Are intracystic chromogranin A and neuron-specific enolase useful in the diagnosis of cystic pancreatic neuroendocrine tumors?

Value of Choromogranin A and neuron-specific enolase intracystic (EUS-FNB) in the preoperatory diagnosis of cystic pancreatic neuroendocrine tumors.

CagA-ASPP2 complex mediates loss of cell polarity and favors H. pylori colonization of human gastric organoids.

The main risk factor for stomach cancer, the third most common cause of cancer death worldwide, is infection with Helicobacter pylori bacterial strains that inject cytotoxin-associated gene A (CagA). As the first described bacterial oncoprotein, CagA causes gastric epithelial cell transformation by promoting an epithelial-to-mesenchymal transition (EMT)-like phenotype that disrupts junctions and enhances motility and invasiveness of the infected cells. However, the mechanism by which CagA disrupts gastric epithelial cell polarity to achieve its oncogenicity is not fully understood. Here we found that the apoptosis-stimulating protein of p53 2 (ASPP2), a host tumor suppressor and an important CagA target, contributes to the survival of cagA-positive H. pylori in the lumen of infected gastric organoids. Mechanistically, the CagA-ASPP2 interaction is a key event that promotes remodeling of the partitioning-defective (PAR) polarity complex and leads to loss of cell polarity of infected cells. Blockade of cagA-positive H. pylori ASPP2 signaling by inhibitors of the EGFR (epidermal growth factor receptor) signaling pathway-identified by a high-content imaging screen-or by a CagA-binding ASPP2 peptide, prevents the loss of cell polarity and decreases the survival of H. pylori in infected organoids. These findings suggest that maintaining the host cell-polarity barrier would reduce the detrimental consequences of infection by pathogenic bacteria, such as H. pylori, that exploit the epithelial mucosal surface to colonize the host environment.

Invasive infections with Purpureocillium lilacinum: clinical characteristics and outcome of 101 cases from FungiScope® and the literature.

OBJECTIVES: To provide a basis for clinical management decisions in Purpureocillium lilacinum infection. METHODS: Unpublished cases of invasive P. lilacinum infection from the FungiScope® registry and all cases reported in the literature were analysed. RESULTS: We identified 101 cases with invasive P. lilacinum infection. Main predisposing factors were haematological and oncological diseases in 31 cases (30.7%), steroid treatment in 27 cases (26.7%), solid organ transplant in 26 cases (25.7%), and diabetes mellitus in 19 cases (18.8%). The most prevalent infection sites were skin (n = 37/101, 36.6%) and lungs (n = 26/101, 25.7%). Dissemination occurred in 22 cases (21.8%). Pain and fever were the most frequent symptoms (n = 40/101, 39.6% and n = 34/101, 33.7%, respectively). Diagnosis was established by culture in 98 cases (97.0%). P. lilacinum caused breakthrough infection in 10 patients (9.9%). Clinical isolates were frequently resistant to amphotericin B, whereas posaconazole and voriconazole showed good in vitro activity. Susceptibility to echinocandins varied considerably. Systemic antifungal treatment was administered in 90 patients (89.1%). Frequently employed antifungals were voriconazole in 51 (56.7%) and itraconazole in 26 patients (28.9%). Amphotericin B treatment was significantly associated with high mortality rates (n = 13/33, 39.4%, P = <0.001). Overall mortality was 21.8% (n = 22/101) and death was attributed to P. lilacinum infection in 45.5% (n = 10/22). CONCLUSIONS: P. lilacinum mainly presents as soft-tissue, pulmonary or disseminated infection in immunocompromised patients. Owing to intrinsic resistance, accurate species identification and susceptibility testing are vital. Outcome is better in patients treated with triazoles compared with amphotericin B formulations.

Significance of proximal ductal margin status after resection of hilar cholangiocarcinoma.

BACKGROUND: The impact of additional resection for positive proximal bile duct margins during hepatic resection of hilar cholangiocarcinoma (HCCA) on survival and disease progression remains unclear. We asked how re-resection of positive proximal bile duct margins affected outcomes. METHODS: Patients undergoing resection between 1993-2017 were reviewed. Both frozen section and final margin status were reviewed. Overall survival was the primary outcome. RESULTS: 153 patients underwent surgical resection for HCCA. Median survival (months) for initial margin negative (M-), margin-positive to margin-negative (M+/M-) and margin-positive to margin-positive (M+/M+) was 45, 33, and 35 months respectively. Nodal metastases increased with margin positivity: 32% with M-, 49% with M+/M- and 63% with M+/M+ (p = 0.016). Local/regional progression more frequently occurred in M+/M- (27.3%) and M+/M+ (33.3%) patients (M+/M- vs. M-: p = 0.41, M+/M+ vs. M-: p = 0.27). Patients receiving postoperative chemotherapy were 33% M-, 46% M+/M- and 63% in M+/M+. Postoperative radiation was used in 13% of M-, 31% of M+/M- and 63% of M+/M+. Most frequent initial recurrences were within the liver and hepaticojejunostomy site. CONCLUSION: Competing risk for systemic disease based on primary characteristics of HCCA outweighs the impact of re-resection to achieve R0 status. Improved survival will likely depend on future regional and systemic therapy.

Azole and Amphotericin B MIC Values against Aspergillus fumigatus: High Agreement between Spectrophotometric and Visual Readings Using the EUCAST EDef 9.3.2 Procedure.

The EUCAST EDef 9.3.2 procedure recommends visual readings of azole and amphotericin B MICs against Aspergillus spp. Visual determination of MICs may be challenging. In this work, we aim to obtain and compare visual and spectrophotometric MIC readings of azoles and amphotericin B against Aspergillus fumigatussensu lato isolates. A total of 847 A. fumigatussensu lato isolates (A. fumigatus sensu stricto [n = 828] and cryptic species [n = 19]) were tested against amphotericin B, itraconazole, voriconazole, posaconazole, and isavuconazole using the EUCAST EDef 9.3.2 procedure. Isolates were classified as susceptible or resistant/non-wild type according to the 2020 updated breakpoints. The area of technical uncertainty for the azoles was defined in the updated breakpoints. Visual and spectrophotometric (fungal growth reduction of >95% compared to the control, read at 540 nm) MICs were compared. Essential (±1 2-fold dilution) and categorical agreements were calculated. Overall, high essential (97.1%) and categorical (99.6%) agreements were found. We obtained 100% categorical agreements for amphotericin B, itraconazole, and posaconazole, and consequently, no errors were found. Categorical agreements were 98.7 and 99.3% for voriconazole and isavuconazole, respectively. Most of the misclassifications for voriconazole and isavuconazole were found to be associated with MIC results falling either in the area of technical uncertainty or within one 2-fold dilution above the breakpoint. The resistance rate was slightly lower when the MICs were obtained by spectrophotometric readings. However, all relevant cyp51A mutants were correctly classified as resistant. Spectrophotometric determination of azole and amphotericin B MICs against A. fumigatussensu lato isolates may be a convenient alternative to visual endpoint readings.

Emergent pancreatectomy for neoplastic disease: outcomes analysis of 534 ACS-NSQIP patients.

BACKGROUND: While emergent pancreatic resection for trauma has been previously described, no large contemporary investigations into the frequency, indications, and outcomes of emergent pancreatectomy (EP) secondary to complications of neoplastic disease exist. Modern perioperative outcomes data are currently unknown. METHODS: ACS-NSQIP was reviewed for all non-traumatic pancreatic resections (DP - distal pancreatectomy, PD - pancreaticoduodenectomy, or TP- total pancreatectomy) in patients with pancreatico-biliary or duodenal-ampullary neoplasms from 2005 to 2013. Patients treated for complications of pancreatitis were specifically excluded. Emergent operation was defined as NSQIP criteria for emergent case and one of the following: ASA Class 5, preoperative ventilator dependency, preoperative SIRS, sepsis, or septic shock, or requirement of > 4 units RBCs in 72 h prior to resection. Chi-square tests, Fisher's exact tests were performed to compare postoperative outcomes between emergent and elective cases as well as between pancreatectomy types. RESULTS: Of 21,452 patients who underwent pancreatectomy for neoplastic indications, we identified 534 (2.5%) patients who underwent emergent resection. Preoperative systemic sepsis (66.3%) and bleeding (17.9%) were most common indications for emergent operation. PD was performed in 409 (77%) patients, DP in 115 (21%), and TP in 10 (2%) patients. Overall major morbidity was significantly higher (46.1% vs. 25.6%, p < 0.001) for emergent vs. elective operations. Emergent operations resulted in increased transfusion rates (47.6% vs. 23.4%, p < 0.001), return to OR (14.0% vs. 5.6%, p < 0.001), organ-space infection (14.6 vs. 10.5, p = 0.002), unplanned intubation (9.% vs. 4.1%, p < 0.001), pneumonia (9.6% vs. 4.2%, p < 0.001), length of stay (14 days vs. 8 days, p < 0.001), and discharge to skilled facility (31.1% vs. 13.9%). These differences persisted when stratified by pancreatic resection type. The 30-day operative mortality was higher in the emergent group (9.4%vs. 2.7%, p < 0.001) and highest for emergent TP (20%). CONCLUSION: Emergent pancreatic resection is markedly uncommon in the setting of neoplastic disease. Although these operations result in increased morbidity and mortality compared to elective resections, they can be life-saving in specific circumstances. The results of this large series of modern era national data may assist surgeons as well as patients and their families in making critical decisions in select cases of acutely complicated neoplastic disease.

Pharmacological Profile of AZD8871 (LAS191351), a Novel Inhaled Dual M3 Receptor Antagonist/ß 2-Adrenoceptor Agonist Molecule with Long-Lasting Effects and Favorable Safety Profile.

AZD8871 is a novel muscarinic antagonist and ß 2-adrenoceptor agonist in development for chronic obstructive pulmonary disease. This study describes the pharmacological profile of AZD8871 in in vitro and in vivo assays. AZD8871 is potent at the human M3 receptor (pIC50 in binding assays: 9.5) and shows kinetic selectivity for the M3 (half-life: 4.97 hours) over the M2 receptor (half-life: 0.46 hour). It is selective for the ß 2-adrenoceptor over the ß 1 and ß 3 subtypes (3- and 6-fold, respectively) and shows dual antimuscarinic and ß 2-adrenoceptor functional activity in isolated guinea pig tissue (pIC50 in electrically stimulated trachea: 8.6; pEC50 in spontaneous tone isolated trachea: 8.8, respectively), which are sustained over time. AZD8871 exhibits a higher muscarinic component than batefenterol in human bronchi, with a shift in potency under propranolol blockade of 2- and 6-fold, respectively, together with a persisting relaxation (5.3% recovery at 8 hours). Nebulized AZD8871 prevents acetylcholine-induced bronchoconstriction in both guinea pig and dog with minimal effects on salivation and heart rate at doses with bronchoprotective activity. Moreover, AZD8871 shows long-lasting effects in dog, with a bronchoprotective half-life longer than 24 hours. In conclusion, these studies demonstrate that AZD8871 is a dual-acting molecule with a high muscarinic component and a long residence time at the M3 receptor; moreover, its preclinical profile in animal models suggests a once-daily dosing in humans and a favorable safety profile. Thus, AZD8871 has the potential to be a next generation of inhaled bronchodilators in respiratory diseases.

Comparison between Vitek MS, Bruker Biotyper, Vitek2, and API20E for differentiation of species of the genus Raoultella.

Rapid and reliable identification of microorganisms in the clinical laboratory is essential for an early and accurate diagnosis guiding timely therapy. However, conventional methods are sometimes unreliable and show controversial outcomes. Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) has been reported as a rapid and reliable method for identification of bacteria and fungi isolated from clinical samples. Members of the genus Raoultella are increasingly recognized as clinically relevant. There are difficulties in their identification at the species level since sequencing the 16S rRNA or the rpoB genes does not show conclusive results. The aim of this study has been to compare two MALDI-TOF MS systems (Vitek MS and Bruker Biotyper) with Vitek2 and API20E systems for differentiation of Raoultella species. A collection of 97 clinical isolates of Raoultella species was identified with Vitek MS, in parallel with Vitek2 and API, and finally with Bruker Biotyper. Among the two most widely used MALDI-TOF MS platforms, results obtained with Vitek MS were slightly superior to those obtained with the Bruker Biotyper system, with sensitivities and specificities of 98.9/57.9% and 98.8/37.0%, respectively. The current commercial phenotypic identification systems are not optimized for the identification of Raoultella species. Our results indicate that MALDI-TOF-based identification is more accurate and sensitive than that provided by phenotypic methods.

Platelet-Rich Plasma as a Treatment for Androgenetic Alopecia.

BACKGROUND: Platelet-rich plasma (PRP) treatment may encourage hair growth by promoting cellular maturation, differentiation, and proliferation. OBJECTIVE: The objective of this study was to evaluate the effectiveness of PRP as a treatment for androgenetic alopecia (AGA). MATERIALS AND METHODS: A literature search combined with meta-analysis was used to calculate the overall standardized mean difference (SMD) in hair density in patients treated with PRP injections in comparison with baseline and placebo treatment. Chi squared analysis and Fisher exact test were used to investigate variation in protocols. RESULTS: The overall SMD in hair density was 0.58 (95% confidence interval [CI]: 0.35-0.80) and 0.51 (95% CI: 0.23-0.80, p < .0004) in favor of PRP treatment when compared with baseline and placebo treatment, respectively. CONCLUSION: Platelet-rich plasma is beneficial in the treatment of AGA. It is recommended that 3 monthly sessions of PRP (once monthly ×3 treatments) be used followed by a 3- to 6-month maintenance period.

Comparison of the Vitek MS and Bruker Matrix-Assisted Laser Desorption Ionization-Time of Flight Mass Spectrometry Systems for Identification of Rhodococcus equi and Dietzia spp.

Rhodococcus equi causes pyogranulomatous pneumonia in domesticated animals and immunocompromised humans. Dietzia spp. are environmental bacteria that have rarely been associated with human infections. R. equi and Dietzia spp. are closely related actinomycetes. Phenotypic discrimination between R. equi and Dietzia on the basis of their Gram stain morphology and colony appearance is problematic. Matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) is a fast, reliable, and cost-effective method for identification of a wide variety of microorganisms. We have evaluated the performance of Bruker Biotyper versus that of Vitek MS for identification of a collection of 154 isolates identified at the source as R. equi that includes isolates belonging to the genus Dietzia PCR amplification of the choE gene, encoding a cholesterol oxidase, and 16S rRNA sequencing were considered the reference methods for R. equi identification. Biotyper identified 131 (85.1%) of the 154 isolates at the species level, and this figure increased to 152 (98.7%) when the species cutoff was reduced from a score of ≥2.000 to ≥1.750. Vitek MS correctly identified at the species level 130 (84.4%) isolates as long as bacteria were extracted with ethanol but only 35 (22.7%) isolates when samples were prepared by direct extraction from colonies. The two systems allowed differentiation between R. equi and Dietzia spp., but identification of all Dietzia sp. isolates at the species level needed sequencing of the 16S rRNA gene.

National Trends in the Use of Neoadjuvant Chemotherapy for Hormone Receptor-Negative Breast Cancer: A National Cancer Data Base Study.

BACKGROUND: Neoadjuvant chemotherapy (NAC) downstages tumor size and nodal disease. This study evaluates national practice patterns of NAC use in hormone receptor-negative breast cancer. METHODS: We identified patients in the National Cancer Data Base (NCDB) with hormone receptor-negative invasive breast cancer (2004-2012). Univariate and multivariable logistic regression was used to assess associations and trends across time. RESULTS: Of 171,985 patients, 130,723 (76.0%) received chemotherapy and 41,262 (24.0%) did not. Chemotherapy use was higher in young patients and higher T- and N-stage disease (all p < 0.001). Of those patients treated with chemotherapy, 23,165 (17.7%) received NAC and 107,558 (82.3%) received adjuvant chemotherapy (AC). NAC use increased from 2004 to 2012 (13.0-23.5%; adjusted odds ratio [aOR] 1.42; p < 0.001). Higher clinical T stage (ORs 3.63, 11.81, and 22.34 for cT2, cT3, and cT4a-c, respectively, vs. cT1) and cN+ disease (OR 2.86) [each p < 0.001] were associated with NAC, as were younger patient age and better Charlson-Deyo comorbidity score. Furthermore, BCS rate was higher in the NAC group in cT2 and cT3 tumors (aOR 1.17 and 1.45, respectively; both p < 0.001). In patients with cN+ disease, NAC converted 43.7% to pN0. Less extensive axillary surgery (one to five nodes removed) was more likely in cN+ patients treated with NAC (aOR 1.66; p < 0.001). CONCLUSIONS: In hormone receptor-negative breast cancer, chemotherapy was mostly administered adjuvantly, but neoadjuvant use increased over time and was more likely in younger patients and higher T- and N-stage disease. Node-positive patients treated with NAC were less likely to have pathologically positive nodes and more likely to have less extensive axillary surgery.

Pharmacological preclinical characterization of LAS190792, a novel inhaled bifunctional muscarinic receptor antagonist /ß2-adrenoceptor agonist (MABA) molecule.

LAS190792 is a novel muscarinic antagonist and ß2-adrenoceptor agonist in development for chronic respiratory diseases. This study investigated the pharmacological profile of LAS190792 in comparison to batefenterol, tiotropium, indacaterol and olodaterol. LAS190792 is potent at the human M3 receptor (pIC50: 8.8 in binding assays). It is selective for the ß2-adrenoceptor over the ß1-and ß3-adrenoceptor, and shows a functional potency in a similar range to batefenterol and LABA compounds (pEC50 in spontaneous tone isolated trachea: 9.6). The relaxant potency of LAS190792 in electrically stimulated tissue is similar to batefenterol, with an antimuscarinic activity in presence of propranolol slightly higher than batefenterol (pIC50 of 8.3 versus 7.9 in human tissue). LAS190792 exhibits a sustained duration of action in isolated tissue longer than that of batefenterol. Nebulized LAS190792 inhibits acetylcholine-induced bronchoconstriction in dog with minimal cardiac effects and sustained bronchodilation (t1/2: 13.3 h). In conclusion, these studies suggest that LAS190792 is a dual-acting muscarinic antagonist ß2-adrenoceptor agonist that has the potential to be a next generation bronchodilator with long-lasting effects and wide safety margin in humans.

Double-Blind, Placebo-Controlled Pilot Study on the Use of Platelet-Rich Plasma in Women With Female Androgenetic Alopecia.

BACKGROUND: Platelet-rich plasma (PRP) has been suggested as a therapeutic intervention for female androgenetic alopecia. OBJECTIVE: To perform a pilot study on the effect of PRP scalp injections in women with female androgenetic alopecia. MATERIALS AND METHODS: This double-blind, multicenter, placebo-controlled study compared the effect of PRP with that of saline placebo as scalp injection. The endpoints were hair count and hair mass index (HMI), along with patient-opinion survey responses. Platelet-rich plasma was manufactured from patients' blood using the Angel PRP system. RESULTS: Hair mass index or hair count did not statistically significantly differ between the study and placebo groups. However, 13.3% of the treatment subjects (vs 0% of the placebo subjects) experienced substantial improvement in hair loss, rate of hair loss, hair thickness, and ease of managing/styling hair, and 26.7% (vs 18.2% of the placebo group) reported that their hair felt coarser or heavier after the treatment. CONCLUSION: Platelet-rich plasma failed to demonstrate any statistically significant improvement in HMI or hair count in women with congenital female pattern hair loss. The patient survey results suggest a therapeutic advantage of PRP as perceived by patients but not according to hair count or HMI.

More isn't always better: antibiotic duration after surgical decortication in pleural empyema.

Background: While ample high-level evidence supports the limited use of antibiotics post-source control in intraabdominal infections, there is a paucity of available data in guiding antibiotic duration for intrathoracic infections. This study aims to analyze patient outcomes among those who have undergone surgical decortication for parapneumonic pleural empyema, comparing cases managed with infectious disease (ID) specialists against those without, and to identify predictive factors influencing antibiotic duration post-source control. We hypothesized that antibiotic duration would vary depending on the involvement of ID specialists. Methods: A retrospective chart review was completed on patients with parapneumonic pleural empyemas who underwent surgical decortication at a single tertiary center from January 2011 to March 2021. Differences in patient characteristics and outcomes for those whose antibiotics were managed by ID or not were compared with Wilcoxon two-sample tests and Fisher's exact tests. Linear regression was used to evaluate for significant factors predictive of antibiotic duration. Results: A total of 116 patients underwent surgical decortication for pleural empyema of parapneumonic etiology. ID specialists were involved with antibiotic management in 62 (53.4%) cases, while the remaining cases were not managed by ID. Demographics and patient comorbidities were similar between both groups. Growth of preoperative fluid cultures was higher in patients managed by ID (40.3% vs. 20.4%, P=0.03). Postoperatively, patients managed by ID had longer durations of antibiotics (28.7 vs. 20.9 days, P<0.001) and were more likely to be on IV antibiotics than patients not managed by ID (59.7% vs. 38.9%, P=0.04). However, postoperative outcomes were similar, including rates of disease recurrence, readmission, and 30-day mortality. Linear regression revealed length of antibiotics was significantly dependent on preoperative ventilator status [estimate: 16.346; 95% confidence interval (CI): 6.365-26.326; P=0.002], growth of preoperative pleural fluid cultures (estimate: 10.203; 95% CI: 2.502-17.904; P=0.01), and ID involvement (estimate: 8.097; 95% CI: 1.003-15.191; P=0.03). Conclusions: Antibiotic duration for pleural empyema managed with surgical decortication is significantly dependent on ID involvement, preoperative growth of cultures, and preoperative ventilator status. However, outcomes, including disease recurrence and 30-day mortality, were similar between patients regardless of ID involvement and longer length of antibiotics, raising the question of what the adequate duration of antibiotics is for patients who receive appropriate source control for pleural empyema. Further study with randomized control trials should be conducted to provide high-level evidence regarding length of antibiotics in this patient population.

Emergent Esophagectomy in Patients with Esophageal Malignancy Is Associated with Higher Rates of Perioperative Complications but No Independent Impact on Short-Term Mortality.

Background: Data on perioperative outcomes of emergent versus elective resection in esophageal cancer patients requiring esophagectomy are lacking. We investigated whether emergent resection was associated with increased risks of morbidity and mortality. Methods: Data on patients with esophageal malignancy who underwent esophagectomy from 2005 to 2020 were retrospectively analyzed from the American College of Surgeons National Surgical Quality Improvement Program database. Thirty-day complication and mortality rates were compared between emergent esophagectomy (EE) and non-emergent esophagectomy. Logistic regression assessed factors associated with complications and mortality. Results: Of 10,067 patients with malignancy who underwent esophagectomy, 181 (1.8%) had EE, 64% had preoperative systemic inflammatory response syndrome, sepsis, or septic shock, and 44% had bleeding requiring transfusion. The EE group had higher American Society of Anesthesiologists (ASA) class and functional dependency. More transhiatal esophagectomies and diversions were performed in the EE group. After EE, the rates of 30-day mortality (6.1% vs. 2.8%), overall complications (65.2% vs. 44.2%), bleeding, pneumonia, prolonged intubation, and positive margin (17.7% vs. 7.4%) were higher, while that of anastomotic leak was similar. On adjusted logistic regression, older age, lower albumin, higher ASA class, and fragility were associated with increased complications and mortality. McKeown esophagectomy and esophageal diversion were associated with a higher risk of postoperative complications. EE was associated with 30-day postoperative complications (odds ratio, 2.39; 95% confidence interval, 1.66-3.43; p<0.0001). Conclusion: EE was associated with a more than 2-fold increase in complications compared to elective procedures, but no independent increase in short-term mortality. These findings may help guide data-driven critical decision-making for surgery in select cases of complicated esophageal malignancy.

Identification and antifungal susceptibility testing of Candida haemulonii complex isolated from clinical samples.

Candida haemulonii complex (Candida haemulonii [I], Candida duobushaemulonii [II], and Candida haemulonii var. vulnera [III]) has become relevant in recent times, not so much because of a high incidence in human clinical sample cultures but because of its remarkable antifungal resistance. The objective of this study was to evaluate several methods for the identification of this uncommon species of Candida. Ten isolates of C. haemulonii were identified by biochemical and proteomic methods, and their antifungal susceptibility testing was performed by both commercial and reference methods. MALDI-TOF MS (Vitek MS and Vitek MS PRIME) and Vitek2 correctly identified these genera but API method did not. There was a good correlation between the commercial methods and the reference methods for the AST. In conclusion Vitek MS, Vitek MS PRIME, and Vitek2 systems, but not API32C, are reliable for identification of C. haemulonii complex. Furthermore, MALDI-TOF MS systems could identify to the subspecies level. Commercial methods for antifungal susceptibility testing are valid for the study of this species and confirm amphotericin B and to azole resistance.

Efficacy and safety of a structured de-escalation from antipseudomonal ß-lactams in bloodstream infections due to Enterobacterales (SIMPLIFY): an open-label, multicentre, randomised trial.

BACKGROUND: De-escalation from broad-spectrum to narrow-spectrum antibiotics is considered an important measure to reduce the selective pressure of antibiotics, but a scarcity of adequate evidence is a barrier to its implementation. We aimed to determine whether de-escalation from an antipseudomonal ß-lactam to a narrower-spectrum drug was non-inferior to continuing the antipseudomonal drug in patients with Enterobacterales bacteraemia. METHODS: An open-label, pragmatic, randomised trial was performed in 21 Spanish hospitals. Patients with bacteraemia caused by Enterobacterales susceptible to one of the de-escalation options and treated empirically with an antipseudomonal ß-lactam were eligible. Patients were randomly assigned (1:1; stratified by urinary source) to de-escalate to ampicillin, trimethoprim-sulfamethoxazole (urinary tract infections only), cefuroxime, cefotaxime or ceftriaxone, amoxicillin-clavulanic acid, ciprofloxacin, or ertapenem in that order according to susceptibility (de-escalation group), or to continue with the empiric antipseudomonal ß-lactam (control group). Oral switching was allowed in both groups. The primary outcome was clinical cure 3-5 days after end of treatment in the modified intention-to-treat (mITT) population, formed of patients who received at least one dose of study drug. Safety was assessed in all participants. Non-inferiority was declared when the lower bound of the 95% CI of the absolute difference in cure rate was above the -10% non-inferiority margin. This trial is registered with EudraCT (2015-004219-19) and ClinicalTrials.gov (NCT02795949) and is complete. FINDINGS: 2030 patients were screened between Oct 5, 2016, and Jan 23, 2020, of whom 171 were randomly assigned to the de-escalation group and 173 to the control group. 164 (50%) patients in the de-escalation group and 167 (50%) in the control group were included in the mITT population. 148 (90%) patients in the de-escalation group and 148 (89%) in the control group had clinical cure (risk difference 1·6 percentage points, 95% CI -5·0 to 8·2). The number of adverse events reported was 219 in the de-escalation group and 175 in the control group, of these, 53 (24%) in the de-escalation group and 56 (32%) in the control group were considered severe. Seven (5%) of 164 patients in the de-escalation group and nine (6%) of 167 patients in the control group died during the 60-day follow-up. There were no treatment-related deaths. INTERPRETATION: De-escalation from an antipseudomonal ß-lactam in Enterobacterales bacteraemia following a predefined rule was non-inferior to continuing the empiric antipseudomonal drug. These results support de-escalation in this setting. FUNDING: Plan Nacional de I+D+i 2013-2016 and Instituto de Salud Carlos III, Subdirección General de Redes y Centros de Investigación Cooperativa, Ministerio de Ciencia, Innovación y Universidades, Spanish Network for Research in Infectious Diseases; Spanish Clinical Research and Clinical Trials Platform, co-financed by the EU; European Development Regional Fund "A way to achieve Europe", Operative Program Intelligence Growth 2014-2020.

Virulence genes of Aeromonas spp. isolates from stool in Spain.

INTRODUCTION: The role of Aeromonas species in gastrointestinal disease is controversial. The aim was to analyze not only the virulence genes between different species of Aeromonas isolated from feces, but the distribution of these virulence genes between enterotoxigenic strains and co-pathogen strains. METHODS: Retrospective study of isolates of Aeromonas spp. in feces (2016-2021). The protocol included coproculture, identification by MALDI-TOF and confirmation by multiplex PCR. SPSS Statistics program was used. RESULTS: A total of 288 strains were studied for the virulence genes between different species of Aeromonas. To compare virulence genes between Aeromonas as co-pathogen and those isolated alone, 218 strains of the global set were used; 52 as co-pathogens compared with 166 Aeromonas without associated pathogen as controls. CONCLUSIONS: We found no significant differences in the distribution of virulence genes versus co-existence of co-pathogens or not. A. hydrophila is the potentially most virulent species of our set.

Characterization, antifungal susceptibility and virulence of Candida parapsilosis complex isolates in a tertiary hospital in Cantabria, Northern Spain.

INTRODUCTION: The correct identification of the species within the Candida parapsilosis complex has become relevant due to the resistance of Candida metapsilosis to antifungals. We describe the characteristics of the Candida parapsilosis complex isolates, with respect to antifungal resistance and biofilm formation. METHODS: We perform a descriptive cross-sectional study in 30 strains, collected in a tertiary hospital. All strains, were identified by Vitek2, Vitek-MS™ systems and by ITS sequencing. The antifungal susceptibility profile was obtained with Sensititre™ panels, while biomass production and metabolic activity were quantified by means of crystal violet and XTT reduction assay, respectively. RESULTS: There was a 100% correlation between Vitek-MS™ and ITS sequencing. All isolates were susceptible to the nine antifungals tested. The metabolic activity and biomass production tests did not show any difference among the subtypes. CONCLUSIONS: The Vitek-MS™ system provides acceptable identification. We did not find significant differences neither in azole resistance nor in biofilm formation.

Outbreak of Arcobacter butzleri? An emerging enteropathogen.

BACKGROUND: Arcobacter butzleri is a gram-negative rod, with microaerobic growth at an optimal temperature of 37°C. It was reported to be the fourth most common Campylobacter-like organism isolated from patients with diarrhoea. OBJECTIVE: Characterise a potential outbreak of A. butzleri detected in a short period of time in the University Hospital Marqués de Valdecilla. METHODS: Eight strains of A. butzleri were detected in our hospital in only two months. Isolates were identified by MALDI-TOF MS system and 16S rDNA sequencing. Enterobacterial repetitive intergenic consensus-PCR (ERIC-PCR) and Pulsed Field Gel Electrophoresis (PFGE) were carried out to assess clonal relationship. Gradient strips (Etest) were used to determine susceptibility by agar diffusion. RESULTS: ERIC-PCR and PFGE confirmed the lack of clonal relationship between strains. Erythromycin or ciprofloxacin might be appropriate for antibiotic treatment of infections. CONCLUSIONS: A. butzleri is an emerging pathogen with increasing incidence, and may be underestimated.