggested how beta-blockers could be associated with reductions of mortality and morbidity in noncardiac surgery. Recently, the POISE trial showed that beta-blockers could be harmful in the perioperative period. The authors performed a meta-analysis to evaluate the clinical effects of esmolol in noncardiac surgery. DESIGN: Meta-analysis. SETTING: Hospitals. PARTICIPANTS: A total of 1765 patients from 32 randomized trials. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Three investigators independently searched BioMedCentral and PubMed. Inclusion criteria were random allocation to treatment and comparison of esmolol versus placebo, other drugs, or standard of care in noncardiac surgery. Exclusion criteria were duplicate publications, nonhuman experimental studies, and no data on clinical outcomes. The use of esmolol was associated with a significant reduction of myocardial ischemia episodes (5/283 [1.76%] in the esmolol group v 16/265 [6.03%] in the control arm, odds ratio [OR] = 0.16 [0.05-0.54], p = 0.003). The authors did not observe significant differences regarding episodes of arrhythmias (8/236 [3.38%] v 22/309 [7.11%], OR = 0.52 [0.23-1.18], p = 0.12) and in the incidence of myocardial infarction (0/148 [0%] v 1/169 [0.59%], OR = 0.23 [0.01-6.09], p = 0.38). Esmolol-treated patients did not experience more episodes of hypotension (17/384 [4.42%] v 38/439 [8.65%], OR = 0.41 [0.22-0.79], p = 0.17) and bradycardia (25/342 [7.30%] v 17/406 [4.18%], OR = 1.42 [0.74-2.74], p = 0.42). CONCLUSIONS: Esmolol seemed to reduce the incidence of myocardial ischemia in noncardiac surgery without increasing the episodes of hypotension and bradycardia. Large randomized trials are necessary to confirm these promising results.