Currently, no vaccine against Pseudomonas is available. IC43 is a new, recombinant, protein (OprF/I)-based vaccine against the opportunistic pathogen, Pseudomonas aeruginosa, a major cause of serious hospital-acquired infections. IC43 has proven immunogenicity and tolerability in healthy volunteers, patients with burns, and patients with chronic lung diseases. In order to assess the immunogenicity and safety of IC43 in patients who are most at risk of acquiring Pseudomonas infections, it was evaluated in mechanically ventilated ICU patients. We conducted a randomized, placebo-controlled, partially blinded study in mechanically ventilated ICU patients. The immunogenicity of IC43 at day 14 was determined as the primary endpoint, and safety, efficacy against P. aeruginosa infections, and all-cause mortality were evaluated as secondary endpoints. Vaccinations (100 μg or 200 μg IC43 with adjuvant, or 100 μg IC43 without adjuvant, or placebo) were given twice in a 7-day interval and patients were followed up for 90 days. Higher OprF/I IgG antibody titers were seen at day 14 for all IC43 groups versus placebo (P < 0.0001). Seroconversion (≥4-fold increase in OprF/I IgG titer from days 0 to 14) was highest with 100 μg IC43 without adjuvant (80.6%). There were no significant differences in P. aeruginosa infection rates, with a low rate of invasive infections (pneumonia or bacteremia) in the IC43 groups (11.2-14.0%). Serious adverse events (SAEs) considered possibly related to therapy were reported by 2 patients (1.9%) in the group of 100 µg IC43 with adjuvant. Both SAEs resolved and no deaths were related to study treatment. Local tolerability symptoms were mild and rare (<5% of patients), a low rate of treatment-related treatment-emergent adverse events (3.1–10.6%) was observed in the IC43 groups. This phase II study has shown that IC43 vaccination of ventilated ICU patients produced a significant immunogenic effect. P. aeruginosa infection rates did not differ significantly between groups. In the absence of any difference in immune response following administration of 100 μg IC43 without adjuvant compared with 200 μg IC43 with adjuvant, the 100 μg dose without adjuvant was considered for further testing of its possible benefit of improved outcomes. There were no safety or mortality concerns. ClinicalTrials.gov, NCT00876252 . Registered on 3 April 2009.

We compared cost-effectiveness of anesthesia maintained with sevoflurane or propofol with and without additional monitoring, in the clinical setting of ear-nose-throat surgery. One hundred twenty adult patients were randomized to four groups. In groups SEVO and SEVO+ anesthesia was maintained with sevoflurane, in group SEVO+ with additional bispectral index (BIS) and train-of-four (TOF) monitoring. In groups PROP and PROP+ anesthesia was maintained with propofol, in group PROP+ with additional BIS and TOF monitoring. Total cost of anesthesia per hour was greater in group SEVO+ compared to SEVO [€ 19.95(8.53) vs. 12.15(5.32), p < 0.001], and in group PROP+ compared to PROP (€ 22.11(8.08) vs. 13.23(4.23), p < 0.001]. Time to extubation was shorter in group SEVO+ compared to SEVO [11.1(4.7) vs. 14.5(3.9) min, p = 0.002], and in PROP+ compared to PROP [12.6(5.4) vs. 15.2(4.7) min, p < 0.001]. Postoperatively, arterial blood pressure returned to its initial values sooner in groups SEVO+ and PROP+. Our study demonstrated that the use of BIS and TOF monitoring decreased the total cost of anesthesia drugs and hastened postoperative recovery. However, in our circumstances, these were associated with higher disposables costs. Detailed cost analysis and further investigations are needed to identify patient populations who would benefit most from additional monitoring. ClinicalTrials.gov, NCT02920749 . Retrospectively registered (date of registration September 2016).

Background/Objectives: Surgical pneumoperitoneum (PP) significantly impacts volume-controlled ventilation, characterized by reduced respiratory compliance, elevated peak inspiratory pressure, and an accelerated expiratory phase due to an earlier onset of the airway pressure gradient. We hypothesized that this would shorten expiratory time, potentially increasing expiratory flow rate compared to pneumoperitoneum conditions. Calculations were performed to establish correlations between respiratory parameters and the mean increase in expiratory flow rate relative to baseline. Methods: Mechanical ventilation parameters were recorded for 67 patients both pre- and post-PP. Ventilator settings were standardized with a tidal volume of 6 mL/kg, a respiratory rate of 12 breaths per minute, a PEEP of 3 cmH₂O, an inspiratory time of 2 s, and an inspiratory-to-expiratory ratio of 1:1.5 (I:E). Results: The application of PP increased both peak inspiratory pressure and mean expiratory flow rate by 28% compared to baseline levels. The elevated intra-abdominal pressure of 20 cmH₂O resulted in a 34% reduction in dynamic chest compliance, a 50% increase in elastance, and a 20% increase in airway resistance. The mean expiratory flow rate increments relative to baseline showed a significant negative correlation with elastance (p = 0.0119) and a positive correlation with dynamic compliance (p = 0.0028) and resistance (p = 0.0240). Conclusions: A PP of 20 cmH₂O resulted in an increase in the mean expiratory flow rate in the conventional I:E ratio in the volume-ventilated mode. PP reduces lung and chest wall compliance by elevating the diaphragm, compressing the thoracic cavity, and increasing airway pressures. Consequently, the lungs and chest wall stiffen, requiring greater ventilatory effort and accelerating expiratory flow due to increased airway resistance and altered pulmonary mechanics. Prolonging the inspiratory phase through I:E ratio adjustment helps maintain peak inspiratory pressures closer to baseline levels, and this method enhances the safety and efficacy of mechanical ventilation in maintaining optimal respiratory function during laparoscopic surgery.

Our aim was to compare the perioperative time courses of matrix metalloproteinase-9 (MMP-9) and its inhibitor (TIMP-1) in during carotid endarterectomy (CEA) and carotid artery stenting (CAS). In our prospective study, twenty-five patients who were scheduled to undergo CAS were enrolled. We used a matched, historical CEA group as controls. Blood samples were collected at four time points: T1: preoperative; T2: 60 min after stent insertion; T3: first postoperative morning; and T4: third postoperative morning. Plasma MMP-9 and TIMP-1 levels were measured by ELISA. In the CEA group, the plasma levels of MMP-9 were significantly elevated at T3 compared to T1. In the CAS group, there was no significant difference in MMP-9 levels in the perioperative period. MMP-9 levels were significantly higher in the T3 samples of the CEA group compared to the CAS group. Significantly lower TIMP-1 levels were measured in both groups at T2 than at T1 in both groups. MMP-9/TIMP-1 at T3 was significantly higher than that at T1 in the CEA group compared to both T1 and the CAS group. CAS triggers smaller changes in the MMP-9-TIMP-1 system during the perioperative period, which may correlate with a lower incidence of central nervous system complications. Additional studies as well as cognitive and functional surveys are warranted to determine the clinical relevance of our findings. NIH U.S. National Library of Medicine, Clinicaltrials.gov,NCT03410576, 24.01.2018, Retrospectively registered

A daganatos betegségek okozzák a magyarországi halálesetek közel egynegyedét. A tumorreszekciós műtétek hosszú távú sikerességét, vagyis a kiújulás- és áttételmentességet, valamint a túlélést az anesztéziai módszerek is befolyásolják. Ezt igazolták a sejttenyészeteken és az állatmodelleken végzett kísérletek. Kiderült, hogy a propofol és a helyi érzéstelenítőszerek – az inhalációs anesztetikumokhoz és az opioidokhoz képest – csökkentik a daganatsejtek életképességét és áttételképző potenciáljukat. A betegcsoportokon végzett vizsgálatok azonban csak a propofol előnyét igazolták az inhalációs anesztetikumokhoz képest. Sajnos az általános anesztéziához a helyi érzéstelenítőszerek epiduralis, kiegészítő jellegű alkalmazása nem csökkentette a betegek kiújulásmentességi és túlélési idejét. További klinikai vizsgálatok szükségesek, hogy a jövőben kiderüljön, az egyes ráktípusokban milyen a műtéti érzéstelenítés tényleges hatása. Orv Hetil. 2023; 164(22): 843–846.