Impact of suppression of the SOS response on protein expression in clinical isolates of Escherichia coli under antimicrobial pressure of ciprofloxacin.

Introduction/objective: Suppression of the SOS response in combination with drugs damaging DNA has been proposed as a potential target to tackle antimicrobial resistance. The SOS response is the pathway used to repair bacterial DNA damage induced by antimicrobials such as quinolones. The extent of lexA-regulated protein expression and other associated systems under pressure of agents that damage bacterial DNA in clinical isolates remains unclear. The aim of this study was to assess the impact of this strategy consisting on suppression of the SOS response in combination with quinolones on the proteome profile of Escherichia coli clinical strains. Materials and methods: Five clinical isolates of E. coli carrying different chromosomally- and/or plasmid-mediated quinolone resistance mechanisms with different phenotypes were selected, with E. coli ATCC 25922 as control strain. In addition, from each clinical isolate and control, a second strain was created, in which the SOS response was suppressed by deletion of the recA gene. Bacterial inocula from all 12 strains were then exposed to 1xMIC ciprofloxacin treatment (relative to the wild-type phenotype for each isogenic pair) for 1 h. Cell pellets were collected, and proteins were digested into peptides using trypsin. Protein identification and label-free quantification were done by liquid chromatography-mass spectrometry (LC-MS) in order to identify proteins that were differentially expressed upon deletion of recA in each strain. Data analysis and statistical analysis were performed using the MaxQuant and Perseus software. Results: The proteins with the lowest expression levels were: RecA (as control), AphA, CysP, DinG, DinI, GarL, PriS, PsuG, PsuK, RpsQ, UgpB and YebG; those with the highest expression levels were: Hpf, IbpB, TufB and RpmH. Most of these expression alterations were strain-dependent and involved DNA repair processes and nucleotide, protein and carbohydrate metabolism, and transport. In isolates with suppressed SOS response, the number of underexpressed proteins was higher than overexpressed proteins. Conclusion: High genomic and proteomic variability was observed among clinical isolates and was not associated with a specific resistant phenotype. This study provides an interesting approach to identify new potential targets to combat antimicrobial resistance.

Dynamic Workflow Proposal for Continuous Frameless Electromagnetic Neuronavigation in Rigid Neuroendoscopy.

BACKGROUND: Ventriculoscopic neuronavigation has been described in several papers. However, there are different ventriculoscopes and navigation systems. Due to these different combinations, it is difficult to find detailed neuronavigation protocols. We describe, step-by-step, a simple method to navigate both the trajectory until reaching the ventricular system, as well as the intraventricular work. METHODS: We use a rigid ventriculoscope (LOTTA, KarlStorz) with an EM-stylet (S8-StealthSystem, Medtronic). The protocol is based on a modified or 3D-printed trocar for navigating the extraventricular step and on a modified pediatric nasogastric tube for the intraventricular navigation. RESULTS: This protocol can be set-up in less than 10 minutes. The extraventricular part is navigated by introducing the EM-stylet inside the modified or 3D-printed trocar. Intraventricular navigation is done by combining a modified pediatric nasogastric tube with the EM-stylet inside the endoscope's working channel. The most critical point is to obtain a blunt-bloodless ventriculostomy while achieving perfect alignment of all targeted structures via pure straight trajectories. CONCLUSIONS: This protocol is easy-to-set-up, avoids head rigid-fixation and bulky optical-based attachments to the ventriculoscope, and allows continuous navigation of both parts of the surgery. Since we have implemented this protocol, we have noticed a significant enhancement in both simple and complex ventriculoscopic procedures because the surgery is dramatically simplified.

First Report of the Emerging Pathogen Kodamaea ohmeri in Honduras.

Kodamaea ohmeri is an environmental yeast considered a rare emerging pathogen. In clinical settings, the correct identification of this yeast is relevant because some isolates are associated with resistance to antifungals. There is a lack of available data regarding the geographical distribution, virulence, and drug resistance profile of K. ohmeri. To contribute to the knowledge of this yeast, this study aimed to describe in depth three isolates of K. ohmeri associated with fungemia in Honduras. The identification of the isolates was carried out by sequencing the ribosomal ITS region. In addition, the susceptibility profile to antifungals was determined, and some properties associated with virulence were evaluated (exoenzyme production, biofilm formation, cell adhesion, and invasion). The isolates showed strong protease, phospholipase, and hemolysin activity, in addition to being biofilm producers. Adherence and invasion capacity were evident in the HeLa and Raw 264.7 cell lines, respectively. This study expands the understanding of the underlying biological traits associated with virulence in K. ohmeri, and it is the first report of the detection and identification of K. ohmeri in Honduras as a cause of human infection.

Differences between GH and PRL co-secreting and GH-secreting pituitary adenomas. A series of 604 cases.

PURPOSE: To evaluate differences in clinical presentation and in surgical outcomes between growth hormone-secreting pituitary adenomas (GH-PAs) and GH and prolactin co-secreting pituitary adenomas (GH&PRL-PAs). METHODS: Multicenter retrospective study of 604 patients with acromegaly submitted to pituitary surgery. Patients were classified into two groups according to serum PRL levels at diagnosis and immunohistochemistry (IHC) for PRL: a) GH&PRL-PAs when PRL levels were above the upper limit of normal and IHC for GH and PRL was positive or PRL levels were >100ng/and PRL IHC was not available (n=130) and b) GH-PAs who did not meet the previously mentioned criteria (n=474). RESULTS: GH&PRL-PAs represented 21.5% (n=130) of patients with acromegaly. The mean age at diagnosis was lower in GH&PRL-PAs than in GH-PAs (P<0.001). GH&PRL-PAs were more frequently macroadenomas (90.6% vs. 77.4%, P=0.001) and tended to be more invasive (33.6% vs. 24.7%, P=0.057) than GH-PAs. Furthermore, they had presurgical hypopituitarism more frequently (OR 2.8, 95% CI 1.83-4.38). IGF-1 upper limit of normality (ULN) levels at diagnosis were lower in patients with GH&PRL-PAs (median 2.4 [IQR 1.73-3.29] vs. 2.7 [IQR 1.91-3.67], P=0.023). There were no differences in the immediate (41.1% vs 43.3%, P=0.659) or long-term post-surgical acromegaly biochemical cure rate (53.5% vs. 53.1%, P=0.936) between groups. However, there was a higher incidence of permanent arginine-vasopressin deficiency (AVP-D) (7.3% vs. 2.4%, P=0.011) in GH&PRL-PAs patients. CONCLUSIONS: GH&PRL-PAs are responsible for 20% of acromegaly cases. These tumors are more invasive, larger and cause hypopituitarism more frequently than GH-PAs and are diagnosed at an earlier age. The biochemical cure rate is similar between both groups, but patients with GH&PRL-PAs tend to develop permanent postsurgical AVP-D more frequently.

Assessing Ecogeographic Rules in Two Sigmodontine Rodents along an Elevational Gradient in Central Chile.

Bergmann's and Allen's rules are two classic ecogeographic rules concerning the physiological mechanisms employed by endotherm vertebrates for heat conservation in cold environments, which correlate with adaptive morphological changes. Thus, larger body sizes (Bergmann's rule) and shorter appendages and limbs (Allen's rule) are expected in mammals inhabiting cold environments (higher latitudes). Both rules may also apply to elevational gradients, due to the decrease in external temperature as elevation increases. In this study, we evaluated whether these patterns were true in two coexisting sigmodontine rodents across an elevational gradient in central Chile. We analyzed whether the size of the skull, body, and appendages of Abrothrix olivacea (n = 70) and Phyllotis darwini (n = 58) correlated with elevation, as predicted by these rules in a range between 154 and 2560 m. Our data revealed weak support for the Bergmann and Allen predictions. Moreover, we observed opposite patterns when expectations of Bergmann's rules were evaluated, whereas Allen's rule just fitted for ear size in both rodent species. Our results suggest that morphological changes (cranial, body, and appendage sizes) may play a minor role in the thermoregulation of these two species at high elevations, although behavioral strategies could be more critical. Other ecological and environmental variables could explain the morphological trends observed in our study. These hypotheses should be assessed in future studies to consider the relative contribution of morphology, behavior, and physiological mechanisms to the thermal adaptation of these two rodent species at high elevations.

Goos-Hänchen shift for coupled vibrational modes in a semiconductor structure.

We present a theoretical investigation of the Goos-Hänchen shift (GHS) experienced by acoustic and optical vibrational modes reflected and transmitted from the surfaces of a semiconductor thin film sandwiched between two semi-infinite media. Our study focuses on the impact of the incident angle on the GHS, considering the coupling between longitudinal and transverse modes. For acoustic vibrations, our findings reveal that the GHS can reach magnitudes up to 7 times larger than the thickness of the thin film and up to 20 times larger than the incident wavelength. Besides, it is shown that this significant amplification of the GHS highlights the strong influence of the incident angle and the frequency of the modes involved. In the case of optical vibrations, we observe even more pronounced GHS values, exceeding 30 times the incident wavelength. This demonstrates the potential of GHS in acoustical systems, which opens up possibilities for applications in the design of acoustic devices. .

Transcortical transcatheter ultrasound-assisted technique for deep-seated brain tumors. Technical note.

PURPOSE: Surgery of deep-seated brain tumors can be challenging. Several methods have been described to facilitate transcortical approaches, including ultrasound-assisted resection. Ultrasound-guided placement of a standard ventricular catheter is a widely reported technique and has been used to approach these lesions via the transcortical route. We describe how we usually perform this useful technique to assist and enhance the transcortical resection of some deep-seated brain tumors. METHODS: Standard electromagnetic frameless navigation (S8 Neuronavigation System, Medtronic, Minneapolis, USA) was employed to focus the craniotomy and to plan the trajectory of the ventricular catheter. After dural opening, an ultrasound device (Arietta 850, Hitachi-Aloka Medical, Tokyo, Japan) was used for intraoperative ultrasound (IOUS) assessment. A ventricular catheter was placed from the cortex to the lateral wall of the tumor under direct real-time IOUS visualization to guide the further transcortical dissection. RESULTS: Transcortical transcatheter ultrasound-assisted technique involved minimal time and infrastructure requirements. There were no major technical difficulties during its use, providing confidence and improving subcortical white matter dissection by guiding the route to the tumor. CONCLUSIONS: Recent improvement of IOUS image-quality devices offers several attractive options for real-time navigation. The combination of conventional neuronavigation systems with real-time IOUS assessment during the intradural step provides a higher degree of control by improving the execution of the surgery. We hope this description may be a useful tool for some selected cases and contribute to the further enhancement and improvement of this widely used technique.

Immunological Cross-Reactivity and Preclinical Assessment of a Colombian Anticoral Antivenom against the Venoms of Three Micrurus Species.

Snakebite accident treatment requires the administration of antivenoms that provide efficacy and effectiveness against several snake venoms of the same genus or family. The low number of immunogenic components in venom mixtures that allow the production of antivenoms consequently gives them partial neutralization and a suboptimal pharmacological response. This study evaluates the immunorecognition and neutralizing efficacy of the polyvalent anticoral antivenom from the Instituto Nacional de Salud (INS) of Colombia against the heterologous endemic venoms of Micrurus medemi, and M. sangilensis, and M. helleri by assessing immunoreactivity through affinity chromatography, ELISA, Western blot, and neutralization capability. Immunorecognition towards the venoms of M. medemi and M. sangilensis showed values of 62% and 68% of the protein composition according to the immunoaffinity matrix, respectively. The analysis by Western blot depicted the highest recognition patterns for M. medemi, followed by M. sangilensis, and finally by M. helleri. These findings suggest that the venom compositions are closely related and exhibit similar recognition by the antivenom. According to enzyme immunoassays, M. helleri requires a higher amount of antivenom to achieve recognition than the others. Besides reinforcing the evaluation of INS antivenom capability, this work recommends the use of M. helleri in the production of Colombian antisera.

Implications of two-component systems EnvZ/OmpR and BaeS/BaeR in in vitro temocillin resistance in Escherichia coli.

BACKGROUND: BaeS/BaeR is a two-component system of Escherichia coli that controls the expression of porins and efflux pumps. Its role in beta-lactam resistance is limited. OBJECTIVES: To study the role of baeS/baeR two-component system in temocillin resistance in E. coli. METHODS: E. coli strain BW25113 and single-gene deletion mutants related to two-component systems were collected from the KEIO collection. Double-gen deletion mutants were generated. Temocillin-resistant mutant frequencies were determined at 32 mg/L. E. coli BW25113 mutants were selected by selective pressure from serial passages. Biological costs were analysed by growth curves. Genomes of the generated mutants were sequenced. The expression level of the mdtA, mdtB, mdtC, acrD and tolC in the ΔbaeS mutant was determined by RT-PCR (with/without temocillin exposure). RESULTS: The frequency of temocillin mutants ranged from 2.12 × 10-8 to 4.51 × 10-8 in single-porin mutants. No mutants were recovered from E. coli BW25113 (>10-9). Selection of temocillin-resistant variants by serial passage yielded mutants up to 128 mg/L. Mutations were found in the baeS gene. Temocillin MICs ranged from 4 to 32 mg/L (highest MICs for ΔbaeS and ΔompR). The efflux pumps mdtA, mdtB, mdtC and acrD pumps were overexpressed 3-10-fold in the presence of temocillin in ΔbaeS compared to control. CONCLUSIONS: Mutations in the sensor histidine kinase, baeS, may be involved in temocillin resistance through the expression of the efflux pumps mdtABC and acrD. In addition, the low mutation rate may be a good predictor of temocillin activity.

Evaluation of temocillin efficacy against KPC-2-producing Klebsiella pneumoniae isolates in a hollow-fibre infection model.

BACKGROUND: Temocillin is an old antimicrobial that is resistant to hydrolysis by ESBLs but has variable activity against carbapenemase-producing Enterobacteriaceae. The current EUCAST susceptibility breakpoints for Enterobacterales are set at ≤16 mg/L (susceptible with increased exposure) based on a dose of 2 g q8h, but there is limited information on the efficacy of this dose against temocillin-susceptible carbapenemase-producing Klebsiella pneumoniae isolates. OBJECTIVES: To evaluate the efficacy of this dose using a hollow-fibre infection model (HFIM) against six KPC-2-producing clinical isolates of K. pneumoniae. METHODS: The isolates were characterized by WGS and temocillin susceptibility was determined using standard and high inoculum temocillin. Mutant frequencies were estimated and temocillin activity was tested in time-kill assays and in the HFIM. At standard conditions, three of the isolates were classified as susceptible (MIC ≤ 16 mg/L) and three as resistant (MIC > 16 mg/L). The HFIM was performed over 3 days to mimic human-like pharmacokinetics of 2 g q8h. Bacterial counts were performed by plating on Mueller-Hinton agar (MHA) and MHA containing 64 mg/L temocillin to detect resistant subpopulations. RESULTS: All isolates showed a reduction in bacterial population of at least 3 log cfu/mL within the first 8 h of simulated treatment in the hollow-fibre assay. Regrowth was observed for the three resistant isolates and one of the susceptible ones. The MIC value for these isolates was higher by at least two dilutions compared with their initial values. CONCLUSIONS: These data suggest that an optimized pharmacokinetic regimen may be of clinical interest for the treatment of KPC-2-producing K. pneumoniae susceptible to temocillin. These data showed activity of temocillin against KPC-2-producing K. pneumoniae susceptible to temocillin; however, a dose of 2g q8h administered over 30 min may be inadequate to prevent the emergence of resistant variants.

Underlying and proximate drivers of biodiversity changes in Mesoamerican biosphere reserves.

Protected areas are of paramount relevance to conserving wildlife and ecosystem contributions to people. Yet, their conservation success is increasingly threatened by human activities including habitat loss, climate change, pollution, and species overexploitation. Thus, understanding the underlying and proximate drivers of anthropogenic threats is urgently needed to improve protected areas' effectiveness, especially in the biodiversity-rich tropics. We addressed this issue by analyzing expert-provided data on long-term biodiversity change (last three decades) over 14 biosphere reserves from the Mesoamerican Biodiversity Hotspot. Using multivariate analyses and structural equation modeling, we tested the influence of major socioeconomic drivers (demographic, economic, and political factors), spatial indicators of human activities (agriculture expansion and road extension), and forest landscape modifications (forest loss and isolation) as drivers of biodiversity change. We uncovered a significant proliferation of disturbance-tolerant guilds and the loss or decline of disturbance-sensitive guilds within reserves causing a "winner and loser" species replacement over time. Guild change was directly related to forest spatial changes promoted by the expansion of agriculture and roads within reserves. High human population density and low nonfarming occupation were identified as the main underlying drivers of biodiversity change. Our findings suggest that to mitigate anthropogenic threats to biodiversity within biosphere reserves, fostering human population well-being via sustainable, nonfarming livelihood opportunities around reserves is imperative.

Professional quality of life and fear of COVID-19 among Spanish nurses: A longitudinal repeated cross-sectional study.

AIM AND OBJECTIVES: To evaluate changes in compassion fatigue (CF), burnout (BO), compassion satisfaction (CS) and fear of COVID-19 among Spanish nurses by comparing two assessment points: before and after the COVID-19 vaccination campaign. BACKGROUND: The COVID-19 pandemic has produced a great impact in healthcare worker's professional quality of life, especially among nurses. CF, BO and fear of COVID-19 decisively affect the care provided by nurses and put them at risk for mental health problems, so longitudinal studies are essential. DESIGN: A repeated cross-sectional design was carried out with a time-lapse of 12 months. METHODS: A total of 439 registered nurses in December 2020 and 410 in December 2021 participated in this study through an online survey. Data were collected using the Professional Quality of Life Questionnaire and the Fear of COVID-19 Scale. Occupational and sociodemographic variables were also analysed. This article adheres to the STROBE guidelines for the reporting of observational studies. RESULTS: The fear of COVID-19 has not been reduced among nurses. The levels of BO remain stable and continue to be high in half of the professionals. CF has been reduced with a small effect size (d = 0.30), while CS has also decreased (d = 0.30). Positive correlations were found in both assessment points between fear of COVID-19 and BO (r = .44, p ≤ .001; r = .41, p ≤ .001) and also between fear of COVID and CF (r = .57, p ≤ .001; r = .50, p ≤ .001). Negative correlations between fear and CS were also found (r = - .16, p = .001; r = - .22, p ≤ .001). RELEVANCE TO CLINICAL PRACTICE: Programmes to reduce fear of COVID-19, BO and CF are needed to improve mental health and to prevent psychological distress among nurses, as well as to increase CS and preserve the productivity and quality of nursing care. PATIENT OR PUBLIC CONTRIBUTION: The nurses collaborated by participating in the present study anonymously and disinterestedly.

Dorsum Sellae as Key Landmark in ETV With Disminished Prepontine Cistern: Technical Note and Case Series.

BACKGROUND AND OBJECTIVES: One of the key aspects in the surgical technique of endoscopic third ventriculostomy (ETV) is the perforation of the floor of the third ventricle because of the high risk of injuring vital structures located in that region. According to the standard technique, this perforation should be performed in the midline halfway between mammillary bodies and the infundibular recess to avoid damage to the structures. This can be performed without excessive complications when the diameter of the prepontine cistern is wide. However, in situations where the diameter is reduced (defined in the literature as having a prepontine interval [PPI] ≤1 mm), the probability of complications increases exponentially.In this article, we propose using dorsum sellae as a key point to safely perform ETV in patients with a decreased PPI, guiding the trajectory and its marking using neuronavigation. METHODS: A review was conducted on the latest 100 ETV procedures performed by our team in the past 5 years. The measurement of the PPI was conducted using archived preoperative MRI imaging studies, specifically between the dorsum sellae and the basilar artery. In cases where the PPI was ≤1 mm and, therefore, the use of the dorsum sellae was applied as a reference point, the technical results and procedural functions were documented. RESULTS: In the cohort, 7 patients with a PPI ≤1 mm were identified. In all 7 cases, fenestration of the tuber cinereum was successfully performed without causing vascular damage or associated complications. ETV was successful in 6 patients, with only one experiencing ETV failure necessitating the placement of a ventriculoperitoneal shunt. CONCLUSION: The utilization of the dorsum sellae as a reference point to perform ETV in reduced PPI constitutes a safe alternative to the classical technique.

Structural, biochemical and immunochemical characterization of an acidic phospholipase A2 from Lachesis acrochorda (Viperidae: Crotalinae) venom.

Viperids of the genus Lachesis, also known as bushmasters, are capable of injecting great amounts of venom that cause severe envenomation incidents. Since phospholipases type A2 are mainly involved in edema and myonecrosis within the snakebite sites, in this work, the isolation, amino acid sequence and biochemical characterization of the first phospholipase type A2 from the venom of Lachesis acrochorda, named Lacro_PLA2, is described. Lacro_PLA2 is an acidic aspartic 49 calcium-dependent phospholipase A2 with 93% similarity to the L. stenophrys phospholipase. Lacro_PLA2 has a molecular mass of 13,969.7 Da and an experimental isoelectric point around 5.3. A combination of N-terminal Edman degradation and MS/MS spectrometry analyses revealed that Lacro_PLA2 contains 122 residues including 14 cysteines that form 7 disulfide bridges. A predicted 3D model shows a high resemblance to other viperid phospholipases. Nevertheless, immunochemical and phospholipase neutralization tests revealed a notorious level of immunorecognition of the isolated protein by two polyclonal antibodies from viperids from different genus, which suggest that Lacro_PLA2 resembles more to bothropic phospholipases. Lacro_PLA2 also showed significantly high edema activity when was injected into mice; so, it could be an alternative antigen in the development of antibodies against toxins of this group of viperids, seeking to improve commercial polyclonal antivenoms.

Clinical Significance of T2-Weighted Sequence Intensity on Magnetic Resonance Imaging in Clinically Non-Functioning Pituitary Adenomas.

BACKGROUND: Little is known about the relationship between signal intensity patterns on T2-weighted magnetic resonance imaging (MRI) in non-functioning pituitary adenomas (NFPAs). OBJECTIVE: In this study, the clinical, hormonal, histological features, and therapeutic responses were evaluated according to the T2 signal intensity in NFPAs. METHODS: This retrospective and multicenter study included a group of 166 NFPA patients (93 men, 56%, mean age 58.5 ±14.8 yr). RESULTS: Approximately half of the tumors (n=84, 50.6%) were hyperintense, while 34.3% (n=57) and 15.1% (n=25) were iso- and hypointense, respectively. The median maximum tumor diameter of the isointense group [16 (13-25) mm] was significantly lower than that of the hyperintense [23 (16.6-29.7) mm] group (p=0.003). Similarly, the tumor volume of the isointense group [1,523 (618-5,226) mm3] was significantly lower than that of the hyperintense [4,012 (2,506-8,320) mm3] group (p=0.002). Chiasmatic compression occurred less frequently in tumors with isointense signal characteristics (38.6%) compared to tumors with hypointense (68%) and hyperintense (65.5%) signal characteristics (p=0.003). Invasive adenomas (p=0.001) and the degree of cavernous sinus invasion (p<0.001) were more frequent in the hyperintense adenoma group compared to the remaining groups. Plurihormonal tumors and silent lactotroph adenomas were more frequent in the isointense tumor group. CONCLUSION: In conclusion, hyperintensity on T2-weighted MRI in NFPAs is associated with larger and more invasive tumors compared to isointense NFPAs.

Severe Pediatric Open Skull Fracture With Exposed Brain Matter: A Case Report.

Head trauma in the pediatric population carries a high rate of morbidity and mortality. The major causes of head trauma are related to falls, recreational activities, motor vehicle accidents, and gunshot wounds. Traumatic brain injury (TBI) can occur after severe head trauma and is defined as an alteration in brain function, or other evidence of brain pathology, caused by an external force. Intracranial edema and herniation are common consequences of a TBI in pediatric patients and are commonly relieved via decompressive craniectomy.  This case study describes a 13-year-old male presenting to the trauma center after an unhelmeted all-terrain vehicle (ATV) accident with a positive head strike and loss of consciousness. The evaluation revealed extensive skull fractures extending from the frontal to the occipital lobe with brain exposure. Computed tomography (CT) scan of the head demonstrated extensive, open skull fractures with significant displacement of the exposed brain, extensive bilateral parietal and frontal bone fractures, and bilateral temporal bone displaced fractures more extensive on the left. A bilateral hemicraniectomy was performed due to diffuse cerebral edema and a left frontal ventriculostomy was placed to monitor and manage intracranial pressure (ICP). It is believed that the unique presentation of an open skull fracture with an exposed brain acted as a decompressive method allowing for extreme lifesaving measures to be performed to save the patient. Further exploration is needed to truly understand the effects of the unique injury presentation and the role of an open fracture in the delay of increased ICP.

A specific gut microbiota signature is associated with an enhanced GLP-1 and GLP-2 secretion and improved metabolic control in patients with type 2 diabetes after metabolic Roux-en-Y gastric bypass.

Objective: To determine changes in incretins, systemic inflammation, intestinal permeability and microbiome modifications 12 months after metabolic RYGB (mRYGB) in patients with type 2 diabetes (T2D) and their relationship with metabolic improvement. Materials and methods: Prospective single-center non-randomized controlled study, including patients with class II-III obesity and T2D undergoing mRYGB. At baseline and one year after surgery we performed body composition measurements, biochemical analysis, a meal tolerance test (MTT) and lipid test (LT) with determination of the area under the curve (AUC) for insulin, C-peptide, GLP-1, GLP-2, and fasting determinations of succinate, zonulin, IL-6 and study of gut microbiota. Results: Thirteen patients aged 52.6 ± 6.5 years, BMI 39.3 ± 1.4 kg/m2, HbA1c 7.62 ± 1.5% were evaluated. After mRYGB, zonulin decreased and an increase in AUC after MTT was observed for GLP-1 (pre 9371 ± 5973 vs post 15788 ± 8021 pM, P<0.05), GLP-2 (pre 732 ± 182 vs post 1190 ± 447 ng/ml, P<0.001) and C- peptide, as well as after LT. Species belonging to Streptococaceae, Akkermansiacea, Rickenellaceae, Sutterellaceae, Enterobacteriaceae, Oscillospiraceae, Veillonellaceae, Enterobacterales_uc, and Fusobacteriaceae families increased after intervention and correlated positively with AUC of GLP-1 and GLP-2, and negatively with glucose, HbA1c, triglycerides and adiposity markers. Clostridium perfringens and Roseburia sp. 40_7 behaved similarly. In contrast, some species belonging to Lachnospiraceae, Erysipelotricaceae, and Rumnicocaceae families decreased and showed opposite correlations. Higher initial C-peptide was the only predictor for T2D remission, which was achieved in 69% of patients. Conclusions: Patients with obesity and T2D submitted to mRYGB show an enhanced incretin response, a reduced gut permeability and a metabolic improvement, associated with a specific microbiota signature.

Diagnostic Accuracy of Abdominal CT for Locally Advanced Colon Tumors: Can We Really Entrust Certain Decisions to the Reliability of CT?

Many different options of neoadjuvant treatments for advanced colon cancer are emerging. An accurate preoperative staging is crucial to select the most appropriate treatment option. A retrospective study was carried out on a national series of operated patients with T4 tumors. Considering the anatomo-pathological analysis of the surgical specimen as the gold standard, a diagnostic accuracy study was carried out on the variables T and N staging and the presence of peritoneal metastases (M1c). The parameters calculated were sensitivity, specificity, positive and negative predictive values, and positive and negative likelihood ratios, as well as the overall accuracy. A total of 50 centers participated in the study in which 1950 patients were analyzed. The sensitivity of CT for correct staging of T4 colon tumors was 57%. Regarding N staging, the overall accuracy was 63%, with a sensitivity of 64% and a specificity of 62%; however, the positive and negative likelihood ratios were 1.7 and 0.58, respectively. For the diagnosis of peritoneal metastases, the accuracy was 94.8%, with a sensitivity of 40% and specificity of 98%; in the case of peritoneal metastases, the positive and negative likelihood ratios were 24.4 and 0.61, respectively. The diagnostic accuracy of CT in the setting of advanced colon cancer still has some shortcomings for accurate diagnosis of stage T4, correct classification of lymph nodes, and preoperative detection of peritoneal metastases.