Nutritional and Inflammatory Aspects of Low Parathyroid Hormone in Maintenance Hemodialysis Patients-A Longitudinal Study.

BACKGROUND: Low serum parathyroid hormone (PTH) is an accepted marker for adynamic bone disease which is characterized by increased morbidity and mortality in maintenance hemodialysis (MHD) patients. In light of the known cross-sectional associations between PTH and malnutrition-inflammation syndrome, we aimed to examine the longitudinal associations between PTH with changes in nutritional and inflammatory parameters and clinical outcomes in MHD patients with low PTH. METHODS: This historical prospective and longitudinal study analyzed a clinical database at a single hemodialysis center, containing the medical records of 459 MHD patients (mean age of 71.4 ± 12.9 years old, 171 women), treated between the years 2007-2020. Bone turnover, nutritional and inflammatory marker levels were recorded at 0, 6, 12, 18, 24, 30, and 36 months followed by a median of 24 additional months of clinical observations. According to previous use of vitamin D analogs and/or calcium-sensing receptor agonists, the study participants were divided into treatment-related and disease-related groups. A linear mixed effects model was adjusted for baseline demographics and clinical parameters. RESULTS: Of 459 MHD patients, 81 (17.6%) had PTH lower than 150pg/mL. Among them, 30 patients had treatment-related and 51 had disease-related low PTH. At baseline, MHD patients with treatment-related low PTH had a higher rate of diabetes compared to the disease-related group. In a linear mixed effects model, increased PTH over time was associated with decreased levels of alkaline phosphatase and C-reactive protein and with increased hemoglobin and albumin, but not the geriatric nutritional risk index at 3-year follow-up. The survival rate did not differ between the groups, with the risk of hospitalizations due to fractures being higher (HR: 4.04 with 95% CI: 1.51-10.8) in the disease-related group. Statistical significance of this association was abolished after adding C-reactive protein or alkaline phosphatase to the multivariate models. CONCLUSIONS: Low serum PTH in MHD patients behaves differently depending on its cause, with a higher risk of fractures in the disease-related group. This association is dependent on inflammation. Our results should be verified in larger epidemiological studies.

Global mortality and readmission rates following COPD exacerbation-related hospitalisation: a meta-analysis of 65 945 individual patients.

Background: Exacerbations of COPD (ECOPD) have a major impact on patients and healthcare systems across the world. Precise estimates of the global burden of ECOPD on mortality and hospital readmission are needed to inform policy makers and aid preventive strategies to mitigate this burden. The aims of the present study were to explore global in-hospital mortality, post-discharge mortality and hospital readmission rates after ECOPD-related hospitalisation using an individual patient data meta-analysis (IPDMA) design. Methods: A systematic review was performed identifying studies that reported in-hospital mortality, post-discharge mortality and hospital readmission rates following ECOPD-related hospitalisation. Data analyses were conducted using a one-stage random-effects meta-analysis model. This study was conducted and reported in accordance with the PRISMA-IPD statement. Results: Data of 65 945 individual patients with COPD were analysed. The pooled in-hospital mortality rate was 6.2%, pooled 30-, 90- and 365-day post-discharge mortality rates were 1.8%, 5.5% and 10.9%, respectively, and pooled 30-, 90- and 365-day hospital readmission rates were 7.1%, 12.6% and 32.1%, respectively, with noticeable variability between studies and countries. Strongest predictors of mortality and hospital readmission included noninvasive mechanical ventilation and a history of two or more ECOPD-related hospitalisations <12 months prior to the index event. Conclusions: This IPDMA stresses the poor outcomes and high heterogeneity of ECOPD-related hospitalisation across the world. Whilst global standardisation of the management and follow-up of ECOPD-related hospitalisation should be at the heart of future implementation research, policy makers should focus on reimbursing evidence-based therapies that decrease (recurrent) ECOPD.

The epidemiology of Stenotrophomonas maltophilia and Achromobacter xylosoxidans infections.

Stenotrophomonas maltophilia and Achromobacter xylosoxidans are emerging nosocomial, non-glucose fermenting, Gram-negative pathogens. In this nested case-control trial, independent predictors for S. maltophilia infections were hemodialysis and recent antibiotic usage (overall), while recent usage of fluoroquinolones, was independently associated with A. xylosoxidans infections. Infections were independently associated with multiple worse outcomes.

Long term outcomes of hyperbaric oxygen therapy in post covid condition: longitudinal follow-up of a randomized controlled trial.

In our previous randomized controlled trial, we documented significant improvements in cognitive, psychiatric, fatigue, sleep, and pain symptoms among long Coronavirus disease 2019 (COVID) patients who underwent hyperbaric oxygen therapy (HBOT). The primary objective of the present study was to evaluate the enduring 1 year long term effects of HBOT on long COVID syndrome. This longitudinal long-term follow-up included 31 patients with reported post COVID-19 cognitive symptoms, who underwent 40 daily sessions of HBOT. Participants were recruited more than one year (486 ± 73) after completion of the last HBOT session. Quality of life, assessed using the short form-36 (SF-36) questionnaire revealed, that the long-term results exhibited a similar magnitude of improvement as the short-term outcomes following HBOT across most domains. Regarding sleep quality, improvements were observed in global score and across five sleep domains with effect sizes of moderate magnitude during the short-term evaluation, and these improvements persisted in the long-term assessment (effect size (ES1) = 0.47-0.79). In the realm of neuropsychiatric symptoms, as evaluated by the brief symptom inventory-18 (BSI-18), the short-term assessment following HBOT demonstrated a large effect size, and this effect persisted at the long-term evaluation. Both pain severity (ES1 = 0.69) and pain interference (ES1 = 0.83), had significant improvements during the short-term assessment post HBOT, which persisted at long term. The results indicate HBOT can improve the quality of life, quality of sleep, psychiatric and pain symptoms of patients suffering from long COVID. The clinical improvements gained by HBOT are persistent even 1 year after the last HBOT session.

The effect of hyperbaric oxygen therapy on myocardial function in post-COVID-19 syndrome patients: a randomized controlled trial.

Post-COVID-19 condition refers to a range of persisting physical, neurocognitive, and neuropsychological symptoms following SARS-CoV-2 infection. Recent evidence revealed that post-COVID-19 syndrome patients may suffer from cardiac dysfunction and are at increased risk for a broad range of cardiovascular disorders. This randomized, sham-control, double-blind trial evaluated the effect of hyperbaric oxygen therapy (HBOT) on the cardiac function of post-COVID-19 patients with ongoing symptoms for at least three months after confirmed infection. Sixty patients were randomized to receive 40 daily HBOT or sham sessions. They underwent echocardiography at baseline and 1-3 weeks after the last protocol session. Twenty-nine (48.3%) patients had reduced global longitudinal strain (GLS) at baseline. Of them, 13 (43.3%) and 16 (53.3%) were allocated to the sham and HBOT groups, respectively. Compared to the sham group, GLS significantly increased following HBOT (- 17.8 ± 1.1 to - 20.2 ± 1.0, p = 0.0001), with a significant group-by-time interaction (p = 0.041). In conclusion, post-COVID-19 syndrome patients despite normal EF often have subclinical left ventricular dysfunction that is characterized by mildly reduced GLS. HBOT promotes left ventricular systolic function recovery in patients suffering from post COVID-19 condition. Further studies are needed to optimize patient selection and evaluate long-term outcomes.This study was registered with ClinicalTrials.gov, number NCT04647656 on 01/12/2020.

Obesity Paradox in Patients Hospitalized with Community Acquired Sepsis: Does Age Make a Difference?

BACKGROUND: Higher body mass index (BMI) has been shown to be a protective factor from mortality in sepsis patients. Yet, whether this effect is different in the very elderly is currently unknown. OBJECTIVES: To investigate the relationship between BMI and sepsis outcomes in patients older and younger than 80 years of age. METHODS: A retrospective analysis of consecutive patients admitted with sepsis to Shamir Medical Center, Israel, was conducted. We compared patients older than and younger than 80 years of age with a BMI higher and lower than 25 kg/m² for hospitalization outcomes. RESULTS: Patients older than 80 years presented with multiple co-morbidities compared to younger patients, but with no difference between BMI groups. Similarly, hospitalization outcomes of functional deterioration, discharge to long-term care facilities, and readmission were not significantly different between BMI groups in the same age category. Mortality was significantly different between BMI groups in patients older than 80 years of age, with higher mortality in BMI < 25 kg/m²: in-hospital mortality (23.4% vs. 14.9%, P < 0.001), 30-day mortality (27.6% vs. 17.9%, P < 0.001), and 90-day mortality (43.4% vs. 28.9%, P < 0.001). This difference was not significant between the groups younger than 80 years old. On logistic regression, BMI over 25 kg/m² was protective in all mortality categories. Nevertheless, there was no significant interaction between age over 80 years to BMI over 25 kg/m² in all mortality outcomes. CONCLUSIONS: Among patients hospitalized with sepsis, higher BMI is a protective factor against mortality in both elderly and younger patients.

Prolonged stay at an acute-care hospital in Israel among older adults awaiting transfer to post-acute care: retrospective study on risk factors and consequences.

BACKGROUND: Older adults frequently experience deconditioning following acute illnesses and require discharge from acute-care facilities to post-acute care facilities, which are limited. Our study aimed to explore predictors and outcomes associated with elongated length of stay (LOS) among older adults awaiting discharge to skilled nursing facility (SNF). METHODS: Retrospective cohort study was conducted at Shamir Medical Center, Israel, among adults (> 65 years) eligible for SNF. ROC curve analysis was used to determine prolonged LOS based on the risk to fall. Logistic and Cox regressions were used to analyze predictors and outcomes. RESULTS: Among 659 older adults awaiting transfer to SNF, 127 patients (24% among survivors of the index hospitalization) had prolonged LOS (> 12 days). The median age of patients was 82 years and 51% were females. The independent predictors for prolonged LOS were lower Norton index, higher MUST score, and admission from home. Prolonged LOS was independently associated with hospital-acquired infections, device related infections, and acquisitions of multidrug-resistant organisms. CONCLUSION: Prolonged LOS among older adults, awaiting transfer to SNF, should be suspected among non-institutionalized older adults with lower nutritional status and higher risk of pressure ulcers. The burden associated with establishing additional SNF beds, must be outweighed vs. the substantial infectious complications among awaiting older adults.

Effects of hyperbaric oxygen therapy on functional and structural connectivity in post-COVID-19 condition patients: A randomized, sham-controlled trial.

INTRODUCTION: Post-COVID-19 condition refers to a range of persisting physical, neurocognitive, and neuropsychological symptoms after SARS-CoV-2 infection. Abnormalities in brain connectivity were found in recovered patients compared to non-infected controls. This study aims to evaluate the effect of hyperbaric oxygen therapy (HBOT) on brain connectivity in post-COVID-19 patients. METHODS: In this randomized, sham-controlled, double-blind trial, 73 patients were randomized to receive 40 daily sessions of HBOT (n = 37) or sham treatment (n = 36). We examined pre- and post-treatment resting-state brain functional magnetic resonance imaging (fMRI) and diffusion tensor imaging (DTI) scans to evaluate functional and structural connectivity changes, which were correlated to cognitive and psychological distress measures. RESULTS: The ROI-to-ROI analysis revealed decreased internetwork connectivity in the HBOT group which was negatively correlated to improvements in attention and executive function scores (p < 0.001). Significant group-by-time interactions were demonstrated in the right hippocampal resting state function connectivity (rsFC) in the medial prefrontal cortex (PFWE = 0.002). Seed-to-voxel analysis also revealed a negative correlation in the brief symptom inventory (BSI-18) score and in the rsFC between the amygdala seed, the angular gyrus, and the primary sensory motor area (PFWE = 0.012, 0.002). Positive correlations were found between the BSI-18 score and the left insular cortex seed and FPN (angular gyrus) (PFWE < 0.0001). Tractography based structural connectivity analysis showed a significant group-by-time interaction in the fractional anisotropy (FA) of left amygdala tracts (F = 7.81, P = 0.007). The efficacy measure had significant group-by-time interactions (F = 5.98, p = 0.017) in the amygdala circuit. CONCLUSIONS: This study indicates that HBOT improves disruptions in white matter tracts and alters the functional connectivity organization of neural pathways attributed to cognitive and emotional recovery in post-COVID-19 patients. This study also highlights the potential of structural and functional connectivity analysis as a promising treatment response monitoring tool.

The Epidemiology of Multidrug-Resistant Sepsis among Chronic Hemodialysis Patients.

Sepsis is one of the leading causes of hospitalization and death among hemodialysis patients. Infections due to multidrug-resistant organisms (MDROs) are common among these patients, but empiric broad-spectrum coverage for every septic patient is associated with unfavorable outcomes. A retrospective case-control study was conducted at Shamir Medical Center, Israel (July 2016-April 2020), to determine predictors of MDRO infections among septic (per SEPSIS-3) ambulatory adult hemodialysis patients with permanent dialysis access (i.e., fistula, graft, or tunneled Perm-A-Cath). MDROs were determined according to established definitions. Least Absolute Shrinkage and Selection Operator (LASSO) regression was used to construct a prediction score and determine its performance. Of 509 patients, 225 (44%) had microbiologically confirmed infection, and 79 patients (35% of 225) had MDROs. The eventual independent predictors of MDRO infections were Perm-A-Cath access (vs. fistula or graft, aOR = 3, CI-95% = 2.1-4.2) and recent hospitalization in the previous three months (aOR = 2.3, CI-95% = 1.6-3.3). The score to predict MDRO sepsis with the highest performances contained seven parameters and displayed an area under the receiver operating characteristic curve (ROC AUC) of 0.74. This study could aid in defining a group of hemodialysis patients for which empiric broad-spectrum agents could be safely avoided.

Empiric Usage of "Anti-Pseudomonal" Agents for Hospital-Acquired Urinary Tract Infections.

Hospital-acquired urinary tract infection (HAUTI) is one of the most common hospital-acquired infections, and over 80% of HAUTI are catheter-associated (CAUTI). Pseudomonas aeruginosa, as well as other non-glucose fermenting Gram negative organisms (NGFGN, e.g., Acinetobacter baumannii), are frequently covered empirically with "anti-Pseudomonals" being administered for every HAUTI (and CAUTI). However, this common practice was never trialed in controlled settings in order to quantify its efficacy and its potential impacts on hospitalization outcomes. There were 413 patients with HAUTI that were included in this retrospective cohort study (2017-2018), 239 (57.9%) had CAUTI. There were 75 NGFGN infections (18.2% of HAUTI, 22.3% of CAUTI). P. aeruginosa was the most common NGFGN (82%). Despite multiple associations per univariable analysis, recent (3 months) exposure to antibiotics was the only independent predictor for NGFGN HAUTI (OR = 2.4, CI-95% = 1.2-4.8). Patients who received empiric anti-Pseudomonals suffered from worse outcomes, but in multivariable models (one for each outcome), none were independently associated with the empiric administration of anti-Pseudomonals. To conclude, approximately one of every five HAUTI (and CAUTI) are due to NGFGN, which justifies the practice of empiric anti-Pseudomonals for patients with HAUTI (and CAUTI), particularly patients who recently received antibiotics. The practice is not associated with independent deleterious impacts on outcomes.

Hyperbaric oxygen therapy improves neurocognitive functions and symptoms of post-COVID condition: randomized controlled trial.

Post-COVID-19 condition refers to a range of persisting physical, neurocognitive, and neuropsychological symptoms after SARS-CoV-2 infection. The mechanism can be related to brain tissue pathology caused by virus invasion or indirectly by neuroinflammation and hypercoagulability. This randomized, sham-control, double blind trial evaluated the effect of hyperbaric oxygen therapy (HBOT or HBO2 therapy) on post-COVID-19 patients with ongoing symptoms for at least 3 months after confirmed infection. Seventy-three patients were randomized to receive daily 40 session of HBOT (n = 37) or sham (n = 36). Follow-up assessments were performed at baseline and 1-3 weeks after the last treatment session. Following HBOT, there was a significant group-by-time interaction in global cognitive function, attention and executive function (d = 0.495, p = 0.038; d = 0.477, p = 0.04 and d = 0.463, p = 0.05 respectively). Significant improvement was also demonstrated in the energy domain (d = 0.522, p = 0.029), sleep (d = - 0.48, p = 0.042), psychiatric symptoms (d = 0.636, p = 0.008), and pain interference (d = 0.737, p = 0.001). Clinical outcomes were associated with significant improvement in brain MRI perfusion and microstructural changes in the supramarginal gyrus, left supplementary motor area, right insula, left frontal precentral gyrus, right middle frontal gyrus, and superior corona radiate. These results indicate that HBOT can induce neuroplasticity and improve cognitive, psychiatric, fatigue, sleep and pain symptoms of patients suffering from post-COVID-19 condition. HBOT's beneficial effect may be attributed to increased brain perfusion and neuroplasticity in regions associated with cognitive and emotional roles.

The Impact of Differences in Surveillance Definitions of Hospital Acquired Urinary Tract Infections (HAUTI).

Hospital-acquired urinary tract infections (HAUTI) are common and most cases are related to catheters (CAUTI). HAUTI and CAUTI surveillance is mandatory in many countries as a measure to reduce the incidence of infections and appropriately direct the allocation of preventable resources. The surveillance criteria issued by the Israeli Ministry of Health (IMOH), differ somewhat from that of the U.S. Centers for Disease Control and Prevention (CDC). Our study aims were to query and quantify the impact of these differences. In a retrospective cohort study conducted at Shamir Medical Center, for calendar year 2017, the surveillance criteria of both IMOH and CDC were applied on 644 patient-unique adults with "positive" urine cultures (per similar definitions). The incidence of HAUTI per IMOH was significantly higher compared to CDC (1.24/1000 vs. 1.02/1000 patient-days, p = 0.02), with no impact on hospitalization's outcomes. The agreement rate between methods was high for CAUTI (92%), but much lower for all HAUTI (83%). The major error rate, i.e., patients diagnosed with HAUTI per IMOH but had no UTI per CDC, was 31%. To conclude, in order for surveillance to reflect the relative situation and direct allocation of preventable resources based on scientific literature, the process should be uniform worldwide.

A "resistance calculator": Simple stewardship intervention for refining empiric practices of antimicrobials in acute-care hospitals.

OBJECTIVE: In the era of widespread resistance, there are 2 time points at which most empiric prescription errors occur among hospitalized adults: (1) upon admission (UA) when treating patients at risk of multidrug-resistant organisms (MDROs) and (2) during hospitalization, when treating patients at risk of extensively drug-resistant organisms (XDROs). These errors adversely influence patient outcomes and the hospital's ecology. DESIGN AND SETTING: Retrospective cohort study, Shamir Medical Center, Israel, 2016. PATIENTS: Adult patients (aged >18 years) hospitalized with sepsis. METHODS: Logistic regressions were used to develop predictive models for (1) MDRO UA and (2) nosocomial XDRO. Their performances on the derivation data sets, and on 7 other validation data sets, were assessed using the area under the receiver operating characteristic curve (ROC AUC). RESULTS: In total, 4,114 patients were included: 2,472 patients with sepsis UA and 1,642 with nosocomial sepsis. The MDRO UA score included 10 parameters, and with a cutoff of ≥22 points, it had an ROC AUC of 0.85. The nosocomial XDRO score included 7 parameters, and with a cutoff of ≥36 points, it had an ROC AUC of 0.87. The range of ROC AUCs for the validation data sets was 0.7-0.88 for the MDRO UA score and was 0.66-0.75 for nosocomial XDRO score. We created a free web calculator (https://assafharofe.azurewebsites.net). CONCLUSIONS: A simple electronic calculator could aid with empiric prescription during an encounter with a septic patient. Future implementation studies are needed to evaluate its utility in improving patient outcomes and in reducing overall resistances.

The association of diabetes and hyperglycemia with sepsis outcomes: a population-based cohort analysis.

The independent association of diabetes and hyperglycemia on the outcomes of sepsis remains unclear. We conducted retrospective cohort analyses of outcomes among patients with community-onset sepsis admitted to Shamir Medical Center, Israel (08-12/2016). Statistical associations were queried by Cox and logistic regressions, controlled for by matched propensity score analyses. Among 1527 patients with community-onset sepsis, 469 (30.7%) were diabetic. Diabetic patients were significantly older, with advanced complexity of comorbidities, and were more often exposed to healthcare environments. Despite statistically significant univariable associations with in-hospital and 90-day mortality, the adjusted Hazard Ratios (aHR) were 1.21 95% CI 0.8-1.71, p = 0.29 and 1.13 95% CI 0.86-1.49, p = 0.37, respectively. However, hyperglycemia at admission (i.e., above 200 mg/dl (was independently associated with: increased in-hospital mortality, aHR 1.48 95% CI 1.02-2.16, p = 0.037, 30-day mortality, aHR 1.8 95% CI 1.12-2.58, p = 0.001), and 90-day mortality, aHR 1.68 95% CI 1.24-2.27, p = 0.001. This association was more robust among diabetic patients than those without diabetes. In this study, diabetes was not associated with worse clinical outcomes in community-onset sepsis. However, high glucose levels at sepsis onset are independently associated with a worse prognosis, particularly among diabetic patients. Future trials should explore whether glycemic control could impact the outcomes and should be part of the management of sepsis, among the general adult septic population.

Antimicrobial use for asymptomatic bacteriuria-First, do no harm.

OBJECTIVE: Administration of antimicrobials to patients with asymptomatic bacteriuria (ASB) is a common error that can lead to worse outcomes. However, controlled analyses quantifying the commonality and impact of this practice are lacking. We analyzed the independent predictors for antimicrobials misuse in ASB and quantified the impact of this practice on clinical outcomes. DESIGN: Retrospective case-control and cohort analyses for calendar year 2017. SETTING: Tertiary-care, university-affiliated medical center. PATIENTS: The study included adult (>18 years) patients with positive urine culture. Pregnant women, renal transplant recipients, and patients who underwent urologic procedures were excluded. METHODS: ASB was determined according to US Centers for Disease Control and Prevention (CDC) criteria. Multivariable logistic regression models were constructed to analyze predictors and outcomes associated with antimicrobial use for patients with ASB. RESULTS: The study included 1,530 patient-unique positive urine cultures. Among these patients, 610 patients (40%) were determined to have ASB. Of the 696 isolates, 219 (36%) were multidrug-resistant organisms (MDROs). Also, 178 (29%) patients received antimicrobials specifically due to the ASB. Independent predictors for improper administration of antimicrobials were dependent functional status (adjusted odds ratio [aOR], 2.3; 95% CI, 1.4-3.6) and male sex (aOR, 2; 95% CI, 1.25-2.6). Use of antimicrobials was independently associated with re-hospitalizations (aOR, 1.7; 95% CI, 1.1-2.6) and later, acute Clostridioides difficile infections (CDI) in the following 90 days (aOR, 4.5; 95% CI, 2-10.6). CONCLUSIONS: ASB is a common condition, frequently resulting from an MDRO. Male sex and poor functional status were independent predictors for mistreatment, and this practice was independently associated with rehospitalizations and CDI in the following 90 days.

Mesenchymal Stromal Cell Uses for Acute Kidney Injury-Current Available Data and Future Perspectives: A Mini-Review.

There is growing evidence concerning the potential use of mesenchymal stromal cells (MSCs) for different tissue injuries. Initially, the intended physiological use of MSCs was due to their ability to differentiate and replace damaged cells. However, MSCs have multiple effects, including being able to significantly modulate immunological responses. MSCs are currently being tested for neurodegenerative diseases, graft vs. host disease, kidney injury, and other chronic unremitting tissue damage. Using MSCs in acute tissue damage is only now being studied. Acute kidney injury (AKI) is a common cause of morbidity and mortality. After the primary insult, overactivation of the immune system culminates in additional secondary potentially permanent kidney damage. MSCs have the potential to ameliorate the secondary damage, and recent studies have shed important light on their mechanisms of action. This article summarizes the basics of MSCs therapy, the newly discovered mechanisms of action, and their potential application in the setting of AKI.

The impact of improper empirical usage of antipseudomonals on admission to an acute care hospital.

BACKGROUND: Many septic patients are receiving empirical antipseudomonal (or Gram-negative non-glucose fermenting [GNNGF]) coverage on admission to acute care hospitals, despite the fact that the indications are not scientifically established. Overuse of antipseudomonals might contribute to the burden of resistance. MATERIALS AND METHODS: Retrospective observational analyses of the characteristics of septic adult patients who received empirical antipseudomonals, along with its impact on outcomes, were executed at Shamir Medical Center, Zerifin, Israel (08-12/2016). Proper empirical antipseudomonal usage was defined by the following: (1) if the patient received the agents as per Infectious Disease Society of America (IDSA) guidelines; (2) if the patient had a positive multidrug-resistant organism (MDRO) test on his or her admission score (https://assafharofe.azurewebsites.net); or (3) if a GNNGF was the eventual causative pathogen. Risk factors and outcomes were queried by logistic and Cox regression. RESULTS: GNNGF was the causative pathogen in only 57 (3.7%) of 1536 patients with acute sepsis. There were 192 (13%) who received empirical antipseudomonals, of whom 161 (84%) were defined as proper. Patients who received empirical antipseudomonals were significantly older (P < 0.001), with higher indices of chronic and acute conditions, and higher rates of past MDRO carriage; 24 patients received empirical antipseudomonals only because of IDSA guidelines (15%), and that was an independent predictor for later acquisition (up to 90 days) of carbapenem-resistant A. baumannii (CRAB; odds ratio [aOR] = 7.1; P = 0.03). CONCLUSIONS: Improper empirical usage of antipseudomonals in acute care hospitals is common. Instituting empirical antipseudomonals solely due to IDSA guidelines was independently associated with later acquisition of CRAB. Empirical antipseudomonal usage should be based on scientifically established prediction tools and not on IDSA guidelines.

Effect of anti-C5 antibody on recuperation from ischemia/reperfusion-induced acute kidney injury.

AbstractAim: The complement system is activated in acute kidney injury (AKI). Anti-C5 antibody targets the common terminal portion of the complement cascade that generate the terminal complex C5b-9 and has a renal-protective effect in paroxysmal nocturnal hemoglobinuria. However, the anti-C5 antibody's role in ischemia/reperfusion (I/R)-induced AKI has not been fully investigated. We therefore evaluated its effect on the pathophysiological cascade of I/R-induced AKI.Methods: Sprague-Dawley rats underwent unilateral right kidney nephrectomies with simultaneous clamping of the contralateral hilum for 60 min (ischemia), followed by reperfusion. In addition to a placebo, two treatment groups received either high or low doses of anti-C5 monoclonal antibody. After 48 h, the rats were euthanized, blood was drawn to evaluate systemic inflammation and to estimate glomerular filtration rate (GFR). The remaining kidney was removed for pathological evaluation and intra-renal complement activation.Results: I/R induced significant intra-renal complement activation and systemic inflammation compared with unilateral nephrectomy group. The anti-C5 antibody ameliorated the intra-renal complement activation (intra-renal C3 and C6), reduced systemic inflammation (C-reactive protein, and systemic C3), decreased intra-renal acute tubular necrosis damage and improved GFR (seen by the sensitive marker, serum cystatin C; 1.63 mg/L (I/R + placebo), 1.36 mg/L (I/R + low dose) and 1.21 mg/L (I/R + high dose), p = .08 and .03 compared with I/R + placebo).Conclusion: In I/R-induced AKI, the monoclonal anti-C5 complement factor ameliorates intra renal complement activation, decreases local and systemic inflammation and may improve GFR.

Human mesenchymal stromal cells ameliorate complement induced inflammatory cascade and improve renal functions in a rat model of ischemia-reperfusion induced acute kidney injury.

INTRODUCTION: The primary rational for using mesenchymal stromal cells (MSCs) to rejuvenate damaged tissue is mostly based on their capacity to trans-differentiate and repair injured organs. However, previous studies have demonstrated that MSCs are beneficial even at very early stages, before differentiation and proliferation can be expected. The aim of the current study was to investigate the multifaceted immunological effects of systemically administrating MSCs in the setting of acute kidney injury (AKI) induced by ischemic-reperfusion (I/R). METHODS: A rat model of I/R induced AKI was used. The rats underwent a unilateral nephrectomy with simultaneously clamping the contralateral kidney for 60 minutes. Four treatment groups received intravenously, increasing doses of human MSCs and after 48 hours, the rats were sacrificed. Blood was taken to evaluate renal functions and to measure systemic inflammatory markers. Kidneys were taken for histopathologic examinations and evaluations of intra-renal complement activation and inflammatory mediators. RESULTS: Renal functions improved in U shaped dose dependent manner. Mean serum creatinine levels were 4.5, 2.9, 2.6, 1.7 and 4.1 mg/dL in I/R + placebo, I/R + 150x103 cells, I/R + 250x103 cells, I/R + 500x103 cells and I/R + 1,000x103 cells respectfully (p-values<0.05). Urea demonstrated consistent results with the same U shape improvement manner. The extensive activation of the complement system was ameliorated in the MSCs treatment groups. In addition, MSCs significantly decreased intra-renal levels of IL-1ß and TNF-α. It should be noted that the highest doses of MSCs induced renal hypoxia, marked by the Hypoxy-probe staining. CONCLUSIONS: The early beneficial effect of MSCs in the setting of AKI may be attributed to their immunomodulatory effects. Safe treatment with MSCs can block the deleterious activation of the complement cascade and alleviate the hazardous inflammatory mediator-related cascade.