Outcomes Analysis of Patients Receiving Local Ablative Therapy for Oligoprogressive Metastatic NSCLC Under First-Line Immunotherapy.

CONTEXT: Nonsmall Cell Lung Cancer (NSCLC) treatment relies on first-line immunotherapy as single agent or combined with chemotherapy. Oligoprogression may be observed in this setting. MATERIAL AND METHOD: We performed a European multicentric retrospective study on patients treated with first-line immunotherapy, who presented with oligoprogressive disease, treated with a local ablative treatment. RESULTS: A total of 61 patients were retrospectively included between 2018 and 2022. Twenty-four patients (39%) received immunotherapy as single agent, and 37 (61%) chemo-immunotherapy. First oligoprogression occurred more frequently in pre-existing metastatic sites (47% of patients). Median PFS1 (defined as time to first oligoprogression) was 11.5 months [IC95%: 10.0-12.3]. We observed that 37 patients (61%) progressed after first oligoprogression, and 20 (54%) from them presented second oligoprogression. Median OS for the whole cohort was 72.0 months [IC95%: 19.3-124.8], with positive correlation between OS and PFS1 (R=0.65, P < .0001). After loco-ablative treatment with radiotherapy, disease control rate was 89% with ablative radiotherapy: 88% with conventional radiotherapy, and 89% with stereotactic radiotherapy. CONCLUSION: Patients with oligoprogression under/after immunotherapy have better prognosis with a high risk of subsequent oligoprogression.

Occurrence of viral DNA in paired samples of corneal rim and cornea preservation fluid.

Corneal transplants have one of the highest success rates among all transplantological procedures. Corneas intended for transplantation are stored in a preservation fluid, which is then tested for bacterial and fungal infections. Among all analyses of infectious complications following corneal transplants, infections caused by bacteria or fungi are the most prominent. Surprisingly, however, apart from a few publications, there is a lack of data regarding the occurrence of viruses in donor corneas and the risk of transmitting these to their recipients. The intention of this research was therefore to determine the frequency with which human herpesvirus 1 (HHV-1), human herpesvirus 2 (HHV-2), and human adenovirus (HAdV) occur in transplanted corneal tissue, as well as in samples of preservation fluid. The study comprised 57 paired samples, with each pair consisting of a fragment of the corneal tissue remaining after its trepanation for transplantation surgery and a sample of corneal preservation fluid. Sample pairs were all tested for the presence of the DNA of three viruses (HHV-1, HHV-2, and HAdV) using real time PCR technique. Viral DNA was found in three of the tested corneas-HHV-1 DNA in one paired sample (1.8%) and adenovirus DNA in two single samples (3.5%). We postulate that virological testing of corneas for transplantation should be considered, particularly in the case of donors with increased risk factors for herpesvirus and adenovirus reactivation. J. Med. Virol. 89:732-736, 2017. © 2016 Wiley Periodicals, Inc.

Invasive Aspergillosis of the Stomach and Co-infection With Candida krusei in a Patient With Terminal Liver Failure: A Case Report.

Invasive aspergillosis (IA) is diagnosed almost exclusively in immunocompromised patients. It is located mainly in the lungs or paranasal sinuses, but occasionally other organs and the gastrointestinal tract may also be affected either alone or as a part of a disseminated disease. The main risk factors predisposing to IA are neutropenia, immunosuppressive and steroid therapy, as well as severe underlying disease. Despite progress in diagnostics and therapy of IA, it is still characterized by a high mortality rate. In the disseminated aspergillosis of the gastrointestinal tract, mainly the small or large intestine are affected, rarely the upper gastrointestinal tract. To our best knowledge only a very few cases of IA of the gastric wall have been reported so far in the literature. We describe a unique case of this very rare location of IA in the stomach in a patient who underwent orthotopic liver transplantation in the course of active IA and Candida krusei infection of the stomach wall. The patient's condition improved on combination therapy of voriconazole and caspofungin.

The role of ABC genes in shaping perianth phenotype in the basal angiosperm Magnolia.

It is generally accepted that the genus Magnolia is characterised by an undifferentiated perianth, typically organised into three whorls of nearly identical tepals. In some species, however, we encountered interesting and significant perianth modifications. In Magnolia acuminata, M. liliiflora and M. stellata the perianth elements of the first whorl are visually different from the others. In M. stellata the additional, spirally arranged perianth elements are present above the first three whorls, which suggests that they have been formed within the domain of stamen primordia. In these three species, we analysed expression patterns of the key flower genes (AP1, AGL6, AP3, PI, AG) responsible for the identity of flower elements and correlated them with results of morphological and anatomical investigations. In all studied species the elements of the first whorl lacked the identity of petals (lack of AP3 and PI expression) but also that of leaves (presence of AGL6 expression), and this seems to prove their sepal character. The analysis of additional perianth elements of M. stellata, spirally arranged on the elongated floral axis, revealed overlapping and reduced activity of genes involved in specification of the identity of the perianth (AGL6) but also of generative parts (AG), even though no clear gradient of morphological changes could be observed. In conclusion, Magnolia genus is capable of forming, in some species, a perianth differentiated into a calyx (sepals) and corolla (petals). Spirally arranged, additional perianth elements of M. stellata, despite activity of AG falling basipetally, resemble petals.

Protective effects of polyphenol-rich blackcurrant preparation on biochemical and metabolic biomarkers of rats fed a diet high in fructose.

The purpose of the study was to compare in vivo effects of dietary supplementation with blackcurrant pomaces containing variable level of phenolic compounds on blood and internal organ parameters in rats. Forty-eight growing Wistar rats were allocated to six treatment groups in which they were fed ad libitum for 4 weeks the following diets: standard chow (group S), high-fructose diet (group F), standard chow supplemented with 7.7% of either rich in polyphenols unprocessed blackcurrant pomace (UB) or polyphenol-deprived processed pomace (PB) (groups SUB and SPB respectively), and high-fructose diet with 7.7% of either UB or PB (groups FUB and FPB respectively). Blackcurrant pomace, irrespective of its phenolic content, selectively modulated the enzymatic activity of the colon microflora, reducing the activity of enzymes with potentially harmful properties and promoting activities of enzymes that might increase the use of carbohydrates that escaped digestion in the upper gastrointestinal tract. Although both pomaces increased antioxidant status of the liver and blood serum, the unprocessed pomace showed a greater ability to inhibit lipid peroxidation in heart and kidney than the pomace that was less abundant in polyphenols. Both of the examined pomaces had a positive influence on serum lipid profile, but better hypocholesterolemic effect was observed after supplementation of the diet with unprocessed preparation. The biochemical action of unprocessed pomace in the normalization of fructose-induced disturbances was more distinct than those of pomace remaining after extraction.

Acinetobacter junii as an aetiological agent of corneal ulcer.

Rods of the Acinetobacter genus are present mainly in the external environment (e.g. water, soil) and in animals, while in humans they may comprise physiological flora. The main pathogenic species is Acinetobacter baumannii complex, which constitutes a common cause of nosocomial infections, particularly in patients with underlying diseases and risk factors (e.g. prior broad-spectrum antibiotic therapy, malignancy, central venous catheter, mechanical ventilation); however, infections of the eye caused by strains of Acinetobacter spp. are very rare. We report a unique case of community-acquired corneal ulcer caused by Acinetobacter non-baumannii (possibly A. junii), in a patient with no risk factors identified. The case highlights the need for obtaining a sample from the cornea for bacteriological culture in the case of suspected ophthalmic infection as identification of the pathogen, and assessment of its susceptibility profile enables proper antibiotic therapy, improves the outcome and may constitute an eyesight-saving management.

Metabolic and immune response of young turkeys originating from parent flocks fed diets with inorganic or organic selenium.

The aim of this study was to verify the hypothesis that the health and growth of turkey poults may be improved by supplementing diets fed to parent flocks with available selenium. Experimental poults originated from parent flocks fed with diets containing 0.3 mg/kg inorganic selenium (control group Se(M)) and organic selenium (experimental group Se(O)). Egg yolk selenium content was comparable in both flocks (0.72 and 0.70 mg/kg d.m., respectively). Eggs from the Se(O) flock had a significantly lower content of thiobarbituric acid reactive substances - TBARS (31.13 vs. 53.10 nmol/g, p > 0.001). Se(O) group poults were characterized by higher activity of glutathione peroxidase (7.54 vs. 5.92 U/mL, P = 0.001) and superoxide dismutase (89.30 vs. 79.23 U/mL, P = 0.026). The thigh muscles of Se(O) group birds had significantly higher selenium concentrations (0.74 vs. 0.57, p = 0.045) and a significantly lower TBARS content (38.42 vs. 65.01, p = 0.001). No differences were found between the groups with respect to the content of total protein, albumins and uric acid, and the activites of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and lactate dehydrogenase (DLH) in day-old poults. On day 28, groups Se(O) and Se(M) differed in the activity of ALT (20.50 vs. 26.33, p = 0.05) and SOD (87.29 vs. 100.02 U/mL, p = 0.035). There were no differences between the groups regarding the percentages of T lymphocyte subpopulations CD4+, CD8+, CD4+CD8+ and B lymphocyte subpopulations (IgM+) at 1 and 28 days of age. Over the experimental period, mortality rates were similar in both groups (7.32 and 8.87%), and so were the final body weights of birds (1108 vs. 1135 g). The results of the study show that the dietary supplementation of organic selenium in turkey parent flocks reduces the rate of oxidation processes in the egg and in the tissues of newly-hatched poults, yet it has no effect on the analyzed parameters of cell-mediated immunity and the growth performance of birds during the first five weeks of their life.

Metabolic response of the gastrointestinal tract and serum parameters of rabbits to diets containing chicory flour rich in inulin.

A 36-day experiment carried out on 54-day-old rabbits addressed the analysis of physiological properties of diets supplemented with chicory roots flour. Twenty-four rabbits were allocated in individual cages to three treatments, in which they were fed each diet with the chicory flour at 0, 25 and 50 g/kg (control, ChF(2.5) and ChF(5) groups respectively). The chicory preparation administered at a higher dose, lowered ileal pH and viscosity, and evoked increased hydration of ileal and caecal digesta, compared to the control treatment (p

Surgical site infections in liver recipients in the early posttransplantation period: etiological agents and susceptibility profiles.

OBJECTIVE: This study evaluated the frequency of microbial isolates and their susceptibility profiles from cultures at the surgical site of 83 liver recipients in the early posttransplantation period. PATIENTS AND METHODS: We prospectively collected microbiologic culture data on 83 adult patients undergoing orthotopic liver transplantation (OLT) using standard procedures and commercially available tests. Susceptibility of the strains to antibacterial agents was performed by the Clinical and Laboratory Standards Institute (CLSI) guidelines. RESULTS: All patients were followed prospectively for the first 4 weeks after surgery. Among 284 microbial isolates from clinical surgical site samples in 80 liver recipients, cultures were positive in 110 samples. The most commonly isolated species were: Gram-positive cocci (n = 222 isolates, 78%) with dominance of methicillin-resistant coagulase-negative staphylococci (MRCNS; 42%) and high-level aminoglycoside-resistant enterococci (HLAR strains; 24.3%). Gram-negative bacteria were identified in 21.5% of positive cultures, including 30 strains (24%) from the Enterobacteriaceae family, with 13.3% of extended spectrum beta-lactamase producers [ESBL(+)]. Significant differences (P = .0012) were observed during the analysis of changes in the occurrence of Gram-positive bacteria isolated from the surgical site in the first week versus the second to the end of the fourth week. CONCLUSION: Gram-positive bacteria predominated as 78% of isolates.

Bacteria isolated from bile samples of liver recipients in the early period after transplantation: epidemiology and susceptibility of the bacterial strains.

OBJECTIVE: We estimated the frequency and susceptibility to antibacterial agents of bacterial isolates from bile samples obtained from 83 liver recipients in the early period after transplantation. PATIENTS AND METHODS: We prospectively collected data on 83 adult patients undergoing orthotopic liver transplantation (OLT), including bile samples taken during the first 30 days after OLT from adult liver recipients suspected to have bile infections. The isolation/identification of cultured bacteria was performed according to standard microbiological procedures and commercially available tests. Susceptibility of the strains to antibacterial agents was determined according to the Clinical and Laboratory Standards Institute (CLSI) guidelines. RESULTS: Among 210 bile samples obtained from 79 liver recipients, bacterial cultures were positive in 110 samples from 59 (75%) recipients yielding 156 bacterial strains. The most commonly isolated species were as follows: gram-positive cocci (109 isolates) with dominance of coagulase-negative staphylococci (52%) and enterococci (36%); and gram-negative bacteria, 21 strains from the Enterobacteriaceae family and 14 of non-fermenting rods. We identified some multidrug-resistant (MDR) bacterial strains. In the first week after OLT, we investigated samples from 59 patients, yielding 36 bacterial strains. From the second to the end of the fourth week after OLT, 120 bacterial strains were isolated from 65 recipients. CONCLUSION: Gram-positive bacteria comprised 68.5%. The dominance of MDR gram-positive bacteria may be related to selection by perioperative antibiotic prophylaxis.

Detection of Clostridium difficile in stool samples from patients in the early period after liver transplantation.

OBJECTIVE: We examined the frequency of detection of Clostridium difficile (CD) toxins compared with the recovery of C. difficile in stool specimen cultures among orthotopic liver transplant (OLT) patients with nosocomial diarrhea in the early period. MATERIALS AND METHODS: The study included stool samples obtained during the first 30 days after OLT in adults who were suspected of CD-associated diseases. The identification of cultured CD strains was performed by standard microbiological methods. The presence of CD toxins was assayed using a commercial immunoassay. RESULTS: All patients were followed prospectively for CD infections from the date of OLT for the first 4 weeks after surgery. Among 54 samples, 16.7% were culture-positive for CD. CD toxins were tested on 54 samples, yielding 63% toxin-positive samples and 30% toxin- and culture-negative results. In the first week after OLT, samples from 19 patients were subjected to CD investigation. Among 19 samples positive for toxin, 52.6% of all samples were culture-negative. We analyzed 35 samples from the second to the fourth week after OLT in 31 recipients. Among 35 samples, 68.6% and 25.7% were positive for CD toxin and for culture, while 20% of samples were negative for toxin and culture. CONCLUSION: In our study, 63% of samples were toxin-positive with 16.7% yielding growth of CD and 30% being negative for toxins and cultures.

Etiological agents of bacteremia in the early period after liver transplantation.

Bacteremia is one of the major infections in orthotopic liver transplantation (OLT). The study of 83 adults who underwent OLT from 2001 to 2004, included patients followed prospectively from the day of transplantation to 4 weeks after the procedure by bacteriological cultures. The microorganisms were investigated according to standard National Committee for Clinical Laboratory Standards (NCCLS) procedures. Blood samples were examined in 59 recipients (71.1%) before and in 76 patients (91.6%) during the month after transplantation. Among 249 investigated samples, 96 were positive, as cultured from 19 recipients before OLT and 48 patients afterward. The most common were Gram-positive cocci (n = 71) and coagulase-negative staphylococci (n = 52), including methicillin-resistant coagulase-negative staphylococci (MRCNS). Enterococcus spp. occurred in 9 isolates (high-level aminoglycoside-resistant enterococci [HLAR] strains were cultured). We cultured the Enterobacteriaceae family (n = 16 isolates) and (n = 15 isolates), Gram-negative nonfermenting rods some of which were extended spectrum beta-lactamase producing [ESBL(+)] strains. The predominance of Gram-positive cocci was caused by CNS, and the use of prophylaxis to reduce Gram-negative bacteria. The increased rate of isolation of bacteria with multidrug resistance (MDR) to antimicrobial agents may be due to their frequent use for prophylaxis of bacterial infections in OLT. These MDR bacterial strains caused severe BSI after OLT.

Emergence and spread of carbapenem-resistant strains of Acinetobacter baumannii in a tertiary-care hospital in Poland.

This study analysed the occurrence of carbapenem resistance among Acinetobacter baumannii isolates from a tertiary-care hospital in Poland, together with the molecular epidemiology of these isolates and the risk-factors for their acquisition and possible nosocomial spread. The medical charts of 21 patients with Acinetobacter infection or colonisation revealed that A. baumannii isolates were obtained most frequently from intensive care unit and surgical patients (particularly those receiving transplantation surgery). First isolation occurred, on average, on day 21 following admission (range 5-45 days). Infection with Acinetobacter contributed directly to the death of seven patients. Several patients were infected with more than one strain, and molecular typing revealed the co-circulation of three predominant clones, of which two belonged to the Acinetobacter lineages designated as European clones I and II. All three clones encoded an OXA-51-type carbapenemase, but were negative for carbapenemases belonging to the OXA-23, OXA-24 and OXA-58 families. The OXA-51 gene was found in both resistant and susceptible isolates, and was not associated directly with carbapenem resistance. Etests with imipenem and imipenem plus EDTA indicated production of a metallo-beta-lactamase (MBL) in carbapenem-resistant isolates. PCRs for IMP-type MBLs were negative, but PCR using consensus primers for VIM-type MBLs were positive for carbapenem-resistant isolates belonging to the European clone II lineage. The occurrence of a VIM-type MBL in association with one of the epidemic lineages of A. baumannii is a cause for concern. Further studies are needed to evaluate possible inter-hospital spread of resistant A. baumannii strains in Poland.

Enzymatic variability of Candida krusei isolates in a course of fungal infection in a liver transplant recipient.

Transplant recipients are at high risk of fungal infections. The main site of fungal infections in patients undergoing liver transplantation is the abdominal cavity. One factor determining the pathogenicity of fungi is their ability to secrete hydrolytic enzymes. The aim of this study was to assess the enzymatic activity of Candida krusei, which caused an infection in a liver transplant recipient. The clinical specimens included swabs of throat, nose, and two drains, as well as bile, stool, and abdominal cavity aspirate. The yeast-like fungi isolated were identified by an ID 32 C test (bioMérieux) and their enzymatic activity assayed with the use of an API-ZYM test. Two biotypes of C. krusei were identified, depending on the source of the clinical specimen. The C. krusei isolates cultured from a throat swab, a nasal swab, and one of the drains secreted esterase lipase C8 (enzyme IV) and valine arylamidase (enzyme VII), in contrast to those isolated from the bile, abdominal cavity fluid, another drain, and stool. Characterization of two biotypes of C. krusei isolates cultured from different clinical samples from several infection sites indicated an ability of C. krusei to adapt to variable environmental conditions.

Infection by a dimorphic fungus Sporothrix schenckii in an immunocompromised patient.

Infections caused by dimorphic fungi, rarely observed in a temperate climate, may cause chronic infections in immunocompromised patients. We describe a case of sporotrichosis in a 50-year-old woman, who underwent mastectomy due to breast carcinoma, followed by radiation and chemotherapy. She developed skin lesions, localized along the lymphatics. Discharge samples repeatedly yielded a characteristic growth of the dimorphic fungus Sporothrix schenckii. The isolate was resistant to all commonly used antifungal agents, except for itraconazole. Therapy with this antifungal agent resulted in disappearance of the clinical symptoms.

Outbreak of nosocomial meningitis caused by Acinetobacter baumannii in neurosurgical patients.

An outbreak of nosocomial meningitis caused by Acinetobacter baumannii, which developed postoperatively in seven neurosurgical patients is described. The clinical isolates of A. baumannii were typed by biochemical profiles and antibiogram patterns, and by random amplified polymorphic DNA polymerase chain reaction (RAPD-PCR) and amplified fragment length polymorphism (AFLP) fingerprinting. The implicated strain was multi-drug resistant, however, susceptibility to imipenem and netilmicin was detected. An extensive search for the environmental source of the epidemic strain was carried out. Two of several isolates from hospital environment, corresponded to the A. baumannii outbreak strain, one being cultured from the suctioning equipment used in the care of these patients. The introduction of multiresistant epidemic A. baumannii into a neurosurgical unit is a severe risk factor for patients undergoing neurosurgical procedures. Genotypic typing methods are important for definitive identification of these strains in patients and their environment.

Physiological effects of lactulose and inulin in the caecum of rats.

A model experiment was performed on rats to evaluate the effect of partial or total substitution of saccharose (S) and cellulose (C) by preparations of lactulose and inulin on the development and metabolism of the caecum. In the experimental diets given to rats for 4 weeks, the examined preparations were administered either with an equivalent amount of cellulose (each at 4% of the diet) or as sole source of dietary fibre at 8% of the diet. Compared to the saccharose group cellulose had no effect, and low doses of lactulose and inulin in the diet increased to a medium extent the weight of the caecum wall and caecal digesta. The addition of lactulose and inulin at 8% increased significantly the content of caecal digesta (4.62 and 4.11 g/100g BW, respectively) and the weight of the caecal wall (1.10 and 0.86 g/100g BW, respectively), compared to the groups with saccharose and cellulose (0.73, 0.90 and 0.24, 0.28 g/100g BW, respectively). Cellulose and cellulose partially-substituted with lactulose and inulin caused an increase in the dry matter content of caecal digesta (26.5-27.5%), compared to other groups (21.8-22.8%). The administration of lactulose and inulin preparations was accompanied by a significant drop in pH (5.47-5.81), compared to the groups with cellulose or saccharose (6.83-6.91), and a decrease in the ammonia concentration in the caecal digesta, compared to the cellulose control (0.27-0.40 and 0.62 mg/g, respectively). The group with 8% lactulose was characterized by the highest activities of microbiological alpha- and beta-galactosidase and beta-glucosidase in the caecal digesta. Cellulose and both preparations significantly decreased the activity of beta-glucuronidase, compared to the saccharose group (0.39-0.89 and 1.52 U/g, respectively). The highest concentration of VFA in the caecal digesta was observed in the saccharose group (89.2 micromol/g), and the lowest concentration in the group where cellulose was totally substituted by lactulose and inulin (55.1 and 57.5 micromol/g, respectively). The total production of VFA in the caecum was fourfold higher with 8 % lactulose and inulin (254.7 and 236.4 micromol/100g BW, respectively) than in both controls groups (65.1 and 67.8 micromol/100g BW, respectively). The high dose of inulin and lactulose increased the share of propionic acid in the VFA profile (C2:C3:C4) compared to both control groups. When 4% inulin was added to the diet a significant increase of butyrate concentration in the caecum was observed.

Mixed bloodstream infection with Staphylococcus aureus and Penicillium chrysogenum in an immunocompromised patient: case report and review of the literature.

We report a case of an immunocompromised patient who developed a mixed bacterial-fungal bloodstream infection involving Staphylococcus aureus and Penicillium chrysogenum. To date, no reports of such mixed bloodstream infection have been found.

Epidemiology and susceptibility to antifungal agents of fungi isolated from clinical specimens from patients hospitalized in the Department of General and Liver Surgery of the Medical University of Warsaw.

The aim of this study was to analyze the type and antibiotic susceptibility of fungi isolated from clinical specimens obtained from patients hospitalized in the Department of General, Transplantation and Liver Surgery of the Medical University of Warsaw between 2000 to 2002. Among the 326 clinical samples found to be positive on mycological culture, 356 strains were cultured. The most common isolates were yeastlike fungi of the genus Candida 334 (93.8%), while others included 33 other types (6.2%). The most commonly isolated species were Candida albicans, 194 strains (54.5%); Candida glabrata, 68 (19.1%); Candida krusei, 20 (5.6%); Candida inconspicua, 20 (5.6%); Candida tropicalis, 17 (4.8%); and Candida parapsilosis, 6 (1.7%). Upon testing for susceptibility to antifungal agents, all strains were susceptible to amphotericin B, while 43.8% of strains showed intermediate susceptibility to fluconazole and 25.3%, to itraconazole. Control of fungal infections in transplant and in immunocompromised patients is hindered by the low percentage of strains susceptible to commonly used antifungal agents, particularly of the triazole group.