[Cryoglobulinemic vasculitis due to hyperviscosity and cryogel formation as the onset of multiple myeloma. Report of one case]. / Vasculitis crioglobulinémica por hiperviscosidad y formación de criogel como debut de mieloma múltiple. Caso clínico.

Multiple Myeloma (MM) is characterized by a clonal expansion of plasma cells in the bone marrow. These cells typically produce a monoclonal immunoglobulin, and its symptoms arise either from plasma cell infiltration in several organs, or secondary to the presence of a monoclonal protein peak. Symptoms can be summarized by the acronym CRAB (hypercalcemia, renal failure, anemia and bone lesions). Sometimes, in the setting of a protein secreting monoclonal gammopathy, formation of cryoglobulins develops. Cryoglobulins are plasma proteins that precipitate at low temperatures, forming a cold - induced precipitate at small vessels, causing a wide range of clinical manifestations. We report a female consulting for ulcers lasting 2 months in the left foot associated with purpuric lesions in both lower limbs. Protein electrophoresis showed a monoclonal peak in the gamma region. Bone marrow aspirate showed 27% of plasma cells with kappa chain restriction by cytometry. The presence of cryoglobulins was confirmed. The patient was treated with dexamethasone and bortezomib, with a progressive healing of lower limb lesions and disappearance of cryoglobulins. She was discharged in good conditions.

Biomarkers as predictors of renal damage in neonates undergoing cardiac surgery.

BACKGROUND: Acute Kidney Injury is a complication in children with heart disease undergoing cardiac surgery with cardiopulmonary bypass. The aim of this study is to describe the behavior of KIM-1 (Kidney Injury Molecule) and NGAL (Neutrophil Gelatinase Associated Lipocalin) as early predictors of renal damage, comparing them with serum creatinine and creatinine clearance, in neonates undergoing cardiac surgery. METHODS: Twenty-one (21) neonates, under 4 kg, with complex congenital heart diseases, RACHS-1 > 3, without preoperative renal failure, were studied. Serum creatinine and creatinine clearance were measured preoperatively and at 24, 48, 72, 96 hours postoperatively. Urinary samples of KIM-1(pg/ml) and NGAL (ng/ml) were collected after induction of anesthesia at 24 and 48 hours post-operatively. RESULTS: nRIFLE criteria were used to divide cohorts in "NO AKI" (12 patients) and "AKI" (nine patients). In the AKI group, serum creatinine increased significantly and creatinine clearance decreased significantly at 24, 48, and 72 hours compared with their respective baseline values. There was no difference in KIM-1 and NGAL values between patients who developed AKI and those who did not at any measured time. CONCLUSIONS: The deterioration of renal function continues to be one of the most frequent complications in this population. In our study, biomarkers did not show any correlation with the appearance of AKI. It remains to be seen whether this behavior of the biomarkers is linked with the non-consistent release of these types of molecules in immature kidneys. It is likely that a larger panel of biomarkers together with other glomerular filtration rate assessment methods will provide more information about AKI diagnosis.

[Use of cystatin C to estimate glomerular filtration rate]. / Uso de la cistatina C como biomarcador para estimar la tasa de filtración glomerular.

Glomerular filtration rate (GFR) is routinely estimated using endogenous biomarkers due to the complexity of direct measurement methods. Cystatin C is a protease inhibitor produced in all nucleated cells. It is freely filtered and then catabolized by renal tubular cells. Therefore, plasma concentration of cystatin C depends primarily on GFR. Serum cystatin C is less affected by muscle mass, diet, race, gender and age than creatinine. In the general population, equations to estimate GFR based on cystatin C do not have a better performance than those based on creatinine. However, formulas that combine creatinine and cystatin C are more accurate and precise. Estimation of GFR based on cystatin C could be useful in populations in which creatinine value may be biased, such as people with extremely low or high muscle mass, cirrhosis and chronic cardiorenal syndrome. Due to its higher cost in comparison to creatinine, we recommend measuring cystatin C on these clinical situations and when a more accurate estimation of GFR is required.

[Estimation of glomerular filtration rate with creatinine]. / Creatinina y su uso para la estimación de la velocidad de filtración glomerular.

Glomerular filtration rate (GFR) is the best approximation to global renal function and its estimation is of great relevance for clinical practice. Since the measurement of GFR by reference methods is complex, costly and not widely available, its routine evaluation is performed using endogenous biomarkers. Within these, creatinine is the most commonly used. It allows the estimation of GFR by means of its clearance or by formulas based on its concentration on plasma. Creatinine measurement should be performed using enzimatic methods as they confer more accurate values than Jaffe methods, especially for normal and low creatinine levels.

[Cardiotoxicity of anticancer therapies. Towards the implementation of cardio-oncology units]. / Cardiotoxicidad inducida por tratamientos oncológicos. Fundamentos para la implementación de equipos de Cardio-Oncología.

Recently, we have witnessed major improvements in cancer treatment. Early diagnosis and development of new therapies have reduced cancer-related mortality. However, these new therapies, along with greater patient survival, are associated with an increase in untoward effects, particularly in the cardiovascular system. Although cardiotoxicity induced by oncologic treatments affects predominantly the myocardium, it can also involve other structures of the cardiovascular system, becoming one of the main causes of morbidity and mortality in those who survive cancer. The main objective of cardio-oncology is to achieve the maximum benefits of oncologic treatments while minimizing their deleterious cardiovascular effects. It harbors the stratification of patients at risk of cardiotoxicity, the implementation of diagnostic tools (imaging techniques and biomarkers) for early diagnosis, preventive strategies and early treatment options for the complications. Herein, we discuss the basic knowledge for the implementation of cardio-oncology units and their role in the management of cancer patients, the diagnostic tools available to detect cardiotoxicity and the present therapeutic options.

[Quality indicators for blood culture: three years of monitoring at a university hospital in Chile]. / Análisis de la monitorización de cinco indicadores de calidad del hemocultivo en un hospital universitario en Chile 2009-2011.

Blood culture is considered the "gold standard" for the diagnosis of bacteremia, critical condition with high morbidity and mortality. Because of its importance, it is estimated that the blood culture is a critical test that requires close monitoring on the quality with which the process is performed. The objective of this work is to show the results of the monitoring carried out during the past three years, of 5 quality indicators of blood cultures in the laboratory of the Hospital Clínico de la Pontificia Universidad Católica de Chile, considering pre-analytical, analytical and post-analytical aspects. In the 3 years monitored the mean contamination was 0,7%, 46% of adult bottles had adequate volume, match between Gram stain with final identification was 99.4%, 100% of correct participations were achieved in surveys of external quality control and Gram staining notification before 1 hour was 88.7%. With regard to proposed aims, in 2011 the laboratory complies with all, except the percentage of bottles with appropriate volume of blood inoculated. This indicator is very low and should be corrected as soon as possible since it is known that it is an important condition for optimum performance of blood cultures.

[Susceptibility to azoles and amphotericin B of isolates of Candida spp. Experience of a university health network, between 2004 and 2010]. / Susceptibilidad a azoles y anfotericina B de aislados de Candida spp. Experiencia de una red de salud universitaria,entre 2004 y 2010.

OBJECTIVE: To describe antifungal susceptibility testing surveillance (December 2004-September 2010) in Candida spp., for amphotericin B, fluconazole and voriconazole, at the Laboratorio de Microbiología, Pontificia Universidad Católica de Chile. METHOD: The study was performed utilizing E test and included yeasts from invasive origin and isolates in which antifungal susceptibility testing was asked for by the patient's physician. RESULTS: The yeasts were mainly recovered from urine samples (n: 64), blood cultures (n: 51) and secretions (n: 24). Two hundred ninety three isolates were studied: C. albicans (38%), C. glabrata (30%), C. tropicalis (11%), C. parapsilosis (10%), C. krusei (4%) and others (7%). All Candida species were 100% susceptible to amphotericin B, except C. krusei (1/12). Fluconazole's global susceptibility in C. albicans was 91.8%, but 100% in isolates from blood cultures versus 76% in isolates from urine. C. tropicalis was 93.9% susceptible to fluconazole, C. parapsilosis, 90% and C. glabrata 30.3%. C. krusei had no susceptible isolates to fluconazole. Voriconazole resistance was mainly present in C. glabrata (11.5%). CONCLUSIONS: We recommend the study of antifungal susceptibility in isolates from invasive origin, selected urine strains and C. glabrata. Fluconazole remains effective in C. albicans from blood.

Pulsed field, PCR ribotyping and multiplex PCR analysis of Yersinia enterocolitica strains isolated from meat food in San Luis Argentina.

The characterization of phenotypic and genotypic virulence markers of Yersinia enterocolitica strains belonging to biotypes (B) 1A, 2 and 3, mostly isolated from food in San Luis, Argentina, and the assessment of their genotypic diversity using PFGE and PCR ribotyping, were performed in our laboratory for the first time. Thirty five Y. enterocolitica strains, two reference strains and 33 strains isolated in our laboratory were studied. The presence of virF, ail, ystA, and myfA genes was investigated by multiplex PCR. The pathogenic potential of B1A strains, the most predominant biotype of Y. enterocolitica strains isolated from meat in our region, was investigated by simple PCR. Four B1A strains were positive for ystB gene. Four Y. enterocolitica 2/O:9 (bio/serotype) and two 3/O:5 strains isolated in our laboratory showed virulence-related results in the phenotypic tests and multiplex PCR. A good correlation between the expression of virulence markers and their corresponding genotypes was observed for most strains. Sixteen genomic types (GT) and 9 different intergenic spacer region (SR) groups were generated by PFGE and PCR ribotyping, respectively. In both cases the Y. enterocolitica 2/O:9 strains were separately clustered from 1A and 3/O:5 strains. Meat foods might be vehicles of transmission of pathogenic Y. enterocolitica strains in our region.

Characterization of the plasmidic or chromosomal cpe gene and metabolic activities in Clostridium perfringens isolates from food in San Luis--Argentina.

Food poisoning and non-food poisoning illnesses due to C. perfringens (by enterotoxin production) have been associated to chromosomal or plasmidic location of the cpe gene, respectively. Clostridial pathogenicity has been correlated to protease and azoreductase production. The aim of this work was: i) to assess the sanitary-hygienic quality of dehydrated soups (100 samples) consumed in San Luis - Argentina; ii) to verify the presence of C. perfringens in these food products using the "Most Probable Number" method (MPN) and plate-counting methods; iii) to characterise enterotoxigenicity in strain isolates by RPLA; iv) to determine the chromosomal or plasmidic location of the cpe gene in enterotoxigenic strains previously isolated from food in our lab, using PCR; v) to correlate chromosomal cpe and spore heat-resistance; vi) to compare protease activity in cpe+ and cpe- strains; and vii) to compare azoreductase activity in cpe+ and cpe- strains. Twenty-six isolates had a count a 3-43 bacteria g(-1) count using MPN; 7.7% exceeded the Argentine Food Code (CAA) limit. All isolates showed protease activity: enterotoxigenic isolates had higher protease activity than non-enterotoxigenic isolates. All isolates showed azoreductase activity: enterotoxigenic isolates had higher activity and shorter reducing times. Enterotoxigenic isolates showed chromosomal location for the gene responsible for the enterotoxin.

A simple RNA preparation method for SARS-CoV-2 detection by RT-qPCR.

The technique RT-qPCR for viral RNA detection is the current worldwide strategy used for early detection of the novel coronavirus SARS-CoV-2. RNA extraction is a key pre-analytical step in RT-qPCR, often achieved using commercial kits. However, the magnitude of the COVID-19 pandemic is causing disruptions to the global supply chains used by many diagnostic laboratories to procure the commercial kits required for RNA extraction. Shortage in these essential reagents is even more acute in developing countries with no means to produce kits locally. We sought to find an alternative procedure to replace commercial kits using common reagents found in molecular biology laboratories. Here we report a method for RNA extraction that takes about 40 min to complete ten samples, and is not more laborious than current commercial RNA extraction kits. We demonstrate that this method can be used to process nasopharyngeal swab samples and yields RT-qPCR results comparable to those obtained with commercial kits. Most importantly, this procedure can be easily implemented in any molecular diagnostic laboratory. Frequent testing is crucial for individual patient management as well as for public health decision making in this pandemic. Implementation of this method could maintain crucial testing going despite commercial kit shortages.

Vancomicina contra metronidazol en infección por Clostridioides difficile leve-moderada de manejo ambulatorio / Vancomycin or metronidazole in the outpatient treatment of mild-moderate Clostridioides difficile infection

INTRODUCCIÓN: En la diarrea asociada a Clostridioides dfficile (DACD) leve-moderada se recomienda tratar con vancomicina por sobre metronidazol, a pesar de su difícil acceso y poca evidencia en el medio ambulatorio. OBJETIVO: Comparar la tasa de cura clínica y recurrencia entre vancomicina y metronidazol en adultos chilenos con primer episodio leve-moderado de DACD de manejo ambulatorio. MÉTODOS: Cohorte retrospectiva entre enero 2015 y diciembre 2020 en centros de una red de salud universitaria de pacientes de ≥ 18 años con DACD tratados ambulatoriamente. RESULTADOS: Se obtuvieron 161 pacientes, 59% mujeres, edad promedio de 53 años (entre 18 y 94 años). De ellos, 109 (67,7%) usaron metronidazol y 52 (32,3%) vancomicina. En el análisis multivariado ajustado por edad y comorbilidades se obtuvo un OR 3,00 (IC 95% 1,12-9,59) para cura clínica y 0,27 (IC 95% 0,06-0,88) para recurrencia a ocho semanas, ambos a favor de vancomicina, sin diferencias en recurrencia a 12 meses, necesidad de hospitalización o mortalidad. CONCLUSIÓN: La terapia con vancomicina comparada contra metronidazol en el tratamiento ambulatorio de la infección leve-moderada por C. dfficile se asocia a mayor cura clínica y menor tasa de recurrencia a corto plazo, sin diferencias en desenlaces a largo plazo.

BACKGROUND: Recommended treatment against mild cases of Clostridioides difficile associated diarrhea is vancomycin despite the difficulties of access compared to metronidazole. AIM: To compare the effectiveness of vancomycin and metronidazole in Chilean adults with first mild-moderate episode of Clostridiodes difficile infection (CDI). METHODS: Retrospective cohort of patients with CDI between January 2015 and December 2020 treated in centers of a university health network. The patients were adults treated for C. difficile infection on an outpatient basis. Recurrent and severe cases were excluded. Outcomes included clinical cure and recurrence rate. RESULTS: Data from 161 patients was recovered. Fifty-nine percent were women and average age was 53 (18-94). One hundred and nine patients were treated with metronidazole (67.7%) and 52 (32.3%) used vancomycin. Multivariate analysis adjusted by age and comorbidities showed an Odds Ratio of 3.00 (IC 95% 1.12-9.59) for clinical cure and 0.27 (IC 95% 0.06-0.88) for 8-week recurrence rate, both in favor of vancomycin, without differences in 12-month recurrence rate, hospitalization rate nor mortality. CONCLUSIONS: Vancomycin is associated with better short-term outcomes in the treatment of outpatient mild-moderate first episode C. difficile infection, without differences in long term recurrence or mortality when compared with metronidazole.

Vasculitis crioglobulinémica por hiperviscosidad y formación de criogel como debut de mieloma múltiple. Caso clínico / Cryoglobulinemic vasculitis due to hyperviscosity and cryogel formation as the onset of multiple myeloma. Report of one case

Multiple Myeloma (MM) is characterized by a clonal expansion of plasma cells in the bone marrow. These cells typically produce a monoclonal immunoglobulin, and its symptoms arise either from plasma cell infiltration in several organs, or secondary to the presence of a monoclonal protein peak. Symptoms can be summarized by the acronym CRAB (hypercalcemia, renal failure, anemia and bone lesions). Sometimes, in the setting of a protein secreting monoclonal gammopathy, formation of cryoglobulins develops. Cryoglobulins are plasma proteins that precipitate at low temperatures, forming a cold - induced precipitate at small vessels, causing a wide range of clinical manifestations. We report a female consulting for ulcers lasting 2 months in the left foot associated with purpuric lesions in both lower limbs. Protein electrophoresis showed a monoclonal peak in the gamma region. Bone marrow aspirate showed 27% of plasma cells with kappa chain restriction by cytometry. The presence of cryoglobulins was confirmed. The patient was treated with dexamethasone and bortezomib, with a progressive healing of lower limb lesions and disappearance of cryoglobulins. She was discharged in good conditions.

Uso de la cistatina C como biomarcador para estimar la tasa de filtración glomerular / Use of cystatin C to estimate glomerular filtration rate

Glomerular filtration rate (GFR) is routinely estimated using endogenous biomarkers due to the complexity of direct measurement methods. Cystatin C is a protease inhibitor produced in all nucleated cells. It is freely filtered and then catabolized by renal tubular cells. Therefore, plasma concentration of cystatin C depends primarily on GFR. Serum cystatin C is less affected by muscle mass, diet, race, gender and age than creatinine. In the general population, equations to estimate GFR based on cystatin C do not have a better performance than those based on creatinine. However, formulas that combine creatinine and cystatin C are more accurate and precise. Estimation of GFR based on cystatin C could be useful in populations in which creatinine value may be biased, such as people with extremely low or high muscle mass, cirrhosis and chronic cardiorenal syndrome. Due to its higher cost in comparison to creatinine, we recommend measuring cystatin C on these clinical situations and when a more accurate estimation of GFR is required.

Genotypic and phenotypic characteristics of Yersinia enterocolitica isolated from the surface of chicken eggshells obtained in Argentina.

The prevalence of Yersinia enterocolitica on chicken eggshell surfaces in San Luis, Argentina, was investigated. The pathogenic potential of recovered isolates was assessed by means of phenotypic virulence tests and the presence of the 72-kb pYV plasmid. Antimicrobial susceptibility was determined by the agar diffusion method. DNA digested with XbaI was analyzed by pulsed-field gel electrophoresis (PFGE), and relationships between genomic DNA profiles were established. Eight Y. enterocolitica B2 O:9 strains were recovered after enrichment, for a prevalence of 2.27%. All strains harbored the virulence pYV plasmid, bound Congo red, grew in a low-calcium medium, and autoagglutinated at 37 degrees C. They lacked pyrazinamidase activity and did not hydrolyze esculin. These Y. enterocolitica strains were susceptible to amikacin, ciprofloxacin, chloramphenicol, and trimethoprim-sulfamethoxazole and were resistant to rifampin. According to the genomic DNA patterns obtained by PFGE, the isolates clustered into two groups, I and II. The highest similarity coefficient observed between Y. enterocolitica strains was 0.947. Microbiological controls on production stages of eggs and good culinary practices are necessary to reduce the risk of Y. enterocolitica infection for consumers.

Coagulase-negative staphylococci: clinical, microbiological and molecular features to predict true bacteraemia.

Coagulase-negative staphylococci (CNS) are frequently isolated from blood cultures, where they may be only a contaminant or the cause of bacteraemia. Determining whether an isolate of CNS represents a true CNS bacteraemia is difficult, and there is no single criterion with sufficient specificity. The aim of this study was to assess those clinical, microbiological, pathogenic and genotypic features that characterize true CNS bacteraemia. Twenty patients having two or more blood cultures positive for CNS and 20 patients with only one positive blood culture were studied. Significant bacteraemia was defined according to clinical and laboratory criteria. Incubation time for blood cultures to become positive, macroscopic appearance of colonies, species determination, biotype, susceptibility to antimicrobials, PFGE pattern and adherence capacity were all studied. Clinical bacteraemia was present in 16/20 patients with two or more positive blood cultures and in 2/20 patients with only one positive blood culture. A significant difference was seen in the median time to positivity between the 18 clinical bacteraemias and 22 contaminations (23.6 versus 29.2 h; P = 0.04, Wilcoxon). There was also a significant difference between the two groups in the median absorbance of the slime test (1.36 versus 0.58; P = 0.005). All significant bacteraemias with two or more positive blood cultures had the same species identified, the same antimicrobial susceptibility pattern and the same PFGE pattern. In two patients with true bacteraemia with only one positive blood culture, the incubation time for the culture to turn positive was <24 h and the slime production absorbance was >2.5. The most useful parameters for the diagnosis of true CNS bacteraemia for patients with two positive blood cultures were incubation time until positive, species identification, antimicrobial susceptibility pattern, slime production and PFGE pattern. For patients with only one blood culture positive for CNS, the useful parameters for prediction of true bacteraemia were incubation time until positive and slime production, both of which are simple, low-cost tests.

Immunogenic protein variations of Clostridium chauvoei cellular antigens associated with the culture growth phase.

The immunoprotective capacity of four Clostridium chauvoei strains at different growth stages is reported. In all the strains tested, the cells coming from the stationary phase were those with the highest immunoprotective capacity and, depending on the strain, this protective capacity diminished or even disappeared in other phases. Protein profiles were similar in all the strains and few proteins were differentially expressed during growth as shown by SDS-PAGE. For strain 17, a local strain, a clear relationship was observed between the diminution of immunogenicity and the total loss of protective capacity of sonicated cells at late stationary phase.

Creatinina y su uso para la estimación de la velocidad de filtración glomerular / Estimation of glomerular filtration rate with creatinine

Glomerular filtration rate (GFR) is the best approximation to global renal function and its estimation is of great relevance for clinical practice. Since the measurement of GFR by reference methods is complex, costly and not widely available, its routine evaluation is performed using endogenous biomarkers. Within these, creatinine is the most commonly used. It allows the estimation of GFR by means of its clearance or by formulas based on its concentration on plasma. Creatinine measurement should be performed using enzimatic methods as they confer more accurate values than Jaffe methods, especially for normal and low creatinine levels.

Atypical presentation of pseudomembranous colitis localized in adenomatous polyps.

The most frequent cause of pseudomembranous colitis is Clostridium difficile (C. difficile) infection. This type of colitis is characterized by an endoscopic pattern of numerous small, yellowish or whitish plaques diffusely distributed, which typically compromises the rectum extending to proximal colon. Occasionally, the pseudomembranes compromise only the transverse or right colon, but their exclusive localization over polyps has not been reported. In this case report we have described a patient with symptoms compatible with C. difficile infection and positive for C. difficile toxigenic culture. Colonoscopy examination showed two small polyps with a whitish surface, and histopathological analysis confirmed them to be pseudomembranes over tubular adenomas. The rest of the colonic mucosa was normal and no other cause was demonstrated. We suggest that this particular distribution might be due to a higher affinity for dysplastic cells such as adenomatous polyps of colon by C. difficile and/or its toxins.

Cardiotoxicidad inducida por tratamientos oncológicos: fundamentos para la implementación de equipos de Cardio-Oncología / Cardiotoxicity of anticancer therapies: towards the implementation of cardio-oncology units

Recently, we have witnessed major improvements in cancer treatment. Early diagnosis and development of new therapies have reduced cancer-related mortality. However, these new therapies, along with greater patient survival, are associated with an increase in untoward effects, particularly in the cardiovascular system. Although cardiotoxicity induced by oncologic treatments affects predominantly the myocardium, it can also involve other structures of the cardiovascular system, becoming one of the main causes of morbidity and mortality in those who survive cancer. The main objective of cardio-oncology is to achieve the maximum benefits of oncologic treatments while minimizing their deleterious cardiovascular effects. It harbors the stratification of patients at risk of cardiotoxicity, the implementation of diagnostic tools (imaging techniques and biomarkers) for early diagnosis, preventive strategies and early treatment options for the complications. Herein, we discuss the basic knowledge for the implementation of cardio-oncology units and their role in the management of cancer patients, the diagnostic tools available to detect cardiotoxicity and the present therapeutic options.