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Rationale: Ventilator-associated pneumonia (VAP) causes substantial morbidity and mortality. The influence of subglottic secretion drainage (SSD) in preventing VAP remains controversial. Objectives: To determine whether SSD reduces the overall incidence of microbiologically confirmed VAP. Methods: Randomized controlled clinical trial conducted at four French centers. A total of 333 adult patients intubated with a tracheal tube allowing drainage of subglottic secretions and expected to require mechanical ventilation for >=48 hours was included. Patients were randomly assigned to undergo intermittent SSD (n = 169) or not (n = 164). Measurements and Main Results: Primary outcome was the overall incidence of VAP based on quantitative culture of distal pulmonary samplings performed after each clinical suspicion. Other outcomes included incidence of early- and late-onset VAP, duration of mechanical ventilation, and hospital mortality. Microbiologically confirmed VAP occurred in 67 patients, 25 of 169 (14.8%) in the SSD group and 42 of 164 (25.6%) in the control group (P = 0.02), yielding a relative risk reduction of 42.2% (95% confidential interval, 10.4-63.1%). Using the Day 5 threshold, the beneficial effect of SSD in reducing VAP was observed in both early-onset VAP (2 of 169 [1.2%] patients undergoing SSD vs. 10 of 164 [6.1%] control patients; P = 0.02) and late-onset VAP (23 of 126 [18.6%] patients undergoing SSD vs. 32 of 97 [33.0%] control patients; P = 0.01). VAP was clinically suspected at least once in 51 of 169 (30.2%) patients undergoing SSD and 60 of 164 (36.6%) control patients (P = 0.25). No significant between-group differences were observed in duration of mechanical ventilation and hospital mortality. Conclusions: Subglottic secretion drainage during mechanical ventilation results in a significant reduction in VAP, including late-onset VAP. Clinical trial registered with www.clinicaltrials.gov (NCT00219661). [ABSTRACT FROM AUTHOR]

Rationale: Intensive care unit (ICU) admission of a relative is a stressful event that may cause symptoms of post-traumatic stress disorder (PTSD). Objectives: Factors associated with these symptoms need to be identified. Methods: For patients admitted to 21 ICUs between March and November 2003, we studied the family member with the main potential decision-making role. Measurements: Ninety days after ICU discharge or death, family members completed the Impact of Event Scale (which evaluates the severity of post-traumatic stress reactions), Hospital Anxiety and Depression Scale, and 36-item Short-Form General Health Survey during a telephone interview. Linear regression was used to identify factors associated with the risk of post-traumatic stress symptoms. Main results: Interviews were obtained for family members of 284 (62%) of the 459 eligible patients. Post-traumatic stress symptoms consistent with a moderate to major risk of PTSD were found in 94 (33.1%) family members. Higher rates were noted among family members who felt information was incomplete in the ICU (48.4%), who shared in decision making (47.8%), whose relative died in the ICU (50%), whose relative died after end-of-life decisions (60%), and who shared in end-of-life decisions (81.8%). Severe post-traumatic stress reaction was associated with increased rates of anxiety and depression and decreased quality of life. Conclusion: Post-traumatic stress reaction consistent with a high risk of PTSD is common in family members of ICU patients and is the rule among those who share in end-of-life decisions. Research is needed to investigate PTSD rates and to devise preventive and early-detection strategies. [ABSTRACT FROM AUTHOR]

Objective: To assess the prognosis of patients with acute ischemic stroke who require mechanical ventilation and to determine early factors influencing mortality.Design: Prospective observational study.Setting: Medical intensive care unit with a cerebrovascular emergency unit in a university-affiliated hospital.Patients: Fifty-eight consecutive patients (mean age 65+/-13 years) requiring mechanical ventilation in the early course of an acute ischemic stroke.Measurements and Results: Clinical data were recorded before intubation according to a standardized procedure. Mortality and functional outcome were assessed after a 1-year follow-up. Mechanical ventilation was started within 48 h after admission in 53 patients (91.4%). The mean duration of ventilation was similar in survivors (9.7+/-9.0 days) and non-survivors (8.6+/-8.7 days). Mortality was 72.4% at 1 year. Among the 16 survivors, none were in a persistent vegetative state and 11 had a Barthel index of 60, reflecting good functional status. Bilateral absence of corneal reflex and bilateral absence of pupillary light reflex had a positive predictive value of death of 1 (95% CI 0.78-1.00 and 0.74-1.00, respectively). After Cox regression analysis, presence of stupor or coma (OR 2.6, 95% CI 1.5-5.0), bilateral absence of corneal reflex before intubation (OR 3.4, 95% CI 1.4-8.7) and presence of ischemic cardiopathy (OR 2.8, 95% CI 1.4-5.5) were independent predictors of mortality.Conclusions: Systematic withholding of endotracheal intubation in patients with AIS is not recommended. Careful and rigorous neurologic examination, including assessment of brain stem reflexes, might help to identify patients with a very high probability of death despite mechanical ventilation. [ABSTRACT FROM AUTHOR]

Chagas disease (CD), caused by Trypanosoma cruzi, is underdiagnosed in the United States. Improved screening strategies are needed, particularly for people at risk for life-threatening sequelae of CD, including people with human immunodeficiency virus (HIV, PWH). Here we report results of a CD screening strategy applied at a large HIV clinic serving an at-risk population., Competing Interests: Potential conflicts of interest. C. B. reports royalties or licenses from Wolters Kluwer. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Chagas disease (CD) is a parasitic disease that affects ∼300 000 people living in the United States. CD leads to cardiac and/or gastrointestinal disease in up to 30% of untreated people. However, end-organ damage can be prevented with early diagnosis and antiparasitic therapy., Methods: We reviewed electronic health records of patients who underwent testing for CD at four hospital systems in California and Texas between 2016 and 2020. Descriptive analyses were performed as a needs assessment for improving CD diagnosis., Results: In total, 470 patients were tested for CD. Cardiac indications made up more than half (60%) of all testing, and the most frequently cited cardiac condition was heart failure. Fewer than 1% of tests were ordered by obstetric and gynecologic services. Fewer than half (47%) of patients had confirmatory testing performed at the Centers for Disease Control and Prevention., Discussion: Four major hospitals systems in California and Texas demonstrated low overall rates of CD diagnostic testing, testing primarily among older patients with end-organ damage, and incomplete confirmatory testing. This suggests missed opportunities to diagnose CD in at-risk individuals early in the course of infection when antiparasitic treatment can reduce the risk of disease progression and prevent vertical transmission., Competing Interests: Potential conflicts of interest. C. B. receives royalties from Wolters Kluwer publishers for UpToDate topics on epidemiology and management of Chagas disease. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Vascular leakage is a major feature of acute respiratory distress syndrome (ARDS). We aimed to evaluate the efficacy of FX06, a drug under development that stabilizes interendothelial cell junctions, at reducing vascular leakage during SARS-CoV-2-induced ARDS., Methods: This multicenter, double-blinded, randomized trial included adults with COVID-19-associated ARDS who had received invasive mechanical ventilation for < 5 days and were randomized to receive either intravenous FX06 (400 mg/d, for 5 days) or its vehicle as placebo. The primary endpoint was the lowering-from day 1 to day 7-of the transpulmonary thermodilution-derived extravascular lung-water index (EVLWi)., Results: Twenty-five patients were randomized to receive FX06 and 24 the placebo. Although EVLWi was elevated at baseline (median [IQR] 15.6 mL/kg [13.5; 18.5]), its declines from day 1 to day 7 were comparable for FX06 recipients and controls (respectively, - 1.9 [- 3.3; - 0.5] vs. - 0.8 [- 5.5; - 1.1] mL/kg; estimated effect - 0.8 [- 3.1; + 2.4], p = 0.51). Cardiac indexes, pulmonary vascular permeability indexes, and fluid balances were also comparable, as were PaO 2 /FiO 2 ratios and durations of mechanical ventilation. Adverse event rates were similar for the 2 groups, although more FX06 recipients developed ventilator-associated pneumonia (16/25 (64%) vs. 6/24 (24%), p = 0.009)., Conclusions: In this unique-dosing-regimen study, FX06 did not lower SARS-CoV-2-induced pulmonary vascular leakage. Future investigations will need to evaluate its efficacy at earlier times during the disease or using other regimens. Trial registration NCT04618042. Registered 5 November 2020., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Multiplex stool polymerase chain reaction (PCR) panels offer rapid comprehensive testing for patients with infectious diarrhea. We compared antibiotic utilization among hospitalized patients with suspected infectious diarrhea who underwent diagnostic testing with either a stool culture or stool PCR panel. No significant differences in antibiotic utilization were identified., Competing Interests: All authors report no conflicts of interest relevant to this article., (© The Author(s) 2023.)

Introduction: Acute kidney injury (AKI) is frequently observed in patients with COVID-19 admitted to intensive care units (ICUs). Observational studies suggest that cardiovascular comorbidities and mechanical ventilation (MV) are the most important risk factors for AKI. However, no studies have investigated the renal impact of longitudinal covariates such as drug treatments, biological variations, and/or MV parameters., Methods: We performed a monocentric, prospective, longitudinal analysis to identify the dynamic risk factors for AKI in ICU patients with severe COVID-19., Results: Seventy-seven patients were included in our study (median age: 63 [interquartile range, IQR: 53-73] years; 58 (75%) men). Acute kidney injury was detected in 28 (36.3%) patients and occurred at a median time of 3 [IQR: 2-6] days after ICU admission. Multivariate Cox cause-specific time-dependent analysis identified a history of hypertension (cause-specific hazard (CSH) = 2.46 [95% confidence interval, CI: 1.04-5.84]; P = .04), a high hemodynamic Sequential Organ Failure Assessment score (CSH = 1.63 [95% CI: 1.23-2.16]; P < .001), and elevated Paco 2 (CSH = 1.2 [95%CI: 1.04-1.39] per 5 mm Hg increase in Pco 2 ; P = .02) as independent risk factors for AKI. Concerning the MV parameters, positive end-expiratory pressure (CSH = 1.11 [95% CI: 1.01-1.23] per 1 cm H 2 O increase; P = .04) and the use of neuromuscular blockade (CSH = 2.96 [95% CI: 1.22-7.18]; P = .02) were associated with renal outcome only in univariate analysis but not after adjustment., Conclusion: Acute kidney injury is frequent in patients with severe COVID-19 and is associated with a history of hypertension, the presence of hemodynamic failure, and increased Pco 2 . Further studies are necessary to evaluate the impact of hypercapnia on increasing the effects of ischemia, particularly in the most at-risk vascular situations., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2023.)

Tropical diseases cause significant morbidity among the world's poorest populations. Although more common in low- and middle-income countries, tropical diseases are also found among underserved populations living in high-income countries such as the United States. The National School of Tropical Medicine at Baylor College of Medicine and the Harris Health System founded a tropical medicine clinic-the Harris Health Tropical Medicine Clinic (HHTMC)-in Houston in 2011 in response to tropical disease-related morbidity in Texas. We conducted a retrospective chart review of a sample of patients older than 18 years of age who were referred to the HHTMC between October 2011 and January 2020. Of the 523 patients reviewed, 185 (35.4%) had mycobacterial infections, 184 (35.2%) had parasitic infections, 38 (7.3%) had fungal infections, 16 (3.1%) had eosinophilia without a confirmed clinical diagnosis, 28 (5.4%) had bacterial infections, and 13 (2.5%) had viral infections. The most common infections overall were extrapulmonary and latent tuberculosis (n = 169), neurocysticercosis (n = 78), strongyloidiasis (n = 28), Chagas disease (n = 25), and schistosomiasis (n = 12). The epidemiology of tropical diseases in the United States is understudied at national and regional levels. This 10-year retrospective study contributes to bridging this knowledge gap by detailing the frequencies of tropical disease diagnoses made at the HHTMC in Houston, TX. These data highlight areas for advancement in the field of tropical medicine within the United States, such as improving front-line health-care provider education; establishing tropical medicine clinics in areas of high prevalence such as the Gulf Coast, Appalachia, and urban areas; and developing comprehensive, systematic national tropical disease screening programs and patient registries.

Trichuriasis known as whipworm infection caused by Trichuris trichiura, is a highly prevalent soil-transmitted helminthiasis in low- and middle-income countries located in tropical and subtropical areas and affecting approximately 360 million people. Children typically harbour the largest burden of T. trichiura and they are usually co-infected with other soil-transmitted helminth (STH), including Ascaris lumbricoides and hookworm. The consequences of trichuriasis, such as malnutrition and physical and cognitive growth restriction, lead to a massive health burden in endemic regions. Despite the implementation of mass drug administration of anthelminthic treatment to school-age children, T. trichiura infection remains challenging to control due to the low efficacy of current drugs as well as high rates of post-treatment re-infection. Thus, the development of a vaccine that would induce protective immunity and reduce infection rate or community faecal egg output is essential. Hurdles for human whipworm vaccine development include the lack of suitable vaccine antigen targets and animal models for human T. trichiura infection. Instead, rodent whipworm T. muris infected mouse models serve as a major surrogate for testing immunogenicity and efficacy of vaccine candidates. In this review, we summarize recent advances in animal models for T. trichiura antigen discovery and testing of vaccine candidates, while providing an overall view of the current status of T. trichiura vaccine development.

Competing Interests: Declaration of Competing Interest None

For the past several decades, there is growing demand for the development of low-power gas sensing technology for the selective detection of volatile organic compounds (VOCs), important for monitoring safety, pollution, and healthcare. Here we report the selective detection of homologous alcohols and different functional groups containing VOCs using the electrostatically formed nanowire (EFN) sensor without any surface modification of the device. Selectivity toward specific VOC is achieved by training machine-learning based classifiers using the calculated changes in the threshold voltage and the drain-source on current, obtained from systematically controlled biasing of the surrounding gates (junction and back gates) of the field-effect transistors (FET). This work paves the way for a Si complementary metal-oxide-semiconductor (CMOS)-based FET device as an electrostatically selective sensor suitable for mass production and low-power sensing technology.

Objectives: Providing appropriate training of procedural skills to residents while ensuring patient safety through trainee supervision is a difficult and constant challenge. We sought to determine how effective and safe procedural skill acquisition is in French ICUs and to identify failure and complication risk factors., Design: Multicenter prospective observational study. Invasive procedures performed by residents were recorded during two consecutive semesters., Setting: Eighty-four residents., Subjects: Eighty-four residents., Intervention: None., Measurements and Main Results: Number of invasive procedures performed, failure and complication rates, supervision, and assistance provided. Five thousand six hundred seventeen procedures were prospectively studied: 1,007 tracheal intubations, 1,272 arterial and 2,586 central venous catheter insertions, 457 fiberoptic bronchoscopies, and 295 chest tube insertions. During the semesters, residents performed a median of 10 intubations, 14 arterial catheter insertions, and 26 central venous catheter insertions. Complication rates were low, similar to those in the literature: 8.6% desaturation and 7.4% esophageal placement during intubation; 0.4% and 2.3% pneumothorax with jugular and subclavian central venous catheter insertions, respectively. We identified risk factors for failure and complications. Higher rates of failure and complications for intubation were associated with residents with no or little previous experience (p < 0.001); failure of internal jugular vein catheterization was associated with left-side insertion (p = 0.005) and absence of mechanical ventilation (p = 0.007). Supervision and assistance were more frequent at the beginning of the semester and for intubation and chest tube insertion. Finally, residents had less access to fiberoptic bronchoscopy and chest tube insertion., Conclusion: Procedural skills acquisition by residents in the ICU appears feasible and safe with complication rates comparable to what has previously been reported. We identified specific procedures and situations associated with higher failure and complication rates that could require proactive training. Questions still remain regarding minimal numbers of procedures to attain competence and how best to provide procedural training.

Objective: To compare the 28-day mortality and hospital length of stay of patients with community-acquired pneumonia who were transferred to an intensive care unit on the same day of emergency department presentation (direct-transfer patients) with those subsequently transferred within 3 days of presentation (delayed-transfer patients)., Design: Secondary analysis of the original data from two North American and two European prospective, multicenter, cohort studies of adult patients with community-acquired pneumonia., Patients: In all, 453 non-institutionalized patients transferred within 3 days of emergency department presentation to an intensive care unit were included in the analysis. Supplementary analysis was restricted to patients without an obvious indication for immediate transfer to an intensive care unit., Interventions: None., Measurements and Main Results: The sample consisted of 138 delayed-transfer and 315 direct-transfer patients, among whom 150 (33.1%) were considered to have an obvious indication for immediate intensive care unit admission. After adjusting for the quintile of propensity score, delayed intensive care unit transfer was associated with an increased odds ratio for 28-day mortality (2.07; 95% confidence interval, 1.12-3.85) and a decreased odds ratio for discharge from hospital for survivors (0.53; 95% confidence interval, 0.39-0.71). In a propensity-matched analysis, delayed-transfer patients had a higher 28-day mortality rate (23.4% vs. 11.7%; p = 0.02) and a longer median hospital length of stay (13 days vs. 7 days; p < .001) than direct-transfer patients. Similar results were found after excluding the 150 patients with an obvious indication for immediate intensive care unit admission., Conclusions: Our findings suggest that some patients without major criteria for severe community-acquired pneumonia, according to the recent Infectious Diseases Society of America/American Thoracic Society consensus guideline, may benefit from direct transfer to the intensive care unit. Further studies are needed to prospectively identify patients who may benefit from direct intensive care unit admission despite a lack of major severity criteria for community-acquired pneumonia based on the current guidelines.

Introduction: To identify risk factors for early (< three days) intensive care unit (ICU) admission of patients hospitalised with community-acquired pneumonia (CAP) and not requiring immediate ICU admission, and to stratify the risk of ICU admission on days 1 to 3., Methods: Using the original data from four North American and European prospective multicentre cohort studies of patients with CAP, we derived and validated a prediction rule for ICU admission on days 1 to 3 of emergency department (ED) presentation, for patients presenting with no obvious reason for immediate ICU admission (not requiring immediate respiratory or circulatory support)., Results: A total of 6560 patients were included (4593 and 1967 in the derivation and validation cohort, respectively), 303 (4.6%) of whom were admitted to an ICU on days 1 to 3. The Risk of Early Admission to ICU index (REA-ICU index) comprised 11 criteria independently associated with ICU admission: male gender, age younger than 80 years, comorbid conditions, respiratory rate of 30 breaths/minute or higher, heart rate of 125 beats/minute or higher, multilobar infiltrate or pleural effusion, white blood cell count less than 3 or 20 G/L or above, hypoxaemia (oxygen saturation < 90% or arterial partial pressure of oxygen (PaO2) < 60 mmHg), blood urea nitrogen of 11 mmol/L or higher, pH less than 7.35 and sodium less than 130 mEq/L. The REA-ICU index stratified patients into four risk classes with a risk of ICU admission on days 1 to 3 ranging from 0.7 to 31%. The area under the curve was 0.81 (95% confidence interval (CI) = 0.78 to 0.83) in the overall population., Conclusions: The REA-ICU index accurately stratifies the risk of ICU admission on days 1 to 3 for patients presenting to the ED with CAP and no obvious indication for immediate ICU admission and therefore may assist orientation decisions.

Background: Although the Pneumonia Severity Index (PSI) has been extensively validated, little is known of the impact of its routine use as an aid to site-of-treatment decisions for patients with pneumonia who present to emergency departments (EDs)., Methods: A prospective, observational, controlled cohort study of patients with pneumonia was conducted in 8 EDs that used the PSI (PSI-user EDs) and 8 EDs that did not use the PSI (PSI-nonuser EDs) in France. The outcomes examined included the proportion of "low-risk" patients (PSI risk classes I-III) treated as outpatients, all-cause 28-day mortality, admission of inpatients to the intensive care unit, and subsequent hospitalization of outpatients., Results: Of the 925 patients enrolled in the study, 472 (51.0%) were treated at PSI-user EDs, and 453 (49.0%) were treated at PSI-nonuser EDs; 449 (48.5%) of all patients were considered to be at low risk. In PSI-user EDs, 92 (42.8%) of 215 patients at low risk were treated as outpatients, compared with 56 (23.9%) of 234 patients at low risk in PSI-nonuser EDs. The adjusted odds ratios for outpatient treatment were higher for patients in PSI risk classes I and II who were treated in PSI-user EDs, compared with PSI-nonuser EDs (adjusted odds ratio, 7.0 [95% confidence interval, 2.0-25.0] and 4.6 [95% confidence interval, 1.3-16.2], respectively), whereas the adjusted odds ratio did not differ by PSI-user status among patients in risk class III or among patients at high risk. After adjusting for pneumonia severity, mortality was lower in patients who were treated in PSI-user EDs; other safety outcomes did not differ between patients treated in PSI-user and PSI-nonuser EDs., Conclusions: The routine use of the PSI was associated with a larger proportion of patients in PSI risk classes I and II who had pneumonia and who were treated in the outpatient environment without compromising their safety.

Objective: To evaluate the extent to which respiratory changes in inferior vena cava (IVC) diameter can be used to predict fluid responsiveness., Design: Prospective clinical study., Setting: Hospital intensive care unit., Patients: Twenty-three patients with acute circulatory failure related to sepsis and mechanically ventilated because of an acute lung injury., Measurements: Inferior vena cava diameter (D) at end-expiration (Dmin) and at end-inspiration (Dmax) was measured by echocardiography using a subcostal approach. The distensibility index of the IVC (dIVC) was calculated as the ratio of Dmax - Dmin / Dmin, and expressed as a percentage. The Doppler technique was applied in the pulmonary artery trunk to determine cardiac index (CI). Measurements were performed at baseline and after a 7 ml/kg volume expansion using a plasma expander. Patients were separated into responders (increase in CI > or =15%) and non-responders (increase in CI <15%)., Results: Using a threshold dIVC of 18%, responders and non-responders were discriminated with 90% sensitivity and 90% specificity. A strong relation (r = 0.9) was observed between dIVC at baseline and the CI increase following blood volume expansion. Baseline central venous pressure did not accurately predict fluid responsiveness., Conclusion: Our study suggests that respiratory change in IVC diameter is an accurate predictor of fluid responsiveness in septic patients.

We describe the first fatal evolution of cellulitis due to Neisseria meningitidis serogroup Y involving an 85-year-old woman. She presented with an extensive cellulitis of the left side of the face, neck, and thorax and septic shock. In spite of active antibiotic therapy, evolution was rapidly fatal.

Results of routine microbiologic cultures of specimens obtained before the onset of ventilator-associated pneumonia (VAP) in intensive care unit (ICU) patients might help to identify the causative microorganisms and thus to select effective initial antimicrobial therapy. To test this hypothesis, we prospectively studied 125 consecutive VAP episodes for which the causative microorganisms were determined using bronchoscopic techniques. Upon entry into the study, each patient's hospital chart was reviewed and culture results of all previously obtained microbiologic specimens were recorded (mean number +/- SD per patient, 45 +/- 38). A total of 220 microorganisms were cultured at significant concentrations (> or = 10(3)/10(4) colony-forming units [cfu]/ml) from bronchoscopic specimens and considered responsible for pneumonia. Of these 220 organisms, only 73 (33%) were recovered before VAP onset, sometimes from multiple sites in the same patient but mainly from prior respiratory secretion cultures (n = 53). Also previously isolated were 342 organisms that were not responsible for VAP, making prospective identifications of the true pathogens difficult. Among the 102 episodes for which prior respiratory secretion culture results had been obtained (mean time before VAP onset, 8 +/- 9 d), all the organisms ultimately responsible for pneumonia were previously recovered from only 36 (35%) of these specimens. Based on these data, the contribution of routine microbiologic specimens in guiding initial antimicrobial therapy decisions for patients with suspected VAP appears limited.

We compared, in three intensive care units, colonization of hubs with hub protection boxes or hubs with needleless closed connectors; 137 central venous catheters and 451 hubs were randomized in two groups with similar characteristics. Catheter and hub colonization were not different between the two groups. Among 30 colonized catheters, the same isolate was found in only two hubs; hub contamination rarely is responsible for catheter colonization in short-term catheters. Further studies are required to evaluate the benefit of protected hubs compared with unprotected hubs.