Vitamin D treatment distinctly modulates cytokine production by peripheral blood mononuclear cells among patients with chronic cardiac and indeterminate clinical forms of Chagas disease.

INTRODUCTION: Chagas disease is caused by the protozoan Trypanosoma cruzi and is clinically divided into acute and chronic phases. Chronic Chagas cardiomyopathy is the most studied manifestation of the disease. Vitamin D deficiency has been suggested as a risk factor for cardiovascular disease. No studies demonstrate the action of this hormone in the cells of patients with chronic Chagas heart disease. OBJECTIVE: To evaluate the in vitro immunomodulatory effect of vitamin D on peripheral blood mononuclear cells of patients with the different chronic clinical forms of Chagas disease. Evaluating vitamin D's in vitro effect on blood cells by producing cytokines. METHODS: Thirteen patients of the undetermined form (IND), 13 of the mild cardiac form (CARD1) and 14 of the severe cardiac form (CARD2) of Chagas disease, and 12 with idiopathic heart disease (CARDid) were included. The cells obtained from peripheral blood were treated in vitro with vitamin D (1 × 10-7 M) for 24 h and cytokines were dosed in the culture supernatant. RESULTS: Although it was not possible to demonstrate statistically significant differences between the groups studied, our data showed that the cells treated with vitamin D modify (p < .05) the production of interferon-γ (IFN-γ) (decrease in IND), tumor necrosis factor-α (TNF-α) (decreased in CARD1 and CARDid), interleukin (IL)-6 (increased in all groups), and IL-10 (decreased in CARD1, CARD2, and CARDid) when compared to untreated cells. CONCLUSION: In vitro treatment with vitamin D distinctly modulated the production of cytokines by mononuclear cells of peripheral blood among patients with chronic and indeterminate cardiac clinical forms of Chagas disease.

Seven-day antibiotic therapy for Enterobacterales bacteremia in high-risk neutropenic patients: toward a new paradigm.

PURPOSE: Data on short courses of antibiotic therapy for Enterobacterales bacteremia in high-risk neutropenic patients are limited. The aim of the study was to describe and compare the frequency of bacteremia relapse, 30-day overall and infection-related mortality, Clostridiodes difficile infection and length of hospital stay since bacteremia among those who received antibiotic therapy for 7 or 14 days. METHODS: This is a multicenter, prospective, observational cohort study in adult high-risk neutropenic patients with hematologic malignancies or hematopoietic stem cell transplant and monomicrobial Enterobacterales bacteremia. They received appropriate empirical antibiotic therapy, had a clinical response within 7 days, and infection source control. Clinical, epidemiological and outcomes variables were compared based on 7 or 14 days of AT. RESULTS: Two hundred patients were included (100, 7-day antibiotic therapy; 100, 14-day antibiotic therapy). Escherichia coli was the pathogen most frequently isolated (47.5%), followed by Klebsiella sp. (40.5%). Among those patients that received 7-day vs. 14-day antibiotic course, a clinical source of bacteremia was found in 54% vs. 57% (p = 0.66), multidrug-resistant Enterobacterales isolates in 28% vs. 30% (p = 0.75), and 40% vs. 47% (p = 0.31) received combined empirical antibiotic therapy. Overall mortality was 3% vs. 1% (p = 0.62), in no case related to infection; bacteremia relapse was 7% vs. 2% (p = 0.17), and length of hospital stay since bacteremia had a median of 9 days (IQR: 7-15) vs. 14 days (IQR: 13-22) (p = < 0.001). CONCLUSIONS: These data suggest that seven-day antibiotic therapy might be adequate for patients with high-risk neutropenia and Enterobacterales bacteremia, who receive appropriate empirical therapy, with clinical response and infection source control.

Letermovir Primary Cytomegalovirus Prophylaxis in Allogeneic Hematopoietic Cell Transplant Recipients: Real-Life Data from a University Hospital in Argentina.

Background: Cytomegalovirus (CMV) infection remains the most common clinically significant infection after allogeneic hematopoietic stem cell transplantation (allo-HCT) and is associated with considerable morbidity and mortality. Objectives: The present study was designed to describe and compare the incidence of untreated CMV reactivation (uCMVr), clinically significant infection (cs-CMVi) and disease (CMVd), as well as CMV-related hospitalization and outcome of allo-HCT patients, either treated with letermovir (LET) primary prophylaxis or managed with preemptive therapy (PET). Methods: This is a prospective observational cohort study of adult CMV seropositive allo-HCT patients who either received primary prophylaxis with LET within the first 100 days after HCT or were managed with PET. Results: The study population comprised 105 patients (28 in the LET group and 77 in the PET group). Compared to the PET group, patients in the LET group received more allo-HCT from alternative donors (54.5% vs. 82.14%, P=0.012). More than half of the patients in both groups were classified as high risk for CMVd. In the LET vs. PET group, cs-CMVi and CMVd developed respectively in 0 vs. 50 (64.94%), P=<0.0001, and 0 vs. 6 (7.79%), P=0.18. In the LET group, uCMVr occurred in 5 (17.8%) and were all considered blips. Hospital admissions related to cs-CMVi or CMVd in the PET group vs. LET group were 47 (61.04%) vs. 0, respectively, P=<0.0001. No differences were observed in 100-day mortality. Conclusions: LET primary prophylaxis proved effective in preventing cs-CMVi and CMVd and reducing hospitalizations in allo-HCT adults. Blips can occur during prophylaxis and do not require LET discontinuation.

Interaction between peripheral blood mononuclear cells and Trypanosoma cruzi-infected adipocytes: implications for treatment failure and induction of immunomodulatory mechanisms in adipose tissue.

Background/Introduction: Adipose tissue (AT) has been highlighted as a promising reservoir of infection for viruses, bacteria and parasites. Among them is Trypanosoma cruzi, which causes Chagas disease. The recommended treatment for the disease in Brazil is Benznidazole (BZ). However, its efficacy may vary according to the stage of the disease, geographical origin, age, immune background of the host and sensitivity of the strains to the drug. In this context, AT may act as an ally for the parasite survival and persistence in the host and a barrier for BZ action. Therefore, we investigated the immunomodulation of T. cruzi-infected human AT in the presence of peripheral blood mononuclear cells (PBMC) where BZ treatment was added. Methods: We performed indirect cultivation between T. cruzi-infected adipocytes, PBMC and the addition of BZ. After 72h of treatment, the supernatant was collected for cytokine, chemokine and adipokine assay. Infected adipocytes were removed to quantify T. cruzi DNA, and PBMC were removed for immunophenotyping. Results: Our findings showed elevated secretion of interleukin (IL)-6, IL-2 and monocyte chemoattractant protein-1 (MCP-1/CCL2) in the AT+PBMC condition compared to the other controls. In contrast, there was a decrease in tumor necrosis factor (TNF) and IL-8/CXCL-8 in the groups with AT. We also found high adipsin secretion in PBMC+AT+T compared to the treated condition (PBMC+AT+T+BZ). Likewise, the expression of CD80+ and HLA-DR+ in CD14+ cells decreased in the presence of T. cruzi. Discussion: Thus, our findings indicate that AT promotes up-regulation of inflammatory products such as IL-6, IL-2, and MCP-1/CCL2. However, adipogenic inducers may have triggered the downregulation of TNF and IL-8/CXCL8 through the peroxisome proliferator agonist gamma (PPAR-g) or receptor expression. On the other hand, the administration of BZ only managed to reduce inflammation in the microenvironment by decreasing adipsin in the infected culture conditions. Therefore, given the findings, we can see that AT is an ally of the parasite in evading the host's immune response and the pharmacological action of BZ.

TNF blockers alone and associated with Benznidazole impact in vitro cytokine dynamics in chronic Chagas disease.

Studies involving the immune response in Chagas disease suggest an imbalance in the immune response of symptomatic patients, with an inflammatory profile dominating in Chagas heart disease, mainly by tumour necrosis factor (TNF). TNF is considered a key cytokine in immunopathology in chronic carriers in several processes during the immune response. Our work aimed to evaluate regulatory (interleukin [IL]-4 and IL-10) and inflammatory (TNF, interferon-gamma [IFN-γ], IL-2 and IL-6) cytokines in peripheral blood mononuclear cells culture supernatants. of affected patients with undetermined clinical forms-IND (n = 13) mild heart form-CARD1 (n = 13) and severe cardiac form-CARD2 (n = 16), treated in vitro with two TNF blockers, Adalimumab (ADA) and Etanercept (ETA) alone or in association with Benznidazole (BZ). The results indicate that ADA was more competent in blocking TNF (compared to ETA) in all groups but with much lower levels in the CARD2 group. ETA statistically decreased TNF levels only in the CARD2 group. IFN-γ increased in the CARD2 group after treatment with ETA relative to ADA. IL-4 had its levels decreased when treated by both drugs. IL-2 was detected in cells from CARD2 carriers compared to the NEG group after treatment with both drugs. The association with BZ decreased levels of IL-2/TNF and increased IL-4. These data reinforce the participation of TNF in severe Chagas heart disease and bring perspectives on using these blockers in the immunological treatment of Chagas disease since the use of BZ is extremely limited in these patients.

Etiología, clínica y evolución de infecciones fúngicas invasoras en pacientes con neoplasias hematológicas en un hospital universitario de Argentina / Etiology, clinical characteristics and outcomes of invasive fungal infection in patients with hematological malignancies in a university hospital in Argentina

INTRODUCCIÓN: Las infecciones fúngicas invasoras (IFI) en pacientes con neoplasias hematológicas (NH) representan un desafío diagnóstico y terapéutico. OBJETIVOS: Describir la etiología, características clínicas, diagnóstico y evolución de los episodios de IFI probadas y probables en pacientes con NH y trasplante de progenitores hematopoyéticos (TPH). PACIENTES Y MÉTODOS: Estudio descriptivo, retrospectivo y de cohorte que incluyó IFI probadas y probables en pacientes adultos con NH y TPH. Se realizó seguimiento hasta el día 90. RESULTADOS: Se incluyeron 80 episodios de IFI: 49% probadas y 51% probables, 67,5% por hongos filamentosos (HF), 30% por hongos levaduriformes (HL) y 2,5% por hongos dimorfos. Los tipos de IFI más frecuentes fueron aspergilosis invasoras pulmonares (AP) y candidiasis invasoras (CI), en su mayoría por Candida spp. no albicans. Todos los casos de AP se diagnosticaron por detección de galactomanano en sangre y/o lavado broncoalveolar, y solamente 22,2% presentaban nódulos con halo en la tomografía computada (TC) de tórax, siendo los infiltrados inespecíficos los hallazgos más frecuentes. Tuvieron coinfección bacteriana y viral el 30 y 17,5%, respectivamente. El 50% fueron IFI de brecha, y la mortalidad global y mortalidad relacionada a la IFI fue 51 y 24%, respectivamente. CONCLUSIÓN: Los HF fueron la principal causa de IFI, con una gran proporción de IFI de brecha, y presentaron elevada mortalidad. Para el diagnóstico, resulta importante la utilización de biomarcadores y jerarquizar cualquier imagen patológica en la TC.

BACKGROUND: Invasive fungal infections (IFI) in patients with hematological malignancies (HM) represent a diagnostic and therapeutic challenge. AIM: To describe the etiology, clinical characteristics, diagnosis and evolution of proven and probable IFI episodes in patients with HM and hematopoietic stem cell transplantation (HSCT). METHODS: Retrospective, descriptive, cohort study performed in adult patients with HM and HSCT, who developed proven and probable IFI. Follow-up was carried out until day 90. RESULTS: A total of 80 IFI episodes were included: 49% proven and 51% probable, 67,5% due to mold (M), 30% to yeast-like fungi (Y) and 2,5% to dimorphic fungi. The most frequent causes were probable pulmonary aspergillosis (PA) and invasive candidiasis (IC), mainly due to non-albicans Candida species. PA were all diagnosed by detection of galactomannan (GM) in blood and bronchoalveolar lavage, and only 22,2% presented halo sign on chest CT. Bacterial and viral coinfections were reported in 30% and 17,5% respectively. Breakthrough IFI occurred in 50%, and global and IFI-related mortality were 51% and 24% respectively. CONCLUSION: Mold was the main cause of IFI, with a large proportion of breakthrough IFI, presenting high mortality. The use of biomarkers and the classification of any pathological image on CT contribute to the diagnosis.

Ceftazidima/avibactam frente a otros antimicrobianos para el tratamiento de bacteriemias por Enterobacterales productores de carbapenemasa KPC: datos de la vida real en un hospital universitario de Argentina / Ceftazidime/avibactam versus other antibiotics for the treatment of KPC carbapenemase-producing Enterobacterales bacteremia: real-life data from a university hospital in Argentina

INTRODUCCIÓN: Las bacteriemias por Enterobacterales productores de carbapenemasa KPC (EPC-KPC) presentan una mortalidad elevada y opciones terapéuticas limitadas. OBJETIVOS: Describir y comparar la evolución de los pacientes con bacteriemia por EPC-KPC tratados con ceftazidima/avibactam (CA) frente a otros antimicrobianos (OA). PACIENTES Y MÉTODOS: Estudio prospectivo y retrospectivo de casos y controles. Se incluyeron pacientes adultos con bacteriemia por EPC-KPC, con una proporción entre casos tratados con CA y controles tratados con OA. de 1:2. Se analizaron variables clínicas, epidemiológicas y de evolución. RESULTADOS: Se incluyeron 48 pacientes (16 CA y 32 OA). Los casos se encontraban más frecuentemente neutropénicos (50 vs.16%, p = 0,012); asimismo, presentaron medianas de score de APACHE II más altas y de score de Pitt más bajas. El 65% de la cohorte total presentó un foco clínico y Klebsiellapneumoniae fue el microorganismo más frecuentemente aislado. Los casos recibieron una mayor proporción de tratamiento antimicrobiano empírico adecuado (81 vs. 53%, p = 0,05). La antibioterapia dirigida en casos y controles fue combinada en 38 y 91%, p = 0,009. Los casos presentaron menor mortalidad al día 7 y al día 30 relacionada a infección (0 vs. 22%, p = 0,04 y 0 vs. 34%, p = 0,008). Solo los controles desarrollaron shock, ingresaron a la unidad de cuidados intensivos y presentaron bacteriemia de brecha. CONCLUSIÓN: CA mostró beneficio clínico frente a OA para el tratamiento de pacientes con bacteriemia por EPC-KPC.

BACKGROUND: KPC-producing Enterobacterales bacteremia (KPCCPE) is associated with a high mortality rate and limited therapeutic options. AIM: To describe and compare the outcome of patients with KPC-CPE bacteremia treated with ceftazidime/avibactam (CA) versus other antibiotics (OA). METHODS: Prospective and retrospective cases and control study performed in adult patients with KPC-CPE bacteremia, with a 1:2 ratio between cases treated with CA. and controls treated with OA. Clinical, epidemiological, and outcome variables were analyzed. RESULTS: Forty-eight patients (16 CA and 32 OA) were included. Cases were more frequently neutropenic (50 vs. 16%, p = 0.012), presented higher median APACHE II score and lower Pitt score. Of the total cohort, 65% had a clinical source, and Klebsiella pneumoniae was the most frequently isolated microorganism. Cases received more adequate empirical antibiotic treatment (81 vs. 53%, p = 0.05). Targeted antibiotic therapy in cases and controls was combined in 38 and 91%, p = 0.009. Cases had a lower 7-day mortality and 30-day infection-related mortality (0 vs. 22%, p = 0.04 and 0 vs. 34%, p = 0.008). Only controls developed shock, were admitted to the intensive care unit, and had breakthrough bacteremia. CONCLUSION: CA. showed clinical benefit over OA in the treatment of patients with EPC-KPC bacteremia.

Letermovir para prevención de la infección por citomegalovirus en receptores de trasplante alogénico de progenitores hematopoyéticos / Letermovir for prevention of cytomegalovirus infection in allogeneic stem cell transplant receivers

INTRODUCCIÓN: La infección por citomegalovirus (CMV) sigue siendo la infección con relevancia clínica más frecuente luego del trasplante alogénico de progenitores hematopoyéticos (TPHa), presentando alta morbilidad y mortalidad. Por este motivo, es importante implementar estrategias de prevención para reducir la frecuencia de la infección por CMV. OBJETIVO: Describir la frecuencia de infección, infección clínicamente significativa (ICS) y enfermedad por CMV en pacientes seropositivos que recibieron un TPHa y profilaxis primaria con letermovir. PACIENTES Y MÉTODOS: Estudio descriptivo de cohorte longitudinal, en pacientes con TPHa seropositivos para CMV que recibieron profilaxis primaria con letermovir hasta el día 100 posTPH. RESULTADOS: Se incluyeron 25 pacientes adultos con una mediana de edad de 41 años, el 44% fue de donante no relacionado y 36% de donante haploidéntico. Ochenta por ciento tenía tres o más factores de riesgo para infección por CMV y a 52% se le estratificó como de alto riesgo para enfermedad por CMV. La profilaxis con letermovir tuvo una mediana de duración de 97 días. Durante los 100 días pos-TPH, 20% de los pacientes presentaron infección por CMV, con carga viral plasmática detectable no cuantificable, que se negativizó en el siguiente control semanal sin discontinuación del letermovir. Ningún paciente presentó ICS ni enfermedad por CMV durante este período. CONCLUSIÓN: La profilaxis con letermovir fue efectiva para prevenir la ICS y la enfermedad por CMV.

BACKGROUND: Cytomegalovirus (CMV) infection remains the most common clinically significant infection after allogeneic stem cell transplantation (aSCT), with a high morbidity and mortality rate. In order to reduce its frequency, prevention strategies should be implemented. AIM: To describe the frequency of infection, clinically significant infection (CSI) and CMV disease in seropositive patients who received aSCT and primary prophylaxis with letermovir. METHODS: Longitudinal descriptive cohort study in seropositive patients who received aSCT and primary prophylaxis with letermovir until day 100 post-SCT. RESULTS: Twenty-five adult patients with a median age of 41 years were included; 44% were unrelated donors, and 36% were haploidentical donors. Eighty percent had three or more risk factors for CMV infection, and 52% were stratified as high risk for CMV disease. Letermovir prophylaxis had a median duration of 97 days. Twenty percent of the patients developed CMV infection through day 100 post-SCT, with detectable non-quantifiable CMV viral load in plasma. This became negative in the following weekly control without discontinuation of letermovir. No patient developed CSI or CMV organ disease during this period. CONCLUSION: Letermovir prophylaxis proved to be effective in preventing CSI and CMV disease.

Chromatin access regulates the formation of Müller glia-derived progenitor cells in the retina.

Chromatin access and epigenetic control over gene expression play important roles in regulating developmental processes. However, little is known about how chromatin access and epigenetic gene silencing influence mature glial cells and retinal regeneration. Herein, we investigate the expression and functions of S-adenosylhomocysteine hydrolase (SAHH; AHCY) and histone methyltransferases (HMTs) during the formation of Müller glia (MG)-derived progenitor cells (MGPCs) in the chick and mouse retinas. In chick, AHCY, AHCYL1 and AHCYL2, and many different HMTs are dynamically expressed by MG and MGPCs in damaged retinas. Inhibition of SAHH reduced levels of H3K27me3 and potently blocks the formation of proliferating MGPCs. By using a combination of single cell RNA-seq and single cell ATAC-seq, we find significant changes in gene expression and chromatin access in MG with SAHH inhibition and NMDA-treatment; many of these genes are associated with glial and neuronal differentiation. A strong correlation across gene expression, chromatin access, and transcription factor motif access in MG was observed for transcription factors known to convey glial identity and promote retinal development. By comparison, in the mouse retina, inhibition of SAHH has no influence on the differentiation of neuron-like cells from Ascl1-overexpressing MG. We conclude that in the chick the activity of SAHH and HMTs are required for the reprogramming of MG into MGPCs by regulating chromatin access to transcription factors associated with glial differentiation and retinal development.

Development of a Clinical Score to Stratify the Risk for Carbapenem-Resistant Enterobacterales Bacteremia in Patients with Cancer and Hematopoietic Stem Cell Transplantation.

Identifying the risk factors for carbapenem-resistant Enterobacterales (CRE) bacteremia in cancer and hematopoietic stem cell transplantation (HSCT) patients would allow earlier initiation of an appropriate empirical antibiotic treatment. This is a prospective multicenter observational study in patients from 12 centers in Argentina, who presented with cancer or hematopoietic stem-cell transplant and developed Enterobacterales bacteremia. A multiple logistic regression model identified risk factors for CRE bacteremia, and a score was developed according to the regression coefficient. This was validated by the bootstrap resampling technique. Four hundred and forty-three patients with Enterobacterales bacteremia were included: 59 with CRE and 384 with carbapenem-susceptible Enterobacterales (CSE). The risk factors that were identified and the points assigned to each of them were: ≥10 days of hospitalization until bacteremia: OR 4.03, 95% CI 1.88-8.66 (2 points); previous antibiotics > 7 days: OR 4.65, 95% CI 2.29-9.46 (2 points); current colonization with KPC-carbapenemase-producing Enterobacterales: 33.08, 95% CI 11.74-93.25 (5 points). With a cut-off of 7 points, a sensitivity of 35.59%, specificity of 98.43%, PPV of 77.7%, and NPV of 90.9% were obtained. The overall performance of the score was satisfactory (AUROC of 0.85, 95% CI 0.80-0.91). Finally, the post-test probability of CRE occurrence in patients with none of the risk factors was 1.9%, which would virtually rule out the presence of CRE bacteremia.

Short Course of Antibiotic Therapy for Gram-Negative Bacilli Bacteremia in Patients with Cancer and Hematopoietic Stem Cell Transplantation: Less Is Possible.

Data about short courses of antibiotic therapy for Gram-negative bacilli (GNB) bacteremia in immunosuppressed patients are limited. This is a prospective observational study performed on adult patients with cancer and hematopoietic stem cell transplant (HSCT) who developed GNB bacteremia and received appropriate empirical antibiotic therapy (EAT), had a clinical response within 7 days and survived 48 h after the end of therapy. They received antibiotic therapy in the range of 7-15 days and were divided into short course, with a median of 7 days (SC), or long course, with a median of 14 days (LC). Seventy-four patients were included (SC: 36 and LC: 38). No differences were observed in baseline characteristics or in the presence of neutropenia: 58.3% vs. 60.5% (p = 0.84). Clinical presentation and microbiological characteristics were similar in SC and LC, respectively: clinical source of bacteremia 72.2% vs. 76.3% (p = 0.68); shock 2.8% vs. 10.5% (p = 0.35) and multidrug-resistant GNB 27.8% vs. 21.1% (p = 0.50). Overall, mortality was 2.8% vs. 7.9% (p = 0.61), and bacteremia relapse was 2.8% vs. 0 (p = 0.30). The length of hospitalization since bacteremia was 7 days (interquartile range (IQR), 6-15) for SC and 12 days (IQR, 7-19) (p = 0.021) for LC. In the case of patients with cancer or HSCT and GNB bacteremia who receive appropriate EAT with clinical response, 7 days of antibiotic therapy might be adequate.

12-Year-Old Girl Diagnosed With Li-Fraumeni Syndrome and Concomitant Adrenocortical Carcinoma (ACC).

Adrenocortical carcinomas (ACC) are classical presentations of germline cancer predisposition syndromes such as the Li-Fraumeni syndrome (LFS). Li-Fraumeni syndrome is a multiple cancer syndrome caused by germline alterations of the tumor protein 53 (TP53) tumor suppressor gene and is often associated with ACC. If minor adrenocortical tumors (ACTs) are detected early, resection has proven to provide patients with better outcomes. However, non-functioning ACCs are particularly insidious since these patients present late and with distant metastases. We present the case of a 12-year-old female with a history of Li-Fraumeni syndrome (LFS) and a non-hormone-secreting ACC in the context of an exceedingly rare c.743G>A (p.Arg248Gln) p53 mutation.

Behavior of echocardiographic parameters of right ventricular function after tricuspid surgery.

Evaluation of right ventricular (RV) function after tricuspid valve surgery is complex. The objective was to identify the most appropriate RV function parameters for this purpose. This prospective study included 70 patients undergoing cardiac and tricuspid valve (TV) surgery. RV size and function parameters were determined at 3 months and 1-year post-surgery. Categorical variables were analyzed with the McNemar test and numerical variables with the Student's t-test for related samples or, when non-normally distributed, the Wilcoxon test. Spearman's rho was used to determine correlations between variables at 3 months and 1 year. RV diameters were reduced at 3 months post-surgery and were then unchanged at 1 year. Tricuspid annular plane systolic excursion (TAPSE) and S' wave values were worse at 3 months and then improved at 1 year (t-score-2.35, p 0.023; t-score-2.68; p 0.010). There was no significant reduction in free wall longitudinal strain (LS) or shortening fraction (SF) at 3 months (t-score 1.421 and - 1.251; p 0.218 and 0.172), and they were only slightly below pre-surgical values at 1 year. No relationship was found between RV function parameters and mortality or major complications. During the first few months after TV surgery, LS may be a more appropriate parameter to evaluate global ventricular function in comparison to TAPSE. At 1 year, good correlations are observed between TAPSE, S' wave, and LS values.

Infective endocarditis on interventricular communication as cause of massive haemoptysis: a case report.

Background: Haemoptysis is a rare symptom associated with endocarditis. We describe the unusual clinical manifestation of endocarditis on regurgitant bicuspid aortic valve and (probably) secondarily on a perimembranous ventricular septal defect (VSD) as massive haemoptysis. Case summary: A 24-year-old male with aortic coarctation, bicuspid aortic valve, and VSD since birth. Previously asymptomatic, he came after an episode of haemoptysis. A computed tomography (CT) scan showed a cavitated lesion in lung. Streptococo viridans was identified in serial blood cultures. Transthoracic echocardiography showed a bicuspid aortic valve with vegetations, suggesting infectious involvement, and severe aortic insufficiency. Transoesophageal echocardiography (TEE) study showed a bicuspid aortic valve with complete fusion of coronary valves. An elongated oscillating tumour, 9.5 mm in length, was observed in the centre of the ventricular side of the non-coronary valve. Another vegetation was seen on the VSD. During his hospital stay and under antibiotic treatment, he reported abdominal pain. Computed tomography examination showed splenic infarction. In the echocardiogram no vegetation masses were observed on the aortic valve or on the VSD closure aneurysm. Discussion: The main debate about this patient's treatment concerned the indication of surgery, especially after the onset of fever with splenic septic embolism while under appropriate antibiotic treatment. He was stable, with no signs of heart failure and the echocardiogram repeated after the septic splenic embolism showed no residual vegetations on the aortic valve or VSD, and the TEE study ruled out a local complication. Finally, the multidisciplinary team decided against surgical management.

Reducing bacterial adhesion to titanium surfaces using low intensity alternating electrical pulses.

BACKGROUND: Orthopedic implant-related infection remains one of the most serious complications after orthopedic surgery. In recent years, there has been an increased scientific interest to improve prevention and treatment strategies. However, many of these strategies have focused on chemical measures. AIM: To analyze the effect of alternating current electrical fields on bacterial adherence to titanium surfaces. METHODS: Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli) were exposed to 6.5 V electrical currents at different frequencies: 0.5 Hz, 0.1 Hz, and 0.05 Hz. After exposure, a bacterial count was then performed and compared to the control model. Other variables registered included the presence of electrocoagulation of the medium, electrode oxidation and/or corrosion, and changes in pH of the medium. RESULTS: The most effective electrical model for reducing S. aureus adhesion was 6.5 V alternating current at 0.05 Hz achieving a 90% adhesion reduction rate. For E. coli, the 0.05 Hz frequency model also showed the most effective results with a 53% adhesion reduction rate, although these were significantly lower than S. aureus. Notable adhesion reduction rates were observed for S. aureus and E.coli in the studied conditions. However, the presence of electrode oxidation makes us presume these conditions are not optimal for in vivo use. CONCLUSION: Although our findings suggest electrical currents may be useful in preventing bacterial adhesion to metal surfaces, further research using other electrical conditions must be examined to consider their use for in vivo trials.

Surgical management of tricuspid regurgitation: a new algorithm to minimise recurrent tricuspid regurgitation.

INTRODUCTION: Recurrent tricuspid regurgitation (TR) is frequently observed after cardiac surgery; however, the correct approach remains controversial. We developed an algorithm for action on the tricuspid valve (TV) and conducted a 1-year follow-up study. The aim was to assess the efficacy of the algorithm to minimise residual TR after TV surgery. The hypothesis was that the TR rate at 1 year would be reduced by selecting the surgical approach in accordance with a set of preoperative clinical and echocardiographic variables. METHODS: A prospective, observational, single-centre study was performed in 76 consecutive patients with TV involvement. A protocol was designed for their inclusion, and data on their clinical and echocardiographic characteristics were gathered at 3 months and 1-year postsurgery. The treatment of patients depended on the degree of TR. Surgery was performed in all patients with severe or moderate-to-severe TR and in those with mild or moderate TR alongside the presence of certain clinical or echocardiographic factors. They underwent annuloplasty or extended valve repair when the TV was distorted. If repair techniques were not feasible, a prosthesis was implanted. Residual TR rates were compared with published reports, and predictors of early/late mortality and residual TR were evaluated. RESULTS: TR was functional in 69.9% of patients. Rigid ring annuloplasty was performed in 35.7% of patients, De Vega annuloplasty in 27.1%, extended repair in 11.4% and prosthetic replacement in 25.7%. TR was moderate or worse in 8.19% of patients (severe in 3.27%) at 1 year postintervention. No clinical, surgical or epidemiological variables were significantly associated with residual TR persistence, although annulus diameter showed a close-to-significant association. Total mortality was 12.85% for all causes and 10% for cardiovascular causes. In multivariate analysis, left ventricular ejection fraction was related to both early and late mortality. CONCLUSIONS: Severe residual TR was significantly less frequent than reported in other series, being observed in less than 4% of patients at 1-year postsurgery.

Is a negative correlation between sTNFR1 and TNF in patients with chronic Chagas disease the key to clinical progression?

Soluble TNF receptors (sTNFR1 and sTNFR2) are natural endogenous inhibitors of TNF and are elevated in inflammatory, autoimmune, and chronic degenerative diseases. In Chagas disease, pleiotropic cytokine TNF is considered key in immunopathology. Thus, we aimed to evaluate the levels of TNF, sTNFR1, and sTNFR2 in the serum of patients with chronic Chagas disease. TNF and its soluble receptors were quantified using Cytometric Bead Array in the serum of 132 patients, of which 51 had the indeterminate form (IND), 39 the mild cardiac form (CARD 1), 42 the severe cardiac form (CARD 2), and 20 non-infected individuals (NI). The results indicate that the soluble receptors may regulate TNF in Chagas disease, as their leves were higher in T. cruzi-infected individuals when compared to non-infected individuals. We found a moderate negative correlation between sTNFR1 and TNF in individuals with the IND form, suggesting a relationship with non-progression to more severe forms, such as heart disease. sTNFR1 and sTNFR2 were increased in all clinical forms, but with a moderate positive correlation in more severe patients (r = 0.50 and p = 0.0005). TNF levels showed no statistical differences in the groups of patients. These findings suggest the importance of the endogenous balance of the levels of soluble TNF receptors in the protection and balance in patients with chronic Chagas disease, besides revealing the immunological complexity in chronic T. cruzi-infected individuals.

Clinical and surgical implications of the pulmonary azygos lobe: a systematic review / Implicaciones clínicas y quirúrgicas del lóbulo ácigos pulmonar: una revisión sistemática

SUMMARY: Azygos lobe is one of the most common pulmonary variations. Although numerous studies discuss to the clinical and surgical implications of anatomical variations, there are few investigations about this topic. The aim of this study was to discuss the anatomy of the pulmonary azygos lobe and its possible clinical and surgical correlations. In this systematic review, a total of 48 results were found between 1968 and 2020. After application of eligibility criteria, 16 articles were included to analysis. Our results showed there were no reports of surgery complications in azygos lobe presence. In all articles that described the anatomical variation, the pulmonary azygos lobe received tertiary segmental branches. Among the surgical implications in the presence of the azygos lobe, complications are of low complexity. It is necessary to teach about this anatomical variation in medical schools in cadavers. Emphasizing the obvious morphological modifications in the superior mediastinum.

RESUMEN: El lóbulo ácigos es una de las variaciones pulmonares más comunes. Aunque numerosos estudios discuten las implicaciones clínicas y quirúrgicas de las variaciones anatómicas, existen pocas investigaciones sobre este tema. El objetivo de este estudio fue discutir la anatomía del lóbulo ácigos pulmonar y sus posibles correlaciones clínicas y quirúrgicas. En esta revisión sistemática se encontraron un total de 48 resultados entre los años 1968 y 2020. Después de la aplicación de los criterios de elegibilidad, 16 artículos fueron incluidos para análisis. Nuestros resultados mostraron que no hubo informes de complicaciones quirúrgicas en presencia del lóbulo ácigos. En todos los artículos que describieron la variación anatómica, el lóbulo ácigos pulmonar recibió ramas segmentarias terciarias. Dentro de las implicaciones quirúrgicas en presencia del lóbulo ácigos, las complicaciones son de baja complejidad. En las escuelas de medicina es necesaria la enseñanza en cadáveres de esta variación anatómica, destacando las evidentes modificaciones morfológicas en el mediastino superior.

Uncommon presentation of coronary sinus endocarditis.

A 79-year-old man, who underwent femoropopliteal bypass surgery 1 month prior to admission, presented with fever and fatigue. ECG showed complete atrioventricular block. Transthoracic echocardiography was performed, revealing a round homogeneous right atrial mass and severe mitral regurgitation. Transoesophageal echocardiography revealed involvement the coronary sinus (CS). Computed tomography imaging demonstrated abscess of the atrioventricular sulcus and infiltration of the CS.

Signs of Central Hypersensitivity, Stress, and Anxiety following Treatment for Breast Cancer: A Case Control Study.

BACKGROUND: With treatment for breast cancer, women treated may present significant sensory abnormalities in the upper extremity. However, there are no conclusive studies that have evaluated pressure pain thresholds (PPT) in the shoulder of postoperated women for breast cancer. The aim of this study was to compare PPT in the shoulder, stress, anxiety, depression symptoms, and quality of sleep among postoperated women for breast cancer (PO group) and asymptomatic women of shoulder pain (control group). METHODS: 40 women participated (n = 20, PO group, age: average ± standard deviation, 49.2 ± 8.3 years; body mass index (BMI): 27.5 ± 3.0 kg/cm2; surgery time: 22.2 ± 34.4 months; n = 20, control group, 46.9 ± 8.1 years; BMI: 26.8 ± 3.5 kg/cm2). The PPT was evaluated with a digital algometer at 32 points in the shoulder region and one control point in the tibialis anterior. Stress, anxiety, and depression were evaluated with the Depression, Anxiety and Stress Scale 21 (DASS-21) and the quality of sleep by the Pittsburgh Sleep Quality Index. RESULTS: Significant differences were observed over 1.5 kgf/cm2 in 33 points evaluated (p < 0.01) with a small to high effect size (Cliff's delta range = 0.16; 0.92) and higher levels of anxiety and stress in the PO group (anxiety: median [first; third quartile], 5[3; 12.5]; stress: 9.7 ± 4.7 (7.8; 11.8)) in comparison with the control group (anxiety: 2.5[1; 4.8]; stress: 6.7 ± 3.31 (5.2; 8.3), (p < 0.05)). No significant differences were found between the groups in depression and sleep quality (p > 0.05). CONCLUSION: Postoperated women for breast cancer present hyperalgesia in the shoulder anterior and posterior region, low PPT in the tibialis anterior, and higher levels of stress and anxiety compared to the control group.