Randomized open-label controlled study of cancer vaccine OSE2101 versus chemotherapy in HLA-A2-positive patients with advanced non-small-cell lung cancer with resistance to immunotherapy: ATALANTE-1.

BACKGROUND: Patients with advanced non-small-cell lung cancer (NSCLC) treated with immune checkpoint blockers (ICBs) ultimately progress either rapidly (primary resistance) or after durable benefit (secondary resistance). The cancer vaccine OSE2101 may invigorate antitumor-specific immune responses after ICB failure. The objective of ATALANTE-1 was to evaluate its efficacy and safety in these patients. PATIENTS AND METHODS: ATALANTE-1 was a two-step open-label study to evaluate the efficacy and safety of OSE2101 compared to standard-of-care (SoC) chemotherapy (CT). Patients with human leukocyte antigen (HLA)-A2-positive advanced NSCLC without actionable alterations, failing sequential or concurrent CT and ICB were randomized (2 : 1) to OSE2101 or SoC (docetaxel or pemetrexed). Primary endpoint was overall survival (OS). Interim OS futility analysis was planned as per Fleming design. In April 2020 at the time of interim analysis, a decision was taken to prematurely stop the accrual due to coronavirus disease 2019 (COVID-19). Final analysis was carried out in all patients and in the subgroup of patients with ICB secondary resistance defined as failure after ICB monotherapy second line ≥12 weeks. RESULTS: Two hundred and nineteen patients were randomized (139 OSE2101, 80 SoC); 118 had secondary resistance to sequential ICB. Overall, median OS non-significantly favored OSE2101 over SoC {hazard ratio (HR) [95% confidence interval (CI)] 0.86 [0.62-1.19], P = 0.36}. In the secondary resistance subgroup, OSE2101 significantly improved median OS versus SoC [11.1 versus 7.5 months; HR (95% CI) 0.59 (0.38-0.91), P = 0.017], and significantly improved post-progression survival (HR 0.46, P = 0.004), time to Eastern Cooperative Oncology Group (ECOG) performance status deterioration (HR 0.43, P = 0.006) and Quality of Life Questionnaire Core 30 (QLQ-C30) global health status compared to SoC (P = 0.045). Six-month disease control rates and progression-free survival were similar between groups. Grade ≥3 adverse effects occurred in 11.4% of patients with OSE2101 and 35.1% in SoC (P = 0.002). CONCLUSIONS: In HLA-A2-positive patients with advanced NSCLC and secondary resistance to immunotherapy, OSE2101 increased survival with better safety compared to CT. Further evaluation in this population is warranted.

Circulating SIRT1 inversely correlates with epicardial fat thickness in patients with obesity.

BACKGROUND AND AIM: Obesity is increasing worldwide and is related to undesirable cardiovascular outcomes. Epicardial fat (EF), the heart visceral fat depot, increases with obesity and correlates with cardiovascular risk. SIRT1, an enzyme regulating metabolic circuits linked with obesity, has a cardioprotective effect and is a predictor of cardiovascular events. We aimed to assess the relationship of EF thickness (EFT) with circulating SIRT1 in patients with obesity. METHODS AND RESULTS: Sixty-two patients affected by obesity and 23 lean controls were studied. Plasma SIRT1 concentration was determined by enzyme-linked immunosorbent assay (ELISA). EFT was measured by echocardiography. Body mass index (BMI), waist circumference, heart rate (HR), blood pressure, and laboratory findings (fasting glucose, insulin, HbA1c, cholesterol, and triglycerides) were assessed. SIRT1 was significantly lower (P = 0.002) and EFT was higher (P < 0.0001) in patients with obesity compared with lean controls. SIRT1 showed a negative correlation with EFT and HR in the obesity group (ρ = -0.350, P = 0.005; ρ = -0.303, P = 0.008, respectively). After adjustment for obesity-correlated variables, multiple linear regression analysis showed that EFT remained the best correlate of SIRT1 (ß = -0.352, P = 0.016). CONCLUSIONS: Circulating SIRT1 correlates with the visceral fat content of the heart. Serum SIRT1 levels might provide additional information for risk assessment of coronary artery disease in patients with obesity.

The effect of maternal immunization on female oxidative status, yolk antioxidants and offspring survival in a songbird.

Immune defense involves inflammatory reactions in which immune cells produce reactive oxygen species (ROS) to fight pathogens. ROS may however cause damage to the host if they are not balanced by antioxidant defenses. Therefore, one should expect individuals undergoing an immune reaction to use antioxidants to prevent oxidative stress. Antioxidants are vital compounds that provide important protection against oxidative damage of embryos and newly hatched chicks. Thus, during egg laying a female that contracted an infection may face a trade-off between the allocation of antioxidants into self-maintenance and into her offspring via the eggs. In our study we investigated whether immunized females face this trade-off and consequently modify the antioxidant allocation into the eggs and whether this allocation affects offspring performance. We injected female zebra finches (Taeniopygia guttata) with lipopolysaccharide prior to egg laying while some females were left unimmunized. We removed the second egg of each clutch, while we allowed the other eggs to hatch. We assessed oxidative stress in females 24h after immunization, yolk antioxidant capacity of the second egg of the clutch and survival success of the offspring until adulthood. Compared to controls, immunized females had higher oxidative damage, but similar plasma non-enzymatic antioxidant levels. The treatment did not affect yolk antioxidants, clutch size, laying date and offspring survival. However, we found a positive correlation between yolk antioxidant capacity and offspring survival, irrespective of the treatment. Our study suggests that our immune challenge may not have changed female strategy of antioxidant allocation between self-maintenance and offspring survival.

Sex-specific effects of prenatal and postnatal nutritional conditions on the oxidative status of great tit nestlings.

The early life period is characterized by fast growth and development, which can lead to high reactive oxygen species (ROS) production. Young animals thus have to balance their investment in growth versus ROS defence, and this balance is likely mediated by resource availability. Consequently resources transferred prenatally by the mother and nutritional conditions experienced shortly after birth may crucially determine the oxidative status of young animals. Here, we experimentally investigated the relative importance of pre- and early postnatal nutritional conditions on the oxidative status of great tit nestlings (Parus major). We show that resources transferred by the mother through the egg and nutritional conditions encountered after hatching affect the oxidative status of nestling in a sex-specific way. Daughters of non-supplemented mothers and daughters which did not receive extra food during the early postnatal period had higher oxidative damage than sons, while no differences between sons and daughters were found when extra food was provided pre- or postnatally. No effect of the food supplementations on growth, fledging mass or tarsus length was observed, indicating that female nestlings maintained their investment in growth at the expense of ROS defence mechanisms when resources were limited. The lower priority of the antioxidant defence system for female nestlings was also evidenced by lower levels of specific antioxidant components. These results highlight the important role of early parental effects in shaping oxidative stress in the offspring, and show that the sensitivity to these parental effects is sex-specific.

Near-field analysis of metallic DFB lasers at telecom wavelengths.

We image in near-field the transverse modes of semiconductor distributed feedback (DFB) lasers operating at λ ≈ 1.3 µm and employing metallic gratings. The active region is based on tensile-strained InGaAlAs quantum wells emitting transverse magnetic polarized light and is coupled via an extremely thin cladding to a nano-patterned gold grating integrated on the device surface. Single mode emission is achieved, which tunes with the grating periodicity. The near-field measurements confirm laser operation on the fundamental transverse mode. Furthermore--together with a laser threshold reduction observed in the DFB lasers--it suggests that the patterning of the top metal contact can be a strategy to reduce the high plasmonic losses in this kind of systems.

In situ generation of surface plasmon polaritons using a near-infrared laser diode.

We demonstrate a semiconductor laser-based approach which enables plasmonic active devices in the telecom wavelength range. We show that optimized laser structures based on tensile-strained InGaAlAs quantum wells-coupled to integrated metallic patternings-enable surface plasmon generation in an electrically driven compact device. Experimental evidence of surface plasmon generation is obtained with the slit-doublet experiment in the near-field, using near-field scanning optical microscopy measurements.

Design of an integrated coupler for the electrical generation of surface plasmon polaritons.

Recently a surface plasmon polariton (SPP) source based on an electrically operated semiconductor laser has been demonstrated. Here we present a numerical investigation of the light-SPP coupling process involved in the device. The problem consists in the coupling via a diffraction grating between a dielectric waveguide mode--the laser mode--and a SPP mode. The issue of the coupling efficiency is discussed, and the dependence on various geometrical parameters of both the grating and the dielectric waveguide is studied in detail. A maximum coupling efficiency of ≈24% is obtained at telecom wavelengths, which could lead to a high-power integrated SPP source when combined to a laser medium.

Variation of a carotenoid-based trait in relation to oxidative stress and endocrine status during the breeding season in the Eurasian kestrel: a multi-factorial study.

Carotenoid-based skin colorations vary seasonally in many bird species and are thought to be honest sexually selected signals. In order to provide more insight in the potential signal function and underlying mechanisms of such colorations we here quantified patterns of variation of leg coloration in adult male and female Eurasian kestrels (Falco tinnunculus tinnunculus) over the breeding season, and evaluated the relationship between coloration and levels of carotenoids, androgens and estrogens, oxidative damage and plasma non-enzymatic antioxidant capacity. We studied both reproducing wild and non-reproducing captive birds to test for the effect of diet and breeding effort. Males were more colored than females only during mating, and independently of diet, suggesting that leg-color is a sexually selected trait. Seasonal variation in leg color was associated with circulating carotenoids, but concentrations of these molecules were not related to antioxidant capacity, body condition or oxidative damage. These results indicate that carotenoid-based colorations may not be an honest signal of health status in this species. Production of carotenoid rich eggs coincided with low levels of circulating carotenoids in females, indicating that carotenoids might be a limited resource for laying female kestrels. Finally, young rearing males had higher levels of oxidative damage than females, and wild birds of both sexes had higher levels of these parameters than captive birds. These results may indicate that parental effort and physical activity are costly, independently from hormonal status. Since androgens did not explain carotenoid variation we suggest that multiple interacting factors can regulate carotenoid levels along the season.

Short restraint time does not influence markers of serum oxidative stress in homing pigeons (Columba livia).

Restraint in a confined space, such as a cage or a box, may be perceived by birds as a stressful condition. Some concern has been expressed about restraining homing pigeons (Columba livia) in transport crates for sport or for scientific research. Therefore, this study sought to test whether short restraint time in a transport crate for 1, 2 or 18 (overnight) h causes oxidative stress in homing pigeons and whether it is more stressful than flying. To isolate the effect of crowding from that of transport per se, the pigeons were kept in an immobile crate, that is, without any movement. To quantify oxidative stress, we measured serum levels of oxidative damage (ROMs) and of antioxidant capacity (OXY). We found that pigeons restrained in transport crates showed no significant variation for both markers of oxidative stress, regardless of the duration of restraint. Conversely, pigeons which had flown around 200 km had increased levels of oxidative damage and decreased levels of serum OXY, both clear manifestations of oxidative stress. These results suggest that maintaining homing pigeons in transport crates for a short time (i.e. 1-18 h) does not cause oxidative stress.

The FXR agonist obeticholic acid inhibits the cancerogenic potential of human cholangiocarcinoma.

Cholangiocarcinoma (CCA) is an aggressive cancer with high resistance to chemotherapeutics. CCA is enriched in cancer stem cells, which correlate with aggressiveness and prognosis. FXR, a member of the metabolic nuclear receptor family, is markedly down-regulated in human CCA. Our aim was to evaluate, in primary cultures of human intrahepatic CCA (iCCA), the effects of the FXR agonist obeticholic acid (OCA), a semisynthetic bile acid derivative, on their cancerogenic potential. Primary human iCCA cell cultures were prepared from surgical specimens of mucinous or mixed iCCA subtypes. Increasing concentrations (0-2.5 µM) of OCA were added to culture media and, after 3-10 days, effects on proliferation (MTS assay, cell population doubling time), apoptosis (annexin V-FITC/propidium iodide), cell migration and invasion (wound healing response and Matrigel invasion assay), and cancerogenic potential (spheroid formation, clonogenic assay, colony formation capacity) were evaluated. Results: FXR gene expression was downregulated (RT-qPCR) in iCCA cells vs normal human biliary tree stem cells (p < 0.05) and in mucinous iCCA vs mixed iCCA cells (p < 0.05) but was upregulated by addition of OCA. OCA significantly (p < 0.05) inhibited proliferation of both mucinous and mixed iCCA cells, starting at a concentration as low as 0.05 µM. Also, CDCA (but not UDCA) inhibited cell proliferation, although to a much lower extent than OCA, consistent with its different affinity for FXR. OCA significantly induced apoptosis of both iCCA subtypes and decreased their in vitro cancerogenic potential, as evaluated by impairment of colony and spheroid formation capacity and delayed wound healing and Matrigel invasion. In general, these effects were more evident in mixed than mucinous iCCA cells. When tested together with Gemcitabine and Cisplatin, OCA potentiated the anti-proliferative and pro-apoptotic effects of these chemotherapeutics, but mainly in mixed iCCA cells. OCA abolished the capacity of both mucinous and mixed iCCA cells to form colonies when administered together with Gemcitabine and Cisplatin. In subcutaneous xenografts of mixed iCCA cells, OCA alone or combined with Gemcitabine or Cisplatin markedly reduced the tumor size after 5 weeks of treatment by inducing necrosis of tumor mass and inhibiting cell proliferation. In conclusion, FXR is down-regulated in iCCA cells, and its activation by OCA results in anti-cancerogenic effects against mucinous and mixed iCCA cells, both in vitro and in vivo. The effects of OCA predominated in mixed iCCA cells, consistent with the lower aggressiveness and the higher FXR expression in this CCA subtype. These results, showing the FXR-mediated capacity of OCA to inhibit cholangiocarcinogenesis, represent the basis for testing OCA in clinical trials of CCA patients.

Molecular and clinical features associated with CFTR gene rearrangements in Italian population: identification of a new duplication and recurrent deletions.

Cystic fibrosis (CF) is mainly caused by small deletions or missense mutations in the CFTR gene. The CF mutation database lists more than 35 large rearrangements that may escape detection using polymerase chain reaction-base techniques. The Innogenetics assay, the denaturing high-performance liquid chromatography and sequencing screening showed a mutation detection rate of 92.6% in our population. We report here the results of multiplex ligation-dependent probe amplification (MLPA) screening for CFTR gene rearrangements, performed on the unidentified alleles of our CF patients. Our sample population consists of 692 non-related Italian CF patients (for a total of 1384 alleles), followed at CF Centres in the Lombardia Region. MLPA analysis was performed in 49 patients who still had one or two unidentified alleles (for a total of 52 unidentified alleles) after extensive analysis of CFTR gene. All patients who were studied had the classical form of CF. We characterized nine different deletions and a new duplication. The deletion of exons 22-23 (7/82) was the most frequent in our cohort. The search for deletion/duplications of the CFTR gene has made it possible to reach a 94.1% detection rate, with an improvement (1.6%) of the carrier detection rate in the Italian population.

Spontaneous hypoglycemia in patients with cystic fibrosis.

OBJECTIVE: Diabetes frequently complicates cystic fibrosis (CF) without fasting hyperglycemia or despite spontaneous hypoglycemia (anecdotally ascribed to malnutrition), whose prevalence, clinical meaning, and relationship with glucose tolerance and clinical/nutritional status were not previously investigated. The relationship of CF genotype with insulin secretion control is also unclear. DESIGN AND METHODS: A total of 129 CF patients without stable diabetes received 188 oral glucose tolerance tests. Distribution of fasting plasma glucose (FPG), glucose, insulin and C-peptide responses, clinical/nutritional variables, and their relationships were analyzed. RESULTS: FPG < 60 mg/dl (3.3 mmo/l) was detected in 14% of studies and reactive hypoglycemia (PG < 50 mg/dl (2.8 mmo/l)) in 15%. OGTT-based diabetes frequency was similar in the lowest quartile (Q1) and Q2-3 for FPG (10 and 8%), with higher glucose increment and area under the curve in Q1. Insulin and C-peptide levels were similar among FPG quartiles. Class I cystic fibrosis transmembrane conductance regulator mutation carriers had higher insulin concentrations than class II, especially in Q1 for FPG. Age, sex, nutritional, and anthropometric parameters including fat and lean body mass were unrelated to FPG. Lower FPG was associated with more frequent hospitalization rates (P = 0.002) and lower Shwachman scores (P = 0.041). Steroids weaning was accurately evaluated but then excluded as a possible cause of hypoglycemia. CONCLUSIONS/INTERPRETATION: Fasting asymptomatic hypoglycemia is frequent and possibly related to inappropriate insulin secretion control in class I mutation carriers. Low FPG does not exclude impaired glucose tolerance (IGT) and diabetes in CF and reflects worse clinical status.

Ionizing radiation, antioxidant response and oxidative damage: A meta-analysis.

One mechanism proposed as a link between exposure to ionizing radiation and detrimental effects on organisms is oxidative damage. To test this hypothesis, we surveyed the scientific literature on the effects of chronic low-dose ionizing radiation (LDIR) on antioxidant responses and oxidative damage. We found 40 publications and 212 effect sizes for antioxidant responses and 288 effect sizes for effects of oxidative damage. We performed a meta-analysis of signed and unsigned effect sizes. We found large unsigned effects for both categories (0.918 for oxidative damage; 0.973 for antioxidant response). Mean signed effect size weighted by sample size was 0.276 for oxidative damage and -0.350 for antioxidant defenses, with significant heterogeneity among effects for both categories, implying that ionizing radiation caused small to intermediate increases in oxidative damage and small to intermediate decreases in antioxidant defenses. Our estimates are robust, as shown by very high fail-safe numbers. Species, biological matrix (tissue, blood, sperm) and age predicted the magnitude of effects for oxidative damage as well as antioxidant response. Meta-regression models showed that effect sizes for oxidative damage varied among species and age classes, while effect sizes for antioxidant responses varied among species and biological matrices. Our results are consistent with the description of mechanisms underlying pathological effects of chronic exposure to LDIR. Our results also highlight the importance of resistance to oxidative stress as one possible mechanism associated with variation in species responses to LDIR-contaminated areas.

Ceftazidime monotherapy vs. combined therapy in Pseudomonas pulmonary infections in cystic fibrosis.

To evaluate whether the addition of an aminoglycoside might enhance the clinical efficacy of ceftazidime in cystic fibrosis patients with acute exacerbations of chronic Pseudomonas lung infections we carried out a prospective, comparative, randomized blind study with three schedules: ceftazidime vs. ceftazidime plus sisomicin (C/S) vs. piperacillin plus sisomicin, for a total of 60 courses of 14 days of treatment. Each treatment led to clinical and radiologic improvement with marked reduction of signs of acute infection. Statistically there was no significant difference in clinical responses among the schedules. No side effect appeared during treatments with ceftazidime or C/S. Hyperpyrexia was seen in 35% of patients receiving piperacillin. Decrease in Pseudomonas aeruginosa count to less than 10(5) colony-forming units/ml of sputum was achieved in 60% of patients treated with C/S and in 30% of patients who received ceftazidime or piperacillin plus sisomicin (statistically not significant). A transient increase in mean geometric minimal inhibitory concentrations for ceftazidime and piperacillin was observed at the end of the combined therapies. A larger percentage of persistent resistant strains of P. aeruginosa was seen after the combined therapies. We conclude that ceftazidime as monotherapy may be an effective alternative in Pseudomonas lung infections in cystic fibrosis patients. Its clinical efficacy seems not to be enhanced by the addition of an aminoglycoside, although reduction of Pseudomonas in the sputum was better achieved by the combination of C/S.

Clinical trials with C 1740, an immunomodulator compound proposed for prevention of acute infectious exacerbations in chronic bronchitis.

C 1740 is an immunmodulating agent of biological origin proposed for the prevention of infectious exacerbations in chronic bronchopathy. The first placebo-controlled double-blind randomized clinical trials have led to opposite conclusions regarding the utility of C 1740. The rate of infectious exacerbations in the placebo group and a large Type II error could explain the "negative clinical trials". However, two out of four "positive clinical trials" were associated with high risk of falsely positive results. The activity of C 1740 is discussed here.

Newborn hearing screening by transient evoked otoacoustic emissions: analysis of response as a function of risk factors.

Hearing loss can be considered as the most common birth defect. Early detection of hearing loss by screening at, or shortly after, birth and appropriate intervention are critical to speech, language and cognitive development. In the present study, the characteristics of Transient Evoked Otoacoustic Emissions have been evaluated as a function of known pre- and perinatal risk factors for hearing loss. All newborns were screened for hearing loss using a physiologic test of hearing function, the Transient Evoked Otoacoustic Emissions. A total of 532 consecutive newborn infants received binaural Transient Evoked Otoacoustic Emission testing (262 males, 270 females; mean gestational age 39.2 +/- 2.1 weeks, range 26-43; birth weight: 3,240 +/- 550 g, range 910-4,780). The population examined comprised 448 control infants and 84 high-risk for hearing loss infants (Joint Committee on Infant Hearing 1994 criteria). All Transient Evoked Otoacoustic Emission recordings were performed at comparable postconceptional ages. Audiological screening by Transient Evoked Otoacoustic Emission recording showed an overall 100% sensitivity, 99.02% specificity, with negative and positive predictive values of 100% and 62.5%, respectively. As compared to controls, high-risk infants showed: 1. increased rates of Fail-1 (Transient Evoked Otoacoustic Emissions absent at first examination, 21.4% vs 9.8%, p = 0.004), Fail-2 (Transient Evoked Otoacoustic Emissions absent on retesting: 8.64% vs 1.37%, p = 0.0014), false positives (Transient Evoked Otoacoustic Emissions absent/V wave present: 3.7% vs 0.46%, p = 0.029) and true positives (Transient Evoked Otoacoustic Emissions absent, V wave absent: 2.47% or 24.5 per 1,000 live births vs 0.22% or 2.2 per 1,000 live births, p = 0.013); 2. significantly reduced Transient Evoked Otoacoustic Emission intensity in the 0.7-1 kHz (right side) and 1-2 kHz (left side) frequency ranges. Multivariate logistic regression analysis showed a significant positive correlation between congenital hearing loss and the following risk factors: assisted ventilation lasting > 10 days (Odds ratio 14.8; 95% confidence interval, 4.5-48.8, p < 0.000001), severe birth asphyxia (Odds ratio 5.8; 95% confidence interval; 2.1-16.1; p = 0.0006) and administration of ototoxic drugs (Odds ratio 4.5; 95% confidence interval; 1.4-13.9; p = 0.009). Results of this study confirm the feasibility and accuracy of universal neonatal hearing screening based on recording Transient Evoked Otoacoustic Emissions. These data stress the importance of the risk factors for hearing loss, including prolonged assisted ventilation, ototoxic drugs, and severe birth asphyxia.

The treatment of cranio-facial pain by electroacupuncture and laser irradiation.

Craniofacial neuralgias represent an interesting medical challenge, especially regarding the complex therapeutical aspects. Our study was performed treating more than 700 patients, applying steel inox needles variable in diameters and length for about 20 minutes, with a total application number ranging between 10 and 20. Results have been defined referring to a 4-grades response scale: excellent, good, fairly good and insufficient. It is important to emphasise that the best results have been achieved with patients who chose the acupuncture as the first therapeutic approach, while patients who underwent other previous medical and/or surgical treatment have had a worse response. The authors assert that acupuncture and infrared laser reflex therapy represent a harmless and effective treatment of such a diffuse and invalidating disease.

[Rare malformation of the bile ducts of surgical interest]. / Rara malformazione delle vie biliari di interesse chirurgico.

Variations from normal anatomy of extrahepatic biliary tract, especially if on the basis of a congenital defect, are often dangerous for the surgeon, as hidden cause of a possible injury during surgery. During a cholecystectomy performed for lithiasis in non functioning gallbladder, whose preoperative cholangiogram revealed nothing of suspect, the dissection of cystic duct was regular at its normal junction with the Common Bile Duct (CBD). Because of the scheduled intraoperative cholangiogram, it was however not severed but only dissected free. The gallbladder was therefore detached from the liver in anterograde progression, after hemostasis and section of a normal cystic artery. During the detaching of gallbladder from the liver what seemed a very large "hepato-cystic" duct coming to the infundibulum was met: for caution the cholangiogram was then made proximally to such "hepato-cystic" duct that instead revealed to be the main right hepatic duct coming to the infundibulum of gallbladder without confluence with the left hepatic duct. The biliary tract going from the gallbladder to the supposed CBD was in fact the cystic duct, as the Heister's valvulae clearly show on the cholangiograms. Cholecystectomy was therefore performed proximally to the confluence of right hepatic duct, and the postoperative course was uneventful. Such kind of extrahepatic tract derangement must be very rare, because of the apparent lacking in literature of any similar case, also if the possibility is mentioned.(ABSTRACT TRUNCATED AT 250 WORDS)

[Effects on ventilation secondary to laparoscopic and laparotomic cholecystectomy]. / Effetti sulla ventilazione secondari a colecistectomia laparoscopica e laparotomica.

OBJECTIVE: Evaluation of respiratory function after 24 hours from intervention related to two different surgical techniques of cholecistectomy. PATIENTS AND METHODS: Thirty patients submitted to cholecystectomy, nine by laparotomy and twenty-one by video-laparoscopy. The ventilatory parameters considered are as follows: CV, FCV, VEF1, FEF25-75%; and moreover also some variables of acid-base balance: pH, paCO2 e paO. RESULTS: In all cases was evidenced a decrease of respiratory activity. This phenomenon was more evident in the laparotomy group (CV = 37, 35, FCV = 41, 47, VEF1 = 40, FEF25-75% = 36.62% related to preoperative values versus 71.20, 80.88, 79.29, 77.91% in the videolaparoscopic group. No significative differences were registered between the two groups as to postoperative paO2, which was moderately lower in all patients, while no variation was observed for pH and paCO2. CONCLUSIONS: Data collected confirm that after laparoscopic cholecystectomy the ventilatory respiratory capacity is better conserved, that clinically means lower incidence of postoperatory pulmonary complications.

["Killing" of pseudomonas aeruginosa isolated from patients with critical post-operative complications. Effect of various antibiotics]. / "Killing" di pseudomonas aeruginosa isolati da pazienti con complicazioni critiche post-operatorie. Influenza di alcuni antibiotici.

We undertook this study to estimate phagocytic killing by neutrophils (PMNs) of Pseudomonas aeruginosa pre-exposed to sub-inhibitory concentration of Amikacin and Imipenem. In particular, we have isolated bacteria from endotracheal aspirates of post-operative patients mechanically ventilated admitted to an ICU with respiratory failure. PMNs were obtained both from these patients (Group A, n. 6) as well as from subjects submitted to surgery with uncomplicated post-operative period (Group B, n. 8). From specimens tested, 6 strains of Pseudomonas aeruginosa were isolated. Results showed that the rate of killing of bacteria treated with Amikacin was no different from that of untreated bacteria, whichever the source of PMNs, either from Group A or Group B patients. On the other hand, the microbicidal effect on P. aeruginosa exposed to Imipenem was significantly enhanced when PMNs were obtained from Group B patients. In the mixture bacteria, Imipenem and PMNs obtained from Group A the rate of killing was low, similar to the controls without antibiotics. Such a finding suggests a possible impairment of PMNs due to the critical disease and in some way responsible for the host adverse interaction between granulocytes, antibiotics and pathogens. The underlying mechanisms remain to be clarified and further studies are required to understand the possible clinical implications.