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Background: The impact of immunosuppression in solid organ transplant recipients with SARS-CoV-2 infection is unknown. The knowledge about the behavior of different immunosuppression schemes in clinical outcomes is scarce. This study aimed to determine the risk of death in kidney transplant recipients with COVID-19 under two different schemes of immunosuppression. Methods: We describe our experience in kidney transplant recipients with SARS-CoV-2 infection in seven transplant centers during the first year of the pandemic before starting the vaccination programs in the city of Bogotá. Demographic characteristics, clinical presentation, immunosuppression schemes at presentation, and global treatment strategies were compared between recovered and dead patients; survival analysis was carried out between calcineurin inhibitors based regimen and free calcineurin inhibitors regimen. Results: Among 165 confirmed cases, 28 died (17%); the risk factors for mortality identified in univariate analysis were age older than 60 years (p = .003) diabetes (p = .001), immunosuppression based on calcineurin inhibitors (CNI) (p = .025) and patients receiving steroids (p = .041). In multivariable analysis, hypoxemia (p = .000) and calcineurin inhibitors regimen (p = .002) were predictors of death. Survival analysis showed increased mortality risk in patients receiving CNI based immunosuppression regimen vs. CNI free regimens mortality rates were, respectively, 21.7% and 8.5% (p = .036). Conclusions: Our results suggest that the calcineurin inhibitors probably do not provide greater protection compared to calcineurin inhibitor free schemes being necessary to carry out analyzes that allow us to evaluate the outcomes with different immunosuppression schemes in solid organ transplant recipients with SARS-CoV-2 infection. Resumen: Introducción: El impacto de los diferentes esquemas de inmunosupresión en receptores de trasplante de órganos sólidos es desconocido. El conocimiento del comportamiento de la enfermedad bajo diferentes esquemas de inmunosupresión es escaso. Nuestra experiencia intenta determinar el riesgo de muerte en receptores de trasplante renal con COVID-19 bajo dos esquemas diferentes de inmunosupresión. Métodos: Describimos la experiencia en receptores de trasplante renal con infección por SARS-CoV-2 en siete centros de trasplante renal en la ciudad de Bogotá, durante el primer año de pandemia y previo al inicio de los programas de vacunación. Las características demográficas, la presentación clínica, los esquemas de inmunosupresión y las estrategias de tratamiento fueron comparadas entre pacientes recuperados y fallecidos, un análisis de sobrevida fue llevado a cabo entre esquemas basados en inhibidores de calcineurina y esquemas libres de inhibidores de calcineurina. Resultados: Entre los 165 casos confirmados, 28 murieron (17%), los factores de riesgo identificados para mortalidad en el análisis univariado fueron: edad mayor de 60 años, diabetes, un esquema de inmunosupresión basado en inhibidores de calcineurina y pacientes recibiendo esteroides en el momento del diagnóstico. En el análisis multivariado, la presencia de hipoxemia en el momento del diagnóstico (p = 0,000) y un esquema de inmunosupresión basado en inhibidores de calcineurina (p = 0,002) fueron predictores independientes de mortalidad. El análisis de sobrevida encontró un riesgo mayor de mortalidad en pacientes bajo esquemas de inmunosupresión con inhibidores de calcineurina vs. aquellos libres de inhibidores de calcineurina, con tasas de mortalidad respectivas en 21,7 y 8,5% (p = 0,036). Conclusiones: Nuestros resultados sugieren que los inhibidores de calcineurina no aportan mayor protección en pacientes con trasplante renal y COVID-19 en comparación con esquemas libres de inhibidores de calcineurina, siendo necesario realizar análisis que permitan evaluar los desenlaces con diferentes esquemas de inmunosupresión en receptores de trasplante renal con infección por SARS-CoV-2.

Background: The impact of immunosuppression in solid organ transplant recipients with SARS-CoV-2 infection is unknown. The knowledge about the behavior of different immunosuppression schemes in clinical outcomes is scarce. This study aimed to determine the risk of death in kidney transplant recipients with COVID-19 under two different schemes of immunosuppression. Methods: We describe our experience in kidney transplant recipients with SARS-CoV-2 infection in seven transplant centers during the first year of the pandemic before starting the vaccination programs in the city of Bogotá. Demographic characteristics, clinical presentation, immunosuppression schemes at presentation, and global treatment strategies were compared between recovered and dead patients; survival analysis was carried out between calcineurin inhibitors based regimen and free calcineurin inhibitors regimen. Results: Among 165 confirmed cases, 28 died (17%); the risk factors for mortality identified in univariate analysis were age older than 60 years (p = .003) diabetes (p = .001), immunosuppression based on calcineurin inhibitors (CNI) (p = .025) and patients receiving steroids (p = .041). In multivariable analysis, hypoxemia (p = .000) and calcineurin inhibitors regimen (p = .002) were predictors of death. Survival analysis showed increased mortality risk in patients receiving CNI based immunosuppression regimen vs. CNI free regimens mortality rates were, respectively, 21.7% and 8.5% (p = .036). Conclusions: Our results suggest that the calcineurin inhibitors probably do not provide greater protection compared to calcineurin inhibitor free schemes being necessary to carry out analyzes that allow us to evaluate the outcomes with different immunosuppression schemes in solid organ transplant recipients with SARS-CoV-2 infection. Resumen: Introducción: El impacto de los diferentes esquemas de inmunosupresión en receptores de trasplante de órganos sólidos es desconocido. El conocimiento del comportamiento de la enfermedad bajo diferentes esquemas de inmunosupresión es escaso. Nuestra experiencia intenta determinar el riesgo de muerte en receptores de trasplante renal con COVID-19 bajo dos esquemas diferentes de inmunosupresión. Métodos: Describimos la experiencia en receptores de trasplante renal con infección por SARS-CoV-2 en siete centros de trasplante renal en la ciudad de Bogotá, durante el primer año de pandemia y previo al inicio de los programas de vacunación. Las características demográficas, la presentación clínica, los esquemas de inmunosupresión y las estrategias de tratamiento fueron comparadas entre pacientes recuperados y fallecidos, un análisis de sobrevida fue llevado a cabo entre esquemas basados en inhibidores de calcineurina y esquemas libres de inhibidores de calcineurina. Resultados: Entre los 165 casos confirmados, 28 murieron (17%), los factores de riesgo identificados para mortalidad en el análisis univariado fueron: edad mayor de 60 años, diabetes, un esquema de inmunosupresión basado en inhibidores de calcineurina y pacientes recibiendo esteroides en el momento del diagnóstico. En el análisis multivariado, la presencia de hipoxemia en el momento del diagnóstico (p = 0,000) y un esquema de inmunosupresión basado en inhibidores de calcineurina (p = 0,002) fueron predictores independientes de mortalidad. El análisis de sobrevida encontró un riesgo mayor de mortalidad en pacientes bajo esquemas de inmunosupresión con inhibidores de calcineurina vs. aquellos libres de inhibidores de calcineurina, con tasas de mortalidad respectivas en 21,7 y 8,5% (p = 0,036). Conclusiones: Nuestros resultados sugieren que los inhibidores de calcineurina no aportan mayor protección en pacientes con trasplante renal y COVID-19 en comparación con esquemas libres de inhibidores de calcineurina, siendo necesario realizar análisis que permitan evaluar los desenlaces con diferentes esquemas de inmunosupresión en receptores de trasplante renal con infección por SARS-CoV-2.

Background: Sterols are the main components of fungal membranes. Inhibiting their biosynthesis is the mode of action of azole antifungal drugs that are widely used to treat fungal disease including aspergillosis. Azole resistance has emerged as a matter of concern but little is known about sterols biosynthesis in azole resistant Aspergillus fumigatus. Methods: We explored the sterol composition of 12 A. fumigatus isolates, including nine azole resistant isolates with TR34/L98H, TR46/Y121F/T289A or TR53 alterations in the cyp51A gene and its promoter conferring azole resistance. Modifications in sterol composition were also investigated after exposure to two azole drugs, itraconazole and voriconazole. Results: Overall, under basal conditions, sterol compositions were qualitatively equivalent, whatever the alterations in the target of azole drugs with ergosterol as the main sterol detected. Azole exposure reduced ergosterol composition and the qualitative composition of sterols was similar in both susceptible and resistant isolates. Interestingly TR53 strains behaved differently than other strains. Conclusions: Elucidating sterol composition in azole-susceptible and resistant isolates is of interest for a better understanding of the mechanism of action of these drugs and the mechanism of resistance of fungi.

Background: Candida auris is a recently reported Candida species that is phenotypically similar to Candida haemulonii and related to hospital outbreaks. This organism can be misidentified as Candida haemulonii, Candida famata, Candida catenulata, or Rhodotorula glutinis by phenotypic approaches. Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) and DNA sequence analysis using internal transcribed spacer rDNA bar-coding provide an accurate identification. Case reports: Three cases of C. auris infection in patients with risk factors for fungal infection (one admitted to the intensive care unit, one with lymphoma, and one with HIV; all three with previous antibiotic use) are reported; these infections were not epidemiologically related. Yeast isolates were recovered from blood, ocular secretion, and bronchoalveolar lavage and were misidentified as C. catenulata and Candida albicans by the phenotypic MicroScan method. The isolates were confirmed to be C. auris by means of MALDI-TOF MS and DNA sequence analysis. Antifungal susceptibility testing was performed on these C. auris isolates, which exhibited high minimum inhibitory concentrations to triazoles and amphotericin B. One patient survived and the other two died. Only one of these deaths was related to fungemia. Conclusions: C. auris is an emerging and opportunistic multidrug-resistant human pathogen. It is necessary to strengthen measures to achieve an accurate and quick identification and also to avoid its dissemination. This will require improvements in health and infection control measures, as well as the promotion of antifungal stewardship in healthcare facilities. Keywords: Candida auris, Multidrug resistance, Sporadic, Fungal, Colombia

Any strategy that proposes solutions to health-related problems recognizes that people, animals, and the environment are interconnected. Fusarium is an example of this interaction because it is capable of infecting plants, animals, and humans. This review provides information on various aspects of these relations and proposes how to approach fusariosis with a One Health methodology (a multidisciplinary, and multisectoral approach that can address urgent, ongoing, or potential health threats to humans, animals, and the environment). Here, we give a framework to understand infection pathogenesis, through the epidemiological triad, and explain how the broad utilization of fungicides in agriculture may play a role in the treatment of human fusariosis. We assess how plumbing systems and hospital environments might play a role as a reservoir for animal and human infections. We explain the role of antifungal resistance mechanisms in both humans and agriculture. Our review emphasizes the importance of developing interdisciplinary research studies where aquatic animals, plants, and human disease interactions can be explored through coordination and collaborative actions.

Ingestion of a foreign body is commonly encountered in clinical practice, but most cause no complications, passing spontaneously through the gastrointestinal tract. However, they can cause obstructive signs and symptoms, and surgical intervention for extraction of the foreign body may be required after identifying its location. We present here the case of a 49-year-old woman who presented to our emergency room with abdominal pain localizing to the right lower quadrant. Evaluation was most consistent with acute appendicitis, and she underwent uncomplicated appendectomy. A keratin nail with Actinomyces was identified in her appendix. Foreign bodies in the appendix can cause simple appendicitis, perforation, periappendiceal abscess, and peritonitis. Regardless of etiology, an appendectomy often ends up the primary treatment, but unusual and rare causes are worth noting if only for the clinician to be aware of when evaluating the next patient with abdominal pain and considering treatment options or future prevention. Our case is an example of a rare scenario in which an Actinomyces-contaminated human nail lodged in the appendix of a woman eventually resulting in acute appendicitis.

Abstract Background The interaction between modelers and policymakers is becoming more common due to the increase in computing speed seen in recent decades. The recent pandemic caused by the SARS-CoV-2 virus was no exception. Thus, this study aims to identify and assess epidemiological mathematical models of SARS-CoV-2 applied to real-world data, including immunization for coronavirus 2019 (COVID-19). Methodology PubMed, JSTOR, medRxiv, LILACS, EconLit, and other databases were searched for studies employing epidemiological mathematical models of SARS-CoV-2 applied to real-world data. We summarized the information qualitatively, and each article included was assessed for bias risk using the Joanna Briggs Institute (JBI) and PROBAST checklist tool. The PROSPERO registration number is CRD42022344542. Findings In total, 5646 articles were retrieved, of which 411 were included. Most of the information was published in 2021. The countries with the highest number of studies were the United States, Canada, China, and the United Kingdom; no studies were found in low-income countries. The SEIR model (susceptible, exposed, infectious, and recovered) was the most frequently used approach, followed by agent-based modeling. Moreover, the most commonly used software were R, Matlab, and Python, with the most recurring health outcomes being death and recovery. According to the JBI assessment, 61.4% of articles were considered to have a low risk of bias. Interpretation The utilization of mathematical models increased following the onset of the SARS-CoV-2 pandemic. Stakeholders have begun to incorporate these analytical tools more extensively into public policy, enabling the construction of various scenarios for public health. This contribution adds value to informed decision-making. Therefore, understanding their advancements, strengths, and limitations is essential.

Objectives: Methicillin-resistant Staphylococcus aureus (MRSA) skin and soft tissue infections (SSTIs) represent a major clinical problem in Colombia. The aim of this study was to evaluate the risk factors associated with MRSA SSTI in Colombia. Methods: A multicenter cohort study with nested case–control design was performed. Patients with an SSTI with at least 48 h of inpatient care were included. Patients with an MRSA SSTI were considered the case group and patients with either a non-MRSA SSTI or with an Methicillin-susceptible S. aureus (MSSA) SSTI were the control groups. A multivariate logistic regression approach was used to evaluate risk factors associated with MRSA SSTI with two different statistical models. Results: A total 1134 patients were included. Cultures were positive for 498 patients, of which 52% (n = 259) were Staphylococcus aureus. MRSA was confirmed in 68.3% of the S. aureus cultures. In the first model, independent risk factors for MRSA SSTI were identified as the presence of abscess (P

Background: During a cross-sectional study on allergic aspergillosis in Chronic Obstructive Pulmonary Disease patients in Bogotá, Colombia, we reported the case of a 65-year-female patient with GOLD 2011 D classification, presenting dyspnea at the time of visit and aspergillus in repeated sputum cultures. Methods: The isolate was identified at the section level based on macroscopic and microscopic characteristics and gene sequencing was used for precise molecular identification. Antifungal sensibility was determined by Sensititre YeastOne™ while virulence was assessed using a Galleria mellonella larvae model. Results: The clinical isolate was first identified as Aspergillus section Flavi and sequencing of β-tubulin and calmodulin genes, in addition to the identification of alfR (aflatoxin regulator) gene, allowed the undoubted identification of the clinical isolate as Aspergillus caelatus. It exhibited virulence in G. mellonella similar to A. flavus and a high in vitro susceptibility against all antifungals except for amphotericin B. Conclusion: This is the first human case of airway colonization attributed to A. caelatus. Resistance pattern justified the interest to discriminate this cryptic species. Keywords: Aspergillus caelatus, COPD, Colonization, Aspergillosis

Antimicrobials are essential for infection management [...]

Abstract Lassa virus is a member of the Arenaviridae family, which causes human infections ranging from asymptomatic to severe hemorrhagic disease with a high case fatality rate. We have designed and generated lipid nanoparticle encapsulated, modified mRNA vaccines that encode for the wild-type Lassa virus strain Josiah glycoprotein complex or the prefusion stabilized conformation of the Lassa virus glycoprotein complex. Hartley guinea pigs were vaccinated with two 10 µg doses, 28 days apart, of either construct. Vaccination induced strong binding antibody responses, specific to the prefusion conformation of glycoprotein complex, which were significantly higher in the prefusion stabilized glycoprotein complex construct group and displayed strong Fc-mediated effects. However, Lassa virus-neutralizing antibody activity was detected in some but not all animals. Following the challenge with a lethal dose of the Lassa virus, all vaccinated animals were protected from death and severe disease. Although the definitive mechanism of protection is still unknown, and assessment of the cell-mediated immune response was not investigated in this study, these data demonstrate the promise of mRNA as a vaccine platform against the Lassa virus and that protection against Lassa virus can be achieved in the absence of virus-neutralizing antibodies.

Diffuse large B-cell lymphoma (DLBCL) is the most common lymphoma in adults. We evaluated the immunohistochemical (IHC) expression of p63 and p53 in DLBCL and their significance on overall survival (OS) and progression-free survival (PFS). We conducted a retrospective cohort study of 177 patients with DLBCL who presented to Mount Sinai Medical Center of Florida (Miami Beach, Florida) between 2010 and 2020. IHC staining for p63 and p53 protein expression was performed. A significant correlation was found between p63 positivity and p53 expression, p53/p63 co-positivity, Ki-67 proliferation index, MYC expression, and MYC/BCL2 double expression. Regardless of the germinal center B-cell like (GCB) subgrouping, there was a trend among p53+ patients to have MYC/BCL2 double expression, positive MYC expression, and lower OS and PFS. A tendency of poor OS was seen in p53+ patients in the non-GCB, GCB, and double expressors subgroups and poor PFS in p53+ patients regardless of the subgrouping. In conclusion, our results suggest that p63 and p53 may represent potential additional prognostic biomarkers in DLBCL and may be included in the initial diagnostic work up of patients with DLBCL.

Background Acute kidney injury (AKI) is a common cause of morbidity and mortality. It mainly targets the renal tubular epithelium with pathological changes, referred to as acute tubular injury. The latter is followed by a regenerative response that is difficult to visualize on routine hematoxylin and eosin (H&E) stains. In this study, we examined the regenerative capacity of renal tubules by correlating vimentin (VIM) immunohistochemical (IHC) expression and pathological findings of AKI and renal tubular regeneration (RTR) on H&E. Methods We reviewed 23 autopsies performed in the clinical setting of AKI and RTR. VIM expression was scored in the renal cortical tubular epithelium using a statistical cutoff ≥ 3% for high expression and < 3% for low expression. Results Of the 23 kidney tissues examined, seven (30.4%) had low VIM expression, and 16 (69.6%) had high VIM expression. Kidney tissues with evidence of AKI and RTR had significantly higher VIM expression. Renal peritubular microenvironment features showing regenerative changes on H&E were associated with high VIM expression. In the univariate model, kidney tissues with RTR were 18-fold more likely to have high VIM expression. Conclusions In conclusion, our findings suggest that VIM could serve as an IHC marker for RTR following AKI. However, correlation with H&E findings remains critical to excluding chronic tubular damage. Collectively, our preliminary results pave the way for future studies including a larger sample size to validate the use of VIM as a reliable biomarker for RTR.

Prostate cancer (PCa) is the second most common cancer in men. Common treatments include active surveillance, surgery, or radiation. Androgen deprivation therapy and chemotherapy are usually reserved for advanced disease or biochemical recurrence, such as castration-resistant prostate cancer (CRPC), but they are not considered curative because PCa cells eventually develop drug resistance. The latter is achieved through various cellular mechanisms that ultimately circumvent the pharmaceutical’s mode of action. The need for novel therapeutic approaches is necessary under these circumstances. An alternative way to treat PCa is by repurposing of existing drugs that were initially intended for other conditions. By extrapolating the effects of previously approved drugs to the intracellular processes of PCa, treatment options will expand. In addition, drug repurposing is cost-effective and efficient because it utilizes drugs that have already demonstrated safety and efficacy. This review catalogues the drugs that can be repurposed for PCa in preclinical studies as well as clinical trials.

Collecting duct carcinoma is a rare neoplasm of the kidney, accounting for only 1–2% of renal tumors. These tumors arise from the principal cells of the renal collecting ducts of Bellini. The majority of patients have lymph node involvement and metastases to lungs, liver, bone, adrenal glands, and brain. We present a case of a 48 year old woman who came to the hospital with a clinical presentation suspicious for pneumonia. One week later her symptoms aggravated. A CT chest and abdominal imaging showed bilateral pulmonary infiltrates, retroperitoneal lymphadenopathy, and left hydroureteronephrosis. She expired after developing acute respiratory failure. An autopsy was performed which revealed chylopericadium of 150 cc; bilateral reticular pattern on the surfaces of the lungs; neck, mediastinal and retroperitoneal lymphadenopathy, and a 5.1 cm left kidney mass located in the mid portion medulla. The kidney tumor was a rhabdoid collecting duct carcinoma. The lungs showed diffuse subpleural lymphangitic spread of the carcinoma. We report a rare case of chylopericardium due to lymphangitic carcinomatosis from a 5.1 cm rhabdoid collecting duct carcinoma not suspected clinically or radiologically. This case highlights the importance of performing autopsies in an era when clinicians heavily rely on high-tech imaging diagnostic modalities.