Domestic Dog Infection with Trypanosoma cruzi from Northern and Southern Regions of Mexico.

Background: Chagas disease or American trypanosomiasis, caused by Trypanosoma cruzi and vectored by triatomines, affects millions of people worldwide. In endemic countries including Mexico, infections in domestic animals, such as dogs, may affect the risk of human disease when they serve as a source of infection to vectors that subsequently infect humans. Materials and Methods: We conducted a cross-sectional study of 296 dogs from two cities near the northern and southern borders of Mexico: Reynosa, Tamaulipas, and Tuxtla Gutierrez, Chiapas. Infection was measured based on testing of blood using T. cruzi quantitative PCR (qPCR) and up to three antibody detection assays. The StatPak immunochromatographic assay was used to screen samples and the indirect fluorescent antibody (IFA) and multiplex microsphere immunoassay (MIA) tests were used as secondary tests on all samples that screened positive and a subset of negatives. Serologic positivity was defined based on reactivity on at least two independent tests. Results: Of the 280 samples tested for parasite DNA, two (0.7%) were positive, one of which (0.4%) was confirmed as T. cruzi discrete typing unit TcIV. Overall, 72 (24.3%) samples were reactive for T. cruzi antibodies via StatPak of which 8 were also positive using MIA and 2 were also positive using IFA (including one of the PCR-positive dogs). Overall, nine dogs (3.4%) met study criteria of positivity based on either/both serology or PCR tests. Positive dogs were found in both regions of Mexico; five (2.7%) from Reynosa and four (3.6%) from Tuxtla Gutierrez. We found no association between infection status and state of origin, sex, age group, breed group, neighborhood, and whether other pets lived in the home. Conclusion: Our results re-emphasize dogs' utility as sentinels for T. cruzi in Mexico and underscore the need for improved veterinary diagnostic tests and parasite surveillance at the household level in endemic countries.

TL1A and IL-18 synergy promotes GM-CSF-dependent thymic granulopoiesis in mice.

Acute systemic inflammation critically alters the function of the immune system, often promoting myelopoiesis at the expense of lymphopoiesis. In the thymus, systemic inflammation results in acute thymic atrophy and, consequently, impaired T-lymphopoiesis. The mechanism by which systemic inflammation impacts the thymus beyond suppressing T-cell development is still unclear. Here, we describe how the synergism between TL1A and IL-18 suppresses T-lymphopoiesis to promote thymic myelopoiesis. The protein levels of these two cytokines were elevated in the thymus during viral-induced thymus atrophy infection with murine cytomegalovirus (MCMV) or pneumonia virus of mice (PVM). In vivo administration of TL1A and IL-18 induced acute thymic atrophy, while thymic neutrophils expanded. Fate mapping with Ms4a3-Cre mice demonstrated that thymic neutrophils emerge from thymic granulocyte-monocyte progenitors (GMPs), while Rag1-Cre fate mapping revealed a common developmental path with lymphocytes. These effects could be modeled ex vivo using neonatal thymic organ cultures (NTOCs), where TL1A and IL-18 synergistically enhanced neutrophil production and egress. NOTCH blockade by the LY411575 inhibitor increased the number of neutrophils in the culture, indicating that NOTCH restricted steady-state thymic granulopoiesis. To promote myelopoiesis, TL1A, and IL-18 synergistically increased GM-CSF levels in the NTOC, which was mainly produced by thymic ILC1s. In support, TL1A- and IL-18-induced granulopoiesis was completely prevented in NTOCs derived from Csf2rb-/- mice and by GM-CSFR antibody blockade, revealing that GM-CSF is the essential factor driving thymic granulopoiesis. Taken together, our findings reveal that TL1A and IL-18 synergism induce acute thymus atrophy while  promoting extramedullary thymic granulopoiesis in a NOTCH and GM-CSF-controlled manner.

Navigating HER2-Low Testing in Invasive Breast Cancer: Update Recommendations for Pathologists.

The article discusses the importance of accurately distinguishing HER2-low from HER2-negative breast cancer, as novel ADCs have demonstrated activity in a large population of patients with HER2-low-expressing BC. While current guidelines recommend a dichotomous classification of HER2 as either positive or negative, the emergence of the HER2-low concept calls for standardization of HER2 testing in breast cancer, using currently available assays to better discriminate HER2 levels. This review covers the evolution and latest updates of the ASCO/CAP guidelines relevant to this important biomarker in breast cancer, including still-evolving concepts such as HER2 low, HER2 heterogeneity, and HER2 evolution. Our group presents the latest Mexican recommendations for HER2 status evaluation in breast cancer, considering the ASCO/CAP guidelines and introducing the HER2-low concept. In the era of personalized medicine, accurate HER2 status assessment remains one of the most important biomarkers in breast cancer, and the commitment of Mexican pathologists to theragnostic biomarker quality is crucial for providing the most efficient care in oncology.

Effectiveness of JYNNEOS vaccine against symptomatic mpox disease in adult men in Los Angeles County, August 29, 2022 to January 1, 2023.

We describe real-world estimates of JYNNEOS vaccine effectiveness (VE) against symptomatic mpox in Los Angeles County (LAC). We conducted a retrospective cohort study of men aged ≥18 years residing in LAC who were at risk for mpox and eligible for the JYNNEOS vaccine from 5/19/2022 to 1/1/2023. Case demographics and route of JYNNEOS administration were obtained through vaccine administration data systems. HIV and sexually transmitted infection (STI) status was obtained through disease reporting systems for HIV and STI diagnoses in LAC. To estimate VE, we calculated weekly incidence of confirmed mpox for unvaccinated, partially vaccinated (episode date ≥14 days after first dose), and fully vaccinated (episode date ≥14 days after second dose) cohorts starting on 8/29/2022, when fully vaccinated coverage exceeded 3 %, and ending on 1/1/2023. Overall, 2,171 men had confirmed mpox, and 1,002 (46 %) of those were persons living with diagnosed HIV (PLWDH). 2,019 (93 %) mpox cases were unvaccinated, 114 (5 %) were partially vaccinated and 38 (2 %) were fully vaccinated. VE was 69 % (95 % CI 59-77) for partially vaccinated and 84 % (95 % CI 80-87) for fully vaccinated individuals. Among PLWDH, VE was 72 % (95 % CI 57-82) for fully vaccinated and 28 % (95 % CI -96 to 73) VE for partially vaccinated individuals. Among persons not living with diagnosed HIV, VE was 88 % (95 % CI 86-90) for fully vaccinated and 80 % (95 % CI 76-83) for partially vaccinated individuals. Of 111 individuals hospitalized with mpox, one was partially vaccinated, and the remaining were unvaccinated. Our results align with other published studies that reported that two doses of the JYNNEOS vaccine provided significant protection against symptomatic mpox.

RIPK1 protects naive and regulatory T cells from TNFR1-induced apoptosis.

The T cell population size is stringently controlled before, during, and after immune responses, as improper cell death regulation can result in autoimmunity and immunodeficiency. RIPK1 is an important regulator of peripheral T cell survival and homeostasis. However, whether different peripheral T cell subsets show a differential requirement for RIPK1 and which programmed cell death pathway they engage in vivo remains unclear. In this study, we demonstrate that conditional ablation of Ripk1 in conventional T cells (Ripk1ΔCD4) causes peripheral T cell lymphopenia, as witnessed by a profound loss of naive CD4+, naive CD8+, and FoxP3+ regulatory T cells. Interestingly, peripheral naive CD8+ T cells in Ripk1ΔCD4 mice appear to undergo a selective pressure to retain RIPK1 expression following activation. Mixed bone marrow chimeras revealed a competitive survival disadvantage for naive, effector, and memory T cells lacking RIPK1. Additionally, tamoxifen-induced deletion of RIPK1 in CD4-expressing cells in adult life confirmed the importance of RIPK1 in post-thymic survival of CD4+ T cells. Ripk1K45A mice showed no change in peripheral T cell subsets, demonstrating that the T cell lymphopenia was due to the scaffold function of RIPK1 rather than to its kinase activity. Enhanced numbers of Ripk1ΔCD4 naive T cells expressed the proliferation marker Ki-67+ despite the peripheral lymphopenia and single-cell RNA sequencing revealed T cell-specific transcriptomic alterations that were reverted by additional caspase-8 deficiency. Furthermore, Ripk1ΔCD4Casp8 ΔCD4 and Ripk1ΔCD4Tnfr1-/- double-knockout mice rescued the peripheral T cell lymphopenia, revealing that RIPK1-deficient naive CD4+ and CD8+ cells and FoxP3+ regulatory T cells specifically die from TNF- and caspase-8-mediated apoptosis in vivo. Altogether, our findings emphasize the essential role of RIPK1 as a scaffold in maintaining the peripheral T cell compartment and preventing TNFR1-induced apoptosis.

Modified Oblique Lobenhoffer (MOL) approach for posterolateral and posteromedial column access in tibial plateau fractures: a detailed cadaveric anatomical study.

BACKGROUND: Tibial plateau fractures involving posteromedial (PM) and posterolateral (PL) columns are complex injuries that require an appropriate approach. The management of the PL column in these cases can be controversial, and limitations using deep posteromedial interval approaches have been referenced. In this paper, a modification of the Lobenhoffer approach, designed to optimize the access to the PL column, is described in detail. The aim of this study was to assess the feasibility of this approach in a cadaveric anatomical study. MATERIALS AND METHODS: In total, five fresh-frozen cadaveric specimens were used for detailed anatomical study surrounding the approach. Relationships with cutaneous and deep neurovascular structures were evaluated. The exposure area of the PL and PM columns using this approach was assessed. RESULTS: The cadaveric study showed safe and adequate exposure. Oblique skin and fascia incision just medial to the posterior midline was safe to protect the medial sural cutaneous nerve and the small saphenous vein. Elevation of the popliteus and tibialis posterior muscles offered safe protection of the anterior tibial artery and popliteal neurovascular bundle during retractor placement. Adequate full proximal exposure of the PM and PL columns, including the posterolateral lateral (PLL) and posterolateral central (PLC) segments, was obtained in all specimens. CONCLUSIONS: The Modified Oblique Lobenhoffer (MOL) approach can be a feasible option to access PL and PM columns in tibial plateau fractures. LEVEL OF EVIDENCE: IV.

Flexible genomic island conservation across freshwater and marine Methylophilaceae.

The evolutionary trajectory of Methylophilaceae includes habitat transitions from freshwater sediments to freshwater and marine pelagial that resulted in genome reduction (genome-streamlining) of the pelagic taxa. However, the extent of genetic similarities in the genomic structure and microdiversity of the two genome-streamlined pelagic lineages (freshwater "Ca. Methylopumilus" and the marine OM43 lineage) has so far never been compared. Here, we analyzed complete genomes of 91 "Ca. Methylopumilus" strains isolated from 14 lakes in Central Europe and 12 coastal marine OM43 strains. The two lineages showed a remarkable niche differentiation with clear species-specific differences in habitat preference and seasonal distribution. On the other hand, we observed a synteny preservation in their genomes by having similar locations and types of flexible genomic islands (fGIs). Three main fGIs were identified: a replacement fGI acting as phage defense, an additive fGI harboring metabolic and resistance-related functions, and a tycheposon containing nitrogen-, thiamine-, and heme-related functions. The fGIs differed in relative abundances in metagenomic datasets suggesting different levels of variability ranging from strain-specific to population-level adaptations. Moreover, variations in one gene seemed to be responsible for different growth at low substrate concentrations and a potential biogeographic separation within one species. Our study provides a first insight into genomic microdiversity of closely related taxa within the family Methylophilaceae and revealed remarkably similar dynamics involving mobile genetic elements and recombination between freshwater and marine family members.

Grass Infusions in Autocidal Gravid Ovitraps to Lure Aedes Albopictus.

Aedes albopictus is a vector of several pathogens of significant public health concern. In this situation, gravid traps have become a common surveillance tool for Aedes spp., which commonly use hay infusions as an attractant. Diverse grass infusions have been assessed to enhance the attraction to this vector mosquito. However, these studies have focused on the oviposition effect, and the attraction potential to gravid Ae. albopictus females has not been evaluated yet. Here we report the attractiveness of infusions of 4 different botanical species (Cenchrus purpureus, Cyanodon dactylon, Megathyrus maximus, Pennisetum ciliare) as baits in sticky ovitraps and autocidal gravid ovitraps (AGOs) under laboratory, semifield, and field conditions. In the laboratory, Cynodon dactylon showed attractiveness, whereas in semifield conditions, both C. dactylon and Megathyrsus maximus were similarly attractive for gravid Ae. albopictus. None of the infusions conducted with AGOs were able to lure Ae. albopictus and other species of mosquitoes in a 14-wk field experiment. Our results demonstrate the feasibility of finding more attractive infusions for Ae. albopictus females to improve the efficacy of AGO traps, but further testing of infusions in AGOs in field settings is needed.

Type 1 immunity enables neonatal thymic ILC1 production.

Acute thymic atrophy occurs following type 1 inflammatory conditions such as viral infection and sepsis, resulting in cell death and disruption of T cell development. However, the impact type 1 immunity has on thymic-resident innate lymphoid cells (ILCs) remains unclear. Single-cell RNA sequencing revealed neonatal thymic-resident type 1 ILCs (ILC1s) as a unique and immature subset compared to ILC1s in other primary lymphoid organs. Culturing murine neonatal thymic lobes with the type 1 cytokines interleukin-12 (IL-12) and IL-18 resulted in a rapid expansion and thymic egress of KLRG1+CXCR6+ cytotoxic ILC1s. Live imaging showed the subcapsular thymic localization and exit of ILC1s following IL-12 + IL-18 stimulation. Similarly, murine cytomegalovirus infection in neonates resulted in thymic atrophy and subcapsular localization of thymic-resident ILC1s. Neonatal thymic grafting revealed that type 1 inflammation enhances the homing of cytokine-producing thymus-derived ILC1s to the liver and peritoneal cavity. Together, we show that type 1 immunity promotes the expansion and peripheral homing of thymic-derived ILC1s.

Mpox Outbreak - Los Angeles County, California, May 4-August 17, 2023.

Since May 2022, approximately 2,500 mpox cases have been reported in Los Angeles County (LAC), California. Beginning in May 2023, the LAC Department of Public Health observed a consistent increase in mpox cases after a prolonged period of low incidence. A total of 56 cases were identified during May 4-August 17, 2023. A minority of mpox patients were fully vaccinated (29%). One patient was hospitalized; no deaths were reported. Two cases of reinfection occurred, both of which were associated with mild illness. The increasing number of cases during this period was significant, as few other health departments in the United States reported an increase in mpox cases during the same period. The outbreak spread similarly to the 2022 U.S. mpox outbreak, mainly through sexual contact among gay, bisexual, and other men who have sex with men. Vaccination against mpox became available in June 2022 and has been shown to be effective at preventing mpox disease. This outbreak was substantially smaller than the 2022 mpox outbreak in LAC (2,280 cases); possible explanations for the lower case count include increased immunity provided from vaccination against mpox and population immunity from previous infections. Nonetheless, mpox continues to spread within LAC, and preventive measures, such as receipt of JYNNEOS vaccination, are recommended for persons at risk of Monkeypox virus exposure.

Novel ultrasound-guided supraclavicular stellate ganglion block.

INTRODUCTION: Stellate ganglion block (SGB) provides diagnostic and therapeutic benefits in pain syndromes in the head, neck, and upper extremity, including complex regional pain syndrome Types I and II, Raynaud's disease, hyperhidrosis, arterial embolism in the region of the arm. METHODS: We present a novel ultrasound-guided supraclavicular stellate ganglion block. Considering the existing anatomical structures of the targeted area. RESULTS AND CONCLUSIONS: We hope that we can provide fewer complications and additional benefits with this new approach.

Descriptores para la enseñanza y el aprendizaje del inglés con fines específicos en Medicina

Fundamento: la lengua inglesa es la más utilizada en la comunicación internacional. Las universidades médicas desarrollan procesos del inglés con fines específicos basados en el Marco Común Europeo de Referencia para las Lenguas. Objetivo: diseñar los descriptores del inglés con fines específicos de la carrera de Medicina para el perfeccionamiento de su proceso enseñanza aprendizaje. Métodos: se realizó un estudio experimental de corte pedagógico en la Facultad de Ciencias Médicas de Mayabeque, de enero 2020 a enero 2022. Se aplicaron métodos teóricos: histórico-lógico, analítico-sintético, inductivo-deductivo y modelación; empíricos: revisión documental, cuestionario, entrevista a profesores y una prueba pedagógica a estudiantes. Se utilizó el porcentaje como unidad de resumen, la técnica IADOV para criterio de usuarios y el método Delphi a especialistas. Resultados: la revisión documental mostró carencias de descriptores del inglés con fines específicos de la carrera de Medicina. Los instrumentos aplicados revelaron insuficiencias en conocimientos y utilización de elementos sugeridos en el Marco Común Europeo de Referencia para las Lenguas, que incluye los descriptores. La prueba pedagógica reveló bajo nivel de competencia comunicativa; por lo que se diseñaron descriptores para el perfeccionamiento de su proceso enseñanza aprendizaje. Conclusiones: los descriptores diseñados para el inglés con fines específicos fueron valorados por usuarios a través de la técnica IADOV, quienes mostraron alto nivel de satisfacción en su aplicación a la docencia, y fueron valorados por especialistas como pertinentes a través del método Delphi.

Background: the English language is the most used in international communication. Medical universities develop English processes for specific purposes based on the Common European Framework of Reference for Languages. Objective: to design English descriptors for specific purposes of the Medicine degree to improve its teaching-learning process. Method: an experimental pedagogical study was carried out at Mayabeque, Faculty of Medical Sciences from January 2020 to January 2022. Theoretical methods were applied: historical-logical, analytical-synthetic, inductive-deductive and modeling; empirical: documentary review, questionnaire, interview with teachers and a pre-test and post-test test with students. The percentage was used as a summary unit, the IADOV technique was used for user criteria, and the Delphi method was used for specialists. Results: the documentary review showed deficiencies in English descriptors for specific purposes of the Medicine degree. The instruments applied revealed deficiencies in knowledge and use of elements suggested in the Common European Framework of Reference for Languages, which includes the descriptors. The pre-test and post-test revealed a low level of communicative competence; Therefore, descriptors were designed to improve the teaching-learning process. Conclusions: the descriptors designed for English for specific purposes were evaluated by users through the IADOV technique, who showed a high level of satisfaction in their application to teaching, and were evaluated by specialists as relevant through the Delphi method.

Usefulness of ultrasound-guided serratus-anterior block in prevention of postoperative pain after breast surgery. A cohort study.

OBJECTIVE: To evaluate superficial serratus anterior plane block's efficacy and side effects in preventing postoperative pain after breast cancer surgery. METHODOLOGY: A prospective cohort study was conducted on 195 adult patients undergoing breast oncological surgery under general anesthesia (Group G, n = 96) or combined general anesthesia with superficial serratus anterior plane block (Group L, n = 99). Validated preoperative data, which are predictors of chronic postoperative pain of patients, were recorded (type of surgery, age, pain in the area of the intervention and the other regions; anesthetic-surgical data, analgesic doses used, duration of surgery; pain intensity (EVN scale) at immediate postoperative period, 24 h, seven days and one month after the surgery, and complications. RESULTS: Pain intensity, measured by the EVN scale, had a mean of 1.02 +/- 1.656 in the Postoperative Unit; 1.20 +/- 1.448 at 24 h; 0.76 +/- 1208 seven days; and 0.34 +/- 0.757 one month after surgery. Patients were operated under general anesthesia (n = 96) or general anesthesia combined with the interfascial block (n = 99). Significant differences (p < 0.05) were found in age, height, and VAS scale in PACU. Ten complications were recorded, six in Group L and four in Group G. There were no differences between groups in complications. CONCLUSIONS: Superficial serratus anterior plane blocks are effective and safe in pain control in the immediate postoperative period for breast cancer surgery as a part of the multimodal approach. No significant differences were found one week and one month after surgery.

Phosphate-related genomic islands as drivers of environmental adaptation in the streamlined marine alphaproteobacterial HIMB59.

IMPORTANCE: These results shed light on the evolutionary strategies of microbes with streamlined genomes to adapt and survive in the oligotrophic conditions that dominate the surface waters of the global ocean. At the individual level, these microbes have been subjected to evolutionary constraints that have led to a more efficient use of nutrients, removing non-essential genes named as "streamlining theory." However, at the population level, they conserve a highly diverse gene pool in flexible genomic islands resulting in polyclonal populations on the same genomic background as an evolutionary response to environmental pressures. Localization of these islands at equivalent positions in the genome facilitates horizontal transfer between clonal lineages. This high level of environmental genomic heterogeneity could explain their cosmopolitan distribution. In the case of the order HIMB59 within the class Alphaproteobacteria, two factors exert evolutionary pressure and determine this intraspecific diversity: phages and the concentration of P in the environment.

Hallazgos por tomografía en pacientes confirmados con SARS-CoV-2 y síndrome de distrés respiratorio agudo / Tomography findings in patients confirmed with SARS-CoV-2 and acute respiratory distress syndrome

Resumen Objetivos: Describir los patrones tomográficos de afectación pulmonar en pacientes con SARS-CoV2 y SDRA. Materiales y Métodos: Estudio retrospectivo, transversal y analítico. Pacientes atendidos en Hospital Regional de Alta Especialidad de Ciudad Victoria "Bicentenario 2010" (HRAEV), con diagnóstico confirmado de COVID-19 por RT-PCR y que contaran con tomografía computarizada de tórax realizada en la institución en el periodo comprendido de 1 marzo de 2020 a 31 julio de 2020. Se realizó un análisis descriptivo y analítico. Resultados: Se analizaron estudios de tomografía de 44 pacientes hospitalizados en HRAEV que cursaron con SDRA y requirieron IOT, de los cuales el 72.7% fueron del sexo masculino, la edad promedio fue de 64 años, de los cuales 47.7% cursaba con Diabetes Mellitus, 63.6 % con Hipertensión Arterial Sistémica 43.1% y con algún grado de sobrepeso u obesidad. Conclusiones: El hallazgo tomográfico característico de los pacientes con SDRA fue mixto de tipo vidrio despulido y consolidación con una afectación severa y generalizada.

Abstract Objective: Describe the tomographic patterns of lung involvement in patients with SARS-CoV2 and ARDS. Materials and methods: Retrospective, cross-sectional and analytical study. Patients treated at the Regional High Specialty Hospital of Ciudad Victoria "Bicentenario 2010" (HRAEV), with a confirmed diagnosis of COVID-19 by RT-PCR and who had a chest computed tomography performed at the institution in the period from March 1, 2020 to July 31, 2020. A descriptive and analytical analysis was carried out. Results: Tomography studies of 44 patients hospitalized in HRAEV who had ARDS and required IOT were analyzed, of which 72.7% were male, the average age was 64 years, of which 47.7% had Diabetes Mellitus, 63.6% with Systemic Arterial Hypertension and 43.1% with some degree of overweight or obesity. Conclusions: The characteristic tomographic finding of patients with ARDS was a mixed type of ground glass and consolidation with severe and generalized involvement. A high mortality rate was observed in these patients with OTI up to 70%.

Trends of Infective Endocarditis at Two Teaching Hospitals: A 12-Year Retrospective Cohort Study in Rio de Janeiro, Brazil.

BACKGROUND: Despite advances in diagnosis and treatment, the incidence and mortality of infective endocarditis (IE) have increased in recent decades. Studies on the risk factors for mortality in endocarditis in Latin America are scarce. METHODS: This retrospective cohort study included 240 patients diagnosed with IE according to the modified Duke criteria who were admitted to two university hospitals in Rio de Janeiro, Brazil from January 2009 to June 2021. Poisson regression analysis was performed for trend tests. The multivariate Cox proportional hazards model was used to estimate the hazard ratio (HR) of predictors of in-hospital mortality. FINDINGS: The median age was 55 years (IQR: 39-66 years), 57% were male, and 41% had a Charlson comorbidity index (CCI) score > 3. Healthcare-associated infective endocarditis (54%), left-sided native valve IE (77.5%), and staphylococcal IE (26%) predominated. Overall, in-hospital mortality was 45.8%, and mortality was significantly higher in the following patients: aged ≥ 60 years (53%), CCI score ≥ 3 (60%), healthcare-associated infective endocarditis (HAIE) (53%), left-sided IE (51%), and enterococcal IE (67%). Poisson regression analysis showed no trend in in-hospital mortality per year. The adjusted multivariate model determined that age ≥ 60 years was an independent risk factor for in-hospital mortality (HR = 1.9; 95% CI 1.2-3.1; p = 0.008). INTERPRETATION: In this 12-year retrospective cohort, there was no evidence of an improvement in survival in patients with IE. Since older age is a risk factor for mortality, consensus is needed for the management of IE in this group of patients.

Role of Relebactam in the Antibiotic Resistance Acquisition in Pseudomonas aeruginosa: In Vitro Study.

BACKGROUND: Pseudomonas aeruginosa shows resistance to several antibiotics and often develops such resistance during patient treatment. OBJECTIVE: Develop an in vitro model, using clinical isolates of P. aeruginosa, to compare the ability of the imipenem and imipenem/relebactam to generate resistant mutants to imipenem and to other antibiotics. Perform a genotypic analysis to detect how the selective pressure changes their genomes. METHODS: The antibiotics resistance was studied by microdilution assays and e-test, and the genotypic study was performed by NGS. RESULTS: The isolates acquired resistance to imipenem in an average of 6 days, and to imipenem/relebactam in 12 days (p value = 0.004). After 30 days of exposure, 75% of the isolates reached a MIC > 64 mg/L for imipenem and 37.5% for imipenem/relebactam (p value = 0.077). The 37.5% and the 12.5% imipenem/relebactam mutants developed resistance to piperacillin/tazobactam and ceftazidime, respectively, while the 87.5% and 37.5% of the imipenem mutants showed resistance to these drugs (p value = 0.003, p value = 0.015). The main biological processes altered by the SNPs were the glycosylation pathway, transcriptional regulation, histidine kinase response, porins, and efflux pumps. DISCUSSION: The addition of relebactam delays the generation of resistance to imipenem and limits the cross-resistance to other beta-lactams. The clinical relevance of this phenomenon, which has the limitation that it has been performed in vitro, should be evaluated by stewardship programs in clinical practice, as it could be useful in controlling multi-drug resistance in P. aeruginosa.

[Barrett's esophagus: histochemical difference between goblet cells and blue cells]. / Esófago de Barrett: diferencia histoquímica entre células caliciformes y células azules.

Background: Barrett's esophagus (BE) is the replacement of the usual esophageal mucosa by a simple columnar epithelium with the presence of goblet cells (GC) of intestinal type. It has been related to different risk factors such as gastroesophageal reflux disease (GERD), inappropriate consumption of irritating foods, smoking and overweight. There are CC mimic cells, known as blue cells (BC), which make the diagnosis of BE difficult, due to the lack of a precise definition of the nature and location of the gastroesophageal junction and the microscopic variations in this area. Objective: To identify morphologically and with histochemical techniques Alcian blue (AA) and periodic acid-Schiff (PAS) between GC and BC. Material and methods: Retrolective cross-sectional analytical study where 45 samples of patients diagnosed with BE were included. Results: The morphological characteristics are similar in both cell varieties. PAS staining was 100%, unlike AA staining, with only 16 cases with staining, corresponding to 35.55%. Conclusions: PAS staining has a high sensitivity and specificity for the identification of GC, this being a fundamental pillar for the correct diagnosis of BE. The presence of BC detected by AA does not exclude the diagnosis of BE, since both cell types can coexist.

Introducción: el esófago de Barrett (EB) es el recambio de la mucosa habitual esofágica por un epitelio cilíndrico simple con presencia de células caliciformes (CC) de tipo intestinal. Se ha relacionado con factores de riesgo como la enfermedad por reflujo gastroesofágico (ERGE), consumo inapropiado de alimentos irritantes, tabaquismo o sobrepeso. Hay células imitadoras de las CC, las células azules (CA), que dificultan el diagnóstico del EB y es debido a falta de una definición precisa sobre la naturaleza y ubicación de la unión gastroesofágica y las variaciones microscópicas en esta zona. Objetivo: identificar morfológicamente y con las técnicas de histoquímica azul alciano (AA) y ácido peryódico de Schiff (PAS) las CC y las CA. Material y métodos: estudio transversal retrolectivo analítico; se incluyeron 45 muestras de pacientes diagnosticados con EB. Resultados: las características morfológicas son similares en ambas variedades celulares. La tinción de PAS fue del 100%, a diferencia de la tinción de AA, con solo 16 casos con tinción, correspondiente al 35.55%. Conclusiones: la tinción de PAS tiene una alta sensibilidad y especificidad para la identificación de CC, lo cual es fundamental para el correcto diagnóstico de la EB. La presencia de CA detectadas mediante AA no excluye el diagnóstico de EB, ya que ambos tipos celulares pueden coexistir.

Phenolysis for Advanced Shoulder Osteoarthritis: A Case Series of a Novel Ultrasound-Guided Approach to Anterior and Posterior Glenohumeral Articular Nerve Branches.

INTRODUCTION: The shoulder is one of the joints most affected by osteoarthritis, with a prevalence of almost 20% in adults over 65 years of age. Various treatments have been proposed to control osteoarthritis pain, including radiofrequency, pulsed and thermal, and recently cryoanalgesia. We propose in this series of cases a new approach to analgesic therapy with chemical denervation with phenol. MATERIALS AND METHOD: Patients who underwent phenolysis for shoulder osteoarthritis at our institutions in Italy and Australia between August 2022 and May 2023 were included. All patients included in our report provided written consent for publication. This chemical neurolysis technique consisted of two injections. First, the anterior shoulder capsule was denervated by a modified deep SHAC (Shoulder Anterior Capsule) approach to cover the anterior terminal articular branches of the axillary nerve, lateral pectoral nerve, and subscapularis nerve. Second, the posterior shoulder capsule was denervated by a posterior glenoid approach to cover the terminal articular branches of the suprascapular nerve (SSN).  Results: We included a total of 11 patients in this case series. Ten of 11 patients were affected by shoulder osteoarthritis, of which three had rotator cuff tendinopathy and three had full-thickness cuff tears. One patient had chronic subluxation of a shoulder prosthesis. After treatment, all patients significantly reduced pain immediately after treatment and, two weeks later, recovered joint movement and improved quality of life. No adverse events or loss of motor function following treatment. CONCLUSION: We presented a novel chemical approach to shoulder denervation, which was shown to be another effective way of improving pain and function in advanced glenohumeral arthritis.