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The aim of the study was to establish a live/dead qPCR with propidium monoazide (PMA) that can quantitatively differentiate between viable/non-viable microorganisms in dental hard tissues. Human premolars (n = 88) were prepared with nickel-titanium instruments and incubated with E. faecalis (21 d). Subsequently, the bacteria in half of the teeth were devitalized by heat inactivation (100 °C, 2 h). The following parameters were tested: PMA concentrations at 0 µmol (control), 50 µmol, 100 µmol, and 200 µmol; PMA incubation times of 30 min and 60 min, and blue light treatment for 30 min and 60 min. The teeth were ground using a cryomill and the bacterial DNA was quantified using qPCR, ANOVA, and p = 0.05. The qPCR of the control group detected a similar number of avital 9.94 × 106 and vital 1.61 × 107 bacterial cells. The use of PMA inhibited the amplification of DNA from non-viable cells during qPCR. As a result, the best detection of avital bacteria was achieved with the following PMA parameters: (concentration, incubation time, blue light treatment) 200-30-30; 5.53 × 104 (avital) and 1.21 × 100.7 (vital). The live/dead qPCR method using PMA treatment is suitable for the differentiation and quantification of viable/non-viable microorganisms in dentin, as well as to evaluate the effectiveness of different preparation procedures and antimicrobial irrigants in other biological hard substances.
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AIM: To compare the effectiveness of strength versus endurance training on reducing visceral fat in individuals with obesity. MATERIALS AND METHODS: For the STrength versus ENdurance (STEN) 24-month randomized clinical trial, we assigned 239 participants with abdominal obesity to either strength or endurance training (two to three times a week, 60 min/training session) in addition to standard nutritional counselling to promote a healthy diet. Changes in abdominal visceral adipose tissue (VAT) area quantified by magnetic resonance imaging after 12 months were defined as a primary endpoint. RESULTS: Participants (aged 44 years, 74% women, body mass index: 37 kg/m2, mean VAT volume: 4050 cm3) had an approximately 50% retention rate and a 30% good training programme adherence at 12 months. There was no difference between strength and endurance training in VAT volume dynamics after 12 and 24 months (p = .13). Only in the good adherence group did we find a trend for reduced VAT volume in both training regimens. Independently of the exercise programme, there was a continuous trend for moderate loss of abdominal subcutaneous AT volume, body fat mass, body mass index and improved parameters of insulin sensitivity. Although parameters of physical fitness improved upon both exercise interventions, the dynamics of resting energy expenditure, glucose and lipid metabolism parameters were not different between the intervention groups and did not significantly improve during the 2-year trial (p > .05). CONCLUSIONS: Despite heterogeneous individual training responses, strength and endurance training neither affected VAT volume nor key secondary endpoints differently.
Subject(s)
Endurance Training , Intra-Abdominal Fat , Obesity, Abdominal , Resistance Training , Humans , Female , Male , Intra-Abdominal Fat/diagnostic imaging , Adult , Endurance Training/methods , Resistance Training/methods , Middle Aged , Obesity, Abdominal/therapy , Obesity, Abdominal/physiopathology , Body Mass Index , Magnetic Resonance Imaging , Treatment Outcome , Energy Metabolism/physiology , Insulin Resistance/physiology , Weight Loss/physiologyABSTRACT
BACKGROUND: Pulmonary embolism is the third most common cardiovascular disease. Interventional treatment options as an alternative to systemic lysis therapy of hemodynamically stable, submassive pulmonary embolisms have received an unprecedented boost in innovation in recent years. The treatment options are heterogeneous and can be roughly divided into local thrombolysis and local thrombectomy. For years in our center we have been carrying out catheter-assisted, locoregional lysis therapy with side-hole lysis catheters and a cumulative dose per pulmonary branch of 10â¯mg alteplase over 15â¯h for hemodynamically stable, submassive pulmonary emboli. AIM: The aim of this retrospective study was to review this therapeutic concept and to collect data on clinical endpoints and possible complications. METHODS: The study included data from 01/2018-03/2023. For this purpose, the patients were selected based on the OPS codes (8.838.60 and 1276.0), and the data was collected using the medical records. Biometric data, data on previous illnesses and vital parameters, laboratory chemistry data, CT diagnostic data, echocardiographic data, data on drug treatment and data on complications were collected anonymously. RESULTS: There was a significant reduction in the strain on the right heart. Peripheral oxygen saturation also improved significantly and heart rate decreased significantly. The complication rate remained low and was almost exclusively limited to access-related problems. CONCLUSION: Catheter-assisted, locoregional lysis therapy is a safe and effective treatment method for submassive pulmonary embolism.
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PURPOSE: In patients with peritoneal metastasis (PM) from gastric cancer (GC), chemotherapy is the treatment of choice. Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) are still being debated. This randomized, controlled, open-label, multicenter phase III trial (EudraCT 2006-006088-22; ClinicalTrials.gov identifier: NCT02158988) explored the impact on overall survival (OS) of HIPEC after CRS. PATIENTS AND METHODS: Adult patients with GC and histologically proven PM were randomly assigned (1:1) to perioperative chemotherapy and CRS alone (CRS-A) or CRS plus HIPEC (CRS + H). HIPEC comprised mitomycin C 15 mg/m2 and cisplatin 75 mg/m2 in 5 L of saline perfused for 60 minutes at 42°C. The primary end point was OS; secondary endpoints included progression-free survival (PFS), other distant metastasis-free survival (MFS), and safety. Analyses followed the intention-to-treat principle. RESULTS: Between March 2014 and June 2018, 105 patients were randomly assigned (53 patients to CRS-A and 52 patients to CRS + H). The trial stopped prematurely because of slow recruitment. In 55 patients, treatment stopped before CRS mainly due to disease progression/death. Median OS was the same for both groups (CRS + H, 14.9 [97.2% CI, 8.7 to 17.7] months v CRS-A, 14.9 [97.2% CI, 7.0 to 19.4] months; P = .1647). The PFS was 3.5 months (95% CI, 3.0 to 7.0) in the CRS-A group and 7.1 months (95% CI, 3.7 to 10.5; P = .047) in the CRS + H group. The CRS + H group showed better MFS (10.2 months [95% CI, 7.7 to 14.7] v CRS-A, 9.2 months [95% CI, 6.8 to 11.5]; P = .0286). The incidence of grade ≥3 adverse events (AEs) was similar between groups (CRS-A, 38.1% v CRS + H, 43.6%; P = .79). CONCLUSION: This study showed no OS difference between CRS + H and CRS-A. PFS and MFS were significantly better in the CRS + H group, which needs further exploration. HIPEC did not increase AEs.
Subject(s)
Hyperthermia, Induced , Peritoneal Neoplasms , Stomach Neoplasms , Adult , Humans , Stomach Neoplasms/drug therapy , Stomach Neoplasms/surgery , Peritoneal Neoplasms/drug therapy , Peritoneal Neoplasms/secondary , Hyperthermic Intraperitoneal Chemotherapy , Combined Modality Therapy , Cytoreduction Surgical Procedures/adverse effects , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Survival Rate , Retrospective StudiesABSTRACT
Background: Optimal initial tacrolimus dosing and early exposure of tacrolimus after renal transplantation is not well studied. Methods: In this open-label, 6 months, multicenter, randomized controlled, non-inferiority study, we randomly assigned 432 renal allograft recipients to receive basiliximab induction, mycophenolate and steroids and either standard prolonged-release tacrolimus (trough levels: 7-9 ng/ml; Standard Care arm), or an initial 7-day fixed 5 mg/day dose of prolonged-release tacrolimus followed by lower tacrolimus predose levels (trough levels: 5-7 ng/ml; Slow & Low arm). The primary end point was the combined incidence rate of biopsy-proven acute rejections (BPAR; including borderline), graft failure, or death at 6 months with a non-inferiority margin of 12.5%. (EudraCT-Nr: 2013-001770-19. Findings: The combined primary endpoint in the Slow & Low arm was non-inferior compared to the Standard Care arm (22.1% versus 20.7%; difference: 1.4%, 90% CI -5.5% to 8.3%). The overall rate of BPAR including borderlines was similar (Slow & Low 17.4% versus Standard Care 16.6%). Safety parameters such as delayed graft function, kidney function, donor specific HLA-antibodies, infections, or post-transplantation diabetes mellitus did not differ. Interpretation: This is the first study to show that an initial fixed dose of 5 mg per day followed by lower tacrolimus exposure is non-inferior compared to standard tacrolimus therapy and equally efficient and safe within 6 months after renal transplantation. These data suggest that therapeutic drug monitoring for prolonged release tacrolimus can be abandoned until start of the second week after transplantation. Funding: Investigator-initiated trial, financial support by Astellas Pharma GmbH.
ABSTRACT
OBJECTIVES: This pilot study aimed to carry out preliminary tests of the removability of an artificial biofilm equivalent (ABE) and to verify the reproducibility of the ABE testing protocol for a planned main study. BACKGROUND: There is a lack of data to develop suitable artificial biofilm substitutes, which may be helpful to perform denture hygiene education and to carry out in vitro examinations of oral hygiene products. MATERIALS AND METHODS: This single-group, prospective, longitudinal, interventional pilot study was conducted in Dresden (Germany) from February until December 2020. Participants were recruited who wore fully functional upper complete dentures. Denture biofilm was grown on acrylic specimens by wearing dentures for 12 h and 36 h using intraoral appliances. Acrylic specimens were coated with ABEs of three compositions: chitosan (ChS) 0.3 g, methylcellulose (MC) 1.7 g; ChS 0.2 g, MC 1.8 g; ChS 0.1 g, MC 1.9 g (labelled 1.7MC, 1.8MC and 1.9MC, respectively). All specimens underwent standardised mechanical brushing. The percentages of remaining biofilm (POB) were measured. RESULTS: Thirty-one participants were prescreened, and eight (26%) were included. The appliances were well tolerated, and biofilm was collected. ABE was prepared and brushed as planned. Three and six brushing strokes were needed to remove 12-h and 36-h natural denture biofilm, respectively. Correspondingly, three brushing strokes were needed to remove 1.9MC ABE and six brushing strokes to remove 1.8MC and 1.7MC ABE. A reproducibility of ABE removal was indicated. CONCLUSION: The removability of ABE and the ABE testing protocol were feasible and reproducible for conducting the future main study.
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BACKGROUND: We previously reported excellent efficacy and improved safety aspects of rapid steroid withdrawal (RSWD) in the randomized controlled 1-year "Harmony" trial with 587 predominantly deceased-donor kidney transplant recipients randomized either to basiliximab or rabbit antithymocyte globulin induction therapy and compared with standard immunosuppressive therapy consisting of basiliximab, low tacrolimus once daily, mycophenolate mofetil and corticosteroids. METHODS: The 5-year post-trial follow-up (FU) data were obtained in an observational manner at a 3- and a 5-year visit only for those Harmony patients who consented to participate and covered clinical events that occurred from the second year onwards. RESULTS: Biopsy-proven acute rejection and death-censored graft loss rates remained low and independent of RSWD. Rapid steroid withdrawal was an independent positive factor for patient survival (adjusted hazard ratio 0.554, 95% confidence interval 0.314-0.976; P = .041).The reduced incidence of post-transplantation diabetes mellitus in RSWD patients during the original 1-year study period was not compensated by later incidences during FU. Incidences of other important outcome parameters such as opportunistic infections, malignancies, cardiovascular morbidity/risk factors, donor-specific antibody formation or kidney function did not differ during FU period. CONCLUSIONS: With all the limitations of a post-trial FU study, the Harmony FU data confirm excellent efficacy and beneficial safety aspects of RSWD under modern immunosuppressive therapy over the course of 5 years after kidney transplantation in an immunologically low-risk, elderly population of Caucasian kidney transplant recipients. Trial registration: Clinical trial registration number: Investigator Initiated Trial (NCT00724022, FU study DRKS00005786).
Subject(s)
Kidney Transplantation , Aged , Humans , Antibodies, Monoclonal , Basiliximab , Follow-Up Studies , Graft Rejection/drug therapy , Graft Rejection/etiology , Graft Rejection/prevention & control , Graft Survival , Immunosuppressive Agents/adverse effects , Kidney Transplantation/adverse effects , Mycophenolic Acid/therapeutic use , Steroids , Tacrolimus/adverse effectsABSTRACT
Background: Appendicitis is a frequent condition, with peak incidences in the second decade of life. Its pathogenesis is under debate, but bacterial infections are crucial, and antibiotic treatment remains essential. Rare bacteria are accused of causing complications, and various calculated antibiotics are propagated, yet there is no comprehensive microbiological analysis of pediatric appendicitis. Here we review different pre-analytic pathways, identify rare and common bacterial pathogens and their antibiotic resistances, correlate clinical courses, and evaluate standard calculated antibiotics in a large pediatric cohort. Method: We reviewed 579 patient records and microbiological results of intraoperative swabs in standard Amies agar media or fluid samples after appendectomies for appendicitis between May 2011 and April 2019. Bacteria were cultured and identified via VITEK 2 or MALDI-TOF MS. Minimal inhibitory concentrations were reevaluated according to EUCAST 2022. Results were correlated to clinical courses. Results: Of 579 analyzed patients, in 372 patients we got 1330 bacterial growths with resistograms. 1259 times, bacteria could be identified to species level. 102 different bacteria could be cultivated. 49% of catarrhal and 52% of phlegmonous appendices resulted in bacterial growth. In gangrenous appendicitis, only 38% remained sterile, while this number reduced to 4% after perforation. Many fluid samples remained sterile even when unsterile swabs had been taken simultaneously. 40 common enteral genera were responsible for 76.5% of bacterial identifications in 96.8% of patients. However, 69 rare bacteria were found in 187 patients without specifically elevated risk for complications. Conclusion: Amies agar gel swabs performed superior to fluid samples and should be a standard in appendectomies. Even catarrhal appendices were only sterile in 51%, which is interesting in view of a possible viral cause. According to our resistograms, the best in vitro antibiotic was imipenem with 88.4% susceptible strains, followed by piperacillin-tazobactam, cefuroxime with metronidazole, and ampicillin-sulbactam to which only 21.6% of bacteria were susceptible. Bacterial growths and higher resistances correlate to an elevated risk of complications. Rare bacteria are found in many patients, but there is no specific consequence regarding antibiotic susceptibility, clinical course, or complications. Prospective, comprehensive studies are needed to further elicit pediatric appendicitis microbiology and antibiotic treatment.
Subject(s)
Appendicitis , Humans , Child , Appendicitis/complications , Appendicitis/epidemiology , Appendicitis/surgery , Retrospective Studies , Prospective Studies , Agar/therapeutic use , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic use , BacteriaABSTRACT
BACKGROUND: Human fingertips can regenerate functionally and cosmetically excellent skin and soft tissues. Physiological conditions suppress scar formation and are thus a prerequisite for regenerative healing. Self-adhesive film dressings can provide such favorable conditions. The semi-occlusive treatment is superior to surgery. However, standard dressings leak malodorous wound fluid eventually until the wound is dry. Therefore, we developed and tested a silicone finger cap that forms a mechanically protected, wet chamber around the injury. Its puncturable reservoir allows access to the wound fluid for diagnostic and research purposes and the delivery of pro-regenerative drugs in the future. METHODS: Patients >2 years with full-thickness fingertip injuries unsuitable for simple primary closure were randomized to start treatment with either the film dressing or the silicone finger cap. After 2 weeks, we changed to the other treatment. Patients' choice on the preferred treatment after 4 weeks was the primary outcome parameter. Additionally, we monitored adverse events, unplanned visits, tissue gain, functionality, cosmetic outcome, and quality of life. RESULTS: We randomized 11 patients 2 to 72 years to each group. Eighteen to 20 (90%, intention-to-treat) patients preferred the finger cap. All patients were satisfied with the cosmetic outcome, 88.9% had no disturbing sensibility changes, and 73.7% could report no distortion in the finger's daily use. Epithelialization took between 5 weeks for Allen II and up to 9 weeks in Allen IV injuries. There were 19 device-related adverse events under film dressing and 13 under the finger cap. There were neither severe adverse device effects nor unexpected severe adverse device effects. CONCLUSION: Employing the summative or synthetic primary endpoint "patient decision for one or the other procedure," our pseudocross-over-designed RCT succeeded in statistically significantly demonstrating the superiority of the silicone finger cap over conventional film therapy. The finger cap was safe and effective, reaching excellent results on all treated injuries without any need for disinfection, antibiotics, shortening of protruding bones, or treatment of hypergranulations. Distal to the tendon insertions, we did not see any limitations regarding injury mechanism, amputation plane, or patients' age.
Subject(s)
Amputation, Traumatic , Finger Injuries , Adult , Amputation, Traumatic/therapy , Child , Finger Injuries/therapy , Humans , Occlusive Dressings , Quality of Life , Silicones/therapeutic useABSTRACT
The removal of bacterial infections within the root canal system is still a challenge. Therefore, the cleansing effect of established and new irrigation-protocols (IP) containing silver diamine fluoride (SDF) 3.8% on the whole root canal system was analyzed using quantitative PCR (qPCR) and 4',6-diamidino-phenylindole-(DAPI)-staining. Extracted human premolars were instrumented up to F2 (ProTaper Gold) under NaCl 0.9% irrigation and incubated with Enterococcus faecalis for 42 days. Subsequently, different ultrasonically agitated IP were applied to the roots: control (no irrigation), 1. NaOCl 3%, EDTA 20%, CHX 2%, 2. NaOCl 3%, EDTA 20%, 3. NaOCl 3%, EDTA 20%, SDF 3.8%, 4. SDF 3.8%, and 5. NaCl 0.9%. One half of the root was investigated fluorescent-microscopically with DAPI. The other half was grinded in a cryogenic mill and the bacterial DNA was quantified with qPCR. The qPCR results showed a statistically significant reduction of bacteria after the application of IP 1, 2, and 3 compared to the control group. While IP 4 lead to a bacterial reduction which was not significant, IP 5 showed no reduction. These data corresponded with DAPI staining. With qPCR a new molecular-biological method for the investigation of the complete root canal system was implemented. The novel IP 3 had an equally good cleansing effect as the already established IP.
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Importance: Adjunctive hydrocortisone therapy is suggested by the Surviving Sepsis Campaign in refractory septic shock only. The efficacy of hydrocortisone in patients with severe sepsis without shock remains controversial. Objective: To determine whether hydrocortisone therapy in patients with severe sepsis prevents the development of septic shock. Design, Setting, and Participants: Double-blind, randomized clinical trial conducted from January 13, 2009, to August 27, 2013, with a follow-up of 180 days until February 23, 2014. The trial was performed in 34 intermediate or intensive care units of university and community hospitals in Germany, and it included 380 adult patients with severe sepsis who were not in septic shock. Interventions: Patients were randomly allocated 1:1 either to receive a continuous infusion of 200 mg of hydrocortisone for 5 days followed by dose tapering until day 11 (n = 190) or to receive placebo (n = 190). Main Outcomes and Measures: The primary outcome was development of septic shock within 14 days. Secondary outcomes were time until septic shock, mortality in the intensive care unit or hospital, survival up to 180 days, and assessment of secondary infections, weaning failure, muscle weakness, and hyperglycemia (blood glucose level >150 mg/dL [to convert to millimoles per liter, multiply by 0.0555]). Results: The intention-to-treat population consisted of 353 patients (64.9% male; mean [SD] age, 65.0 [14.4] years). Septic shock occurred in 36 of 170 patients (21.2%) in the hydrocortisone group and 39 of 170 patients (22.9%) in the placebo group (difference, -1.8%; 95% CI, -10.7% to 7.2%; P = .70). No significant differences were observed between the hydrocortisone and placebo groups for time until septic shock; mortality in the intensive care unit or in the hospital; or mortality at 28 days (15 of 171 patients [8.8%] vs 14 of 170 patients [8.2%], respectively; difference, 0.5%; 95% CI, -5.6% to 6.7%; P = .86), 90 days (34 of 171 patients [19.9%] vs 28 of 168 patients [16.7%]; difference, 3.2%; 95% CI, -5.1% to 11.4%; P = .44), and 180 days (45 of 168 patients [26.8%] vs 37 of 167 patients [22.2%], respectively; difference, 4.6%; 95% CI, -4.6% to 13.7%; P = .32). In the hydrocortisone vs placebo groups, 21.5% vs 16.9% had secondary infections, 8.6% vs 8.5% had weaning failure, 30.7% vs 23.8% had muscle weakness, and 90.9% vs 81.5% had hyperglycemia. Conclusions and Relevance: Among adults with severe sepsis not in septic shock, use of hydrocortisone compared with placebo did not reduce the risk of septic shock within 14 days. These findings do not support the use of hydrocortisone in these patients. Trial Registration: clinicaltrials.gov Identifier: NCT00670254.
Subject(s)
Anti-Inflammatory Agents/administration & dosage , Hydrocortisone/administration & dosage , Sepsis/complications , Shock, Septic/prevention & control , Adult , Aged , Anti-Inflammatory Agents/adverse effects , Delirium/diagnosis , Disease Progression , Double-Blind Method , Drug Administration Schedule , Female , Hospital Mortality , Humans , Hydrocortisone/adverse effects , Intensive Care Units , Intention to Treat Analysis/statistics & numerical data , Male , Middle Aged , Sepsis/mortality , Shock, Septic/mortality , Time FactorsABSTRACT
Sepsis is the dysregulated host response to an infection which leads to life-threatening organ dysfunction that varies by host genomic factors. We conducted a genome-wide association study (GWAS) in 740 adult septic patients and focused on 28day mortality as outcome. Variants with suggestive evidence for an association (p≤10-5) were validated in two additional GWA studies (n=3470) and gene coding regions related to the variants were assessed in an independent exome sequencing study (n=74). In the discovery GWAS, we identified 243 autosomal variants which clustered in 14 loci (p≤10-5). The best association signal (rs117983287; p=8.16×10-8) was observed for a missense variant located at chromosome 9q21.2 in the VPS13A gene. VPS13A was further supported by additional GWAS (p=0.03) and sequencing data (p=0.04). Furthermore, CRISPLD2 (p=5.99×10-6) and a region on chromosome 13q21.33 (p=3.34×10-7) were supported by both our data and external biological evidence. We found 14 loci with suggestive evidence for an association with 28day mortality and found supportive, converging evidence for three of them in independent data sets. Elucidating the underlying biological mechanisms of VPS13A, CRISPLD2, and the chromosome 13 locus should be a focus of future research activities.
Subject(s)
Genetic Predisposition to Disease , Genetic Variation , Sepsis/genetics , Sepsis/mortality , Chromosome Mapping , Cohort Studies , Disease Progression , Exome , Female , Genome-Wide Association Study , Genomics , High-Throughput Nucleotide Sequencing , Humans , Male , Mortality , Polymorphism, Single Nucleotide , Prognosis , Quantitative Trait Loci , Reproducibility of Results , Sepsis/diagnosis , Sepsis/microbiology , Time FactorsABSTRACT
IMPORTANCE: High-dose intravenous administration of sodium selenite has been proposed to improve outcome in sepsis by attenuating oxidative stress. Procalcitonin-guided antimicrobial therapy may hasten the diagnosis of sepsis, but effect on outcome is unclear. OBJECTIVE: To determine whether high-dose intravenous sodium selenite treatment and procalcitonin-guided anti-infectious therapy in patients with severe sepsis affect mortality. DESIGN, SETTING, AND PARTICIPANTS: The Placebo-Controlled Trial of Sodium Selenite and Procalcitonin Guided Antimicrobial Therapy in Severe Sepsis (SISPCT), a multicenter, randomized, clinical, 2 × 2 factorial trial performed in 33 intensive care units in Germany, was conducted from November 6, 2009, to June 6, 2013, including a 90-day follow-up period. INTERVENTIONS: Patients were randomly assigned to receive an initial intravenous loading dose of sodium selenite, 1000 µg, followed by a continuous intravenous infusion of sodium selenite, 1000 µg, daily until discharge from the intensive care unit, but not longer than 21 days, or placebo. Patients also were randomized to receive anti-infectious therapy guided by a procalcitonin algorithm or without procalcitonin guidance. MAIN OUTCOMES AND MEASURES: The primary end point was 28-day mortality. Secondary outcomes included 90-day all-cause mortality, intervention-free days, antimicrobial costs, antimicrobial-free days, and secondary infections. RESULTS: Of 8174 eligible patients, 1089 patients (13.3%) with severe sepsis or septic shock were included in an intention-to-treat analysis comparing sodium selenite (543 patients [49.9%]) with placebo (546 [50.1%]) and procalcitonin guidance (552 [50.7%]) vs no procalcitonin guidance (537 [49.3%]). The 28-day mortality rate was 28.3% (95% CI, 24.5%-32.3%) in the sodium selenite group and 25.5% (95% CI, 21.8%-29.4%) (P = .30) in the placebo group. There was no significant difference in 28-day mortality between patients assigned to procalcitonin guidance (25.6% [95% CI, 22.0%-29.5%]) vs no procalcitonin guidance (28.2% [95% CI, 24.4%-32.2%]) (P = .34). Procalcitonin guidance did not affect frequency of diagnostic or therapeutic procedures but did result in a 4.5% reduction of antimicrobial exposure. CONCLUSIONS AND RELEVANCE: Neither high-dose intravenous administration of sodium selenite nor anti-infectious therapy guided by a procalcitonin algorithm was associated with an improved outcome in patients with severe sepsis. These findings do not support administration of high-dose sodium selenite in these patients; the application of a procalcitonin-guided algorithm needs further evaluation. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00832039.