Assessing the Utility of Multiplexed Polymerase Chain Reaction in Detecting Microorganisms Causing Infections in Critically ill Patients.

Early sepsis diagnosis is crucial for implementing adequate antibiotic therapy and for patient survival. This study investigated whether using multiplexed PCR for detecting microorganisms in critical septic patients affects initial antibiotic treatment and compared it to microbiological culture. It also explored scenarios where PCR is more effective in clinical practice. One hundred nineteen specimens (83 blood and 36 respiratory specimens) belonging to 93 patients were analyzed. Multiplexed PCR determinations were performed using the FA-BCID Panel (bioMérieux) for blood samples and the FA-Pneumo for respiratory samples. The mean turnaround times were 1.7 h for the FA-BCID and 1.5h for the FA-Pneumo. Conversely, they were 96.1 h for blood cultures and 72.3 h for respiratory cultures. FA-BCID showed a mean sensitivity of 97% and specificity of 100%. FA-Pneumo showed a sensitivity of 100% and specificity of 90%. However, the positive predictive value was only 39%. Discrepancies were common in polymicrobial samples. Based on the PCR results, initial empirical treatment should have been changed in 71% of patients with bloodstream infections and 61% with respiratory infections. We conclude that multiplexed PCR improves the response time in identifying germs with a high degree of coincidence for blood cultures and moderate for respiratory cultures. These results highlight the importance of PCR in choosing an appropriate antibiotic therapy.

Molecular and clinical characterization of transient antithrombin deficiency: A new concept in congenital thrombophilia.

Antithrombin deficiency, the most severe thrombophilia, might be underestimated, since it is only investigated in cases with consistent functional deficiency or family history. We have analyzed 444 consecutive, unrelated cases, from 1998 to 2021, with functional results supporting antithrombin deficiency in at least one sample. Plasma antithrombin was evaluated by functional and biochemical methods in at least two samples. SERPINC1 gene was analyzed by sequencing and MPLA. Hypoglycosylation was studied by electrophoresis and high-performance liquid chromatography (HPLC). In 260 of 305 cases (85.2%) with constitutive deficiency (activity < 80% in all samples), a SERPINC1 (N = 250), or N-glycosylation defect (N = 10) was observed, while 45 remained undetermined. The other 139 cases had normal antithrombin activity (≥ 80%) in at least one sample, what we called transient deficiency. Sixty-one of these cases (43.9%) had molecular defects: 48 had SERPINC1 variants, with two recurrent mutations (p.Ala416Ser[Cambridge II], N = 15; p.Val30Glu[Dublin], N = 12), and 13 hypoglycosylation. Thrombotic complications occurred in transient deficiency, but were less frequent, latter-onset, and had a higher proportion of arterial events than in constitutive deficiency. Two mechanisms explained transient deficiency: The limitation of functional methods to detect some variants and the influence of external factors on the pathogenic consequences of these mutations. Our study reveals a molecular defect in a significant proportion of cases with transient antithrombin deficiency, and changes the paradigm of thrombophilia, as the pathogenic effect of some mutations might depend on external factors and be present only at certain timepoints. Antithrombin deficiency is underestimated, and molecular screening might be appropriate in cases with fluctuating laboratory findings.

The Role of RNA-Binding Proteins in Hematological Malignancies.

Hematological malignancies comprise a plethora of different neoplasms, such as leukemia, lymphoma, and myeloma, plus a myriad of dysplasia, such as myelodysplastic syndromes or anemias. Despite all the advances in patient care and the development of new therapies, some of these malignancies remain incurable, mainly due to resistance and refractoriness to treatment. Therefore, there is an unmet clinical need to identify new biomarkers and potential therapeutic targets that play a role in treatment resistance and contribute to the poor outcomes of these tumors. RNA-binding proteins (RBPs) are a diverse class of proteins that interact with transcripts and noncoding RNAs and are involved in every step of the post-transcriptional processing of transcripts. Dysregulation of RBPs has been associated with the development of hematological malignancies, making them potential valuable biomarkers and potential therapeutic targets. Although a number of dysregulated RBPs have been identified in hematological malignancies, there is a critical need to understand the biology underlying their contribution to pathology, such as the spatiotemporal context and molecular mechanisms involved. In this review, we emphasize the importance of deciphering the regulatory mechanisms of RBPs to pinpoint novel therapeutic targets that could drive or contribute to hematological malignancy biology.

Microbial evolution of vascular graft infections in a tertiary hospital based on positive graft cultures.

BACKGROUND: Vascular graft infections are a serious complication in vascular surgery. Correct antibiotic therapy targeted to the most likely infecting species is essential to treat these patients, although the bacterial epidemiology and pathogenesis are still not completely understood. We analyzed the behavior of vascular graft infections and the microbiologic patterns of resistance. METHODS: A 10-year (2008-2018), single-center, retrospective cohort study was performed of all patients admitted with vascular graft infection identified by positive direct graft cultures. An extensive microbiologic study was performed to analyze the bacterial strains, antibiotic resistance and sensitivity, and prevalence stratified by the year. RESULTS: A total of 72 vascular graft infections with positive graft cultures occurring in 65 patients were found. Their mean age was 67 ± 9.6 years, and 85% were men. Infection-related mortality was 11%. Of the 65 patients, 14 had undergone aortobifemoral bypass, 13 axillofemoral bypass, 5 femorofemoral bypass, 27 femoropopliteal bypass, and 4 femoral endarterectomy with synthetic patch angioplasty. The median interval from the index procedure to infection was longer for intracavitary than for extracavitary grafts (P = .011). Of the 72 infections, 48 were monomicrobial and 24 were polymicrobial. Gram-negative bacteria were predominantly identified in intracavitary graft infections (54%). In contrast, gram-positive bacteria were most frequent in the extracavitary graft group (58%). Multidrug-resistant bacterial species occurred more frequently in early graft infections (P = .002). Throughout the study duration, an overall decrease in gram-positive infections and an increase in gram-negative infections was observed, especially in extensively drug-resistant strains. A similar progression was found in all nosocomial infections. CONCLUSIONS: The present study has shown that vascular graft infection microbiology changed in accordance with graft location and interval to infection from revascularization surgery and had also evolved over the study period with patterns similar to those for all nosocomial infections. This highlights the importance of studying the specific microbiology of each healthcare center and its relationship to vascular graft infections to achieve the best treatment possible.

Clinical value of procalcitonin in critically ill patients infected by SARS-CoV-2.

Background Blood procalcitonin (PCT) levels usually increase during infectious diseases and might be helpful to differentiate bacterial from non-bacterial origin. COVID-19 patients could present co-infections at initial presentation in the Emergency Department and nosocomial infections during stay in the ICU. However, the published literature has not established whether PCT changes could aid in the diagnosis of infectious complication during the COVID-19 pandemic. Methods Retrospective, single-center, cohort study, including COVID-19 patients admitted between March and May 2020. The data were prospectively collected for department purposes; laboratory results were collected automatically at admission and during the whole patient admission. Results 56 patients were analyzed (female 32%, male 68%), 35 were admitted to ICU, and 21 received general ward care. 21 ICU patients underwent mechanical ventilation (88%), and 9 died during admission (26%). Non-survivors had higher initial blood PCT levels than survivors at ICU admission (p.

Clinical aspects and present challenges of the seat belt aorta.

OBJECTIVE: Seat belt aorta is rare and difficult to manage. The lack of data and follow-up increases the complexity of treating such patients. We aimed to create a decision algorithm by reviewing our current experience and analyzing the presentation and management of our patients. METHODS: We performed a descriptive case series based on retrospective analysis of all consecutive patients admitted with the diagnosis of seat belt aorta from 2008 to 2018. Seat belt aorta was defined as any blunt abdominal aortic lesion resulting from a seat belt compression mechanism after a car accident. RESULTS: Nine consecutive patients were admitted with the diagnosis of seat belt aorta, all of whom developed lesions in the infrarenal aorta. Eight patients were assessed in the acute phase and one patient presented with late-onset symptoms. Associated injuries were present in all acute patients, and seat belt sign and small bowel injury were present in 88%. One patient presented with a small intimal tear and was treated conservatively. All other patients diagnosed with large intimal flaps (seven patients) and pseudoaneurysm (one patient) underwent open repair in five cases and endovascular repair in three cases. In-hospital mortality for the acute cases was 38%, with no mortality seen during follow-up. Two patients submitted to endovascular repair required reinterventions. CONCLUSIONS: Seat belt aorta is a deadly condition, frequently associated with blunt thoracoabdominal trauma with concomitant injuries; the presence of a seat belt sign or lower limb ischemia must lead to a high diagnostic suspicion. Management must take into account the other concomitant injuries. Follow-up is crucial as most patients are young; they may develop complications and subsequently require further intervention.

Photodynamic therapy in dermatology: Beyond current indications.

Photodynamic therapy (PDT) has long been used in dermatology as a therapeutic strategy for several malignant and premalignant conditions. Currently, it is approved in Europe for the treatment of actinic keratosis, squamous cell carcinoma in situ, and some forms of basal cell carcinoma, with favorable clearance rates associated with satisfying aesthetic results. Nonetheless, in the past few years, PDT has also demonstrated efficacy in many other conditions, including inflammatory and infectious dermatoses. These results, probably explained by its immunomodulatory, anti-inflammatory, and bactericidal effects, may lead to an expansion of PDT indications in the upcoming years. In this article, conditions where PDT may be useful are reviewed, thus highlighting the potential of this therapeutic modality for the dermatologist.

Fouling communities and degradation of archeological metals in the coastal sea of the Southwestern Gulf of Mexico.

Corrosion and biofouling phenomena of cast iron and brass were evaluated under natural conditions to determine the degradation process of archeological artifacts. Field exposure studies of experimental materials were conducted over 15 months at an offshore position in the sea of Campeche in the Gulf of Mexico. Corrosion was determined by gravimetric measurements. The community structure of the benthic assemblage inhabiting the surfaces of both materials was evaluated. A total of 53 species was identified. The community in both cases was composed of a small number of species. Encrusting, attached and erect life forms were dominant on iron. Attached life forms were dominant on brass. Biofouling produced a decrease in the weight loss measurements of cast iron samples. Biofouling provided a beneficial factor for in situ preservation of iron archeological artifacts in wreck sites.

Symmetries in fluctuations far from equilibrium.

Fluctuations arise universally in nature as a reflection of the discrete microscopic world at the macroscopic level. Despite their apparent noisy origin, fluctuations encode fundamental aspects of the physics of the system at hand, crucial to understand irreversibility and nonequilibrium behavior. To sustain a given fluctuation, a system traverses a precise optimal path in phase space. Here we show that by demanding invariance of optimal paths under symmetry transformations, new and general fluctuation relations valid arbitrarily far from equilibrium are unveiled. This opens an unexplored route toward a deeper understanding of nonequilibrium physics by bringing symmetry principles to the realm of fluctuations. We illustrate this concept studying symmetries of the current distribution out of equilibrium. In particular we derive an isometric fluctuation relation that links in a strikingly simple manner the probabilities of any pair of isometric current fluctuations. This relation, which results from the time-reversibility of the dynamics, includes as a particular instance the Gallavotti-Cohen fluctuation theorem in this context but adds a completely new perspective on the high level of symmetry imposed by time-reversibility on the statistics of nonequilibrium fluctuations. The new symmetry implies remarkable hierarchies of equations for the current cumulants and the nonlinear response coefficients, going far beyond Onsager's reciprocity relations and Green-Kubo formulas. We confirm the validity of the new symmetry relation in extensive numerical simulations, and suggest that the idea of symmetry in fluctuations as invariance of optimal paths has far-reaching consequences in diverse fields.

Spectrum of cutaneous lesions in a cohort of patients with neurofibromatosis type 2.

BACKGROUND: Neurofibromatosis type 2 (NF2) is a rare autosomal dominant syndrome with a predisposition to the development of central nervous system tumors, ophthalmic manifestations, and dermatological lesions. The latter are present in 70-95% of patients and can precede the evolution of other tumors. However, they are not included in the diagnostic criteria and are frequently undervalued during follow-up. METHODS: An observational cross-sectional study characterizing cutaneous lesions in a cohort of NF2 patients was carried out. Dermatological examinations were performed, and lesions were classified into neural cutaneous tumors (superficial, SNCT, and deep, DNCT), hyperpigmented patches (HyperP), and hypopigmented patches (HypoP). The Dermatology Life Quality Index (DLQI) and EQ-5D questionnaires were applied to evaluate the impact on quality of life. RESULTS: Nineteen patients with a mean age of 36 years were included. Sixteen (84%) patients had cutaneous lesions, mostly developed 10 or more years before the diagnosis. SNCT, DNCT, and HyperP showed similar frequencies (58%). HypoP were observed in only one patient. HyperP developed, on average, earlier than NCT (9.6 vs. 16.5 SNCT, 17.0 DNCT; years). The excised lesions had different histological patterns, including neurofibromas, schwannomas, and a hybrid tumor. Most patients reported a low impact of cutaneous manifestations on the quality of life (DLQI 0 or 1). CONCLUSIONS: Cutaneous lesions are frequent in NF2 and may precede the diagnosis by several years. Their identification is important to establish the diagnosis earlier and potentially reduce morbidity and mortality.