Urinary Sepsis Research Articles

Trends in infectious complications after partial colectomy for colon cancer over a decade: A national cohort study

BackgroundThe American College of Surgeons National Surgical Quality Improvement Program helps participating hospitals track and report surgical complications with the goal of improving patient care. We sought to determine whether postoperative infectious complications after elective colectomy for malignancy improved among participating centers over time. MethodsPatients with colon malignancies who underwent elective partial colectomy with primary anastomosis (categorized as low or non-low) were identified from the American College of Surgeons National Surgical Quality Improvement Program database (2011–2019). Thirty-day postoperative infectious complications analyzed by year included superficial, deep, and organ space surgical site infections, urinary tract infection, pneumonia, and sepsis. Trends in patient and treatment characteristics were investigated using log-linear regression along with their association with infectious outcomes. ResultsOf the 78,827 patients identified, 51% were female, and the median age was 68. The majority (84%) underwent partial colectomy without a low anastomosis. There was a decrease in all infectious complications except for organ space infections which increased 35% overall from 2.0 to 2.7% (P = .037), driven by patients without a low anastomosis (1.9%–2.7%, P = .01). There was no change in most patient factors associated with organ space infections, except for a notable increase in American Society of Anesthesiologists class III and IV–V patients over time, both associated with organ space infections (P < .001; P = .002). ConclusionInfectious complications have decreased significantly overall after colectomy for colon cancer, whereas there has been an increase in organ space infection rates specifically. Although changing patient characteristics may contribute to this observed trend, further study is needed to better understand its etiology to help mitigate this complication.

DIFFUSE ALVEOLAR HEMORRHAGE DUE TO AMIODARONE

DIFFUSE ALVEOLAR HEMORRHAGE DUE TO AMIODARONE

Molecular Analysis of Ndm-1 Positive Klebsiella pneumoniae Strains Isolated From Patients With Bacteremia Due to Urinary System Infection

Introduction: Health concerns about Klebsiella pneumoniae, which causes urinary tract infections (UTIs) and sepsis, are increasing worldwide. In addition, New Delhi metallo-ß-lactamase (NDM) carrier K. pneumoniae and other Gram-negative bacteria appear to cause serious clinical problems. This study aimed to reveal NDM-1 positive K. pneumoniae carrier status, molecular properties, and antibiotic resistance differences of patients who have bacteremia due to urinary system infections. Methods: Blood culture, biochemical tests, Vitek2, polymerase chain reaction, sequencing, phylogenetic analysis, and multilocus sequence typing (MLST) methods were used for the microbiological analysis of K. pneumoniae strains. Results: Overall, 146 K. pneumoniae strains were obtained from the cultures, 16 of which were found to be NDM-1 positive. Although these strains were discovered to have resistance to the authorized antibiotics, they were sensitive to gentamicin (CN), colistin (CT), and trimethoprim/sulfamethoxazole (SXT). Furthermore, it was found that the resistance rates of carbapenem (ertapenem (Etp), imipenem (Ipm), and meropenem (Mem)) were high. All K. pneumoniae strains represented extended-spectrum beta-lactam resistance. It was found that the phylogenetic affinities of K. pneumoniae strains were higher with Asian strains. Five and eleven K. pneumoniae isolates were determined to be ST17 and ST147 type variations, respectively, as a conclusion of the MLST study. Conclusions: It was observed that the presence of NDM-1-positive K. pneumoniae may pose a serious problem in patients with bacteremia caused by UTI. It has been demonstrated that it is important to develop preventive and control measures in the hospital by considering NDM-1-positive K. pneumoniae strains with multi-drug resistance.

The risk of classical galactosaemia in newborns with borderline galactose metabolites on newborn screening.

Newborn screening (NBS) for classical galactosaemia (CG) facilitates early diagnosis and treatment to prevent life-threatening complications, but remains controversial, and screening protocols vary widely between programmes. False-negatives associated with first-tier screening of total galactose metabolites (TGAL) are infrequently reported; however, newborns with TGAL below the screening threshold have not been systematically studied. Following the diagnosis of CG in two siblings missed by NBS, a retrospective cohort study of infants with TGAL just below the cut-off (1.5 mmol/L blood) was conducted. Children born in New Zealand (NZ) from 2011 to 2019, with TGAL 1.0-1.49 mmol/L on NBS were identified from the national metabolic screening programme (NMSP) database, and clinical coding data and medical records were reviewed. GALT sequencing was performed if CG could not be excluded following review of medical records. 328 infants with TGAL 1.0-1.49 mmol/L on NBS were identified, of whom 35 had ICD-10 codes relevant to CG including vomiting, poor feeding, weight loss, failure to thrive, jaundice, hepatitis, Escherichia coli urinary tract infection, sepsis, intracranial hypertension and death. CG could be excluded in 34/35, due to documentation of clinical improvement with continued dietary galactose intake, or a clear alternative aetiology. GALT sequencing in the remaining individual confirmed Duarte-variant galactosaemia (DG). In conclusion, undiagnosed CG appears to be rare in those with TGAL 1.0-1.49 mmol/L on NBS; however, our recent experience with missed cases is nevertheless concerning. Further work is required to establish the optimum screening strategy, to maximize the early detection of CG without excess false-positives.

Analysis of the Causes and Preventive Strategies of Urogenic Sepsis after Flexible Ureteroscopic Lithotripsy.

Objective To explore the causes of urogenic sepsis in patients after flexible ureteroscopic lithotripsy and analyze the preventive strategies. Methods A total of 240 patients who underwent flexible ureteroscopic lithotripsy in our hospital from January 2019 to June 2022 were selected and divided into 2 groups according to whether postoperative ureteral sepsis occurred. 24 cases occurred in the observation group. Logistics multivariate regression analysis was used to analyze the risk factors of urogenic sepsis after flexible ureteroscopic lithotripsy, and the serum albumin (ALB), the peripheral blood neutrophil-to-lymphocyte ratio (NLR), and the level of procalcitonin (PCT) were correlated, and the ROC curve was used to analyze the predictive value of each index for urosepsis. Results Univariate analysis showed that there were differences in gender, age, diabetes, stone diameter, and urine culture ratio between the two groups (P < 0.05). The results of multivariate regression analysis showed that female, age ≥60 years, stone diameter >2.5 cm, and positive urine culture were the main influencing factors for the occurrence of urogenic sepsis. After operation, the ALB levels in the two groups were lower than those before operation, and the levels of NLR and PCT in the two groups were higher than those before operation; the ALB levels in the observation group were lower than those in the control group, and the NLR and PCT in the observation group were higher than those in the control group (P < 0.05). According to Spearman's correlation analysis, ALB was negatively correlated with the occurrence of uremia (P < 0.05), r = −0.320, NLR and PCT were positively correlated with the occurrence of uremia (P < 0.05), r = 0.313, respectively, and 0.417; in addition, Pearson's correlation analysis showed that ALB was negatively correlated with NLR and PCT in the two groups (P < 0.05, r = −0.507, −0.605 in the control group, respectively, and r were −0.452 and −0.412 in the observation group). There was a positive correlation between NLR and PCT (P < 0.05), r = 0.840, and there was no correlation between NLR and PCT in the observation group (P > 0.05). According to the ROC curve analysis, the predictive value AUC of ALB, NLR, PCT and combined use were 0.808, 0.801, 0.901, and 0.925 (P < 0.05). Conclusion Gender, age, stone diameter, and urine culture results are the main influencing factors for the occurrence of urinary sepsis. Therefore, preventive measures should be strengthened for this group of patients. In addition, the combined use of postoperative ALT, NLR, and PCT level tests can be better.

Introduction of surgical site surveillance post transrectal ultrasound (TRUS) guided prostate biopsy and the impact on infection rates

Transrectal ultrasound (TRUS)-guided prostate biopsy is associated with infection rates between 0.3 % and 3.2%. Infectious complications include urinary tract infection, prostatitis, bacteraemia and sepsis. Surgical site surveillance in this patientcohort is becoming increasingly important given global increases in antimicrobial resistance. Surgical site surveillance for patients undergoing TRUS biopsies was introduced in our hospital in 2017. All patients had a risk assessment form completed to assess for carriage or risk of carriage of multi-drug resistant organisms. An intense analysis was completed on any patient who developed an infection post-TRUS biopsy. Data was fed back on a quarterly basis to a multi-disciplinary working group. Members of this group include a Consultant Microbiologist, Infection Prevention and Control Nurse, Consultant Urologist, Antimicrobial Pharmacists and Clinical Nurse Ward Managers. 784 TRUS-guided biopsy of the prostate procedures were performed between January 1 st 2017 and the end of the third quarter, 2021. The rate of infection post-TRUS was 2.7% in 2017, 3.4% in 2018 and 3.2% in 2019. This improved to 0% in 2020 and 0.8% in the first three quarters of 2021. Several interventions were introduced resulting in a sustained reduction in infection rates in this cohort. These include changing the choice of surgical antibiotic prophylaxis, improvement in the timing of antibiotic prophylaxis and scheduling of other urology procedures. The introduction of surgical site surveillance and multi-disciplinary input has demonstrated a reduction in infection rates post TRUS biopsy.

Protocolo diagnóstico y terapéutico de la infección urinaria en el paciente mayor

Urinary tract infections (UTIs) are, after respiratory infections, the most common infectious disease in elderly patients. Their form of presentation ranges from asymptomatic bacteriuria to cystitis, pyelonephritis, or urinary sepsis. The diagnosis is based on clinical suspicion and the detection of pyuria and a urine culture with significant bacteriuria. In geriatric patients, the disease's often atypical presentation and the high prevalence of asymptomatic bacteriuria hinder its diagnosis. Asymptomatic bacteriuria is the colonization of the urinary tract by bacteria and must be differentiated from a symptomatic UTI, as it does not require treatment. When choosing empirical antibiotic treatment, the possible adverse effects, previous microbiological isolations, and local resistance rate must be taken into account.

Fever Management after TEVAR in Patients with Aortic Dissection.

Post-implantation syndrome (PIS) is characterised as a noninfectious continuous fever and a concomitant rise in inflammatory markers shortly after thoracic endovascular aortic repair (TEVAR). This current study aims to analyse the risk factors of PIS, postoperative major adverse cardiac events (MACE), and overall survival as well as the correlation between new-onset mural thrombus and the risk of developing PIS after TEVAR in patients with type B aortic dissection (TBAD). Patients were included who had a B dissection, both acute and chronic forms. In the acute form, both acutely complicated and uncomplicated patients were included in the study. A main point of our investigation is the postoperative fever management of PIS patients. A total of 90 patients with type B dissection underwent TEVAR in the University Hospital of Muenster between 2016 and 2020. The occurrence of PIS was defined as the presence of fever (>38°C lasting longer than 24 hours in hospital) and leucocytosis (white blood cell count >12000/µL). Patients with other possible reasons for fever and/or leucocytosis, such as a urinary tract infection (UTI), pneumonia, or sepsis, were excluded beforehand. Besides demographic and operation-related data, inflammatory markers and therapeutic measures were evaluated before and 5 days postoperatively. Computed tomography scans were examined to calculate the volume of preexistent and new-onset mural thrombus after TEVAR. Of 90 patients, 40 patients were excluded because of recent infection or bypass surgery. Of the 50 patients included in the study, 10 patients developed post-implantation syndrome. Younger patients significantly more often developed PIS after TEVAR (52.2±11.6 vs. 61.5±13.6, p=0.045). New-onset thrombus after TEVAR was significantly higher in PIS patients (61cm³ vs. 12cm³, p<0.001) and PIS patients often received more medical examinations (investigation of X-ray, U status, and blood cultures). There was no significant difference in overall survival for 40 months and in the incidence of MACE. PIS may be related to an increased rate of new-onset thrombus. A more robust conclusion is not justified according to our study. There is no difference in overall survival.

Undertriage of Geriatric Trauma Patients in Florida

IntroductionElderly undertriage rates are estimated up to 55% in the United States. This study examined risk factors for undertriage among hospitalized trauma patients in a state with high volumes of geriatric trauma patients. Materials and methodsThis is a population–based retrospective cohort study of 62,557 patients admitted to Florida hospitals between 2016 and 2018 from the Agency for Healthcare Administration database. Severely injured trauma patients were defined by American College of Surgeons definitions and an International Classification of Disease Injury Severity Score <0.85. Undertriage was defined as definitive care of these severely injured patients at any Florida hospital other than a state-designated trauma center (TC). Univariate analyses were used to identify risk factors associated with inpatient mortality and undertriage. Multiple variable regression was used to estimate risk-adjusted odds of mortality after admission to either a designated or nondesignated TC. ResultsUndertriaged patients were more likely to have isolated traumatic brain injuries, lower International Classification of Disease Injury Severity Scores, multiple comorbidities, and older age. Trauma patients aged 65 and older were more than twice as likely to be undertriaged (34% versus 15.7%, P < 0.0001). Undertriaged patients of all ages were also more likely to suffer from pneumonia, urinary tract infection, arrhythmias, and sepsis. After risk adjustment, severely injured trauma patients admitted to non-TC were also more likely to be at risk for mortality (adjusted odds ratio, 1.27; 95% confidence interval, 1.17-1.38). ConclusionsAge and multiple comorbidities are significant predictors of mortality among undertriage of trauma patients. As a result, trauma triage guidelines should account for high-risk geriatric trauma patients who would benefit from definitive treatment at designated TCs.

In-Hospital Mortality of Sepsis Differs Depending on the Origin of Infection: An Investigation of Predisposing Factors.

Sepsis is a heterogeneous syndrome characterized by a variety of clinical features. Analysis of large clinical datasets may serve to define groups of sepsis with different risks of adverse outcomes. Clinical experience supports the concept that prognosis, treatment, severity, and time course of sepsis vary depending on the source of infection. We analyzed a large publicly available database to test this hypothesis. In addition, we developed prognostic models for the three main types of sepsis: pulmonary, urinary, and abdominal sepsis. We used logistic regression using routinely available clinical data for mortality prediction in each of these groups. The data was extracted from the eICU collaborative research database, a multi-center intensive care unit with over 200,000 admissions. Sepsis cohorts were defined using admission diagnosis codes. We used univariate and multivariate analyses to establish factors relevant for outcome prediction in all three cohorts of sepsis (pulmonary, urinary and abdominal). For logistic regression, input variables were automatically selected using a sequential forward search algorithm over 10 dataset instances. Receiver operator characteristics were generated for each model and compared with established prognostication tools (APACHE IV and SOFA). A total of 3,958 sepsis admissions were included in the analysis. Sepsis in-hospital mortality differed depending on the cause of infection: abdominal 18.93%, pulmonary 19.27%, and renal 12.81%. Higher average heart rate was associated with increased mortality risk. Increased average Mean Arterial Pressure (MAP) showed a reduced mortality risk across all sepsis groups. Results from the LR models found significant factors that were relevant for specific sepsis groups. Our models outperformed APACHE IV and SOFA scores with AUC between 0.63 and 0.74. Predictive power decreased over time, with the best results achieved for data extracted for the first 24 h of admission. Mortality varied significantly between the three sepsis groups. We also demonstrate that factors of importance show considerable heterogeneity depending on the source of infection. The factors influencing in-hospital mortality vary depending on the source of sepsis which may explain why most sepsis trials have failed to identify an effective treatment. The source of infection should be considered when considering mortality risk. Planning of sepsis treatment trials may benefit from risk stratification based on the source of infection.

Determination of multidrug-resistant populations and molecular characterization of complex Klebsiella spp. in wild animals by multilocus sequence typing.

Background and Aim:One of the most significant public health concerns is multidrug-resistant (MDR) microorganisms. Klebsiella spp. have been at the forefront of causing different types of infections such as bacteremia, urinary tract infections, pneumonia, enteritis, and sepsis in humans as well as animals. This study aimed to determine the genomic similarity between Klebsiella spp. isolated from wild animal samples and those described in the Institut Pasteur genomic database to verify the spread of resistant clones regionally in the state of Mato Grosso, and to compare the epidemiological data in different regions of Brazil and the world.Materials and Methods:Isolates from various sites of injury in wild animals were identified by sequencing the 16S rRNA gene. Antimicrobial susceptibility testing was performed using the disk diffusion method to verify the resistance profile, and then, multilocus sequence typing was performed to verify the population structure and compare the isolates from other regions of Brazil and the world.Results:Twenty-three sequence types (STs) were observed; of these, 11 were new STs, as new alleles were detected. There was no predominant ST among the isolates. All isolates were MDR, with high rates of resistance to sulfonamides, ampicillin, amoxicillin, and nitrofurantoin and low resistance to meropenem, imipenem, and amikacin.Conclusion:Improving our understanding of the population structure of Klebsiella spp. in wild animals may help determine the source of infection during outbreaks in humans or animals, as the One Health concept emphasizes the interlinks between humans, animals, and environmental health.

EARLY DIFFERENTIATION BETWEEN SEPSIS AND STERILE INFLAMMATION VIA URINARY GENE SIGNATURES OF METABOLIC DYSREGULATION.

ABSTRACTObjective: The aim of this study was to characterize early urinary gene expression differences between patients with sepsis and patients with sterile inflammation and summarize in terms of a reproducible sepsis probability score. Design: This was a prospective observational cohort study. Setting: The study was conducted in a quaternary care academic hospital. Patients: One hundred eighty-six sepsis patients and 78 systemic inflammatory response syndrome (SIRS) patients enrolled between January 2015 and February 2018. Interventions: Whole-genome transcriptomic analysis of RNA was extracted from urine obtained from sepsis patients within 12 hours of sepsis onset and from patients with surgery-acquired SIRS within 4 hours after major inpatient surgery. Measurements and Main Results: We identified 422 of 23,956 genes (1.7%) that were differentially expressed between sepsis and SIRS patients. Differentially expressed probes were provided to a collection of machine learning feature selection models to identify focused probe sets that differentiate between sepsis and SIRS. These probe sets were combined to find an optimal probe set (UrSepsisModel) and calculate a urinary sepsis score (UrSepsisScore), which is the geometric mean of downregulated genes subtracted from the geometric mean of upregulated genes. This approach summarizes the expression values of all decisive genes as a single sepsis score. The UrSepsisModel and UrSepsisScore achieved area under the receiver operating characteristic curves 0.91 (95% confidence interval, 0.86–0.96) and 0.80 (95% confidence interval, 0.70–0.88) on the validation cohort, respectively. Functional analyses of probes associated with sepsis demonstrated metabolic dysregulation manifest as reduced oxidative phosphorylation, decreased amino acid metabolism, and decreased oxidation of lipids and fatty acids. Conclusions: Whole-genome transcriptomic profiling of urinary cells revealed focused probe panels that can function as an early diagnostic tool for differentiating sepsis from sterile SIRS. Functional analysis of differentially expressed genes demonstrated a distinct metabolic dysregulation signature in sepsis.

Economic and clinical burden from carbapenem-resistant bacterial infections and factors contributing: a retrospective study using electronic medical records in Japan

BackgroundAntimicrobial resistance is a major threat to global health and the world economy. The economic burden of carbapenem-resistant infections has not previously been evaluated. We aimed to compare the potential economic burden and clinical outcomes between carbapenem-resistant infections and carbapenem-susceptible infections in Japan.MethodsWe conducted a retrospective cohort study using electronic medical records. Patients aged 15 years or older and with the diagnosis of pneumonia, urinary tract infection, biliary infection, and sepsis were included. Multivariable regression models with random effects were used to estimate the impact of carbapenem resistance on cost, length of hospital stay, and in-hospital mortality.ResultsAmong the 9,517 patients, 86 (0.9%) had carbapenem-resistant (CR) infections. Compared to carbapenem-susceptible (CS) infections, the patients with the CR infections were significantly more likely to receive mechanical ventilation (37.2 vs. 21.2%, P-value = 0.003), antibiotics (88.4 vs. 63.0%, P-value < 0.001), and especially carbapenem (31.4 vs. 8.3%, P-value < 0.001), before the bacterial culture test positive. Significantly higher median costs were found for the CR infections than the CS infections in the categories of medications (3477 US dollars vs. 1609 US dollars), laboratory tests (2498 US dollars, vs. 1845 US dollars), and hospital stay (14,307 US dollars vs. 10,560 US dollars). In the multivariable regression analysis, the length of stay was 42.1% longer and the cost was 50.4% higher in the CR infections than in the CS infections. The risk of in-hospital mortality did not differ between the two groups (odds ratio 1.24, 95% CI 0.72–2.11), due to the small sample size. The result was robust with a similar trend in the analysis using the inverse probability treatment weighting method.ConclusionsCompared to carbapenem-susceptible infections, carbapenem-resistant infections were associated with a higher cost and a longer length of stay. Detailed cost analysis showed significant differences in the categories of medication, laboratory tests, and hospital stay. To our knowledge, this study is the first to assess the potential economic burden of carbapenem-resistant infections using a large hospital-based database.

Patterns, Predictors, and Intercenter Variability in Empiric Gram-Negative Antibiotic Use Across 928 United States Hospitals.

Empiric antibiotic use among hospitalized adults in the United States (US) is largely undescribed. Identifying factors associated with broad-spectrum empiric therapy may inform antibiotic stewardship interventions and facilitate benchmarking. We performed a retrospective cohort study of adults discharged in 2019 from 928 hospitals in the Premier Healthcare Database. "Empiric" gram-negative antibiotics were defined by administration before day 3 of hospitalization. Multivariable logistic regression models with random effects by hospital were used to evaluate associations between patient and hospital characteristics and empiric receipt of broad-spectrum, compared to narrow-spectrum, gram-negative antibiotics. Of 8 017 740 hospitalized adults, 2 928 657 (37%) received empiric gram-negative antibiotics. Among 1 781 306 who received broad-spectrum therapy, 30% did not have a common infectious syndrome present on admission (pneumonia, urinary tract infection, sepsis, or bacteremia), surgery, or an intensive care unit stay in the empiric window. Holding other factors constant, males were 22% more likely (adjusted odds ratio [aOR], 1.22 [95% confidence interval, 1.22-1.23]), and all non-White racial groups 6%-13% less likely (aOR range, 0.87-0.94), to receive broad-spectrum therapy. There were significant prescribing differences by region, with the highest adjusted odds of broad-spectrum therapy in the US West South Central division. Even after model adjustment, there remained substantial interhospital variability: Among patients receiving empiric therapy, the probability of receiving broad-spectrum antibiotics varied as much as 34+ percentage points due solely to the admitting hospital (95% interval of probabilities: 43%-77%). Empiric gram-negative antibiotic use is highly variable across US regions, and there is high, unexplained interhospital variability. Sex and racial disparities in the receipt of broad-spectrum therapy warrant further investigation.

Cellular RNA Targets of Cold Shock Proteins CspC and CspE and Their Importance for Serum Resistance in Septicemic Escherichia coli.

ABSTRACTThe RNA chaperones, cold shock proteins CspC and CspE, are important in stress response and adaptation. We studied their role in the pathogenesis of a virulent Escherichia coli, representative of extraintestinal pathogenic E. coli (ExPEC) which are serum resistant and septicemic. We performed a global analysis to identify transcripts that interact with these cold shock proteins (CSPs), focusing on virulence-related genes. We used CLIP-seq, which combines UV cross-linking, immunoprecipitation and RNA sequencing. A large number of transcripts bound to the CSPs were identified, and many bind both CspC and CspE. Many transcripts were of genes involved in protein synthesis, transcription and energy metabolism. In addition, there were virulence-related genes, (i.e., fur and ryhB), essential for iron homeostasis. The CLIP-seq results were validated on two transcripts, clpX and tdcA, reported as virulence-associated. Deletion of either CspC or CspE significantly decreased their transcript levels and in a double deletion mutant cspC/cspE, the transcript stability of tdcA and clpX was reduced by 32-fold and 10-fold, respectively. We showed that these two genes are important for virulence, as deleting either of them resulted in loss of serum resistance, a requirement for sepsis. As several virulence-related transcripts interact with CspC or CspE, we determined the importance of these proteins for growth in serum and showed that deletion of either gene significantly reduced serum survival. This phenotype could be partially complemented by cspE and fully complemented by cspC. These results indicate that the two RNA chaperones are essential for virulence, and that CspC particularly critical.IMPORTANCE Virulent Escherichia coli strains that cause infections outside the intestinal tract—extraintestinal pathogenic E. coli (ExPEC)—constitute a major clinical problem worldwide. They are involved in several distinct conditions, including urinary tract infections, newborn meningitis, and sepsis. Due to increasing antibiotic resistance, these strains are a main factor in hospital and community-acquired infections. Because many strains, which do not cross-react immunologically are involved, developing a simple vaccine is not possible. Therefore, it is essential to understand the pathogenesis of these bacteria to identify potential targets for developing drugs or vaccines. One of the least investigated systems involves RNA binding proteins, important for stability of transcripts and global gene regulation. Two such proteins are CspC and CspE (“cold shock proteins”), RNA chaperones involved in stress adaptation. Here we performed a global analysis to identify the transcripts which are affected by these two chaperones, with focus on virulence-associated transcripts.

Osteoporosis is a novel risk factor of infections and sepsis: A cohort study.

SummaryBackgroundAccumulating evidence suggests the interaction of bone metabolism and the immune system, but how bone health is associated with the risk of infections remains unknown.MethodsThis study aimed to investigate the relationship of bone mineral density (BMD) with the risk of common infections and sepsis in Hong Kong Osteoporosis Study (HKOS). A prospective cohort study, initiated in 1995 and followed until 31 December 2020, of 5,717 participants examined the association of BMD at three skeletal sites (lumbar spine, femoral neck, and total hip) with common infections - pneumonia, urinary tract infection (UTI), skin infection, and sepsis. Cox proportional hazards models were used to estimate hazard ratios (HR) and 95% confidence intervals (CI).FindingsDuring the median follow-up of 17 years, higher BMD T-scores at the femoral neck and total hip were significantly associated with the reduced risk of pneumonia (HRs 0.89 and 0.87; 95% CIs 0.82 to 0.98 and 0.81 to 0.95), UTI (HRs 0.85 and 0.86; 95% CIs 0.76 to 0.94 and 0.78 to 0.95), skin infection (HRs 0.85 and 0.82; 95% CIs 0.74 to 0.97 and 0.73 to 0.93), and sepsis (HRs 0.83 and 0.82; 95% CIs 0.71 to 0.97 and 0.72 to 0.94). A significant association was observed for the lumbar spine BMD T-score with the risk of skin infection (HR 0.86; 95% CI: 0.78 to 0.95) but not with other infections and sepsis. Similarly, participants with osteoporosis, but not osteopenia, were significantly associated with an increased risk of infections and sepsis compared to those with normal BMD.InterpretationBMD is a novel risk factor of infections and sepsis. People with low BMD, particularly those with osteoporosis, are at higher risk of infections and sepsis than those with normal BMD. Further studies on whether improving bone health can reduce the risk of infections and sepsis are warranted.FundingNone.

Hyperthermic intraperitoneal chemotherapy does not increase risk of major complication or failure to rescue in cytoreductive surgery.

Failure to rescue (FTR) is defined as death after a major complication. We evaluated FTR after cytoreductive surgery (CRS) with and without hyperthermic intraperitoneal chemotherapy (HIPEC). The ACS NSQIP database 2005-2018 was reviewed for all cases of CRS. Propensity score matching was used to compare outcomes between those undergoing CRS alone and those undergoing CRS/HIPEC. Patients were matched on age, sex, ascites, diabetes, hypertension and resection of liver, pancreas, colon/rectum, diaphragm, stomach, small bowel, and/or spleen. Thirty nine thousand one hundred and twenty-six patients underwent CRS; 38,387 underwent CRS alone; 739 underwent CRS/HIPEC. After matching there were 726 patients in each arm. Patients undergoing CRS/HIPEC had higher risk of reintubation (25 [3.4%] vs. 13 [1.8%] p = 0.049), urinary tract infection UTI (44 [6.1%] vs. 25 [3.4%] p = 0.019) and sepsis (73 [10.1%] vs. 44 [6.1%] p = 0.005). Patients in the CRS arm required more transfusions (229 [31.5%] vs. 176 [24.2%] p = 0.002). There was no significant difference in FTR between the CRS and CRS/HIPEC groups (11 [4.0%] vs. 6 [2.3%] p = 0.258), nor in the pooled incidence of major complications (275 [37.9%] vs. 262 [36.1%] p = 0.48). CRS/HIPEC is associated with increased rates of reintubation, UTI, and sepsis while CRS alone was associated with increased transfusion. However, the addition HIPEC to CRS did not increase the risk of pooled major complication or FTR.

Dimethyl fumarate is associated with lower rates of infection and lower infection-related healthcare costs when compared with ocrelizumab

BackgroundInfections in people with multiple sclerosis (PwMS) may have a detrimental effect on disease progression, risk of hospitalization, and healthcare resource utilization (HRU). The infection risk and HRU costs may vary between disease-modifying therapies (DMTs); however, the individual risks and differences associated with DMTs are not well characterized. Some DMTs may increase the risk for infections in PwMS; however, previous studies have reported an intact humoral immune response in dimethyl fumarate (DMF)-treated patients. The objective was to compare infection-related HRU and healthcare costs (HCCs) between PwMS treated with DMF or ocrelizumab (OCR). MethodsEligible patients were identified from the Optum US claims database between April 2017 and September 2020 (DMF n = 1429; OCR n = 3170). Patients were followed from index date to first occurrence of: (1) end of study, (2) end of insurance eligibility, (3) discontinuation of index DMT, or (4) switch from index DMT to another DMT. Outcomes were annualized rate of infection encounters (defined as infection encounters [n] during follow-up window / days followed [n] × 365); annualized infection-related HCCs (defined as aggregated costs of infection encounters during follow-up window / days followed [n] × 365); location-specific infections, and overall infection-related events. Propensity score matching (PSM) 1:1 method was used; PS was calculated via logistic regression for probability of DMF treatment conditional on demographics and comorbidities. Mean differences (MD) were reported for infection encounter measures. ResultsAfter PSM, DMF and OCR cohorts (n = 1094 in each cohort) were balanced based on baseline characteristics (standardized MD of adjusted baseline characteristics <0.1). Mean (standard deviation) follow-up was 296 (244) days for DMF patients and 297 (243) for OCR patients. DMF patients experienced lower annualized rates of overall infection encounters vs OCR patients (MD –0.51 [95% confidence interval (CI): –0.92 to –0.11], p = 0.01). When stratified by type of infection encounter, DMF patients experienced significantly lower annualized rates of outpatient (MD [95% CI]: –0.44 [–0.80 to –0.08], p = 0.02) and inpatient/hospitalization infection encounters (–0.08 [–0.14 to –0.02], p<0.01) vs OCR patients. A trend towards a shorter duration of infection-related hospitalization in the DMF vs the OCR group was observed (MD [95% CI]: –2.20 [–4.73 to 0.26] days, p = 0.08). The most common infection types in both DMT groups were urinary tract infections, sepsis, and pneumonia. DMF patients experienced lower annualized infection-related HCCs (MD [95% CI]: –$3642 [–$6380 to –$904], p < 0.01) vs OCR patients, which were driven largely by infection-related hospitalization costs (–$3639 [–$6019 to –$1259], p < 0.01). ConclusionDMF-treated patients PS-matched with OCR patients experienced lower annualized rates of infection encounters and lower infection-related HCCs.

Efficacy and safety of atezolizumab concurrent with radiotherapy in patients with muscle-invasive bladder cancer: An interim analysis of the ATEZOBLADDERPRESERVE phase II trial (SOGUG-2017-A-IEC(VEJ)-4).

4588 Background: Combined-modality treatments are bladder-preserving alternatives for patients (pts) who are not candidates for radical cystectomy by medical reasons, refusal, or patient´s choice. Immune therapies seem to potentiate tumor-specific immune response induced by radiotherapy (RT). Combination of RT with anti-PD-1/PD-L1 therapy appears safe and there are signs of promising activity. The aim of this study is to assess the efficacy and safety of atezolizumab (ATZ) concurrent with external beam radiotherapy (EBRT) for the treatment of muscle-invasive bladder cancer (MIBC) with bladder preservation intent. Here we present an interim analysis. Methods: This is an open, multicenter, and phase II trial, sponsored by SOGUG, in pts with confirmed diagnosis of MIBC in clinical stages cT2-T4a N0 M0 who are not candidates for radical cystectomy. Treatment consists of 6 doses of ATZ 1200 mg IV every 3 weeks, starting on day 1 of EBRT, and 60 Gy of RT in 30 fractions over 6 weeks at 2 Gy/day. The primary endpoint of the study is pathological complete response (pCR) defined as a response of grade 5 according to Miller and Payne criteria, 1 to 2 months after the last dose of ATZ. A planned interim analysis has been performed (data cut-off date: November 2021) on the primary endpoint to avoid exposure to ineffective treatment according to the minimax two-stages Simon’s design (stopping rule: 9 out of the first 13 evaluable pts should achieve pCR). Incidence of adverse events (AE) and serious AE (SAE) has been also secondarily assessed. Results: From September 2019 to November 2021, 39 pts were screened, of whom 13 were excluded due to non-compliance with eligibility criteria. Thus, the evaluable population consisted of 26 pts. The safety analysis was performed in 22 pts who had received at least one dose of ATZ. 14 pts were assessed pathologically and, thus, included in interim efficacy analysis (median age: 78.6 years; clinical stage: 71.4% T2a, 14.3% T2b, 7.1% T3a, 7.1% T3b). All 14 pts had achieved pCR at the cut-off date. 20/22 (91%) pts experienced at least one AE, with asthenia (11 pts), diarrhea (9 pts), and urinary tract infection (4 pts) being the most common. 9 SAEs were reported in 7 (32%) pts (bacteriemia, COVID-19 infection, depressed LVEF, unknown origin fever, hepatic toxicity, kidney failure, rectorrhagia, respiratory infection, and urinary sepsis). 6 (27%) pts suffered AEs leading to treatment discontinuation. No AEs leading to death occurred. 17 pts with available data on survival were alive at the cut-off date. Conclusions: Interim results suggest that ATZ combined with EBRT is a feasible and effective treatment in terms of pCR, with a manageable safety profile. The final results from this trial will provide information about its effects on clinical outcome, including survival and updated safety findings. Clinical trial information: NCT04186013.

Are beta blockers effective in preventing stroke-associated infections? - a systematic review and meta-analysis.

Background: Excessive sympathoexcitation could lead to stroke associated infection. Inhibiting sympathetic excitation may reduce the infection risk after stroke. Thus, the present study aimed to determine the protective effect of beta blockers on stroke associated infection through systematic review and meta-analysis.Methods: A systematic search of multiple databases were performed up to February 2022. The included studies required beta blockers therapy in stroke patients and assessed the incidence of stroke-associated infections. Outcomes of interest included infections, pneumonia, urinary tract infection and sepsis. Random-effects model was used for analysis. Heterogeneity was evaluated using I2 statistics and publication bias was evaluated by the funnel plot.Result: A total of 83 potentially relevant publications was identified in the initial search. Six studies met the inclusion criteria for meta-analysis. The risk of bias in the included articles satisfies the quality requirement of meta-analysis. No significant associations between beta blockers therapy and the prevention of stroke associated infection, stroke associated pneumonia and septicemia were found, However, subgroup analyses revealed an association between beta blockers treatment and the increased risk of post-stroke urinary tract infection or stroke associated pneumonia in some stroke patients (OR = 1.69 [1.33, 2.14], P < 0.0001; OR = 1.85 [1.51, 2.26], P < 0.0001).Conclusion: Due to the lack of robust evidence, this meta-analysis may not support the preventive effect of beta blockers on stroke associated infection. But beta blockers treatment may be associated with development of post-stroke urinary tract infection and stroke associated pneumonia in some stroke patients.