Systemic acidemia impairs cardiac function in critically Ill patients.

BACKGROUND: Acidemia, is associated with reduced cardiac function in animals, but no studies showing an effect of acidemia on cardiac function in humans are reported. In the present study, we examined the effect of acidemia on cardiac function assessed with transpulmonary thermodilution technique with integrated pulse contour analysis (Pulse Contour Cardiac Output, PiCCO™) in a large cohort of critically ill patients. METHODS: This was a prospective multicenter observational cross-sectional study of 297 patients from 6 intensive care units in London, England selected from all patients admitted consecutively between May 2018 and March 2019. Measurements of lowest plasma pH and concurrent assessment of cardiac function were obtained. FINDINGS: There was a significant difference between two pH categories (pH ≤ 7.28 vs. pH > 7.28) for the following variables of cardiac function: SVI (difference in means 32.7; 95% CI: 21 to 45 mL/m2; p < 0.001); GEF (18; 95% CI: 11 to 26%; p < 0.001), dPmax (-331; 95% CI: -510 to -153 mmHg/s; p = 0.001), CFI (0.7; 95% CI: 0.2 to 1.3 1/min; p = 0.01) and CPI (0.09; 95% CI: 0.03 to 0.15 W/m2; p < 0.001). However, there was no significant difference in CI (0.13; 95% CI: -0.20 to 0.47 L/min/m2; p = 0.12) between the pH categories. Also, a significant relationship was found between the quantitative pH and the following variables: SVI (132; 95% CI: 77 to 188 mL/m2; p < 0.001), GEF (74.7; 95% CI: 37.1 to 112.4%; p < 0.001), dPmax (-1587; 95% CI: -2361 to -815 mmHg/s; p < 0.001), CFI (3.5; 95% CI: 0.9 to 6.1 /min; p = 0.009), CPI (0.62; 95% CI: 0.36 to 0.88 W/m2; p < 0.001) and CI (regression coefficient 1.96; 95% CI:0.45 to 3.47 L/min/m2; p = 0.01). INTERPRETATION: Acidemia is associated with impaired cardiac function in seriously ill patients hospitalized in the intensive care unit supporting the potential value of early diagnosis and improvement of arterial pH in these patients. FUNDING: The study was partially supported by unrestricted funds from the UCLA School of Medicine.

The arterial blood gas algorithm: Proposal of a systematic approach to analysis of acid-base disorders. / El algoritmo de la gasometría arterial: propuesta de un enfoque sistemático para el análisis de los trastornos del equilibrio ácido-base.

Abnormalities in the acid-base balance are common clinical problems and can have deleterious effects on cellular function and be a clue to various disorders. Therefore, it is important for the clinician to make a precise diagnosis of the acid-base disorder(s) present for a proper treatment. Three approaches have been proposed to evaluate acid-base disorders: a bicarbonate-centric approach; the Stewart approach, and the base excess approach. Although the latter two have many adherents, we will only discuss the bicarbonate-centric approach. This approach is simpler to utilize at the bedside, has a physiological evaluation of the acid-base disorder, presents an easily understandable approach to assess severity, and provides a more solid foundation for the development of effective therapies. Therefore, the following discussion will be limited to an examination of this approach. In this case-centric review, important new concepts will be introduced first; their benefits and limitations discussed; and then their utilization to analyze actual cases will be shown. A systematic approach algorithm that incorporates these new concepts has been generated and will be highlighted.

Logistic early warning scores to predict death, cardiac arrest or unplanned intensive care unit re-admission after cardiac surgery.

NHS England recently mandated that the National Early Warning Score of vital signs be used in all acute hospital trusts in the UK despite limited validation in the postoperative setting. We undertook a multicentre UK study of 13,631 patients discharged from intensive care after risk-stratified cardiac surgery in four centres, all of which used VitalPACTM to electronically collect postoperative National Early Warning Score vital signs. We analysed 540,127 sets of vital signs to generate a logistic score, the discrimination of which we compared with the national additive score for the composite outcome of: in-hospital death; cardiac arrest; or unplanned intensive care admission. There were 578 patients (4.2%) with an outcome that followed 4300 sets of observations (0.8%) in the preceding 24 h: 499 out of 578 (86%) patients had unplanned re-admissions to intensive care. Discrimination by the logistic score was significantly better than the additive score. Respective areas (95%CI) under the receiver-operating characteristic curve with 24-h and 6-h vital signs were: 0.779 (0.771-0.786) vs. 0.754 (0.746-0.761), p < 0.001; and 0.841 (0.829-0.853) vs. 0.813 (0.800-0.825), p < 0.001, respectively. Our proposed logistic Early Warning Score was better than the current National Early Warning Score at discriminating patients who had an event after cardiac surgery from those who did not.

Analysis of the gut microbiota in alopecia areata: identification of bacterial biomarkers.

BACKGROUND: Alopecia areata is a T-cell-mediated autoimmune disease with an unknown etiopathogenesis. Gut microbiota has been revealed as a key modulator of systemic immunity. OBJECTIVE: To determine whether patients affected by alopecia universalis present differences in gut bacteria composition compared with healthy controls and investigate possible bacterial biomarkers of the disease. METHODS: We conducted a cross-sectional study that involved 15 patients affected by alopecia universalis and 15 controls. Gut microbiome of the study subjects was analysed by sequencing the 16SrRNA of stool samples. We searched for bacterial biomarkers of alopecia universalis using the linear discriminant analysis effect size (LEFse) tool. RESULTS: In total, 30 study subjects (46.6% female; mean [SD] age, 40.1 [9.8] years) were enrolled. Neither alpha (Shannon diversity index 5.31 ± 0.43 vs. 5.03 ± 0.43, P 0.1) or beta diversity (ADONIS P value: 0.35) of gut microbiota showed statistically significant differences between cases and controls. In patients affected with alopecia, we found an enriched presence (LDA SCORE > 2) of Holdemania filiformis, Erysipelotrichacea, Lachnospiraceae, Parabacteroides johnsonii, Clostridiales vadin BB60 group, Bacteroides eggerthii and Parabacteroides distasonis. A predictive model based on the number of bacterial counts of Parabacteroides distasonis and Clostridiales vadin BB60 group correctly predicted disease status in 80% of patients (AUC 0.804 (0.633-0.976), P 0.004). CONCLUSION: Alopecia universalis does not seem to affect broadly gut microbiota structure. Bacterial biomarkers found associated with the disease (Holdemania filiformis, Erysipelotrichacea, Lachnospiraceae, Parabacteroides johnsonii, Eggerthellaceae, Clostridiales vadin BB60 group, Bacteroides eggerthii and Parabacteroides distasonis) should be further studied as they could be involved in its pathophysiology or be used as diagnostic tools.

Evaluation of kidney function in HIV-infected patients receiving an antiretroviral regimen containing one or two inhibitors of the tubular secretion of creatinine.

OBJECTIVES: The aim of this study was to determine the evolution of renal function in patients receiving one or two inhibitors, according to different baseline factors. Some antiretroviral drugs such as rilpivirine (RPV), dolutegravir (DTG), or cobicistat (COBI), interact with the tubular secretion of creatinine, but there are no data about their impact in renal function evaluation in patients with renal disease or when these drugs are used concomitantly. METHODS: A prospective cohort study was carried out in HIV-infected patients who switched to a dual regimen including DTG, RPV or darunavir/COBI, separately or in combination. The primary endpoint was the evolution of the serum creatinine-based estimated glomerular filtration rate (eGFR-scr). A control group not receiving any transporter inhibitor was included. RESULTS: A total of 288 patients on different dual regimens were included (DTG + RPV, 92; DTG + darunavir/COBI, 23; DTG, 26; COBI, 19; control group, 128). In patients receiving two transporter inhibitors, eGFR-scr decreased by a mean of -8.4 mL/min/1.73 m2 , similar to that observed with the separate use of DTG or COBI (mean of both groups, -8.6 mL/min/1.73 m2 ), while eGFR-scr improved in the control group. Similar evolution of proteinuria and tubular dysfunction was observed in all the groups, and there were no significant changes in the cystatin C-based eGFR. Mean eGFR-scr change inversely correlated with baseline eGFR-scr value (r = -0.39; P < 0.01), with a lower eGFR-scr decrease in patients with chronic kidney disease. CONCLUSIONS: Similar eGFR-scr decreases were observed in patients using different antiretroviral drugs inhibiting the tubular transport of creatinine, separately or in combination, with no alterations in proteinuria or cystatin C-based eGFR. The lack of additional changes when the drugs were used in combination, and the lower impact in cases of previous chronic kidney disease, suggest that there are compensatory mechanisms for creatinine secretion.

Measurement of extravascular lung water to diagnose severe reperfusion lung injury following pulmonary endarterectomy: a prospective cohort clinical validation study.

The measurement of extravascular lung water is a relatively new technology which has not yet been well validated as a clinically useful tool. We studied its utility in patients undergoing pulmonary endarterectomy as they frequently suffer reperfusion lung injury and associated oedematous lungs. Such patients are therefore ideal for evaluating this new monitor. We performed a prospective observational cohort study during which extravascular lung water index measurements were taken before and immediately after surgery and postoperatively in intensive care. Data were analysed for 57 patients; 21 patients (37%) experienced severe reperfusion lung injury. The first extravascular lung water index measurement after cardiopulmonary bypass failed to predict severe reperfusion lung injury, area under the receiver operating characteristic curve 0.59 (95%CI 0.44-0.74). On intensive care, extravascular lung water index correlated most strongly at 36 h, area under the receiver operating characteristic curve 0.90 (95%CI 0.80-1.00). Peri-operative extravascular lung water index is not a useful measure to predict severe reperfusion lung injury after pulmonary endarterectomy, however, it does allow monitoring and measurement during the postoperative period. This study implies that extravascular lung water index can be used to directly assess pulmonary fluid overload and that monitoring patients by measuring extravascular lung water index during their intensive care stay is useful and correlates with their clinical course. This may allow directed, pre-empted therapy to attenuate the effects and improve patient outcomes and should prompt further studies.

Antibiotic-resistant hypervirulent Klebsiella pneumoniae causing community- acquired liver abscess: an emerging disease.

We report a case of a patient with fatal community-acquired pyogenic liver abscess (CA-PLA) caused by multi drug-resistant, hypervirulent, Klebsiella pneumoniae (mdrhvKP). HvKP causing PLA has been described in East and South East Asia and it is recognized as an emerging infection worldwide. The syndrome is characterized by cryptogenic liver abscess formation without a previous history of hepatobiliary or colonic disease and metastatic spread of infection via the bloodstream to distant sites, including lungs, central nervous system and other organ systems. Diabetes mellitus is a recognized risk factor. Most previously reported cases have involved antibiotic susceptible strains of hvKP although reports of bloodstream infections caused by resistant strains, including carbapenemase producers, are increasing. Our report highlights the need for awareness of this devastating infection in patients presenting with sepsis and liver abscess without underlying hepatobiliary or colonic disease.

Umbilical hernia repair with composite prosthesis: a single-centre experience.

PURPOSE: Since 2004, composite prosthesis repair is the preferred procedure for umbilical hernia repair in our centre, although long-term results of this technique are lacking. The aim of this study was to analyze the long-term results of a cohort of patients who underwent umbilical hernia repair with this procedure. METHODS: A retrospective cohort study of patients who underwent umbilical hernia repair with composite prosthesis was conducted. Data were obtained from electronic medical records. Univariate and multivariate analyses were performed to analyze the factors associated with postoperative complications and hernia recurrence. RESULTS: Between March 2004 and December 2015, 2135 patients underwent umbilical hernia repair and composite prosthesis (Ventralex or Ventralex ST®) was used in 1538 patients. 179 patients were lost during the follow-up. Finally, 1359 patients were included in the study. The prosthesis was placed in the preperitoneal space in 93.4% of the patients. 86.3% of the patients underwent same-day surgery. Only 2.1% of the patients developed a complication during the follow-up, and 1.8% of the patients required a new surgery. After a mean follow-up of 4.1 years, hernia recurrence rate was 3.9%. Multivariate analysis showed that hernia recurrence was associated with female gender, recurrent hernia, and postoperative complication. Postoperative complications were related to follow-up time and smoking patients. CONCLUSIONS: Long-term results after umbilical hernia repair with composite prosthesis are satisfactory, with a low percentage of complications and recurrences.

Nondiabetic ketoacidosis in a pregnant woman due to acute starvation with concomitant influenza A (H1N1) and respiratory failure. / Cetoacidosis no diabética en una mujer embarazada, debido a inanición aguda con gripe A (H1N1) concomitante e insuficiencia respiratoria.

Threatening refractory metabolic acidosis due to short-term starvation nondiabetic ketoacidosis is rarely reported. Severe ketoacidosis due to starvation itself is a rare occurrence, and more so in pregnancy with a concomitant stressful clinical situation. This case report presents a nondiabetic woman admitted in intensive care for respiratory failure type 1 during the third trimester of pregnancy with a severe metabolic acidosis refractory to medical treatment. We diagnosed the patient with acute starvation ketoacidosis based on her history and the absence of other causes of high anion gap metabolic acidosis after doing a rigorous analysis of her acid-base disorder.

Papillary architecture of the lingual surface in the puma (Puma concolor).

This research presents the first anatomical description of the tongue and lingual papillae of the mountain lion (puma). The tongues of three adult male pumas were used in this study. The tongues were dissected and studied firstly by gross and stereomicroscopy. Samples of each part were processed by study with scanning electron microscopy. The margins of the lingual apex were surrounded by numerous filiform papillae, which had a bulky papillary body and a bifurcated tip. On the dorsal surface of the lingual apex, filiform papillae were remarkably pointed and had many secondary projections, which emerged from the base of the main papilla. In the rostral half of the lingual body, filiform papillae were longer, cylindrical and had blunt tips. On the caudal half of the lingual body, filiform papillae gave place to conical ones exhibiting a pointed tip. The fungiform papillae were scattered on the whole dorsal surface of the tongue. On each lateral half of the tongue, four circumvallate papillae were observed and each circumvallate papilla was surrounded by thick and horseshoe-like annular pad, which were composed by pointed conical papillae on the caudal border of the lingual body. The dorsal surface of the circumvallate papilla was covered by many finger-like protrusion, and the tip of each protrusion had a central orifice. Anatomical distribution of lingual papillae was different to other carnivores and represents the adaptation to the feeding habits of this mammal. General morphology of the lingual structures was similar to those of the tiger.

Repair of nerve injury by implanting prostheses obtained from isogenic acellular nerve segments. / Reparación de lesiones en nervios mediante el implante de prótesis obtenidas de segmentos acelulares de nervio isogénico.

INTRODUCTION: When a nerve section with a significant gap occurs, it is necessary to use a prosthesis to suture it. To date an autologous nerve segment graft appears to be the best treatment; but it has several important disadvantages. Our goal is to study the effectiveness of an isogenic acellular nerve prosthesis comparing a simple suture with tubulisation. MATERIAL AND METHOD: Four groups of Wistar rats were used. The animals in Group 0 served as donors of nerve segments to graft. Group 1 received the implant with an end-to-end suture. In group 2, the implant was sutured inside an ɛ-caprolactone tube. Group 3 received it in a polylactic-co-glycolic acid tube. We evaluated the motor function (sciatic index and step test in motion), and the regeneration length by histological study of regeneration, after a maximum of 3 weeks. RESULTS: Regeneration was uneven in the three groups. In all groups, there were implants with regenerated nerve fibres at the maximum studied length (15mm) and others where regeneration was scarce. The mean regeneration length was greater in the direct end-to-end suture group (G1), although the regeneration speed was similar in the three groups. Group 1 showed the highest percentage of regeneration, but the variability of results prevents this difference reaching statistical significance. We found no significant differences between the two groups with polymer tubes. CONCLUSION: For the implantation of isogenic acellular nerve prosthesis, under our experimental conditions, the direct end-to-end suture was more effective than when it isprotected with biopolymer tubes.

Modeling cancer driver events in vitro using barrier bypass-clonal expansion assays and massively parallel sequencing.

The information on candidate cancer driver alterations available from public databases is often descriptive and of limited mechanistic insight, which poses difficulties for reliable distinction between true driver and passenger events. To address this challenge, we performed in-depth analysis of whole-exome sequencing data from cell lines generated by a barrier bypass-clonal expansion (BBCE) protocol. The employed strategy is based on carcinogen-driven immortalization of primary mouse embryonic fibroblasts and recapitulates early steps of cell transformation. Among the mutated genes were almost 200 COSMIC Cancer Gene Census genes, many of which were recurrently affected in the set of 25 immortalized cell lines. The alterations affected pathways regulating DNA damage response and repair, transcription and chromatin structure, cell cycle and cell death, as well as developmental pathways. The functional impact of the mutations was strongly supported by the manifestation of several known cancer hotspot mutations among the identified alterations. We identified a new set of genes encoding subunits of the BAF chromatin remodeling complex that exhibited Ras-mediated dependence on PRC2 histone methyltransferase activity, a finding that is similar to what has been observed for other BAF subunits in cancer cells. Among the affected BAF complex subunits, we determined Smarcd2 and Smarcc1 as putative driver candidates not yet fully identified by large-scale cancer genome sequencing projects. In addition, Ep400 displayed characteristics of a driver gene in that it showed a mutually exclusive mutation pattern when compared with mutations in the Trrap subunit of the TIP60 complex, both in the cell line panel and in a human tumor data set. We propose that the information generated by deep sequencing of the BBCE cell lines coupled with phenotypic analysis of the mutant cells can yield mechanistic insights into driver events relevant to human cancer development.

Clinical residual symptomatology and associated factors in multiple organ failure survivors: A long-term mortgage. / Sintomatología clínica residual y factores asociados en supervivientes de un fracaso multiorgánico: una hipoteca a largo plazo.

PURPOSE: To evaluate which residual clinical symptoms multi-organ failure (MOF) patients may exhibit post discharge from Intensive Care Units (ICU) and to identify the associated factors that cause such symptoms. MATERIAL AND METHODS: A total of 545 adult patients admitted to a medical & surgical ICU in Spain diagnosed with MOF on admission were included in the study. Follow up in the form of a telephone survey regarding the patients clinical symptoms were conducted at 6 and 12 months after discharge from ICU. RESULTS: A total of 266 patients were followed up at both 6 and 12 months post ICU discharge; 62.2% were male; age 60±18 years; 67.8% medical patients. The most common symptoms to appear following hospital discharge included: asthenia (173; 76%), sleep disturbances (112; 50%) and depression (109; 48%). CONCLUSIONS: The study revealed frequent residual clinical symptoms persisting for almost a year post ICU discharge, most notably arthromyalgia and asthenia. Depression symptoms during the first 6 months post-hospital discharge were also common among multiple organ failure survivors. The presence of symptomatology over time was found to be related to a poor functional situation at 6 and12 months post ICU discharge, length of hospital stay and severity of illness score on ICU admission.

Raman spectroscopy detection of biomolecules in biocrusts from differing environmental conditions.

Lichens and cyanobacteria colonize inhospitable places covering a wide climate range due to their different survival strategies, such as the synthesis of protective biomolecules. The effect of ecological factors on the synthesis of biomolecules has not been widely analysed. This study aimed to assess the effects of four factors (species, microclimate, seasonality and hydration state) and their interactions on the biomolecule frequency detected by Raman Spectroscopy. We included cyanobacterial biocrusts, and the lichens Diploschistes diacapsis, Squamarina lentigera, and Lepraria isidiata; two contrasted microclimates (typical and marginal), two contrasted seasons (hot and dry vs cool and wet) and two hydration states (dry and wet). "Species" was the most influential factor in the identity and frequency of the main biomolecules. Microclimatic differences in the range of the local specific habitats only influenced the biomolecules in cyanobacteria. There was a quadruple interaction among the factors, the effects being different mainly depending on the species. At D. diacapsis, the production of their main biomolecules depended on microclimate, although it also depended on seasonality. Nevertheless, in L. isidiata and S. lentigera microclimatic differences did not significantly affect the production of biomolecules. In the lichen species, the microhabitats exposed to relatively larger incident radiation did not show significantly larger relative frequency of photoprotective biomolecules. No clear connection between higher production of oxalates and drier microhabitats was found, suggesting that the synthesis of oxalates is not related to water reserve strategy. The pros and cons of monitor biomolecules in biocrust by Raman spectrometry were also discussed.

The effects of prebiotics on microbial dysbiosis, butyrate production and immunity in HIV-infected subjects.

Altered interactions between the gut mucosa and bacteria during HIV infection seem to contribute to chronic immune dysfunction. A deeper understanding of how nutritional interventions could ameliorate gut dysbiosis is needed. Forty-four subjects, including 12 HIV+ viremic untreated (VU) patients, 23 antiretroviral therapy-treated (ART+) virally suppressed patients (15 immunological responders and 8 non-responders) and 9 HIV- controls (HIV-), were blindly randomized to receive either prebiotics (scGOS/lcFOS/glutamine) or placebo (34/10) over 6 weeks in this pilot study. We assessed fecal microbiota composition using deep 16S rRNA gene sequencing and several immunological and genetic markers involved in HIV immunopathogenesis. The short dietary supplementation attenuated HIV-associated dysbiosis, which was most apparent in VU individuals but less so in ART+ subjects, whose gut microbiota was found more resilient. This compositional shift was not observed in the placebo arm. Significantly, declines in indirect markers of bacterial translocation and T-cell activation, improvement of thymic output, and changes in butyrate production were observed. Increases in the abundance of Faecalibacterium and Lachnospira strongly correlated with moderate but significant increases of butyrate production and amelioration of the inflammatory biomarkers soluble CD14 and high-sensitivity C-reactive protein, especially among VU. Hence, the bacterial butyrate synthesis pathway holds promise as a viable target for interventions.

[Free circulating DNA as a tool for lung cancer patients management]. / Intérêts de l'ADN circulant pour la prise en charge du cancer broncho-pulmonaire.

Free circulating DNA (cfDNA) has been known for several decades. These small DNA fragments are released into the circulation from nucleated cells through necrosis, apoptosis and/or active secretion. These genomic fragments are mainly constitutional (nucleated blood cell DNA), but in patients with cancer, a fraction comes from tumor cells. Although poorly known in the field of thoracic oncology, quantitative and qualitative analysis of the cDNA is nevertheless of great interest. Total cfDNA concentration appears to be an independent prognostic factor in lung cancer. Although changes in total cfDNA concentration is not informative to assess the effectiveness of chemotherapy, following-up the fraction of mutated genes such as EGFR during therapy with tyrosine kinase inhibitors appears to be particularly promising for the early detection of disease progression. The use of cfDNA as liquid biopsy is also very promising for the non-invasive somatic molecular profile either at baseline either for sampling at follow-up. Thus, cfDNA is a very promising tool in thoracic oncology and its translation into practice should be developed quickly.