Commensal production of a broad-spectrum and short-lived antimicrobial peptide polyene eliminates nasal Staphylococcus aureus.

Antagonistic bacterial interactions often rely on antimicrobial bacteriocins, which attack only a narrow range of target bacteria. However, antimicrobials with broader activity may be advantageous. Here we identify an antimicrobial called epifadin, which is produced by nasal Staphylococcus epidermidis IVK83. It has an unprecedented architecture consisting of a non-ribosomally synthesized peptide, a polyketide component and a terminal modified amino acid moiety. Epifadin combines a wide antimicrobial target spectrum with a short life span of only a few hours. It is highly unstable under in vivo-like conditions, potentially as a means to limit collateral damage of bacterial mutualists. However, Staphylococcus aureus is eliminated by epifadin-producing S. epidermidis during co-cultivation in vitro and in vivo, indicating that epifadin-producing commensals could help prevent nasal S. aureus carriage. These insights into a microbiome-derived, previously unknown antimicrobial compound class suggest that limiting the half-life of an antimicrobial may help to balance its beneficial and detrimental activities.

Fidel Pagés, el auténtico descubridor de la anestesia epidural, en el centenario de su publicación Anestesia metamérica (1921-2021) / Fidel Pagés, the true discoverer of epidural anesthesia, on the centenary of his publication Anestesia metamérica (1921-2021)

Resumen: Pocas han sido las Figuras españolas que han aportado alguna interesante novedad al mundo de la anestesia, pero ninguna tan injustamente tratada y olvidada como la de Pagés, verdadero pionero de la anestesia epidural, que él denominaría «anestesia metamérica¼ en su artículo publicado en el mes de marzo de 1921 en la Revista Española de Cirugía, fundada por él mismo. Años después, en 1931, Dogliotti, profesor de Cirugía de Módena publicó sus experiencias sobre la anestesia epidural, a la que llamó «anestesia peridural segmentaria¼, ignorando el trabajo de Pagés publicado 10 años antes. El trabajo de Dogliotti fue rápidamente reconocido, asumiendo todos los méritos de la paternidad de la técnica epidural, quedando Pagés relegado a un olvido injusto que con este trabajo tratamos de reparar. La idea central de este texto versará sobre el reconocimiento de Pagés como verdadero promotor del abordaje epidural con fines quirúrgicos. Destacar sus ideas innovadoras sobre el bienestar del paciente y la minimización de los efectos adversos de las técnicas anestésicas y quirúrgicas, así como valorar una obra que, aunque corta, bien podría incluirse entre los mejores cirujanos españoles de principio del siglo XX, un cirujano con alma de anestesiólogo.

Abstract: Few Spanish Figures have contributed any interesting novelty to the world of anesthesia. But none so unjustly treated and forgotten such as Pagés, a true pioneer of epidural anesthesia, which he would call «metameric anesthesia¼ in his article published in March 1921 in the Spanish Journal of Surgery, founded by himself. Later, in 1931, Dogliotti, Modena Professor of Surgery published his experiences on epidural anesthesia, which he called «segmental peridural anesthesia¼, ignoring Pagés work published 10 years earlier. Dogliotti's work was quickly recognized, assuming all the merits of the paternity of the epidural technique, leaving Pagés relegated to an unjust oblivion that with this work we try to repair. The central idea of this text will focus on the recognition of Pagés as a true promoter of the epidural approach for surgical purposes. Highlight his innovative ideas about patient well-being and minimizing the adverse effects of anesthetic and surgical techniques. As well as assessing a work that, although short, could well be included among the best Spanish surgeons of the early twentieth century, a surgeon with the soul of an anesthesiologist.

Synthetic Lugdunin Analogues Reveal Essential Structural Motifs for Antimicrobial Action and Proton Translocation Capability.

Lugdunin, a novel thiazolidine cyclopeptide, exhibits micromolar activity against methicillin-resistant Staphylococcus aureus (MRSA). For structure-activity relationship (SAR) studies, synthetic analogues obtained from alanine and stereo scanning as well as peptides with modified thiazolidine rings were tested for antimicrobial activity. The thiazolidine ring and the alternating d- and l-amino acid backbone are essential. Notably, the non-natural enantiomer displays equal activity, thus indicating the absence of a chiral target. The antibacterial activity strongly correlates with dissipation of the membrane potential in S. aureus. Lugdunin equalizes pH gradients in artificial membrane vesicles, thereby maintaining membrane integrity, which demonstrates that proton translocation is the mode of action (MoA). The incorporation of extra tryptophan or propargyl moieties further expands the diversity of this class of thiazolidine cyclopeptides.

Adipose-derived mesenchymal stem cells slow disease progression of acute-on-chronic liver failure.

A serious complication of chronic hepatic insufficiency is acute-on-chronic liver failure, a recognized syndrome characterized by acute decompensation of cirrhosis and organ/system failure. We investigated the use of adipose-derived mesenchymal stem cells (AD-MSCs) in an experimental model of acute-on-chronic liver failure, developed by microsurgical extrahepatic cholestasis in rats. Rats undergoing microsurgical extrahepatic cholestasis were treated by intraparenchymal liver injection of human or rat AD-MSCs, undifferentiated or previously differentiated in vitro toward the hepatocyte lineage. The groups treated with rat AD-MSCs showed less ascites, lower hepato- and splenomegaly, less testicular atrophy, and an improvement in serum biochemical hepatic parameters. There was also an improvement in histological liver changes, in which the area of fibrosis and bile duct proliferation were significantly decreased in the group treated with predifferentiated rat AD-MSCs. In conclusion, an isograft of hepatocyte-predifferentiated AD-MSCs injected intraparenchymally 2 weeks after microsurgery in extrahepatic cholestatic rats prevents secondary complications of acute-on-chronic hepatic failure. These data support the potential use of autologous AD-MSCs in the treatment of human cholestasis, and specifically of newborn biliary atresia, which could be beneficial for patients awaiting transplant.

Effects of pneumoperitoneum on severe hypernatremia in an adult patient who underwent laparoscopic surgery of hydatid cysts.

We describe the first case of severe hypernatremia associated to laparoscopic surgery for hydatid cyst in an adult patient after the use of hypertonic saline solution with complete resolution. Severe hypernatremia is an unusual fact at the immediate postoperative period but may have fatal consequences for the patient and need immediate action. The patient reached a serum sodium concentration of 179 mmol/L without adverse effects after 6 days of treatment. Laparoscopy could play a crucial role in Na+ absorption due to high intraabdominal pressure caused by the pneumoperitoneum and its limitations to avoid peritoneal absorption of hypertonic saline solution. The relation between this surgical technique and the severe complication is discussed. More experience is needed in terms of safety for the patient.

Randomized double-blind comparison of remifentanil and alfentanil in patients undergoing laparoscopic cholecystectomy using total intravenous anesthesia.

BACKGROUND AND AIMS: To compare the use of remifentanil and alfentanil to suppress intraoperative adrenergic response of pain and the influence of these drugs on the recovery profile in patients undergoing laparoscopic cholecystectomy using a total intravenous anesthesia (TIVA) technique. MATERIAL AND METHODS: One hundred patients undergoing elective laparoscopic cholecystectomy were randomized to be managed with either remifentanil (group R) or alfentanil (group A). During general anesthesia, we evaluated adrenergic responses to intubation to first surgical incision and over the surgical procedure. We also recorded time to first spontaneous breathing, time to successful ventilation, time to respond to verbal orders, and time to extubation. RESULTS: The R group reported a significantly lower number of responses to intubation and responses to first surgical incision (14% vs. 30%; P = 0.013 and 8% vs. 18%; P = 0,037, respectively). The event of one or more responses during the surgical procedure was also lower in the R group (56% vs. 70%; P = 0.017). Hypertensive response to surgical stimuli during the procedure was lower in the R group as well as a lower frequency of tachycardia episodes in this group (34% vs. 56%; P = 0.033 and 28% vs. 44%; P = 0.041, respectively). No differences were found between groups relating to the percentage of hypotensive episodes and no episodes of bradycardia were appreciated. Both groups were similar relating to recovery times: time to the first spontaneous breathing, time to successful ventilation, time to respond to verbal orders, and time to extubation. CONCLUSION: Remifentanil showed a more stable hemodynamic response during the surgery compared with the use of alfentanil in anesthetized patients undergoing laparoscopic cholecystectomy using TIVA. Both opioids, alfentanil and remifentanil, have a similar recovery profile, and they do not delay time to awakening.

Role of laryngeal mask airway in laparoscopic cholecystectomy.

Laparoscopic cholecystectomy is one of the most commonly performed surgical procedures and the laryngeal mask airway (LMA) is the most common supraglottic airway device used by the anesthesiologists to manage airway during general anesthesia. Use of LMA has some advantages when compared to endotracheal intubation, such as quick and ease of placement, a lesser requirement for neuromuscular blockade and a lower incidence of postoperative morbididy. However, the use of the LMA in laparoscopy is controversial, based on a concern about increased risk of regurgitation and pulmonary aspiration. The ability of these devices to provide optimal ventilation during laparoscopic procedures has been also questioned. The most important parameter to secure an adequate ventilation and oxygenation for the LMA under pneumoperitoneum condition is its seal pressure of airway. A good sealing pressure, not only state correct patient ventilation, but it reduces the potential risk of aspiration due to the better seal of airway. In addition, the LMAs incorporating a gastric access, permitting a safe anesthesia based on these commented points. We did a literature search to clarify if the use of LMA in preference to intubation provides inadequate ventilation or increase the risk of aspiration in patients undergoing laparoscopic cholecystectomy. We found evidence stating that LMA with drain channel achieves adequate ventilation for these procedures. Limited evidence was found to consider these devices completely safe against aspiration. However, we observed that the incidence of regurgitation and aspiration associated with the use of the LMA in laparoscopic surgery is very low.

Robust and sustained effect of ketamine infusions coadministered with conventional antidepressants in a patient with refractory major depression.

Antidepressant treatments show low capacity to achieve full clinical remissions. Electroconvulsive therapy is an alternative treatment which has been shown to be more effective but it is not well tolerated and there are concerns regarding its safety. We present the case of a patient with resistant depression and modest and transient response to ECT and who showed a robust and maintained response after six i.v. ketamine (0.5 mg/kg) infusions without withdrawing her antidepressant regimen. Ketamine was very well tolerated. This case illustrates the potential role of ketamine as a booster to standard antidepressants.

Laryngeal mask, laryngeal tube, and Frova introducer in simulated difficult airway.

BACKGROUND: The use of supraglottic devices is rising in the prehospital management of difficult airway; moreover, we think that patients with multiple trauma or cervical instability can take advantage of these devices without opening or retiring the cervical collar. OBJECTIVE: To compare speed and ease of use between Laryngeal Tube S (LTS) and the Ambu AuraOnce laryngeal mask (LMA).Our second objective was to evaluate changing these devices to an endotracheal tube (ETT) using a Frova introducer. METHODS: We studied the use of LTS and LMA in an experimental model, represented by a manikin with a rigid cervical collar and a limited mouth opening. This study was carried out in Complutense University of Madrid with 145 2(nd)-year students for the degree in Dentistry who have knowledge of the airway but lack experience in intubation. Number of attempts and time for the device's insertion were measured, as well as time for the exchange maneuver using the Frova introducer. RESULTS: Insertion of all devices was possible on the first attempt; time for insertion was LTS 12.2 ± 1.28 s and LMA 6.87 ± 0.97 s. Once these devices were inserted, a Frova introducer is used to perform an exchange by an endotracheal tube; all devices could be exchanged on the first attempt, and exchange time was LTS 26.9 ± 1.2 s and LMA 16.79 ± 1.32 s. Results for both time for insertion and exchange of the LMA were significantly lower than those for the LTS (p < 0.001). CONCLUSION: The method used can be considered quick and easy, even for personnel inexperienced in intubation. This exchange maneuver has not been described previously, so we can consider it as a new application of the Frova introducer.

Comparison of Laryngeal Mask Airway Supreme and Laryngeal Mask Airway Proseal with respect to oropharyngeal leak pressure during laparoscopic cholecystectomy: a randomised controlled trial.

CONTEXT: A comparison of the efficacy and safety of the Laryngeal Mask Airway (LMA) Supreme (LMAS) versus the LMA Proseal (LMAP) in elective laparoscopic cholecystectomy. OBJECTIVES: To compare the LMAS with LMAP in terms of ventilatory efficacy, airway leak pressure (airway protection), ease-of-use and complications. DESIGN: Prospective, single-blind, randomised, controlled study. SETTING: The Hospital del Sureste and Hospital Ramon y Cajal, Madrid, between May 2009 and March 2011. The Hospital del Sureste is a secondary hospital and Hospital Ramon y Cajal is a tertiary hospital. PATIENTS: Patients undergoing elective laparoscopic cholecystectomy were studied following informed consent. Inclusion criteria were American Society of Anesthesiologists physical status I to III and age 18 or more. Exclusion criteria were BMI more than 40 kg m, symptomatic hiatus hernia or severe gastro-oesophageal reflux. INTERVENTIONS: Anaesthesiologists experienced in the use of LMAP and LMAS participated in the trial. One hundred twenty-two patients were randomly allocated to LMAS or LMAP. MAIN OUTCOME MEASURES: Our primary outcome measure was the oropharyngeal leak pressure (OLP). Secondary outcomes were the time and number of attempts for insertion, ease of insertion of the drain tube, adequacy of ventilation and the incidence of complication. Patients were interviewed postoperatively to evaluate the presence of sore throat, dysphagia or dysphonia. RESULTS: Two patients were excluded when surgery changed from laparoscopic to open. A total of 120 patients were finally included in the analysis. The mean OLP in the LMAP group was significantly higher than that in the LMAS group (30.7 ±â€Š6.2 versus 26.8 ±â€Š4.1 cmH2O;P < 0.01). This was consistent with a higher maximum tidal volume achieved with the LMAP compared to the LMAS (511 ±â€Š68 versus 475 ±â€Š55 ml; P = 0.04). The success rate of the first attempt insertion was higher for the LMAS group than the LMAP group (96.7 and 71.2%, respectively; P < 0.01). The time taken for insertion, ease of insertion of the drain tube, complications and postoperative pharyngolaryngeal adverse events were similar in both groups. CONCLUSION: The LMAP has a higher OLP and achieves a higher maximum tidal volume compared to the LMAS, in patients undergoing elective laparoscopic cholecystectomy. The success of the first attempt insertion was higher for the LMAS.

The Laryngeal Mask Airway Supreme for positive pressure ventilation during laparoscopic cholecystectomy.

STUDY OBJECTIVE: To evaluate the Laryngeal Mask Airway Supreme (SLMA) in patients undergoing laparoscopic cholecystectomy. DESIGN: Prospective observational study. SETTING: University-affiliated hospital. PATIENTS: 100 ASA physical status 1, 2, and 3 adult patients undergoing laparoscopic cholecystectomy with general anesthesia. INTERVENTIONS: The SLMA was inserted in all study patients. Patients were placed in the reverse Trendelenburg position. MEASUREMENTS: Ease of insertion of the device and the drain tube, oropharyngeal leak pressure, frequency of postoperative sore throat, and other adverse events were recorded. The surgeon scored stomach size on an ordinal scale of 0-10 at insertion of the laparoscope and before decompression of the pneumoperitoneum. MAIN RESULTS: Insertion of the SLMA was successful in all patients (91 pts on the first attempt, 9 pts on the second attempt). Gastric tube insertion was successful in all patients (easy in 97 pts, difficult in 3 pts). Initial mechanical ventilation was adequate in all cases. Mean oropharyngeal leak pressure at the 60 cm H(2)O cuff pressure level was 28.8 cm H(2)O (±5.2; range 18-40 cm H(2)O). Mean airway pressure before pneumoperitoneum was 17.5 cm H(2)O (±3.3; cm; range 11-26 cm H(2)O) and 22.9 cm H(2)O (±4 cm; range 16-32 cm H(2)O) after pneumoperitoneum. Median (range) stomach size on insertion of the laparoscope and change in stomach size during surgery did not interfere with the procedure in any patient. Twelve patients (12%) complained of a mild sore throat postoperatively. No other complications were reported. CONCLUSIONS: The SLMA is easy to insert and it is an effective ventilatory device for laparoscopic cholecystectomy.

Bronchial compression due to stent placement in pulmonary artery in a child with congenital heart disease.

Congenital heart disease, such as transposition of the great vessels (TGV), requires surgical procedures which can lead to important complications. We report on a case of bronchial obstruction following placement of a pulmonary artery stent in a 4-year-old boy who had undergone a Rastelli procedure to correct TGV, ventricular septal defect and pulmonary stenosis. There are many complications that can arise as a consequence of intravascular stents in heart surgery, as well as many causes of bronchial compression. However we have not found any report which describes bronchial compression as a direct consequence of endovascular stent.