Heat Dissipation Mechanisms in Hybrid Superconductor-Semiconductor Devices Revealed by Joule Spectroscopy.

Understanding heating and cooling mechanisms in mesoscopic superconductor-semiconductor devices is crucial for their application in quantum technologies. Owing to their poor thermal conductivity, heating effects can drive superconducting-to-normal transitions even at low bias, observed as sharp conductance dips through the loss of Andreev excess currents. Tracking such dips across magnetic field, cryostat temperature, and applied microwave power allows us to uncover cooling bottlenecks in different parts of a device. By applying this "Joule spectroscopy" technique, we analyze heat dissipation in devices based on InAs-Al nanowires and reveal that cooling of superconducting islands is limited by the rather inefficient electron-phonon coupling, as opposed to grounded superconductors that primarily cool by quasiparticle diffusion. We show that powers as low as 50-150 pW are able to suppress superconductivity on the islands. Applied microwaves lead to similar heating effects but are affected by the interplay of the microwave frequency and the effective electron-phonon relaxation time.

Risk assessment and strontium isotopic tracing of potentially toxic metals in creek sediments around a uranium mine, China.

The contamination of creek sediments near industrially nuclear dominated site presents significant environmental challenges, particularly in identifying and quantifying potentially toxic metal (loid)s (PTMs). This study aims to measure the extent of contamination and apportion related sources for nine PTMs in alpine creek sediments near a typical uranium tailing dam from China, including strontium (Sr), rubidium (Rb), manganese (Mn), lithium (Li), nickel (Ni), copper (Cu), vanadium (V), cadmium (Cd), zinc (Zn), using multivariate statistical approach and Sr isotopic compositions. The results show varying degrees of contamination in the sediments for some PTMs, i.e., Sr (16.1-39.6 mg/kg), Rb (171-675 mg/kg), Mn (224-2520 mg/kg), Li (11.6-78.8 mg/kg), Cd (0.31-1.38 mg/kg), and Zn (37.1-176 mg/kg). Multivariate statistical analyses indicate that Sr, Rb, Li, and Mn originated from the uranium tailing dam, while Cd and Zn were associated with abandoned agricultural activities, and Ni, Cu, and V were primarily linked to natural bedrock weathering. The Sr isotope fingerprint technique further suggests that 48.22-73.84% of Sr and associated PTMs in the sediments potentially derived from the uranium tailing dam. The combined use of multivariate statistical analysis and Sr isotopic fingerprint technique in alpine creek sediments enables more reliable insights into PTMs-induced pollution scenarios. The findings also offer unique perspectives for understanding and managing aqueous environments impacted by nuclear activities.

Ferric and sulfate coupled ammonium oxidation enhanced nitrogen removal in two-stage partial nitrification - Anammox/denitrification process for food waste liquid digestate treatment.

Liquid digestate of food waste is an ammonium-, ferric- and sulfate-laden leachate produced during digestate dewatering, where the carbon source is insufficient for nitrogen removal. A two-stage partial nitrification-anammox/denitrification process was established for nitrogen removal of liquid digestate without pre-treatment (>300 d), through which nitrogen (95 %), biodegradable organics (100 %), sulfate (78 %) and iron (100 %) were efficiently removed. Additional ammonium conversion (20 %N) might be coupled with ferric and sulfate reduction, while produced nitrite could be further converted to di-nitrogen gas through anammox (75 %) and denitrification (25 %). Notably, since increasingly contribution of hydroxylamine producing nitrous oxide, and up-regulated expression of electron transfer and cytochrome c protein, the enhanced ammonium oxidation was probably conducted through extracellular polymeric substances-mediated electron transfer between sulfate/ferric-reducers and aerobic ammonium oxidizers. Thus, the established partial nitrification-anammox/denitrification process might be a cost-efficient nitrogen removal technology for liquid digestate, benefitting to domestic waste recycling and carbon neutralization.

Distribution and migration of uranium, chromium, and accompanying metal(loid)s in soil-plants system around a uranium hydrometallurgical area.

The extraction and utilization of uranium (U) ores have led to the release of significant amounts of potentially toxic metal(loid)s (PTMs) into the environment, constituting a grave threat to the ecosystem. However, research on the distribution and migration mechanism of U, chromium (Cr), and their accompanying PTMs in soil-plant system around U hydrometallurgical area remains insufficient and poorly understood. Herein, the distribution, migration, and risk level of PTMs were evaluated in soil and plant samples around U hydrometallurgical area, Northern Guangdong, China. The results demonstrated that the maximum content of U and Cr found in the analyzed soils were up to 84.2 and 238.9 mg/kg, respectively. These values far exceed the soil background values in China and other countries. The highest content of U (53.6 mg/kg) was detected in Colocasia antiquorum Schott, and the highest content of Cr (349.5 mg/kg) was observed in Pteridium aquilinum, both of which were enriched in their roots. The risk assessment of PTMs demonstrated that the study area suffered from severe pollution (PN > 3), especially from U, Cr, Th, and As, suggesting the non-negligible anthropogenic impacts. Hence, in light of the significant ecological hazard posed by the U hydrometallurgical area, it is imperative to implement appropriate restoration measures to ensure the human health and maintain the stability of the ecosystem.

Noninferiority of 16-Week vs 8-Week Guselkumab Dosing in Super Responders for Maintaining Control of Psoriasis: The GUIDE Randomized Clinical Trial.

Importance: Psoriasis is a chronic inflammatory skin disease with unmet needs for tailored treatment and therapy de-escalation strategies. Objective: To evaluate early intervention with and prolonging the dosing interval for guselkumab, a p19 subunit-targeted interleukin (IL)-23 inhibitor, in patients with moderate to severe psoriasis. Design, Setting, and Participants: The GUIDE clinical trial is an ongoing phase 3b, randomized, double-blinded trial conducted across 80 centers in Germany and France comprising 3 parts evaluating the impact of early disease intervention, prolonged dosing interval, and maintenance of response following treatment withdrawal among adults with moderate to severe plaque psoriasis. In study part 2, reported herein, first and last patient visits were September 2019 and March 2022, respectively. Interventions: In GUIDE part 1 (week [W]0-W28), patients received guselkumab, 100 mg, at W0, W4, W12, and W20. Those achieving a Psoriasis Area and Severity Index (PASI) of 0 at both W20 and W28 were termed super responders (SRes). In part 2 (W28-W68), SRes were randomized to guselkumab, 100 mg, every 8 weeks or every 16 weeks; non-SRes continued open-label guselkumab every 8 weeks. Main Outcomes and Measures: Primary objective was to demonstrate noninferiority (with a 10% margin) of guselkumab every 16 weeks vs every 8 weeks dosing among SRes for maintenance of disease control (PASI <3 at W68). Biomarker substudies assessed immunologic effects in skin and blood. Results: Overall, 822 patients received guselkumab in part 2 (297 [36.1%] SRes [every 8 weeks/every 16 weeks; n = 148/n = 149] and 525 [63.9%] non-SRes). Among SRes, mean (SD) age was 39.4 (14.1) years, 95 (32.0%) were female, and 202 (68.0%) were male. The primary end point of noninferiority for guselkumab every 16 weeks vs every 8 weeks in SRes was met (P = .001), with 91.9% (137/149; 90% CI, 87.3%-95.3%) of SRes receiving every 16 weeks and 92.6% (137/148; 90% CI, 88.0%-95.8%) of SRes receiving dosing every 8 weeks having PASI lower than 3 at W68. Clinical effects corresponded with immunologic changes; skin CD8-positive tissue-resident memory T (TRM)-cell count decreased quickly from baseline, remaining low in both dosing groups. Similarly, serum IL-17A, IL-17F, IL-22, and ß defensin (BD)-2 levels decreased significantly from baseline, remaining low in both dosing groups to W68. Guselkumab was well-tolerated; no new safety signals were identified. Conclusions and Relevance: Psoriasis treatment guidelines lack or provide inconsistent advice on patient stratification and treatment de-escalation. We present the first randomized trial providing evidence that, in patients with early complete skin clearance at 2 consecutive visits (W20 and W28), extending the guselkumab dosing interval may control disease activity. Trial Registration: ClinicalTrials.gov Identifier: NCT03818035.

Evolution and Prognostic Significance of Patient-Reported Symptoms After Intervention in Severe Aortic Stenosis.

OBJECTIVE: To describe the evolution of symptoms in patients with symptomatic severe aortic stenosis (sSAS) undergoing valve replacement, the predictors of the persistence of these symptoms, and their prognostic significance. The evolution of symptoms after intervention in sSAS and their association with outcome are unknown. PATIENTS AND METHODS: Data from patients with sSAS who underwent intervention were collected. All-cause mortality and cardiovascular mortality were considered events. The evolution of symptoms and their association with events were studied. RESULTS: In this study, 451 consecutive patients with sSAS and no other valvular or coronary disease who were alive 30 days after intervention were included. Before valve replacement, 133 of the 451 patients (29.5%) had congestive heart failure requiring hospitalization. Of the remaining 318 patients, 287 (90.2%) had dyspnea on effort, 129 (40.6%) had angina, and 59 had syncope (18.6%). Symptoms disappeared after intervention in 192 of the 451 patients (42.6%) and remained in 259 (57.4%): 193 dyspnea, 9 angina, 17 syncope, and 60 admission for heart failure. Syncope on effort persisted in 4 of 33 patients (12.1%) and at rest in 11 of 20 (55.0%; P<.001). Age, body mass index, previous admission for heart failure, and chronic obstructive pulmonary disease were independently related to persistence of symptoms. Over a median follow-up of 56 months in our cohort of 451 patients, 129 deaths were registered (28.6%), 40 of which were cardiovascular (8.9%). Age, chronic obstructive pulmonary disease, chronic kidney disease, atrial fibrillation, heart failure, and persistence of symptoms were independently associated with all-cause mortality. CONCLUSION: Symptoms attributed to SAS remain after intervention in a high proportion of patients, particularly dyspnea on effort and syncope at rest. The persistence of symptoms after intervention identifies patients with poor outcome.

TAV-in-TAV in patients with prosthesis embolization: Impact of commissural alignment and global outcomes.

BACKGROUND: Optimal strategies to manage embolization of transcatheter aortic valve implantation (TAVI) devices are unclear; valve-in-valve (ViV) is often used. We aimed to describe through one-single center experience its rate, causes, consequences, and management as well as the rate and relevance of commissural alignment (CA) in this context. METHODS: We identified across 1038 TAVI cases, those cases requiring ViV for the management of first device embolization. CA (absence or mild misalignment) after first and second device was assessed by CT or fluoroscopy. RESULTS: A total of 23 cases (2.2%) were identified, 52.3% embolized towards the aorta and 47.7% towards the ventricle. Suboptimal implant height (38%) and embolization at the time of post-dilation (23%) were the most frequent mechanisms together with greater rate of bicuspid valve (p < 0.001) and a trend to greater annular eccentricity. Procedural and 1-year death occurred in 13% and 34%, respectively (vs. 1.1% and 7.8% in the global cohort, p < 0.001). CA was present in 76.9% of the prostheses initially implanted but was only spontaneously achieved in 30.8% of the second ViV device. Adequate CA of both prostheses was identified in only two cases (8.7%). There were no cases of coronary obstruction. CONCLUSIONS: TAVI device embolization mechanisms can often be predicted and prevented. Mortality following bail-out ViV is higher than in regular TAVI procedures but 2/3 of these patients survived beyond 1-year follow-up. In them, valve degeneration or coronary re-access might be particularly challenging since CA was rarely achieved with both devices suggesting that greater efforts should be made in this regard.

Incidence, Predictors, and Outcomes of Paravalvular Regurgitation After TAVR in Sievers Type 1 Bicuspid Aortic Valves.

BACKGROUND: Transcatheter aortic valve replacement (TAVR) in patients with bicuspid aortic valve (BAV) stenosis is technically challenging and is burdened by an increased risk of paravalvular regurgitation (PVR). OBJECTIVES: The aim of this study was to identify the incidence, predictors, and clinical outcomes of PVR after TAVR in Sievers type 1 BAV stenosis. METHODS: Consecutive patients with Sievers type 1 BAV stenosis undergoing TAVR with current-generation transcatheter heart valves (THVs) in 24 international centers were enrolled. PVR was graded as none/trace, mild, moderate, and severe according to echocardiographic criteria. The endpoint of major adverse events (MAEs), defined as a composite of all-cause death, stroke, or hospitalization for heart failure, was assessed at the last available follow-up. RESULTS: A total of 946 patients were enrolled. PVR occurred in 423 patients (44.7%)-mild, moderate, and severe in 387 (40.9%), 32 (3.4%), and 4 (0.4%) patients, respectively. Independent predictors of moderate or severe PVR were a larger virtual raphe ring perimeter (adjusted OR: 1.07; 95% CI: 1.02-1.13), severe annular or left ventricular outflow tract calcification (adjusted OR: 5.21; 95% CI: 1.45-18.77), a self-expanding valve (adjusted OR: 9.01; 95% CI: 2.09-38.86), and intentional supra-annular THV positioning (adjusted OR: 3.31; 95% CI: 1.04-10.54). At a median follow-up of 1.3 years (Q1-Q3: 0.5-2.4 years), moderate or severe PVR was associated with an increased risk of MAEs (adjusted HR: 2.52; 95% CI: 1.24-5.09). CONCLUSIONS: After TAVR with current-generation THVs in Sievers type 1 BAV stenosis, moderate or severe PVR occurred in about 4% of cases and was associated with an increased risk of MAEs during follow-up.

Frankincense preparation promotes formation of inflammation-resolving lipid mediators by manipulating lipoxygenases in human innate immune cells.

Introduction: Frankincense preparations are frequently used as traditional anti-inflammatory remedies in folk medicine with increasing popularity. Boswellic acids (BAs), especially 3-O-acetyl-11-keto-ßBA (AKBA), are unique anti-inflammatory principles of frankincense, with multiple pharmacological actions and target proteins. We recently showed that AKBA favorably impacts lipid mediator (LM) networks in innate immune cells, by modulation of lipoxygenase (LOX) activities. Thus, AKBA binds to allosteric sites in 5-LOX, shifting the regiospecificity to a 12/15-lipoxygnating enzyme, and to an analogous site in 15-LOX-1, leading to enzyme activation, which favors specialized pro-resolving mediator (SPM) formation at the expense of leukotriene production. Methods: Here, we investigated Boswellin super® (BSR), a commercially available frankincense extract with ≥30% AKBA, used as remedy that approved efficacy in osteoarthritis trials, for its ability to modulate LM pathways in human monocyte-derived macrophage (MDM) phenotypes, neutrophils, and neutrophil/platelet co-incubations. LM profiling was performed by using targeted ultraperformance liquid chromatography-tandem mass spectrometry (UPLC-MS-MS). Results: BSR concentration-dependently (10-100 µg/ml) suppressed formation of pro-inflammatory 5-LOX products including LTB4 in exotoxin-stimulated M1-MDM and neutrophils, and strongly elevated 12/15-LOX products and SPM in activated M2-MDM and neutrophil/platelet cocultures, starting at 10 µg/mL. Also, BSR (≥10 µg/mL) induced robust 12/15-LOX product and SPM generation in resting M2-MDM, which was further markedly elevated when exogenous docosahexaenoic acid (DHA) and eicosahexaenoic acid (EPA) were supplied, and induced translocation of 15-LOX from a soluble to a particulate locale in M2 MDM. Discussion: We conclude that BSR especially when co-added with DHA and EPA, promotes the LM class switch in innate immune cells from pro-inflammatory to pro-resolving mediators, which might be a plausible mechanism underlying the anti-inflammatory actions of BSR.

Unveiling the Probiotic Potential of the Anaerobic Bacterium Cetobacterium sp. nov. C33 for Enhancing Nile Tilapia (Oreochromis niloticus) Cultures.

The bacterium strain Cetobacterium sp. C33 was isolated from the intestinal microbial content of Nile tilapia (O. niloticus) under anaerobic conditions. Given that Cetobacterium species are recognized as primary constituents of the intestinal microbiota in cultured Nile tilapia by culture-independent techniques, the adaptability of the C33 strain to the host gastrointestinal conditions, its antibacterial activity against aquaculture bacterial and its antibiotic susceptibility were assessed. The genome of C33 was sequenced, assembled, annotated, and subjected to functional inference, particularly regarding pinpointed probiotic activities. Furthermore, phylogenomic comparative analyses were performed including closely reported strains/species relatives. Comparative genomics with closely related species disclosed that the isolate is not phylogenetically identical to other Cetobacterium species, displaying an approximately 5% sequence divergence from C. somerae and a 13% sequence divergence from Cetobacterium ceti. It can be distinguished from other species through physiological and biochemical criteria. Whole-genome annotation highlighted that Cetobacterium sp. nov. C33 possesses a set of genes that may contribute to antagonism against competing bacteria and has specific symbiotic adaptations in fish. Additional in vivo experiments should be carried out to verify favorable features, reinforcing its potential as a probiotic bacterium.

Validation of Quantitative Flow Ratio-Derived Virtual Angioplasty with Post-Angioplasty Fractional Flow Reserve-The QIMERA-I Study.

Background: Quantitative flow ratio (QFR) virtual angioplasty with pre-PCI residual QFR showed better results compared with an angiographic approach to assess post-PCI functional results. However, correlation with pre-PCI residual QFR and post-PCI fractional flow reserve (FFR) is lacking. Methods: A multicenter prospective study including consecutive patients with angiographically 50-90% coronary lesions and positive QFR results. All patients were evaluated with QFR, hyperemic and non-hyperemic pressure ratios (NHPR) before and after the index PCI. Pre-PCI residual QFR (virtual angioplasty) was calculated and compared with post-PCI fractional flow reserve (FFR), QFR and NHPR. Results: A total of 84 patients with 92 treated coronary lesions were included, with a mean age of 65.5 ± 10.9 years and 59% of single vessel lesions being the left anterior descending artery in 69%. The mean vessel diameter was 2.82 ± 0.41 mm. Procedural success was achieved in all cases, with a mean number of implanted stents of 1.17 ± 0.46. The baseline QFR value was 0.69 ± 0.12 and baseline FFR and NHPR were 0.73 ± 0.08 and 0.82 ± 0.11, respectively. Mean post-PCI FFR increased to 0.87 ± 0.05 whereas residual QFR had been estimated as 0.95 ± 0.05, showing poor correlation with post-PCI FFR (0.163; 95% CI:0.078-0.386) and low diagnostic accuracy (30.9%, 95% CI:20-43%). Conclusions: In this analysis, the results of QFR-based virtual angioplasty did not seem to accurately correlate with post-PCI FFR.

Sin elevación, también puede haber oclusión / Without elevation, there may also be occlusion

Resumen Ante un dolor torácico agudo y evidencia de elevación del segmento ST, se debe instaurar un tratamiento de reperfusión urgente, con el objetivo de abrir la arteria ocluida y minimizar el daño miocárdico y, así, mejorar el pronóstico del paciente. Por ello, es necesario conocer aquellos patrones eléctricos de alto riesgo equivalentes a una elevación del segmento ST e indicativos de una oclusión coronaria aguda, para evitar que se produzca una demora inadmisible en los tiempos de actuación, tal y como ocurrió en el caso que se presenta.

Abstract In light of an acute chest pain and evidence of ST-segment elevation, an emergent reperfusion treatment should be started with the objective of opening the occluded artery and reducing myocardial damage, thus, improving the patients´s prognosis. Therefore, it is mandatory to keep in mind those high-risk electrical patterns equivalent to a ST-segment elevation and indicative of an acute coronary occlusion to avoid an unacceptable delay in the times of action, such was the case that is reported.

Neurological disease in the time of COVID-19. A case series

Introduction: we present a series of patients with neurological problems and SARS-CoV-2 infection, and review the respective evidence. Patients and methods: a retrospective descriptive study of consecutive RT-PCR SARS-CoV-2-positive patients in a neurology department from August 1 to December 31, 2020. Results: we recorded 30 patients: 16 men (53%), with a mean age of 65±17.3. In 53%, the neu rological problem preceded the respiratory symptoms and SARS-CoV-2 infection diagnosis. At the syndromic level, the following were found: CVAs 43% (13), seizures 10% (3), posterior reversible encephalopathy 10% (3), encephalopathy 7% (2), brief psychotic disorder 7% (2), myelopathy 3% (1), Guillain-Barré syndrome 3% (1), headache 3% (1), vasculitis 3% (1), intracerebral hemorrhage 3% (1), myasthenic crisis 3% (1) and recurrent optic neuritis 3% (1). Conclusions: SARS-CoV-2 induced neurological problems produce a wide variety of symptoms and may be the first manifestation, even without the development of respiratory symptoms from this infection. (Acta Med Colomb 2022; 47. DOI:https://doi.org/10.36104/amc.2022.2233).

Introducción: se presenta una serie de pacientes con compromiso neurológico e infección por SARS-CoV-2 y se revisa la evidencia al respecto. Pacientes y métodos: estudio descriptivo, retrospectivo de pacientes consecutivos RT-PCR positivos para SARS-CoV-2 del servicio de neurología desde el 1° de agosto hasta 31 de diciembre de 2020. Resultados: registramos 30 pacientes, 16 hombres (53%), edad media: 65±17.3. En el 53% el compromiso neurológico antecedió los síntomas respiratorios y el diagnóstico de infección por SARS-CoV-2. A nivel sindromático se observó: ACV 43% (13), crisis convulsivas 10% (3), encefalopatía posterior reversible 10% (3), encefalopatía 7% (2), trastorno psicótico breve 7% (2), mielopatía 3% (1), síndrome de Guillain-Barré 3% (1), cefalea 3% (1), vasculitis 3% (1), hemorragia intracerebral 3% (1), crisis miasténica 3% (1) y neuritis óptica recurrente 3% (1). Conclusiones: el compromiso neurológico por el SARS-CoV-2 produce una gran variedad de síntomas y puede ser la primera manifestación incluso sin el desarrollo de síntomas respiratorios por esta infección. (Acta Med Colomb 2022; 47. DOI:https://doi.org/10.36104/amc.2022.2233).

Qué hay de nuevo sobre el síndrome inflamatorio multisistémico pediátrico asociado a SARS-COV-2

Con la aparición de la COVID-19, la edad pediátrica parecía menos vulnerable, hasta cierto momento donde se empezó a describir casi de forma simultánea en distintos países; primero en Italia, luego España e Inglaterra y por último en Estados Unidos brotes de una nueva enfermedad que en principio se pensó que era una presentación atípica de Enfermedad de Kawasaki, con el denominador común de la infección previa de SARS-COV-2, por lo cual pasó a denominarse como una patología nueva; su causa aun es desconocida, la hipótesis más aceptada es que se trata de una respuesta inadecuada del sistema inmunitario; en vista del aumento de pacientes con esta sintomatología las principales organizaciones de salud a nivel mundial como la Organización Mundial para la Salud (OMS) y los Centros para el Control y la Prevención de Enfermedades de Estados Unidos (CDC) se vieron en la necesidad de proponer protocolos de manejo; manteniendo un patrón similar al usado en la Enfermedad de Kawasaki, los cuales lastimosamente no se han actualizado con el paso de tiempo; partiendo de estos y bajo sus propias experiencias distintos colegios médicos a nivel mundial han desarrollado consensos de diagnóstico y manejo los cuales valen la pena ser revisados y tener en cuentan ya que muchos han probado ser de utilidad en distintos ensayos clínicos y los cuales tienen potencial para ser estudiados y seguirse desarrollando ya que pueden orientar al médico de forma mas rápida y eficaz a un diagnóstico

With the appearance of COVID-19, the pediatric age seemed less vulnerable, until a certain moment when it began to be described almost simultaneously in different countries; first in Italy, then Spain and England, and finally in the United States outbreaks of a new disease that at first was thought to be an atypical presentation of Kawasaki disease, with the common denominator of the previous infection of SARS-COV-2, for which happened to be denominated like a new pathology; its cause is still unknown, the most widely accepted hypothesis is that it is an inadequate response of the immune system; In view of the increase in patients with this symptomatology, the main global health organizations such as the World Health Organization (WHO) and the United States Center for Disease Control and Prevention (CDC) were in need to propose management protocols; maintaining a pattern similar to that used in Kawasaki disease, which unfortunately has not been updated over time; based on these and under their own experiences, different medical schools worldwide have developed diagnostic and management consensus which are worth reviewing and taking into account since many have proven to be useful in different clinical trials and which have the potential to be studied and continue to develop as they can guide the doctor more quickly and effectively to a diagnosis

Familial hypocalciuric hypercalcemia as a differential diagnosis of primary hyperparathyroidism with negative images / Hipercalcemia hipocalciúrica familiar como diagnóstico diferencial de hiperparatiroidismo primario con imágenes negativas / Hipercalcemia hipocalciúrica familiar como diagnóstico diferencial de hiperparatireoidismo primário com imagens negativas

Introduction. Familial hypocalciuric hypercalcemia is a rare inherited calcium metabolism disorder in which an alteration of the parathyroid hormone secretion set-point causes hypercalcemia with relative hypocalciuria. Some data suggest that its prevalence is around 74.1 per 100,000 inhabitants. Often, patients are asymptomatic. However, they can develop mild symptoms and an overactive parathyroid adenoma, its main differential diagnosis. The objective was to describe a patient's case and highlight the importance of clinical suspicion and diagnosis to avoid unnecessary surgical neck explorations for parathyroid adenomas. Case report. This is the case of a 40-year-old man with a biochemical profile compatible with primary hyperparathyroidism with anatomical and functional images negative for adenoma and a calcium/creatinine clearance ratio below 0.001, considering familial hypocalciuric hypercalcemia. Genetic studies evidence a mutation in the calcium sensor receptor gene and confirm the diagnosis. Discussion. Familial hypocalciuric hypercalcemia's main differential diagnosis is an overactive parathyroid adenoma. For both, mild or no symptoms may be present; serum calcium exceeds the upper limit, and parathormone is more than 25pg/ml. The calcium/creatinine clearance ratio should be used to differentiate one from the other and avoid unnecessary surgical neck explorations. Besides the lack of information on this topic, evidence supports the use of calcimimetics to treat symptomatic hypercalcemia. Conclusions. Patients with mild hypercalcemia with parathyroid hormone readings above 25pg/ml and a calcium/creatinine clearance ratio below 0.001, or patients with primary hyperparathyroidism with negative imaging, should not undergo surgical neck explorations. In these cases, familial hypocalciuric hypercalcemia is a reliable diagnosis; Cinacalcet may be administered in cases of symptomatic hypercalcemia.

Introducción. La hipercalcemia hipocalciúrica familiar es un trastorno hereditario poco común del metabolismo del calcio en donde una alteración del punto de ajuste de la secreción de hormona paratiroidea ocasiona hipercalcemia con hipocalciuria relativa. Algunos datos sugieren que su prevalencia es de alrededor de 74.1 por 100,000 habitantes. Los pacientes muchas veces son asintomáticos. Sin embargo, pueden desarrollar síntomas leves y un adenoma paratiroideo hiperactivo, que representa su principal diagnóstico diferencial. El objetivo fue describir el caso de un paciente y resaltar la importancia de la sospecha y el diagnóstico clínico para evitar exploraciones quirúrgicas cervicales innecesarias en búsqueda de adenomas paratiroideos. Reporte de caso. Este es el caso de un hombre de 40 años con un perfil bioquímico compatible con hiperparatiroidismo primario, con imágenes anatómicas y funcionales negativas para adenoma, además de una relación de depuración de calcio/creatinina menor a 0.001, con consideración de hipercalcemia hipocalciúrica familiar. Los estudios genéticos evidencian una mutación en el gen del receptor sensor del calcio y confirman el diagnóstico. Discusión. El principal diagnóstico diferencial de la hipercalcemia hipocalciúrica familiar es un adenoma paratiroideo hiperactivo. En ambos casos, es posible que no haya síntomas o que estos sean leves; el calcio sérico excede al límite superior, y la paratohormona es mayor de 25pg/ml. Se debe usar la relación de depuración de calcio/creatinina para diferenciar entre estas patologías y evitar exploraciones quirúrgicas cervicales innecesarias. Aparte de la falta de información sobre este tema, la evidencia apoya el uso de calciomiméticos para tratar la hipercalcemia sintomática. Conclusiones. Los pacientes con hipercalcemia leve, con valores de hormona paratiroidea mayores de 25pg/ml y con una relación de depuración de calcio/creatinina menor de 0.001, o los pacientes con hiperparatiroidismo primario con imágenes negativas, no deben ser sometidos a exploraciones quirúrgicas cervicales. En estos casos, la hipercalcemia hipocalciúrica familiar representa un diagnóstico confiable; se puede administrar Cinacalcet en casos de hipercalcemia sintomática.

Introdução. A hipercalcemia hipocalciúrica familiar é um distúrbio hereditário raro do metabolismo do cálcio, no qual uma alteração no ponto de ajuste da secreção do hormônio da paratireóide causa hipercalcemia com hipocalciúria relativa. Alguns dados sugerem que sua prevalência gira em torno de 74.1 por 100,000 habitantes. Os pacientes geralmente são assintomáticos. No entanto, eles podem desenvolver sintomas leves e um adenoma de paratireoide hiperativo, que representa seu principal diagnóstico diferencial. O objetivo foi descrever o caso de um paciente e destacar a importância da suspeita clínica e do diagnóstico para evitar exploração cirúrgica cervical desnecessária em busca de adenomas de paratireoide. Relato de caso. É o caso de um homem de 40 anos com perfil bioquímico compatível com hiperparatireoidismo primário, com imagens anatômicas e funcionais negativas para adenoma, além de relação depuração de cálcio/creatinina menor que 0.001, considerando hipercalcemia hipocalciúrica familiar. Estudos genéticos revelam uma mutação no gene receptor da sensibilidade ao cálcio e confirmam o diagnóstico. Discussão. O principal diagnóstico diferencial da hipercalcemia hipocalciúrica familiar é um adenoma de paratireoide hiperativo. Em ambos os casos, os sintomas podem estar ausentes ou leves; o cálcio sérico excede o limite superior e o hormônio da paratireóide é superior a 25pg/ml. A relação depuração de cálcio/creatinina deve ser usada para diferenciar entre essas patologias e evitar exploração cirúrgica cervical desnecessária. Além da falta de informações sobre esta questão, as evidências apoiam o uso de calcimiméticos para tratar a hipercalcemia sintomática. Conclusões. Pacientes com hipercalcemia leve, com valores de hormônio da paratireóide maiores que 25pg/ml e uma relação de depuração de cálcio/creatinina menor que 0.001, ou pacientes com hiperparatireoidismo primário com imagens negativas, não devem ser submetidos a exploração cirúrgica cervical. Nesses casos, a hipercalcemia hipocalciúrica familiar representa um diagnóstico confiável; Cinacalcet pode ser administrado em casos de hipercalcemia sintomática.

Medicina de precisión en sepsis: utilidad de los en sepsis: utilidad de los biomarcadores en pacientes críticamente enfermos / Precision medicine in sepsis: usefulness of biomarkers In critically ill patientsbiomarkers In critically ill patients

Durante años la evolución del cuidado intensivo ha intentado ofrecer una atención basada en protocolos y paquetes de manejo agrupados por patologías y cuadro sindromáticos. Aunque se logró disminuir la mortalidad en diferentes patologías (sepsis y síndromes coronario agudo y de distrés respiratorio agudo), no se han resuelto por completo los problemas clínicos, en especial el diagnóstico y el manejo. Una nueva opción ha surgido en el horizonte denominada "medicina de precisión", entendida como estrategia de prevención y tratamiento que tiene en cuenta la variabilidad individual. La sepsis es un síndrome con múltiples aristas en cuanto al fenotipo y genotipo, cuyo diagnóstico temprano es relevante para los desenlaces clínicos. Hasta el momento el enfoque principal ha sido la identificación de un germen etiológico para diferenciarla del síndrome de respuesta inflamatoria sistémica (SIRS). En los últimos años el paradigma en enfermedades infecciosas ha cambiado debido a estudios que demuestran como la respuesta inmunitaria del paciente séptico tiene un papel clave en el desarrollo de la enfermedad, con implicaciones en el diagnóstico, pronóstico y tratamiento, que podrían ayudar a cambiar el abordaje en los próximos años gracias a una estrategia basada en medicina de precisión. Hoy los aislamientos microbiológicos y los cultivos siguen siendo el estándar de referencia con varias desventajas como el tiempo para obtener resultados, sobre todo en infecciones por gérmenes resistentes u hongos, que pueden retrasar el inicio de la terapia antimicrobiana. Como alternativa se ha planteado el uso de biomarcadores en sepsis que, siendo productos de la respuesta inflamatoria del individuo ante la infección, son útiles para el diagnóstico y pronóstico primordialmente en los críticamente enfermos. Decidimos realizar esta revisión narrativa acerca de la utilidad de los biomarcadores en pacientes con sepsis críticamente enfermos, para enfocarlos en un modelo de medicina personalizada.

For many years, critical care practice has been based on protocols and management guidelines categorized by pathologies or syndromes. Although mortality caused by various diseases such as sepsis, acute coronary syndrome and acute respiratory distress has decreased, clinical problems, particularly diagnosis and management, have not been completely resolved. A new option known as "precision medicine" is on the horizon, a prevention and treatment strategy based on individual variability. Sepsis is a syndrome encompassing multiple clinical phenotypes and genotypes coding and a prompt diagnosis is relevant to obtain better outcomes. To this moment the main approach has been the identification of microorganisms causing sepsis to distinguish sepsis from systemic inflammatory response (SIRS). Infectious diseases paradigm has changed during recent years due to studies demonstrating how septic patient immune response plays a key role in the development of the disease, with implications on diagnosis, prognosis and treatment, which may help change the approach in the next years thanks to a strategy based on precision medicine. Today microbiological identification and cultures continue to be the reference standard with several disadvantages such as turnaround time for test results predominantly in infections caused by resistant bacteria or fungi that may delay commencement of antibiotic therapy. The use of sepsis biomarkers determined by the individual ́s inflammatory response to infection have been proposed as a useful alternative for establishing diagnosis and prognosis mainly in critically ill patients. We decided to conduct this narrative review on the usefulness of biomarkers in critically ill septic patients using a personalized medicine model.

Determinacion de los factores de riesgo en sepsis por Enterococcus vancomicino resistente. Estudio de casos y controles en pacientes criticamente enfermos / Determination of risk factors in sepsis by Enterococcus vancomicyn resistant. Study of cases and control in criticall ill patients

Resumen Introducción: las infecciones causadas por Enterococcus resistente a Vancomicina (EVR) presentan mayor mortalidad en pacientes críticos, asociado a un aumento gradual en este patrón de resistencia, especialmente en el continente americano, por lo cual la adecuada terapia antimicrobiana empírica es fundamental para mejorar los desenlaces. Objetivo: determinar los factores de riesgo asociados al desarrollo de infección por EVR en pacientes sépticos en la Unidad de Cuidados Intensivos (UCI) del Hospital San José en Bogotá, Colombia. Métodos: Estudio descriptivo de casos y controles en pacientes sépticos ingresados a la UCI durante 2016 y 2017. Los casos se definieron como pacientes con infección por EVR y los controles los pacientes con infección por otro germen. Resultados: se incluyeron 32 pacientes con aislamiento de EVR y 96 controles. Los factores de riesgo asociados a infección por EVR fueron: nutrición parenteral (OR 15,7 IC 4,2-71,4), lavado peritoneal (OR 8,9 IC 3,2-24,8), cultivo polimicrobiano (OR 19,9 IC 6,0-83,4). La mortalidad fue 56,2% en casos y 33,3% en controles. Conclusiones: Los factores de riesgo hallados con mayor frecuencia fueron: múltiples lavados peritoneales, nutrición parenteral y cultivos polimicrobianos. Encontramos una correlación significativa en el uso de antibiótico empírico adecuado y la reducción en la mortalidad.

Summary Introduction: infections caused by Vancomycin-resistant Enterococcus (VRE) have higher mortality in critically ill patients, associated with increase in this pattern of resistance, especially in the Americas, which is why adequate empirical antimicrobial therapy is essential to improve outcomes Objective: to determine the risk factors associated with the development of infection by VRE in septic patients in the Intensive Care Unit (ICU) of San José Hospital in Bogotá, Colombia. Methods: Case-control study in septic patients admitted to the ICU during 2016 and 2017. The cases were defined as patients with VRE infection and the controls were patients with infection by another germ. Results: 32 patients with EVR isolation and 96 controls were included. The risk factors associated with infection by EVR were: parenteral nutrition (OR 15.7 IC 4.2-71.4), peritoneal lavage (OR 8.9 IC 3.2-24.8), polymicrobial culture (OR 19,9 IC 6.0-83.4). Mortality was 56.2% in cases and 33.3% in controls. Conclusions: The risk factors found most frequently were: multiple peritoneal lavage, parenteral nutrition and polymicrobial cultures. We found a significant correlation in the use of adequate empirical antibiotic and the reduction in mortality

Reporte de dos casos de inusual infección no letal por Chromobacterium violaceum. Revisión literaria / Report two cases non lethal infectious diseases for Chromobacterium violaceum. Review of the literature

Chromobacterium violaceum es una bacteria gramnegativa anaeróbica facultativa, que habita en el suelo y el agua de las áreas tropicales y subtropicales. La infección en seres humanos es rara. A continuación se presentan dos casos; una lactante mayor, indígena, quien posterior a baño de inmersión en aguas estancadas comienza a presentar fiebre con aumento de volumen y limitación funcional y gonalgia izquierda, se realiza lavado articular, se toma muestra para cultivo con crecimiento para Chromobacterium violaceum. Un escolar masculino de 7 años de edad con antecedente de Leucemia Linfoblastica Aguda con recaída en sistema nervioso central, cumpliendo esquema de altas dosis de metotrexate; quien comienza a presentar fiebre y signos de flogosis en sitio de colocación de cáteter de vía central, el cual es retirado y cultivado con crecimiento para Chromobacterium violaceum. Esta infección en humanos es una enfermedad grave y sistémica con una alta tasa de mortalidad.

Chromobacterium violaceum is a Gram-negative facultative anaerobic bacterium, which lives in the soil and water of subtropical and tropical areas. Infection in humans is rare. Here we present two cases. One was in one indigenous newborn, who after one immersion in stagnant waters presented fever and increase in the volume of testicle and limitation in movility of the left limb. After arthrocentesis of left knee and culture of the sinovial liquid, growth of Cromabacterium violaceum was reported. Another case was a male school of 7 years old with a history of acute lymphoblastic leukemia relapse in the central nervous system, that completed his high dose methotexate scheme. Some days after he presented fever and edema at the site of central venous catheterization. The catheter was retired and it was obtained growth of Chromobacterium violaceum. Human infection with Chromobacterium violaceum is a severe and systemic disease with a high mortality rate.

Utilidad de la proteína C reactiva para identificar los recién nacidos con riesgo de infección

Desde hace años, numerosos estudios han buscado parámetros que puedan ser útiles en el diagnóstico precoz de las infecciones neonatales. Se conoce la utilidad que presenta la Proteína C Reactiva (PCR) en las infecciones neonatales; sin embargo, su elevación no se produce hasta pasadas 12 a 24 horas de iniciarse la infección. La utilidad de la Proteína C Reactiva se encuentra en la realización de determinaciones seriadas, ya que sus concentraciones séricas se incrementan a partir de las 12-24 horas de iniciarse la infección. Objetivo: Determinar la utilidad de la Proteína C Reactiva para identificar los recién nacidos con riesgo de infección. Metodología: La población de estudio fue de 80 neonatos que tuviesen más de 24 horas de haber sido ingresados, con factores de riesgo para infección y/o con factores de riesgo para sufrimiento fetal agudo. Se utilizó un kit comercial de medición de Proteína C Reactiva de forma semicuantitativa. Resultados: Los recién nacidos estudiados presentaron una media de edad gestacional de 38 ± 3,4 semanas, con peso promedio de 2 760 ± 867 g. Aquellos con antecedentes de parto vaginal, o con antecedente materno de preeclampsia y/o infección urinaria presentaron mayor tendencia a elevación de los niveles de Proteína C Reactiva. Conclusión: La Proteína C Reactiva presenta una sensibilidad y especificidad baja para identificar pacientes con riesgo de infección; debido a diversos estados de estrés neonatal que pueden ocasionarse elevaciones de la misma.

For years, numerous studies have sought parameters that may be useful in early diagnosis of neonatal infection. Utility of C-Reactive Protein in neonatal infections is known; however, its elevation does not occur until after 12 to 24 hours of initiation of the infection. Utility of C-Reactive Protein lies in the realization of its serial determinations because increase of serum concentrations begins 12 to 24 hours after infection. Objective: To determine the usefulness of C-Reactive Protein to identify babies at risk of infection. Methodology: The study population was 80 newborns who were in the hospital for more than 24 hours with risk factors for infection and acute fetal distress. A commercial kit for measuring semiquantitative C-Reactive Protein was used. Results: The newborns studied had a mean gestational age of 38 ± 3.4 weeks, with an average weight of 2 760 ± 867 grams. Those with a history of vaginal delivery, maternal history of preeclampsia and / or urinary tract infection showed a greater tendency to have elevated C-Reactive Protein levels. Conclusion: C-Reactive Protein has a low sensitivity and specificity for identifying patients at risk of infection; due to different states of neonatal stress can produce increased levels of it.