Mortality and associated risk factors in patients hospitalized due to COVID-19 in a Peruvian reference hospital.

OBJECTIVES: To determine the risk factors for in-hospital mortality in patients with COVID-19 from a Peruvian national hospital. METHODS: Retrospective cohort study of medical records of patients with COVID-19 hospitalized at Hospital Nacional Hipólito Unanue (HNHU) during the months of April to August 2020. The dependent variable was in-hospital mortality. Independent variables included sociodemographic and clinical characteristics, physical examination findings, oxygen saturation (SaO2) at admission, treatment received during hospitalization and laboratory results at admission. A Cox regression model was used to evaluate the crude and adjusted hazard ratios for associated factors. RESULTS: We included 1418 patients. Median age was 58 years (IQR 47-68 years) and 944 (66.6%) were male. The median length of hospitalization was 7 (4-13) days, and the mortality rate was 46%. The most frequent comorbidities were type 2 diabetes mellitus, hypertension, and obesity. In the adjusted analysis, mortality was associated with age (HR 1.02; 95%CI 1.02-1.03), history of surgery (HR 1.89; 95%CI 1.31-2.74), lower oxygen saturation at admission (HR 4.08; CI95% 2.72-8.05 for SaO2<70% compared to SaO2>94%), the presence of poor general condition (HR 1.81; 95% CI 1.29-2.53), altered state of consciousness (HR 1.58; 95%CI 1.18-2.11) and leukocyte levels (HR 1.01; 95%CI 1.00-1. 02). Treatment with ivermectin (HR 1.44; 95%CI 1.18-1.76) and azithromycin (HR 1.25; 95%CI 1.03-1.52) were associated with higher mortality. Treatment with corticosteroids at low to moderate doses was associated with lower mortality (HR 0.56 95%CI 0. 37-0. 86) in comparison to no steroid use. CONCLUSION: A high mortality was found in our cohort. Low oxygen saturation at admission, age, and the presence of hematological and biochemical alterations were associated with higher mortality. The use of hydroxychloroquine, ivermectin or azithromycin was not useful and was probably associated with unfavorable outcomes. The use of corticosteroids at moderate doses was associated with lower mortality.

Daytime Restricted Feeding Modifies the Temporal Expression of CYP1A1 and Attenuated Damage Induced by Benzo[a]pyrene in Rat Liver When Administered before CYP1A1 Acrophase.

The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor that heterodimerizes with the AhR nuclear translocator (ARNT) to modulate CYP1A1 expression, a gene involved in the biotransformation of benzo[a]pyrene (BaP). The AhR pathway shows daily variations under the control of the circadian timing system. Daytime restricted feeding (DRF) entrains the expression of genes involved in the processing of nutrients and xenobiotics to food availability. Therefore, we evaluate if temporal AhR, ARNT, and CYP1A1 hepatic expression in rats are due to light/dark cycles or fasting/feeding cycles promoted by DRF. Our results show that AhR oscillates throughout the 24 h period in DRF and ad libitum feeding rats (ALF), showing maximum expression at the same time points. DRF modified the peak of ARNT expression at ZT5; meanwhile, ALF animals showed a peak of maximum expression at ZT17. An increased expression of CYP1A1 was linked to the meal time in both groups of animals. Although a high CYP1A1 expression has been previously associated with BaP genotoxicity, our results show that, compared with the ALF group, DRF attenuated the BaP-CYP1A1 induction potency, the liver DNA-BaP adducts, the liver concentration of unmetabolized BaP, and the blood aspartate aminotransferase and alanine aminotransferase activities when BaP is administered prior to the acrophase of CYP1A1 expression. These results demonstrate that DRF modifies the ARNT and CYP1A1 expression and protects from BaP toxicity.

Genome-Wide Analysis of Targets for Post-Transcriptional Regulation by Rsm Proteins in Pseudomonas putida.

Post-transcriptional regulation is an important step in the control of bacterial gene expression in response to environmental and cellular signals. Pseudomonas putida KT2440 harbors three known members of the CsrA/RsmA family of post-transcriptional regulators: RsmA, RsmE and RsmI. We have carried out a global analysis to identify RNA sequences bound in vivo by each of these proteins. Affinity purification and sequencing of RNA molecules associated with Rsm proteins were used to discover direct binding targets, corresponding to 437 unique RNA molecules, 75 of them being common to the three proteins. Relevant targets include genes encoding proteins involved in signal transduction and regulation, metabolism, transport and secretion, stress responses, and the turnover of the intracellular second messenger c-di-GMP. To our knowledge, this is the first combined global analysis in a bacterium harboring three Rsm homologs. It offers a broad overview of the network of processes subjected to this type of regulation and opens the way to define what are the sequence and structure determinants that define common or differential recognition of specific RNA molecules by these proteins.

"Bringing on the light" in a complex clinical scenario: Optical coherence tomography-guided discontinuation of antiplatelet therapy in cancer patients with coronary artery disease (PROTECT-OCT registry).

BACKGROUND: Cancer patients with recently placed drug-eluting stents (DESs) often require premature dual antiplatelet therapy (DAPT) discontinuation for cancer-related procedures. Optical coherence tomography (OCT) can identify risk factors for stent thrombosis such as stent malapposition, incomplete strut coverage and in-stent restenosis and may help guide discontinuation of DAPT. METHODS: We conducted a single-center prospective study in cancer patients with recently placed (1-12 months) DES who required premature DAPT discontinuation. Patients were evaluated with diagnostic coronary angiogram and OCT. Individuals with appropriate stent strut coverage, expansion, apposition, and absence of in-stent restenosis or intraluminal masses were considered low risk and transiently discontinued DAPT to allow optimal cancer therapy. Patients who did not meet all these criteria were considered high risk and underwent further endovascular treatment when appropriate and bridging with low-molecular weight heparin. The incidence of adverse cardiovascular events was assessed after the procedure and at 12 months. RESULTS: A total of 40 patients were included. Twenty-seven patients (68%) were considered low risk by OCT criteria and DAPT was transiently discontinued. Thirteen patients (32%) were considered high risk with one or more OCT findings: uncovered stent struts (4 patients, 10%); stent underexpansion (3 patients, 8%); malapposition (8 patients, 20%); in-stent restenosis (2 patients, 5%). The high-risk patients with uncovered stent struts and malapposition underwent additional stent dilatation. There were no cardiovascular events in the low-risk group. One myocardial infarction occurred in the high-risk group. Fourteen non-cardiac deaths were registered before 12 months due to cancer progression or cancer therapy. CONCLUSION: OCT imaging allows identification of low-risk cancer patients with DES placed who may safely discontinue DAPT and proceed with cancer-related surgery or procedures.

The Pseudomonas putida CsrA/RsmA homologues negatively affect c-di-GMP pools and biofilm formation through the GGDEF/EAL response regulator CfcR.

Expression of cfcR, encoding the only GGDEF/EAL response regulator in Pseudomonas putida, is transcriptionally regulated by RpoS, ANR and FleQ, and the functionality of CfcR as a diguanylate cyclase requires the multisensor CHASE3/GAF hybrid histidine kinase named CfcA. Here an additional level of cfcR control, operating post-transcriptionally via the RNA-binding proteins RsmA, RsmE and RsmI, is unraveled. Specific binding of the three proteins to an Rsm-binding motif (5'CANGGANG3') encompassing the translational start codon of cfcR was confirmed. Although RsmA exhibited the highest binding affinity to the cfcR transcript, single deletions of rsmA, rsmE or rsmI caused minor derepression in CfcR translation compared to a ΔrsmIEA triple mutant. RsmA also showed a negative impact on c-di-GMP levels in a double mutant ΔrsmIE through the control of cfcR, which is responsible for most of the free c-di-GMP during stationary phase in static conditions. In addition, a CfcR-dependent c-di-GMP boost was observed during this stage in ΔrsmIEA confirming the negative effect of Rsm proteins on CfcR translation and explaining the increased biofilm formation in this mutant compared to the wild type. Overall, these results suggest that CfcR is a key player in biofilm formation regulation by the Rsm proteins in P. putida.

Isotopic composition in precipitation and groundwater in the northern mountainous region of the Central Valley of Costa Rica.

The linkage between precipitation and recharge is still poorly understood in the Central America region. This study focuses on stable isotopic composition in precipitation and groundwater in the northern mountainous region of the Central Valley of Costa Rica. During the dry season, rainfall samples corresponded to enriched events with high deuterium excess. By mid-May, the Intertropical Convergence Zone poses over Costa Rica resulting in a depletion of 18O/16O and 2H/H ratios. A parsimonious four-variable regression model (r2 = 0.52) was able to predict daily δ18O in precipitation. Air mass back trajectories indicated a combination of Caribbean Sea and Pacific Ocean sources, which is clearly depicted in groundwater isoscape. Aquifers relying on Pacific-originated recharge exhibited a more depleted pattern, whereas recharge areas relying on Caribbean parental moisture showed an enrichment trend. These results can be used to enhance modelling efforts in Central America where scarcity of long-term data limits water resources management plans.

Genetic Dissection of the Regulatory Network Associated with High c-di-GMP Levels in Pseudomonas putida KT2440.

Most bacteria grow in nature forming multicellular structures named biofilms. The bacterial second messenger cyclic diguanosine monophosphate (c-di-GMP) is a key player in the regulation of the transition from planktonic to sessile lifestyles and this regulation is crucial in the development of biofilms. In Pseudomonas putida KT2440, Rup4959, a multidomain response regulator with diguanylate cyclase activity, when overexpressed causes an increment in the intracellular levels of c-di-GMP that gives rise to a pleiotropic phenotype consisting of increased biofilm formation and crinkly colony morphology. In a broad genomic screen we have isolated mutant derivatives that lose the crinkly morphology, designed as cfc (crinkle free colony). A total of 19 different genes have been identified as being related with the emergence of the cfc phenotype either because the expression or functionality of Rup4959 is compromised, or due to a lack of transduction of the c-di-GMP signal to downstream elements involved in the acquisition of the phenotype. Discernment between these possibilities was investigated by using a c-di-GMP biosensor and by HPLC-MS quantification of the second messenger. Interestingly five of the identified genes encode proteins with AAA+ ATPase domain. Among the bacterial determinants found in this screen are the global transcriptional regulators GacA, AlgU and FleQ and two enzymes involved in the arginine biosynthesis pathway. We present evidences that this pathway seems to be an important element to both the availability of the free pool of the second messenger c-di-GMP and to its further transduction as a signal for biosynthesis of biopolimers. In addition we have identified an uncharacterized hybrid sensor histidine kinase whose phosphoaceptor conserved histidine residue has been shown in this work to be required for in vivo activation of the orphan response regulator Rup4959, which suggests these two elements constitute a two-component phosphorelay system.

Self-Regulation and Interplay of Rsm Family Proteins Modulate the Lifestyle of Pseudomonas putida.

UNLABELLED: In the plant-beneficial bacterium Pseudomonas putida KT2440, three genes have been identified that encode posttranscriptional regulators of the CsrA/RsmA family. Their regulatory roles in the motile and sessile lifestyles of P. putida have been investigated by generating single-, double-, and triple-null mutants and by overexpressing each protein (RsmA, RsmE, and RsmI) in different genetic backgrounds. The rsm triple mutant shows reduced swimming and swarming motilities and increased biofilm formation, whereas overexpression of RsmE or RsmI results in reduced bacterial attachment. However, biofilms formed on glass surfaces by the triple mutant are more labile than those of the wild-type strain and are easily detached from the surface, a phenomenon that is not observed on plastic surfaces. Analysis of the expression of adhesins and exopolysaccharides in the different genetic backgrounds suggests that the biofilm phenotypes are due to alterations in the composition of the extracellular matrix and in the timing of synthesis of its elements. We have also studied the expression patterns of Rsm proteins and obtained data that indicate the existence of autoregulation mechanisms. IMPORTANCE: Proteins of the CsrA/RsmA family function as global regulators in different bacteria. More than one of these proteins is present in certain species. In this study, all of the RsmA homologs in P. putida are characterized and globally taken into account to investigate their roles in controlling bacterial lifestyles and the regulatory interactions among them. The results offer new perspectives on how biofilm formation is modulated in this environmentally relevant bacterium.

The role of intravascular optical coherence tomography in peripheral percutaneous interventions.

Frequency domain optical coherence tomography (FD-OCT) is a new intravascular imaging modality utilizing near-infrared light to generate high-quality images. It provides a unique and detailed view of the vessel wall and vessel lumen. FD-OCT has been increasingly used in coronary interventions; however, there is limited experience regarding the use of FD-OCT in the evaluation and treatment of peripheral arterial disease (PAD). We report three cases in which FD-OCT helped elucidate and guide femoral artery interventions and renal artery stenting. With the help of these cases, we depict how FD-OCT is uniquely positioned to be a promising imaging tool in the diagnosis and treatment of peripheral artery disease.

A new algorithm to allow early prediction of mortality in elderly burn patients.

INTRODUCTION: The elderly are the fastest growing population segment, and particularly susceptible to burns. Predicting outcomes for these patients remains difficult. Our objective was to identify early predictors of mortality in elderly burn patients. METHODS: Our Burn Center's prospective database was reviewed for burn patients 60+ treated in the past 10 years. Predictor variables were identified by correlative analysis and subsequently entered into a multivariate logistic regression analysis examining survival to discharge. RESULTS: 203 patients of 1343 (15%) were eligible for analysis. The average age was 72 ± 10 (range 60-102) and the average total body surface area (TBSA) burned was 23 ± 18% (range 1-95). Age, TBSA, base deficit, pO(2), respiratory rate, Glasgow Coma Score (GCS), and Revised Trauma Score (RTS, based on systolic blood pressure, respiratory rate, and GCS) all correlated with mortality (p ≤0 .05). Using multiple logistic regression analysis, a model with age, TBSA and RTS was calculated, demonstrating: In this model, ß(0) is a constant that equals -8.32. CONCLUSIONS: Predicting outcomes in elderly burn patients is difficult. A model using age, TBSA, and RTS can, immediately upon patient arrival, help identify patients with decreased chances of survival, further guiding end-of-life decisions.

Tracking non-burn center care: what you don't know may surprise you.

The American Burn Association publishes a list of defined criteria for patients who require admission or transfer to a burn center. This study examines the extent to which those criteria are observed within a regional burn network. Hospital discharge data for 2008 were obtained for all hospitals within the South Florida regional burn network. Patients with International Classification of Diseases, 9th revision discharge diagnoses for burns were reviewed, and their triage destination was compared with the burn triage referral criteria to determine whether patients were inappropriately triaged. Descriptive statistics were used to analyze the data. Four hundred ninety-eight burn admissions were documented to non-burn center center hospitals, 269 (54%) of which were deemed inappropriate by burn triage referral criteria. Burn center patients had greater length of stay when compared with non-burn center patients (14 vs 7 days), but a greater percentage were discharged home for self-care (88 vs 57%). Thirty-three percent of the inappropriate admissions were in a neighboring county, whereas 27% were in the same county where the burn center is located. Inappropriate burn patient triage may be occurring to more than half of the burn patients within our regional burn network despite better functional outcomes at the burn center. This may be because of a lack of knowledge regarding triage criteria, patient insurance status, or other factors. Further studies are necessary to fully characterize the problem and implement education or incentives to encourage appropriate burn patient triage.

Infragenicular stent implantation for below-the-knee atherosclerotic disease: clinical evidence from an international collaborative meta-analysis on 640 patients.

PURPOSE: To report a systematic review of the literature published on the outcomes of stenting for below-the-knee disease in patients with critical limb ischemia (CLI). METHODS: Potentially relevant studies of stent implantation in the infragenicular arteries in >or=5 patients with >or=1-month follow-up were systematically sought in BioMedCentral, ClinicalTrials.gov, The Cochrane Collaboration Register of Controlled Trials (CENTRAL), Google Scholar, and PubMed. Data were abstracted and pooled with a random-effect model to generate risk estimates with 95% confidence intervals (CI). Interaction tests were performed to compare different stent types. A risk of bias assessment was conducted separately, as were appraisals for small study bias, statistical heterogeneity, and inconsistency. RESULTS: Eighteen nonrandomized studies were retrieved comprising 640 patients. After a median follow-up of 12 months, binary in-stent restenosis occurred in 25.7% (95% CI 11.6% to 40.0%), primary patency in 78.9% (95% CI 71.8% to 86.0%), improvement in Rutherford class in 91.3% (95% CI 85.5% to 97.1%), target vessel revascularization in 10.1% (95% CI 6.2% to 13.9%), and limb salvage in 96.4% (95% CI 94.7% to 98.1%). Head-to-head comparisons showed that sirolimus-eluting stents were superior to balloon-expandable bare metal stents in preventing restenosis and increasing primary patency (both p<0.001); sirolimus-eluting stents were also better than paclitaxel-eluting stents in terms of primary patency (p<0.001) and repeat revascularizations (p = 0.014). CONCLUSION: Percutaneous infragenicular stent implantation after failed or unsuccessful balloon angioplasty is associated with favorable clinical results in patients with CLI. Notwithstanding limitations of primary studies, sirolimus-eluting stents appear superior to bare metal and paclitaxel-eluting stents in terms of angiographic and/or clinical outcomes.

Drug eluting stents for below the knee lesions in patients with critical limb ischemia : long-term follow-up.

OBJECTIVES: The purpose of this study was to assess the long-term limb preservation and/or healing of ulcers in patients with critical limb ischemia (CLI) and severe infrapopliteal atherosclerotic disease treated with drug eluting stents (DES). BACKGROUND: Percutaneous revascularization has become an effective treatment for CLI in patients with infrapopliteal atherosclerotic disease. Recent reports using DES in patients with CLI have documented excellent short-term infrapopliteal vessel patency. Higher primary patency rates in infrapopliteal vessels treated with DES could translate into better long-term clinical outcomes and improved limb salvage rates. METHODS: Twenty-four consecutive patients with CLI (defined as rest pain, nonhealing ulcers, or gangrene) because of severe infrapopliteal disease were treated with DES from August 2004 to June 2006. RESULTS: Procedural success was achieved in 96% (27/28) of targeted lesions. There were no procedure-related deaths, acute vessel thrombosis events, or need for urgent surgical intervention. There was one case of distal embolization. Clinical follow up, ranging 8-34 months, is available for 100% of patients of which 83% (20/24) achieved limb preservation and healing. Angiographic and/or sonographic follow up, ranging 6-34 months, is available in 79% (19/24) of patients of which 95% (18/19) had patent target vessels. CONCLUSIONS: DES is a safe and effective long-term option for CLI due to severe infrapopliteal arterial disease. Long-term vascular patency led to a high rate of limb preservation and low amputation rate. A multicenter trial should further elucidate the role of DES in the treatment of CLI.

A portable, universal patient positioning and holding system for use in the burn patient 'The Burnwalter'.

A technique is described for the intra-operative positioning of the burn patient, which allows circumferential access without the need for specialized equipment or extra personnel. The equipment is available in any standard operating room and table without the need for redesign or new construction. In addition, it allows full 360 degrees access and eliminates the need for extra personnel to hold proper positioning. This allows for more efficient operating and should minimize the unwanted sequelae of hypothermia and blood loss. Operating time may be decreased and the patient may require less operative procedures. The same or more work can be done by less personnel, in less time, with no added cost.

The use of brachytherapy to treat renal artery in-stent restenosis.

The percutaneous treatment of renal artery stenosis has become the accepted revascularization strategy by most physicians treating this disorder. Unfortunately, as renal artery angioplasty and stent implantation become increasingly prevalent the Achilles heel of angioplasty, in-stent restenosis, also rises. There are currently no data suggestive of the optimal treatment strategy for renal artery in-stent restenosis. However, given the similarities in the pathophysiology between renal artery and coronary artery in-stent restenosis, brachytherapy is considered a reasonable option. This is the strategy that has been suggested and used by a number of operators. This case report describes two examples of renal artery in-stent restenosis treated with angioplasty and brachytherapy.

Wireless laser-assisted angioplasty of the superficial femoral artery in patients with critical limb ischemia who have failed conventional percutaneous revascularization.

Percutaneous revascularization has become an effective treatment for patients suffering from chronic critical limb ischemia (CLI) due to chronic atherosclerotic obstructions, including total occlusions. Unlike other vascular beds, total chronic occlusions of the femoropopliteal arteries are frequently found in patients with severe claudication or CLI. As a consequence, patients with long chronic total occlusions of the femoropopliteal arteries are generally not considered optimal candidates for percutaneous revascularization and are frequently referred for surgical revascularization. In the present study, we sought to evaluate the feasibility, safety, and outcome of a modified wireless laser ablation technique to recanalize total occlusions in patients with CLI who had failed conventional percutaneous techniques for limb salvage. Procedural success, complications, actuarial freedom of limb loss, and surgical revascularization were evaluated in 25 patients after a mean follow-up of 13 +/- 8 months. Procedural success was achieved in 21 patients (84%). Actuarial freedom from surgical revascularization or limb loss was 72%. There was one vascular perforation. No deaths or distal embolization occurred. Three patients (12%) required limb amputation during follow-up, whereas four patients (16%) had surgical revascularization in the presence of feasible vascular targets. Limb salvage was achieved in 88% of patients when laser recanalization was combined with surgical revascularization. These results suggest that the use of laser ablation is safe and facilitates angioplasty and stenting in patients with CLI that failed conventional endovascular revascularization. This technique might prevent limb loss in patients with CLI due to femoropopliteal total occlusions, particularly in patients with unsuitable anatomy for surgical revascularization.

Cardiovascular drugs: adenosine role in coronary syndromes and percutaneous coronary interventions.

Adenosine is an endogenous nucleoside available for the diagnosis and treatment of various cardiovascular conditions. It may be given for pharmacologic stress tests as well as administered directly into the coronary arteries during cardiac catheterization. The latter treatment may be utilized to measure fractional flow reserve in addition to treating the no-reflow phenomenon. Adenosine has also been shown to improve the clinical outcome of thrombolytics given in the setting of acute myocardial infarction. Adenosine is a useful agent for evaluation and treatment of the cardiovascular system.

The dilemma of success: percutaneous coronary interventions in patients > or = 75 years of age-successful but associated with higher vascular complications and cardiac mortality.

Elderly patients are increasingly referred to percutaneous coronary interventions (PCIs). Recent reports suggest complications rates are declining in the elderly. We sought to determine whether procedural and in-hospital outcomes are different in patients aged > or = 75 years undergoing nonemergent PCI as compared to patients age < 75 years. The outcome of 266 consecutive patients age > or = 75 years undergoing nonemergent PCI was compared to that of 1,681 consecutive patients age < 75 years. Compared with younger patients, greater proportions of elderly patients were women and had a history of hypertension, peripheral vascular disease, and cerebral vascular events. Elderly patients had more extensive coronary involvement. Procedural success was similar in both groups (94%). The in-hospital cardiac death rate was significantly higher in the elderly patients (2.3% vs. 0.7%; P = 0.03). Aged patients also had a significantly higher incidence of vascular and bleeding complications. Blood transfusion was required more often in the elderly group (4.5% vs. 2.6%; P = 0.07). The hospitalization length was significantly higher in the elderly group (4.1 +/- 6.0 vs. 2.5 +/- 4.3 day; P = 0.0004). By multivariate logistic regression (adjusted for baseline clinical and angiographic variables), age > or = 75 years was found to be an independent predictor of in-hospital cardiac death (odds ratio = 3.9; 95% CI = 1.3-11.5; P = 0.015). Although PCI is technically successful in patients aged > or = 75 years; it is associated with more acute cardiac and vascular complications and higher in-hospital cardiac mortality.