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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.

Melioidosis is an endemic disease in Southeast Asia and Oceania caused by the gram-negative bacillus Burkholderia pseudomallei. We studied 15 adult patients from Colombia with microbiologically diagnosed pulmonary melioidosis. We reviewed 15 chest X-rays and 10 chest computed tomography (CT) studies. Of the 15 patients, 87% met the criteria for acute infection and 13% met the criteria for chronic infection. The most common findings on chest X-rays were consolidation (86%), nodules (26%), and cavitation (20%). On CT studies, consolidation and nodules were observed in 90% of cases; the areas of consolidation were predominantly located in the basal and central zones in 60%. Areas of cavitation were observed in 50%, pleural effusion in 60%, and mediastinal lymph nodes in 30%. In patients with acute pulmonary melioidosis (n=8), the findings observed were nodules (100%), mixed pattern with nodules and consolidation (87%), pleural effusion (88%), and mediastinal lymph nodes (25%). The two patients with chronic pulmonary melioidosis both had cavitation. Acute lung infection with B. Pseudomallei has radiologic manifestations similar to those of pneumonia due to other causes. In areas where the disease is endemic, it is essential to include acute melioidosis in the differential diagnosis of pulmonary nodules and chronic melioidosis in the differential diagnosis of cavitated chronic lung lesions.

HIV/AIDS information systems are a critical tool for keeping track of the HIV pandemic in any country, leading to the AIDS elimination to 2030 and achievement of the 95-95-95 goals set by 2025. In this article, we describe the data management process of the Colombian National HIV/AIDS registry, its epidemiological results and contributions to research and health risk management. This registry is a longitudinal database. Variables and periodicity are defined by The Ministry of Health and Social Protection. Reporting is done by health insurers and their healthcare providers on annual bases. The information is uploaded through a web platform run by the High-Cost Diseases Fund, in charge of the validation, auditing process, consolidation, analysis and publication of the data. Security and confidentiality of the information is also taken care of by the High-Cost Disease Fund. Main results include epidemiological follow up of the epidemic, periodic evaluation of 25 risk management indicators, publication of research studies and the calculation of an economic incentive for insurers to improve health risk management. The registry has shown to be useful not only for the management of clinical information but also for administrative purposes.

Background The public health impact of the coronavirus disease 2019 (COVID-19) pandemic has motivated a rapid search for potential therapeutics, with some key successes. However, the potential impact of different treatments, and consequently research and procurement priorities, have not been clear. Methods Using a mathematical model of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission, COVID-19 disease and clinical care, we explore the public-health impact of different potential therapeutics, under a range of scenarios varying healthcare capacity, epidemic trajectories; and drug efficacy in the absence of supportive care. Results The impact of drugs like dexamethasone (delivered to the most critically-ill in hospital and whose therapeutic benefit is expected to depend on the availability of supportive care such as oxygen and mechanical ventilation) is likely to be limited in settings where healthcare capacity is lowest or where uncontrolled epidemics result in hospitals being overwhelmed. As such, it may avert 22% of deaths in high-income countries but only 8% in low-income countries (assuming R = 1.35). Therapeutics for different patient populations (those not in hospital, early in the course of infection) and types of benefit (reducing disease severity or infectiousness, preventing hospitalization) could have much greater benefits, particularly in resource-poor settings facing large epidemics. Conclusions Advances in the treatment of COVID-19 to date have been focused on hospitalized-patients and predicated on an assumption of adequate access to supportive care. Therapeutics delivered earlier in the course of infection that reduce the need for healthcare or reduce infectiousness could have significant impact, and research into their efficacy and means of delivery should be a priority.

Introduction COVID-19 vaccines have been highly effective in reducing morbidity and mortality during the pandemic. However, the emergence of the Omicron (B.1.1.529) variant and subvariants as the globally dominant strains have raised doubts about the effectiveness of currently-available vaccines and prompted debate about potential future vaccination strategies. Areas covered Using the publicly available IVAC VIEW-hub platform, we reviewed 52 studies on vaccine effectiveness (VE) after booster vaccinations. VE data were reported for SARS-CoV-2 symptomatic infection, severe disease and death and stratified by vaccine schedule and age. In addition, a non-systematic literature review of safety was performed to identify single or multi-country studies investigating adverse event rates for at least two of the currently-available COVID-19 vaccines. Expert opinion Booster shots of the current COVID-19 vaccines provide consistently high protection against Omicron-related severe disease and death. Additionally, this protection appears to be conserved for at least 3 months, with a small but significant waning after that time. The positive risk-benefit ratio of these vaccines is well established, thus increasing confidence in administering additional doses as required. Future vaccination strategies will likely include a combination of schedules based on a person’s risk profile, as overly frequent boosting may be neither beneficial nor sustainable for the general population.

Urothelial carcinoma of the urinary bladder is the most common malignancy of the urinary system. Patients with low grade papillary urothelial carcinoma (LGPUC) usually have a low risk for tumor recurrence and progression; yet a subset of patients develop recurrence or grade/stage progression to high-grade papillary urothelial carcinoma (HGPUC). The clinicopathological and molecular factors that contribute to this progression are yet to be determined.In our study, we aimed to assess the incidence and clinicopathological factors associated with tumor recurrence/progression of LGPUC.Using a pathological database of surgical specimens from patients who underwent bladder biopsies and/or transurethral resection of bladder tumors (TURBTs) between August 01, 2011, and July 31, 2021, at a large academic medical center, a single-center retrospective cohort analysis was performed, and medical charts of patients were reviewed.Of the total 258 patients included, 157 (60.9 %) had "no recurrence", 85 (32.9 %) had ≥1 "recurrence of LGPUC", and 16 (6.2 %) had "grade progression to HGPUC". The mean follow-up time was 31.5 ± 32 months. Patients with "grade progression" and "recurrence of LGPUC" had larger mean tumor size on initial biopsy and multiple lesions on initial cystoscopy compared to those with "no recurrence." Interestingly, former smokers had 2.5- and 8.5-times higher risk of recurrence of LGPUC and grade progression, respectively.Since the majority of our patients did not develop recurrence, we question whether there is tendency to overclassify the papillomas as LGPUC based on the 2004 WHO/ISUP consensus grading classification.

BackgroundAfter 8 months of the COVID-19 pandemic, Latin American countries have some of the highest rates in COVID-19 mortality. Despite being one of the most unequal regions of the world, there is a scarce report of the effect of socioeconomic conditions on COVID-19 mortality in their countries. We aimed to identify the effect of some socioeconomic inequality-related factors on COVID-19 mortality in Colombia.MethodsWe conducted a survival analysis in a nation-wide retrospective cohort study of confirmed cases of COVID-19 in Colombia from 2 March 2020 to 26 October 2020. We calculated the time to death or recovery for each confirmed case in the cohort. We used an extended multivariable time-dependent Cox regression model to estimate the HR by age groups, sex, ethnicity, type of health insurance, area of residence and socioeconomic strata.ResultsThere were 1 033 218 confirmed cases and 30 565 deaths for COVID-19 in Colombia between 2 March and 26 October. The risk of dying for COVID-19 among confirmed cases was higher in males (HR 1.68 95% CI 1.64 to 1.72), in people older than 60 years (HR 296.58 95% CI 199.22 to 441.51), in indigenous people (HR 1.20 95% CI 1.08 to 1.33), in people with subsidised health insurance regime (HR 1.89 95% CI 1.83 to 1.96) and in people living in the very low socioeconomic strata (HR 1.44 95% CI 1.24 to 1.68).ConclusionOur study provides evidence of socioeconomic inequalities in COVID-19 mortality in terms of age groups, sex, ethnicity, type of health insurance regimen and socioeconomic status.

Metaplastic breast carcinoma (MBC) represents a heterogeneous group of aggressive primary breast cancers that can show differentiation into carcinomatous and sarcomatous elements. Due to its rapid growth, this malignancy can replace precursor lesions, which remain unknown in most cases. Herein, we describe a MBC presenting as a deceptive post-biopsy hematoma. Histopathological and immunohistochemical evaluation of the primary tumor revealed a squamous cell carcinoma arising in a background of squamous metaplasia of lactiferous ducts (SMOLD). In the absence of ductal carcinoma in situ, we consider SMOLD as a nonobligatory precursor of MBC. The tumor showed 'dedifferentiation' into spindle, mucin-producing, osteoclast-like giant cell and fibromatosis-like carcinoma. Next-generation sequencing revealed the driver mutations HRASQ61R and PIK3R1c.1738_1745+2del in addition to MYH11S638L and amplification of ERCC5 and FGF14, which were potential contributors to tumor phenotype. Tumor dedifferentiation was probably facilitated by epithelial-to-mesenchymal transition (EMT) with aberrant expression of platelet and endothelial adhesion molecule-1, leading to early metastasis via hematogenous route rather than lymphatic. The co-occurrence of phosphoinositide 3-kinase and mitogen-activated protein kinase pathway abnormalities along with EMT could mediate divergent growth in breast cancer.

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.

The susceptibility of 31 Candida auris clinical isolates was evaluated by four methods, namely the microdilution reference method according to Clinical and Laboratory Standards Institute (CLSI) and European Committee on Antimicrobial Susceptibility Testing (EUCAST) guidelines as well as Etest and VITEK®2. Essential agreement between the two reference methods was 90%. Etest showed a better overall agreement with the reference methods (94% and 81% for CLSI and EUCAST, respectively) than VITEK®2 (70% and 72%, respectively). Discrepancies were found for fluconazole (FLC) and amphotericin B. Considering categorical agreement (CDC tentative breakpoints), the majority of isolates were considered FLC-resistant (93.6% and 80.6% by CLSI and EUCAST, respectively). Furthermore, all isolates were considered susceptible to echinocandins by all methods. Susceptibility results should be interpreted with care if the VITEK®2 system is used to guide therapeutic decisions for C. auris infections.

BackgroundThe unprecedented public health impact of the COVID-19 pandemic has motivated a rapid search for potential therapeutics, with some key successes. However, the potential impact of different treatments, and consequently research and procurement priorities, have not been clear.Methods and FindingsWe develop a mathematical model of SARS-CoV-2 transmission, COVID-19 disease and clinical care to explore the potential public-health impact of a range of different potential therapeutics, under a range of different scenarios varying: i) healthcare capacity, ii) epidemic trajectories; and iii) drug efficacy in the absence of supportive care. In each case, the outcome of interest was the number of COVID-19 deaths averted in scenarios with the therapeutic compared to scenarios without. We find the impact of drugs like dexamethasone (which are delivered to the most critically-ill in hospital and whose therapeutic benefit is expected to depend on the availability of supportive care such as oxygen and mechanical ventilation) is likely to be limited in settings where healthcare capacity is lowest or where uncontrolled epidemics result in hospitals being overwhelmed. As such, it may avert 22% of deaths in high-income countries but only 8% in low-income countries (assuming R=1.35). Therapeutics for different patient populations (those not in hospital, early in the course of infection) and types of benefit (reducing disease severity or infectiousness, preventing hospitalisation) could have much greater benefits, particularly in resource-poor settings facing large epidemics.ConclusionsThere is a global asymmetry in who is likely to benefit from advances in the treatment of COVID-19 to date, which have been focussed on hospitalised-patients and predicated on an assumption of adequate access to supportive care. Therapeutics that can feasibly be delivered to those earlier in the course of infection that reduce the need for healthcare or reduce infectiousness could have significant impact, and research into their efficacy and means of delivery should be a priority.

BACKGROUNDThe effectiveness of rosuvastatin plus colchicine, emtricitabine/tenofovir, and of their combined use in hospitalized patients with coronavirus disease 2019 (Covid-19) pneumonia is unclear.METHODSIn each hospital, hospitalized adults with Covid-19 pneumonia, were randomly assigned, in a 1:1 ratio, to receive: a) standard of care; or b) emtricitabine/tenofovir; or c) colchicine + rosuvastatin; or d) emtricitabine/tenofovir + colchicine + rosuvastatin. The primary outcome was all-cause mortality within the first 28 days after randomization. Severe adverse events (SAE) were those with a high probability of being treatment-related.RESULTS633 patients were randomized in 6 hospitals in Bogota, Colombia. Overall, 98% of the patients received glucocorticoids during hospitalization. The cumulative incidence of death through day 28 was 10.7% in the emtricitabine/tenofovir + colchicine + rosuvastatin arm, 14.4% in the colchicine + rosuvastatin arm, 13.8% in the emtricitabine/tenofovir arm, and 17.4% in the standard of care arm, with adjusted risk differences (aRD) against the standard treatment of -0.07 (95% confidence interval [CI], -0.17 to 0.04), aRD -0.03 (95%CI: -0.11 to 0.05) and aRD: -0.05 (95%CI: -0.15 to 0.05), respectively. Need for invasive mechanical ventilation was lower in the emtricitabine/tenofovir + colchicine + rosuvastatin arm compared to the standard treatment arm, aRD: -0.06 (95%CI: -0.11 to -0,01), but no differences were found between the other comparisons. SAE occurred in 3 patients distributed in the 3 treatment arms.CONCLUSIONSAmong patients hospitalized with moderate and severe SARS Covid-19, the use of the emtricitabine/tenofovir + colchicine + rosuvastatin combination emerges as a treatment alternative.ClinicalTrials.gov number:NCT04359095

Brain tumors in adults may be infrequent when compared with other cancer etiologies, but they remain one of the deadliest with bleak survival rates. Current treatment modalities encompass surgical resection, chemotherapy, and radiotherapy. However, increasing resistance rates are being witnessed, and this has been attributed, in part, to cancer stem cells (CSCs). CSCs are a subpopulation of cancer cells that reside within the tumor bulk and have the capacity for self-renewal and can differentiate and proliferate into multiple cell lineages. Studying those CSCs enables an increasing understanding of carcinogenesis, and targeting CSCs may overcome existing treatment resistance. One approach to weaponize new drugs is to target these CSCs through drug repurposing which entails using drugs, which are Food and Drug Administration–approved and safe for one defined disease, for a new indication. This approach serves to save both time and money that would otherwise be spent in designing a totally new therapy. In this review, we will illustrate drug repurposing strategies that have been used in brain tumors and then further elaborate on how these approaches, specifically those that target the resident CSCs, can help take the field of drug repurposing to a new level.

BackgroundEchinocandin resistance represents a great concern, as these drugs are recommended as first-line therapy for invasive candidiasis. Echinocandin resistance is conferred by mutations in FKS genes. Nevertheless, pathways are crucial for enabling tolerance, evolution, and maintenance of resistance. Therefore, understanding the biological processes and proteins involved in the response to caspofungin may provide clues indicating new therapeutic targets.ObjectivesWe determined the resistance mechanism and assessed the proteome response to caspofungin exposure. We then evaluated the phenotypic impact of calcineurin inhibition by FK506 and cephalosporine A (CsA) on caspofungin-resistant Candida glabrata isolates.MethodsTwenty-five genes associated with caspofungin resistance were analysed by NGS, followed by studies of the quantitative proteomic response to caspofungin exposure. Then, susceptibility testing of caspofungin in presence of FK506 and CsA was performed. The effects of calcineurin inhibitor/caspofungin combinations on heat stress (40°C), oxidative stress (0.2 and 0.4 mM menadione) and on biofilm formation (polyurethane catheter) were analysed. Finally, a Galleria mellonella model using blastospores (1 × 109 cfu/mL) was developed to evaluate the impact of the combinations on larval survival.ResultsF659-del was found in the FKS2 gene of resistant strains. Proteomics data showed some up-regulated proteins are involved in cell-wall biosynthesis, response to stress and pathogenesis, some of them being members of calmodulin–calcineurin pathway. Therefore, the impact of calmodulin inhibition was explored. Calmodulin inhibition restored caspofungin susceptibility, decreased capacity to respond to stress conditions, and reduced biofilm formation and in vivo pathogenicity.ConclusionsOur findings confirm that calmodulin-calcineurin-Crz1 could provide a relevant target in life-threatening invasive candidiasis.

Aim: To assess the epidemiological situation of people living with HIV and AIDS (PLWHA) in the municipalities and regions of Colombia in 2018. Materials and methods: A cross-sectional study was conducted with secondary data from the High-Cost Diseases Fund from February 1st, 2018 to January 31st, 2019. We included sociodemographic, clinical variables, and related to geographic location. We calculated incidence, prevalence, and mortality according to the Colombian geographical regions, department and municipality of residence. Crude and age-standardized rates were estimated. Results: By 2018, 10,930 new cases of PLWHA were reported, being more frequent in males, aged between 25 to 49 years. 39.32% were reported with AIDS and 35.27% had undetectable HIV viral load. During 2018, there are 109,056 PLWHA in Colombia. The highest age-standardized incidence and prevalence were reported in Florencia (Cauca) (354.28 per 100,000 and 3.32 per 100people, respectively). The age-standardized incidence rate was 22.12 per 100,000 population (95% CI 21.71-22.54). Age-standardized prevalence and mortality were 0.23 per 100 population (95% CI 0.22-0.23) and 3.78 per 100,000 population (95% CI 3.61-3.96), respectively. Conclusion: Different strategies should be implemented to improve the identification of risk factors in the population, especially in some regions of Colombia and prevent transmission. Resumen Objetivo: Evaluar la situación epidemiológica de las personas que viven con el VIH y el SIDA (PVVS) en los municipios y regiones de Colombia en 2018. Materiales y métodos: Se realizó un estudio transversal con datos secundarios del Fondo Colombiano de Enfermedades de Alto Costo entre febrero 1 de 2018 al 31 de enero de 2019. Incluimos variables sociodemográficas, clínicas y relacionadas con la ubicación geográfica. Calculamos la incidencia, prevalencia y mortalidad según la región geográfica colombiana, el departamento de residencia y el municipio. Se estimaron tasas crudas y estandarizadas por edad. Resultados: Para el 2018, 10.930 nuevos casos de PVVS fueron reportados, siendo más frecuentes en hombres, en edades entre 25 a 49 años. 39.32% fueron reportados con SIDA y 35.27% tuvieron una carga viral de VIH indetectable. 109,056 PVVS en Colombia. Las incidencia y prevalencia ajustadas por edad más altas se informaron en Florencia (Cauca) (354.28 por 100,000 y 3.32 por 100 personas, respectivamente). La tasa de incidencia estandarizada por edad fue de 22.12 por 100,000 habitantes (IC 95% 21.71-22.54). La prevalencia y mortalidad ajustadas por edad fueron 0.23 por 100 habitantes (IC 95% 0.22-0.23) y 3.78 por 100.000 habitantes (IC 95% 3.61-3.96), respectivamente. Se deben implementar diferentes estrategias para mejorar la identificación de los factores de riesgo en la población, especialmente en algunas regiones geográficas de Colombia y prevenir la transmisión.

Purpose of review Fungal outbreaks have been reported in healthcare settings, showing that construction activities are a serious threat to immunocompromised hosts. Preventive measures to control fungal outbreaks (especially Aspergillus spp.) are considered essential during hospital construction. In this article, we update the main advances in each of preventive strategies. Recent findings Anticipation and multidisciplinary teamwork are the keystone for fungal outbreaks prevention. Strategies focused on environmental control measures of airborne dissemination of fungal spores have proven to be successful. It is important to recommend azole-resistant Aspergillus fumigatus active surveillance from both air (outdoors and indoors) and clinical samples during hospital construction works. Apart from genotyping, studies should be further encouraged to understand the environmental dynamics. Risk assessment and implement preventive measures (environment control strategies, air surveillance, inpatients immunocompromised patients in high-efficiency particulate air filters rooms, patient education, antifungal prophylaxis in high-risk patient groups, etc.) have shown that these accomplish to reduce the incidence of invasive fungal infection (IFI). Summary In general, it is not only a strategy that should be implemented to reduce the risk of IFI but is a bundle of preventive measures, which have proven to be successful in control infection and prevention of airborne transmission of fungi.

La melioidosis es una enfermedad infecciosa causada por Burkholderia pseudomallei cuyo diagnóstico clínico puede ser difícil debido a su variada presentación clínica y a las dificultades del diagnóstico microbiológico, por lo cual pueden requerirse técnicas moleculares para su adecuada identificación una vez se sospecha su presencia.Son pocos los antibióticos disponibles para el tratamiento de esta enfermedad y, además, deben usarse durante un tiempo prolongado. Aunque se conoce por ser endémica en Tailandia, Malasia, Singapur, Vietnam y Australia, en Colombia se han reportado algunos pocos casos.Se presenta un caso de melioidosis en la región norte de Colombia, se hace una revisión de las características clínicas y el tratamiento, y se describe la epidemiología local de esta enfermedad.

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

Aspergillus fumigatus resistant to azole as first-line therapy has been reported in azole-naïve patients. This worldwide resistance phenomenon has been linked to fungicide-driven alterations in the cyp51A gene and its promoter region (such as TR34/L98H and TR46/Y121F/T289A). Azole-resistant A. fumigatus related to the use of triazole fungicides in flower fields was recently reported In Colombia. The purpose of this study was to investigate the presence of azole-resistant A. fumigatus in soil samples from vegetable crops such as carrots, potatoes, maize, strawberries, and pea, and from prepared farming land surrounding the city of Bogotá. Species identification was based on sequencing of the β-tubulin and calmodulin genes. All A. fumigatus strains were screened for azole resistance on agar supplemented with itraconazole or voriconazole. Among the 60 soil samples, 34 (56.6%) were positive for A. fumigatus and 15 samples exhibited strains (n = 18) that grew on agar supplemented with itraconazole or voriconazole. Triazole-resistant strains were isolated from soil samples associated with carrot, potato, maize, and pea crops. Sequencing of the cyp51A gene and its promoter region indicated polymorphism, mainly with the presence of TR46/Y121F/T289A (n = 8), TR34/L98H, and TR53. Eight resistant isolates exhibited cyp51A wild type without alterations in the promoter region. Our study showed evidence of dissemination of azole-resistant A. fumigatus, with high genetic diversity, in vegetable crops in Colombia. These data underline the need to determine the prevalence of azole resistance in A. fumigatus in clinical and environmental settings for other regions of Colombia as well as Latin America.

Antimicrobials are essential for infection management [...]

Background Appendectomy is the most common emergent surgical procedure. Primary appendiceal neoplasms are rare entities that are usually detected incidentally in less than 2% of all appendectomies. The increase in the incidence rates of appendiceal neoplasms over time raises the question whether there is an actual change in the disease occurrence or is it a matter of increased recognition and reporting of what would have been previously missed and undiagnosed. Objectives In our study, we aimed to review the archived tissue specimens of patients who were diagnosed with appendiceal neoplasms during the past decade at our institution and compare our clinical experience with published data to identify possible reasons that contribute to the increase in incidence rates of such neoplasms over the past few years. Methods Using a pathological database of surgical specimens from patients who underwent appendectomies between January 01, 2010 and September 30, 2020 at a large academic medical center, a single-center retrospective cohort analysis was performed, and medical charts of patients were reviewed. Results Of the total 1568 patients included, 102 (6.5%) had appendiceal neoplasms divided between primary (79.4%) and secondary/metastatic (20.6%) neoplasms. Annual incidence of appendiceal neoplasms over the past 10 years in our institution demonstrated an increasing trend from 5.6% in 2010 to 12.7% in 2020, which we hypothesize might be attributed to submitting more representative sections of the appendix for pathological examination than we had previously. Our results also showed that 2.8% of patients initially presenting with a typical clinical picture of acute appendicitis had appendiceal neoplasms as a truly incidental finding, while 20.3% of patients who underwent elective appendectomies for a suspicious appendiceal mass were found to be neoplastic. Interestingly, among the 80 cases of epithelial neoplasms, more non-carcinoid neoplasms were detected than carcinoid tumors. Conclusion Based on our results and what has been published recently, we confirm an additional increase in incidental appendiceal neoplasms found in appendectomies performed for a clinical picture of acute appendicitis, which may be related to more thorough specimen assessment. Whether this is clinically impactful remains to be determined. However, these data support a modification in the way appendectomy specimens are handled in pathology labs post-operatively.

La infección por SARS-CoV-2 es hoy el principal problema de salud pública en el mundo. No es claro el papel de las citoquinas en la fisiopatología del COVID-19, que en algunos individuos presenta una progresión rápida, severa y mortal asociada con proinflamación sistémicos relacionada con coagulopatías y fallas multiorgánicas. En este estudio, evaluamos los niveles séricos de citoquinas y su correlación con IgM, IgG e IgA, en 24 muestras de individuos positivos y 8 muestras de individuos negativos, para SARS-CoV-2. Hallamos concentraciones significativamente menores de IFN-g, TNF, IL-2 e IL-4 y un aumento significativo de IL-6 en el grupo de infectados hospitalizados respecto a los no infectados, así como una tendencia significativa al aumento, para IgG e IgA en el mismo grupo de individuos, respecto a infectados asintomáticos. Nuestros datos soportan el papel de la IL-6 en la severidad de la enfermedad destacando su potencial papel como biomarcador en la prognosis de esta patología. También, soportan la hipótesis sobre la función de los anticuerpos en el control efectivo del patógeno; se observa una respuesta inmune humoral más débil, frente a la proteína de la nucleocápside viral, en individuos con un mejor curso de la enfermedad.

Latin America accounts for roughly one-quarter of global COVID-19 cases and one-third of deaths. Health inequalities in the region lead to barriers regarding the best use of diagnostic tests during the pandemic. There is a need for a simplified guideline in the region that takes into consideration the available health resources, international guidelines, medical literature, and local expertise. Nine experts from different Latin American countries developed a simplified algorithm for COVID-19 diagnosis in the region, using a modified Delphi method. Twenty-four questions related to diverse diagnostic settings were initially proposed, followed by an extensive discussion of the literature and experts’ experience. According to time from close contact or symptom onset, the algorithm considers three different timeframes (≤7 days, 8–13 days, and ≥14 days) and discusses diagnostic options for each one. SARS-CoV-2 real-time reverse transcription polymerase chain reaction (rRT-PCR) continues to be the diagnostic test of choice from Day 1 to Day 14 after symptom onset or close contact, although antigen testing may be used in high-prevalence settings or in particular situations (such as from Day 0 to Days 5–7 of symptom onset). Antibody assays may be used for diagnostic confirmation, mainly after Day 14, if there is an epidemiological or individual need. If the clinical suspicion is very high, but other tests are negative, these assays may be used as an adjunct to decision-making from Days 8–13. The proposed algorithm is intended to be used as a support for COVID-19 diagnosis decision-making in Latin America.

"Spread through airspace" (STAS) is defined as micropapillary clusters, solid nests or single cells of tumor extending beyond the edge of the tumor into the air spaces of the surrounding lung parenchyma. It is associated with reduced overall survival and disease-free survival. Assessment of STAS in lung cancer appears to be necessary to guide clinical interventions. However, data on the correlation between the status of STAS and other lung cancer clinicopathological parameters are scarce.We reviewed 240 resected lung cancers and investigated the clinical significance of STAS in relation to other relevant lung cancer clinicopathological variables. We performed univariate and multivariate logistic regression analyses with STAS as a dependent variable.Of the total 240 patients, STAS was observed in 67 (27.9 %) of them. STAS is highly prevalent in adenocarcinoma with a micropapillary growth pattern (70.0 %) than in other lung cancer growth patterns. STAS was frequently reported in wedge resections (31.0%) than in lobectomy specimens (26.7 %). STAS was significantly associated with advanced pN stage (p0.001) and lymphovascular invasion (p = 0.005). In multivariate models, we found that lung cancers in the right lower lobe (RLL) (OR, 2.674; 95 % CI = 1.313-5.448, p = 0.007), micropapillary lung cancer growth pattern (OR = 5.199, 95 % CI = 1.220-22.162, p = 0.026), and pN2 stage (OR = 3.683, 95 % CI = 1.324-10.245, p = 0.013) serve as independent predictors for STAS.Our findings suggest that the presence of STAS is associated with right lower lobe tumors, micropapillary adenocarcinoma, and pN2 tumor stage. Hence, it could serve as one of the prognostically significant histologic findings in lung cancer. It is thus valid to mandate reporting STAS status in CAP surgical pathology lung cancer case summaries.

Hongchao Pan (University of Oxford. Nuffield Department of Population Health. Medical Research Council Population Health Research Unit. Oxford, United Kingdom); Richard Peto (University of Oxford. Nuffield Department of Population Health. Medical Research Council Population Health Research Unit. Oxford, United Kingdom); Ana-Maria Henao-Restrepo (World Health Organization. Geneva, Switzerland); Marie-Pierre Preziosi (World Health Organization. Geneva, Switzerland); Vasee Sathiyamoorthy (World Health Organization. Geneva, Switzerland); Quarraisha Abdool Karim (Centre for the AIDS Programme of Research in South Africa. Durban, South Africa); Marissa M. Alejandria (University of the Philippines. National Institutes of Health. Institute of National Epidemiology. Manila, Philippines); Cesar Hernandez Garcia (Spanish Agency of Medicines and Medical Devices. Madrid, Spain / Hospital Clinico San Carlos. Madrid, Spain); Marie-Paule Kieny (Institut National de la Sante et de la Recherche Medicale. Paris, France); Reza Malekzadeh (Tehran University of Medical Sciences. Digestive Disease Research Institute. Tehran, Iran); Srinivas Murthy (University of British Columbia. Vancouver, Canada); K. Srinath Reddy (Public Health Foundation of India. New Delhi, India); Mirta Roses Periago (National Academy of Sciences of Buenos Aires. Buenos Aires, Argentina); Pierre Abi Hanna (Rafic Hariri University Hospital. Beirut, Lebanon); Florence Ader (Hospices Civils de Lyon. Lyon, France); Abdullah M. Al-Bader (Ministry of Health. Kuwait City, Kuwait); Almonther Alhasawi (Infectious Diseases Hospital. Kuwait City, Kuwait); Emma Allum (University of Bristol. Bristol, United Kingdom); Athari Alotaibi (Ministry for Preventive Health. Riyadh, Saudi Arabia); Carlos A. Alvarez-Moreno (Universidad Nacional de Colombia. Bogota, Colombia / Clinica Colsanitas. Bogota, Colombia); Sheila Appadoo (University of Bern. Bern, Switzerland); Abdullah Asiri (Ministry for Preventive Health. Riyadh, Saudi Arabia); Pal Aukrust (Oslo University Hospital. Oslo, Norway); Andreas Barratt-Due (Oslo University Hospital. Oslo, Norway); Samir Bellani (University of Bristol. Bristol, United Kingdom); Mattia Branca (University of Bern. Bern, Switzerland); Heike B.C. Cappel-Porter (University of Bristol. Bristol, United Kingdom); Nery Cerrato (Secretaria de Salud de Honduras. Tegucigalpa, Honduras); Ting S. Chow (Penang Hospital. Penang, Malaysia); Najada Como (University Hospital Center "Mother Teresa". Tirana, Albania); Joe Eustace (University College Cork. HRB Clinical Research Facility. Cork, Ireland); Patricia J. Garcia (Universidad Peruana Cayetano Heredia. Lima, Peru); Sheela Godbole (Indian Council of Medical Research. New Delhi, India / National AIDS Research Institute. Pune, Maharashtra, India); Eduardo Gotuzzo (Universidad Peruana Cayetano Heredia. Lima, Peru); Laimonas Griskevicius (Vilnius University Hospital Santaros Klinikos. Vilnius, Lithuania); Rasha Hamra (Ministry of Public Health. Beirut, Lebanon); Mariam Hassan (Shaukat Khanum Memorial Cancer Hospital and Research Centre. Lahore, Pakistan); Mohamed Hassany (National Hepatology and Tropical Medicine Research Institute. Cairo, Egypt); David Hutton (University of Bristol. Bristol, United Kingdom); Irmansyah Irmansyah (National Institute of Health Research and Development. Jakarta, Indonesia); Ligita Jancoriene (Vilnius University. Faculty of Medicine. Institute of Clinical Medicine. Vilnius, Lithuania); Jana Kirwan (University of Bristol. Bristol, United Kingdom); Suresh Kumar (Sungai Buloh Hospital. Selangor, Malaysia / Jalan Hospital. Selangor, Malaysia); Peter Lennon (Department of Health and Children. Dublin, Ireland); Gustavo Lopardo (Fundacion del Centro de Estudios Infectologicos. Buenos Aires, Argentina); Patrick Lydon (World Health Organization. Geneva, Switzerland); Nicola Magrini (Italian Medicines Agency. Rome, Italy); Teresa Maguire (Department of Health and Children. Dublin, Ireland); Suzana Manevska (Ministry of Health. Skopje, North Macedonia); Oriol Manuel (Lausanne University Hospital. Lausanne, Switzerland); Sibylle McGinty (University of Bern. Bern, Switzerland); Marco T. Medina (Universidad Nacional Autonoma de Honduras. Tegucigalpa, Honduras); Maria L. Mesa Rubio (Ministry of Health. Bogota, Colombia); Maria C. Miranda-Montoya (World Health Organization. Geneva, Switzerland); Jeremy Nel (University of the Witwatersrand. Johannesburg, South Africa); Estevao Portela Nunes (Fundacao Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Rio de Janeiro, RJ, Brasil); Markus Perola (National Institute for Health and Welfare of Finland. Helsinki, Finland / University of Finland. Helsinki, Finland); Antonio Portoles (Universidade Complutense de Madrid. Madrid, Spain / Spanish Clinical Research Network. Madrid, Spain / Hospital Clinico San Carlos. Instituto de Investigacion Sanitaria San Carlos. Madrid, Spain); Menaldi R. Rasmin (Rumah Sakit Umum Pusat Persahabatan. Jakarta, Indonesia); Aun Raza (Shaukat Khanum Memorial Cancer Hospital and Research Centre. Lahore, Pakistan); Helen Rees (Wits Reproductive Health and HIV Institute. Johannesburg, South Africa); Paula P. S. Reges (Fundacao Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Rio de Janeiro, RJ, Brasil); Chris A. Rogers (University of Bristol. Bristol, United Kingdom); Kolawole Salami (World Health Organization. Geneva, Switzerland); Marina I. Salvadori (Public Health Agency of Canada. Ottawa, Canada); Narvina Sinani (National Agency for Medicines and Medical Devices. Tirana, Albania); Jonathan A. C. Sterne (University of Bristol. Bristol, United Kingdom); Milena Stevanovikj (University Clinic of Infectious Diseases and Febrile Conditions. Skopje, North Macedonia); Evelina Tacconelli (University of Verona. Verona, Italy); Kari A. O. Tikkinen (Helsinki University Hospital. Helsinki, Finland / South Karelian Central Hospital. Lappeenranta, Finland); Sven Trelle (University of Bern. Bern, Switzerland); Hala Zaid (Ministry of Health and Population. Cairo, Egypt); John-Arne Rottingen (Research Council of Norway. Oslo, Norway); Soumya Swaminathan (World Health Organization. Geneva, Switzerland).

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.

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.

A strategy to propose solutions to health-related problems recognizes that people, animals, and the environment are interconnected. Fusarium and Neocosmospora are an example of this interaction due to the capable of infecting plants, animals, and human. This review provides information on various aspects of these relations and proposes how to approach fusariosis with a One Health methodology. 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 mechanism in both humans and agriculture. Our review emphasizes the importance of developing interdisciplinarity research studies where aquatic animals, plants, and human disease interactions can be explored through coordination and collaborative actions.

Burkholderia pseudomallei is an emerging pathogen in the Americas. Cases of mother-to-child transmission of B. pseudomallei are rare and probably occur by placental or perinatal infection. We report the first case of native gestational and neonatal melioidosis in the Western hemisphere. The isolated strains in the mother and newborn were confirmed by whole-genome sequencing and identified as a novel sequence type ST1748. The comparison of both genomes revealed a nucleotide similarity of 100%. Melioidosis should be considered within the differential diagnosis of febrile illness or pneumonia in pregnant women and newborns from endemic areas of the Americas.Burkholderia pseudomallei is an emerging pathogen in the Americas. Cases of mother-to-child transmission of B. pseudomallei are rare and probably occur by placental or perinatal infection. We report the first case of native gestational and neonatal melioidosis in the Western hemisphere. The isolated strains in the mother and newborn were confirmed by whole-genome sequencing and identified as a novel sequence type ST1748. The comparison of both genomes revealed a nucleotide similarity of 100%. Melioidosis should be considered within the differential diagnosis of febrile illness or pneumonia in pregnant women and newborns from endemic areas of the Americas.

Purpose: The present article describes retrospectively a case of a patient with chronic mucocutaneous candidiasis (CMC) who presented recurrent Candida albicans infection since he was 6 months old. We obtained 16 isolates recovered during a 4-year period. Our purpose was to determinate the susceptibility, genotyping, and the pathogenicity profile in all the isolates. Methods: Sixteen C. albicans were isolated from a 25-year-old male with several recurrent fungal infections admitted to Hospital. The isolates were recovered during 4 years from a different anatomical origin. We typified them by multilocus sequence typing, also we evaluated susceptibility to fluconazole, itraconazole, voriconazole, posaconazole, isavuconazole, caspofungin, and amphotericin B by microdilution method and we also test the pathogenic capacity in the Galleria mellonella model. Results: Genotyping of all clinical isolates showed the persistence of the same diploid sequence type (DST). Isolates changed their susceptibility profile over time, but there were no significant statistical differences in pathogenicity. Conclusion: Herein, a persistent clonal isolates of C. albicans (DST 918) in a patient with CMC, showed changes in its susceptibility profile after several antifungal treatments acquiring gradual resistance to the azole drugs, which did not affect their pathogenicity. © 2020 Journal of Global Infectious Diseases

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.

Clinical practice guidelines: An Opportunity to provide health care with excellence and the new Colombian Guidelines for the diagnosis and management of Skin and Soft tissue infections (SSTIs)

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