First Report of Pectobacterium brasiliense Causing Bacterial Blackleg and Soft Rot of Potato in Pennsylvania.

Potato (Solanum tuberosum) plants showing blackleg and soft rot symptoms were collected at a commercial vegetable farm near Newmanstown, PA in August 2021 (Fig. S1). The incidence of potato blackleg in the unirrigated field was about 5 to 8%, but approximately 30% in the irrigated field. The diseased stems were cut into 5 cm and surface disinfected. The stem segments were placed into a 50-mL tube containing 15 mL of sterile water for 15 min for bacterial release. The bacterial suspension was streaked on crystal violet polypectate (CVP) (Hélias et al. 2012) plates and incubated at 28°C for 48 h. Three single colonies produced pits on CVP were picked and purified. Genomic DNA of all three isolates were extracted using the FastDNA Spin Kit (MP Biomedicals, Santa Ana, CA). Polymerase chain reaction (PCR) was performed using all three extracted DNAs as a template with the primer pairs gapA 7F/938R (Cigna et al. 2017), recA F/R (Waleron et al. 2001), dnaA F/R (Schneider et al. 2011) and dnaX F/R (Slawiak et al. 2009) targeting the gapA, recA, dnaA and dnaX genes, respectively. Isolate 21PA01 was further studied as a representative isolate. PCR amplicons derived from both forward and reverse primers were sequenced and analyzed using the BLAST algorithm against the NCBI database (https://www.ncbi.nlm.nih.gov). The regions of gapA (GenBank accession No. ON989738), recA (ON989739), dnaA (OP121183), and dnaX (OP121184) had 99.86%, 100%, 98.88%, and 100% identities with Pectobacterium brasiliense strains S1.16.01.3M (MN167062.1), BL-2 (MW721598.1), IPO:4132 (CP059956.1), and BL-2 (MW721603.1), respectively. A phylogenetic maximum-likelihood tree of the concatenated genes with the length of 2551 bp was constructed to visualize the relationship among different species of Dickeya and Pectobacterium. As a result, 21PA01 was in a single monophyletic cluster with other Pectobacterium brasiliense reference strains (Fig. S2 C). To confirm the pathogen, Koch's postulates were performed. Seed pieces of potato 'Lamoka' were planted in potting mix in one-gallon plastic pots in a greenhouse. Three weeks after emergence, the stems of three plants were each injected with 10 µL of bacteria suspension of either 21PA01 at 107 CFU/mL, P. parmentieri ME175 in tryptic soy broth (TSB) at 107 CFU/mL or TSB at 2 cm above the soil line. Seven days after inoculation, stems inoculated with 21PA01 and ME175 showed black and rotten symptoms, whereas the TSB-injected control plants remained symptomless. In addition, 'Lamoka' tubers were inoculated by placing 10 µL 21PA01 and ME175 suspensions at 107 CFU/mL, and TSB in a 1-cm-deep hole poked in a tuber separately and then sealed with petroleum gel, followed by incubation in a moist chamber at 22 °C for 4 d. The 21PA01 and ME175 inoculated tubers showed soft rot symptoms, but the TSB treatment had no symptoms. Bacterial colonies were isolated from the infected stems and confirmed by the DNA sequences as described above. PCR result was negative on control plant samples. Both stem and tuber inoculation trials were repeated two times, and the results were consistent. Thus, 21PA01 was identified as Pectobacterium brasiliense. To our knowledge, this is the first report of P. brasiliense infecting potatoes in Pennsylvania, USA, although it has been reported somewhere else (van der Merwe et al. 2010, Zhao et al. 2018). This could be a new species in Northeastern US.

Risk Evaluation of Benzovindiflupyr Resistance of Verticillium dahliae Population in Maine.

Verticillium dahliae causes Verticillium wilt, resulting in significant losses to potato production. Benzovindiflupyr, a succinate dehydrogenase inhibitor, effectively controls V. dahliae. However, frequent applications of the chemical may expedite the development of fungicide resistance in the pathogen population. To evaluate the risk of benzovindiflupyr resistance, 38 V. dahliae strains were obtained from diseased potatoes in Maine. The sensitivity of the field population was determined based on effective concentration for 50% inhibition (EC50), which ranged from 0.07 to 11.28 µg ml-1 with a median of 1.08. Segregated clusters of EC50 values indicated that Maine V. dahliae populations have developed benzovindiflupyr resistance. By exposing conidia of V. dahliae to a high concentration of benzovindiflupyr, 18 benzovindiflupyr-resistant mutants were obtained. To examine their fitness, the mutants were continuously subculture-transferred for up to 10 generations. Mycelial growth, conidial production, competitiveness, pathogenicity, and cross resistance of the 10th generation mutants were examined. Results showed that 50% of the resistant mutants retained an adaptive level in mycelial growth, and 60% maintained conidial production similar to their parents. Pathogenicity did not change for any of the mutants. No cross resistance was detected between benzovindiflupyr and either azoxystrobin, boscalid, fluopyram, or pyrimethanil. Thus, the resistance risk in V. dahliae to benzovindiflupyr should be considered in Maine potato production.

Species of Dickeya and Pectobacterium Isolated during an Outbreak of Blackleg and Soft Rot of Potato in Northeastern and North Central United States.

An outbreak of bacterial soft rot and blackleg of potato has occurred since 2014 with the epicenter being in the northeastern region of the United States. Multiple species of Pectobacterium and Dickeya are causal agents, resulting in losses to commercial and seed potato production over the past decade in the Northeastern and North Central United States. To clarify the pathogen present at the outset of the epidemic in 2015 and 2016, a phylogenetic study was made of 121 pectolytic soft rot bacteria isolated from symptomatic potato; also included were 27 type strains of Dickeya and Pectobacterium species, and 47 historic reference strains. Phylogenetic trees constructed based on multilocus sequence alignments of concatenated dnaJ, dnaX and gyrB fragments revealed the epidemic isolates to cluster with type strains of D. chrysanthemi, D. dianthicola, D. dadantii, P. atrosepticum, P. brasiliense, P. carotovorum, P. parmentieri, P. polaris, P. punjabense, and P. versatile. Genetic diversity within D. dianthicola strains was low, with one sequence type (ST1) identified in 17 of 19 strains. Pectobacterium parmentieri was more diverse, with ten sequence types detected among 37 of the 2015-2016 strains. This study can aid in monitoring future shifts in potato soft rot pathogens within the U.S. and inform strategies for disease management.

Pangenomic Analysis of Dickeya dianthicola Strains Related to the Outbreak of Blackleg and Soft Rot of Potato in the United States.

Dickeya dianthicola has caused an outbreak of blackleg and soft rot of potato in the eastern half of the United States since 2015. To investigate genetic diversity of the pathogen, a comparative analysis was conducted on genomes of D. dianthicola strains. Whole genomes of 16 strains from the United States outbreak were assembled and compared with 16 previously sequenced genomes of D. dianthicola isolated from potato or carnation. Among the 32 strains, eight distinct clades were distinguished based on phylogenomic analysis. The outbreak strains were grouped into three clades, with the majority of the strains in clade I. Clade I strains were unique and homogeneous, suggesting a recent incursion of this strain into potato production from alternative hosts or environmental sources. The pangenome of the 32 strains contained 6,693 genes, 3,377 of which were core genes. By screening primary protein subunits associated with virulence from all U.S. strains, we found that many virulence-related gene clusters, such as plant cell wall degrading enzyme genes, flagellar and chemotaxis related genes, two-component regulatory genes, and type I/II/III secretion system genes, were highly conserved but that type IV and type VI secretion system genes varied. The clade I strains encoded two clusters of type IV secretion systems, whereas the clade II and III strains encoded only one cluster. Clade I and II strains encoded one more VgrG/PAAR spike protein than did clade III. Thus, we predicted that the presence of additional virulence-related genes may have enabled the unique clade I strain to become predominant in the U.S. outbreak.

Interaction between Dickeya dianthicola and Pectobacterium parmentieri in Potato Infection under Field Conditions.

Dickeya and Pectobacterium spp. both cause blackleg and soft rot of potato, which can be a yield-reducing factor to potato production. The purpose of this study was to examine the interaction between these two bacterial genera causing potato infection, and subsequent disease development and yield responses under field conditions. Analysis of 883 potato samples collected in Northeastern USA using polymerase chain reaction determined that Dickeya dianthicola and P. parmentieri were found in 38.1% and 53.3% of all samples, respectively, and that 20.6% of samples contained both D. dianthicola and P. parmentieri. To further investigate the relationship between the two bacterial species and their interaction, field trials were established. Potato seed pieces of "Russet Burbank", "Lamoka", and "Atlantic" were inoculated with bacterial suspension of D. dianthicola at 107 colony-forming unite (CFU)/mL using a vacuum infiltration method, air dried, and then planted in the field. Two-year results showed that there was a high correlation (p < 0.01) between yield loss and percent of inoculated seed pieces. In a secondary field trial conducted in 2018 and 2019, seed pieces of potato "Shepody", "Lamoka" and "Atlantic" were inoculated with D. dianthicola, P. parmentieri, or mixture of both species, and then planted. In 2019, disease severity index, as measured by the most sensitive variety "Lamoka", was 16.2 with D. dianthicola inoculation, 10.4 with P. parmentieri, 25.4 with inoculation with both bacteria. Two-year data had a similar trend. Thus, D. dianthicola was more virulent than P. parmentieri, but the co-inoculation of the two species resulted in increased disease severity compared to single-species inoculation with either pathogen.

Genotyping Dickeya dianthicola Causing Potato Blackleg and Soft Rot Outbreak Associated With Inoculum Geography in the United States.

An outbreak of blackleg and soft rot of potato, caused primarily by the bacterial pathogen Dickeya dianthicola, has resulted in significant economic losses in the northeastern United States since 2015. The spread of this seedborne disease is highly associated with seed distribution; therefore, the pathogen likely spread with seed tubers. To describe the blackleg epidemic and track inoculum origins, a total of 1,183 potato samples were collected from 11 states associated with blackleg outbreak from 2015 to 2019. Of these samples, 39.8% tested positive for D. dianthicola. Seventeen isolates of D. dianthicola were recovered from these samples and the genetic diversity of these isolates was examined. Fingerprinting with BOX-A1R-based repetitive extragenic palindromic PCR and phylogenetic analysis based on sequences of the 16S rRNA and gapA genes indicated that D. dianthicola isolates were divided into three genotypes, denoted types I, II, and III. Ninety-five percent of samples from Maine were type I. Type II was found in Maine only in 2015 and 2018. Type II was present throughout the 5 years in some states at a lower percentage than type I. Type III was found in Pennsylvania, New Jersey, and Massachusetts, but not in Maine. Therefore, type I appears to be associated with Maine, but type II appeared to be distributed throughout the northeastern United States. The type II and rarer type III strains were closer to the D. dianthicola type strain isolated from the United Kingdom. This work provides evidence that the outbreak of blackleg of potato in the northeastern United States was caused by multiple strains of D. dianthicola. The geographic origins of these strains remain unknown.

The Recombinant Potato virus Y (PVY) Strain, PVYNTN, Identified in Potato Fields in Victoria, Southeastern Australia.

Potato virus Y (PVY) is one of the main viruses affecting potato in Australia. However, molecular characterization of PVY isolates circulating in potato in different states of Australia has not yet been thoroughly conducted. Only nonrecombinant isolates of three biological PVY strains collected from potato were reported previously from Western Australia and one from Queensland. Here, PVY isolates collected from seed potato originating in Victoria, Australia, and printed on FTA cards, were subjected to strain typing by RT-PCR, with three isolates subjected to whole genome sequencing. All the 59 PVY isolates detected during two growing seasons were identified to be recombinants based on two RT-PCR assays. No nonrecombinant PVY isolates were identified. All the RT-PCR typed isolates belonged to the PVYNTN strain. Sequence analysis of the whole genomes of three isolates suggested a single introduction of the PVYNTN strain to Australia but provided no clues as to where this introduction originated. Given the association of the PVYNTN strain with potato tuber damage, growers in Australia should implement appropriate strategies to manage PVYNTN in potato.

Regulatory and strategic considerations for addressing immunogenicity and related responses in biopharmaceutical development programs.

The last three decades have seen the biotherapeutic drug market evolve from promising concept to market dominance in a range of clinical indications. This growth has been spurred by the success of established drug classes like monoclonal antibodies, but also by the introduction of biosimilars, and more recently, multiple novel cell and gene therapies. Biotherapeutic drug development presents many unique challenges, but unintended immune responses are among the most common reasons for program attrition. Anti-drug antibodies can impact the safety and efficacy of drug products, and related immune responses, like the cytokine release syndrome that occurred in the infamous TGN-1412 clinical trial, can be challenging to predict with nonclinical models. For this reason, it is important that development programs proceed with a scientifically grounded and measured approach to these responses. This process begins at the discovery stage with the application of "quality by design," continues into the clinic with the development of quality assays and management strategies, and culminates in the effective presentation of this information in regulatory documents. This review provides an overview of some of the key strategic and regulatory considerations for biotherapeutics as they pertain to immunogenicity and related responses.

A comprehensive review of topical hemostatic agents: The good, the bad, and the novel.

Uncontrolled exsanguination remains the leading cause of death for trauma patients, many of whom die in the pre-hospital setting. Without expedient intervention, trauma-associated hemorrhage induces a host of systemic responses and acute coagulopathy of trauma. For this reason, health care providers and prehospital personal face the challenge of swift and effective hemorrhage control. The utilization of adjuncts to facilitate hemostasis was first recorded in 1886. Commercially available products haves since expanded to include topical hemostats, surgical sealants, and adhesives. The ideal product balances efficacy, with safety practicality and cost-effectiveness. This review of hemostasis provides a guide for successful implementation and simultaneously highlights future opportunities.

Genetic Variation within Clonal Lineages of Phytophthora infestans Revealed through Genotyping-By-Sequencing, and Implications for Late Blight Epidemiology.

Genotyping-by-sequencing (GBS) was performed on 257 Phytophthora infestans isolates belonging to four clonal lineages to study within-lineage diversity. The four lineages used in the study were US-8 (n = 28), US-11 (n = 27), US-23 (n = 166), and US-24 (n = 36), with isolates originating from 23 of the United States and Ontario, Canada. The majority of isolates were collected between 2010 and 2014 (94%), with the remaining isolates collected from 1994 to 2009, and 2015. Between 3,774 and 5,070 single-nucleotide polymorphisms (SNPs) were identified within each lineage and were used to investigate relationships among individuals. K-means hierarchical clustering revealed three clusters within lineage US-23, with US-23 isolates clustering more by collection year than by geographic origin. K-means hierarchical clustering did not reveal significant clustering within the smaller US-8, US-11, and US-24 data sets. Neighbor-joining (NJ) trees were also constructed for each lineage. All four NJ trees revealed evidence for pathogen dispersal and overwintering within regions, as well as long-distance pathogen transport across regions. In the US-23 NJ tree, grouping by year was more prominent than grouping by region, which indicates the importance of long-distance pathogen transport as a source of initial late blight inoculum. Our results support previous studies that found significant genetic diversity within clonal lineages of P. infestans and show that GBS offers sufficiently high resolution to detect sub-structuring within clonal populations.

Protocols and Hospital Mortality in Critically Ill Patients: The United States Critical Illness and Injury Trials Group Critical Illness Outcomes Study.

OBJECTIVE: Clinical protocols may decrease unnecessary variation in care and improve compliance with desirable therapies. We evaluated whether highly protocolized ICUs have superior patient outcomes compared with less highly protocolized ICUs. DESIGN: Observational study in which participating ICUs completed a general assessment and enrolled new patients 1 day each week. PATIENTS: A total of 6,179 critically ill patients. SETTING: Fifty-nine ICUs in the United States Critical Illness and Injury Trials Group Critical Illness Outcomes Study. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The primary exposure was the number of ICU protocols; the primary outcome was hospital mortality. A total of 5,809 participants were followed prospectively, and 5,454 patients in 57 ICUs had complete outcome data. The median number of protocols per ICU was 19 (interquartile range, 15-21.5). In single-variable analyses, there were no differences in ICU and hospital mortality, length of stay, use of mechanical ventilation, vasopressors, or continuous sedation among individuals in ICUs with a high versus low number of protocols. The lack of association was confirmed in adjusted multivariable analysis (p = 0.70). Protocol compliance with two ventilator management protocols was moderate and did not differ between ICUs with high versus low numbers of protocols for lung protective ventilation in acute respiratory distress syndrome (47% vs 52%; p = 0.28) and for spontaneous breathing trials (55% vs 51%; p = 0.27). CONCLUSIONS: Clinical protocols are highly prevalent in U.S. ICUs. The presence of a greater number of protocols was not associated with protocol compliance or patient mortality.

Impact of speed cameras on trauma centers.

BACKGROUND: While studies, mostly from Europe and Australia, have examined the effect of speed cameras on motor vehicle collisions, limited data exist regarding their impact on charges and number of patients taken to Level 1 trauma centers (L1TCs). Because of conflicting perceptions and data on their value, speed cameras were implemented along select Arizona highways in 2008 but then removed in 2010. The hypotheses of our study were twofold. (1) Speed cameras reduce admissions to L1TCs, and (2) speed cameras reduce crash kinetic energy, resulting in lower Injury Severity Score (ISS), mortality, hospital costs, and length of stay (LOS). METHODS: A retrospective review of all patients admitted to L1TCs who were injured in motor vehicle crashes along a 26-mile segment of interstate I-10 in urban Phoenix was performed. Patients were identified using both the Arizona State Trauma Registry and the Arizona Department of Transportation collision data for 2009 to 2011. This specific 26-mile segment of I-10 was selected because it contained at least one speed camera within 1 mile along its entire length from October 2008 to October 2010. Two time frames were evaluated: January 1 to December 31, 2009, when cameras were in place (2009 camera group) and January 1 to December 31, 2011, when no cameras were in place (2011 no-camera group). Variables analyzed include number of collisions, number of injuries, on-scene mortality, trauma center admissions, number of collisions with admissions, in-hospital mortality, ISS, hospital charges, LOS, age, sex, race, and ethnicity. Five confounding variables were eliminated. Analysis was performed using Fisher's exact test and linear regression. RESULTS: Camera removal was associated with a twofold increase in L1TC admissions as well as increased resource use. There were no significant differences between the two time frames for ISS, mortality, median charges, or median LOS. CONCLUSION: In this study, removal of speed cameras resulted in increased trauma center admissions and resource use. LEVEL OF EVIDENCE: Care management study, level IV.

Structure, process, and annual ICU mortality across 69 centers: United States Critical Illness and Injury Trials Group Critical Illness Outcomes Study.

OBJECTIVE: Hospital-level variations in structure and process may affect clinical outcomes in ICUs. We sought to characterize the organizational structure, processes of care, use of protocols, and standardized outcomes in a large sample of U.S. ICUs. DESIGN: We surveyed 69 ICUs about organization, size, volume, staffing, processes of care, use of protocols, and annual ICU mortality. SETTING: ICUs participating in the United States Critical Illness and Injury Trials Group Critical Illness Outcomes Study. SUBJECTS: Sixty-nine intensivists completed the survey. MEASUREMENTS AND MAIN RESULTS: We characterized structure and process variables across ICUs, investigated relationships between these variables and annual ICU mortality, and adjusted for illness severity using Acute Physiology and Chronic Health Evaluation II. Ninety-four ICU directors were invited to participate in the study and 69 ICUs (73%) were enrolled, of which 25 (36%) were medical, 24 (35%) were surgical, and 20 (29%) were of mixed type, and 64 (93%) were located in teaching hospitals with a median number of five trainees per ICU. Average annual ICU mortality was 10.8%, average Acute Physiology and Chronic Health Evaluation II score was 19.3, 58% were closed units, and 41% had a 24-hour in-house intensivist. In multivariable linear regression adjusted for Acute Physiology and Chronic Health Evaluation II and multiple ICU structure and process factors, annual ICU mortality was lower in surgical ICUs than in medical ICUs (5.6% lower [95% CI, 2.4-8.8%]) or mixed ICUs (4.5% lower [95% CI, 0.4-8.7%]). We also found a lower annual ICU mortality among ICUs that had a daily plan of care review (5.8% lower [95% CI, 1.6-10.0%]) and a lower bed-to-nurse ratio (1.8% lower when the ratio decreased from 2:1 to 1.5:1 [95% CI, 0.25-3.4%]). In contrast, 24-hour intensivist coverage (p = 0.89) and closed ICU status (p = 0.16) were not associated with a lower annual ICU mortality. CONCLUSIONS: In a sample of 69 ICUs, a daily plan of care review and a lower bed-to-nurse ratio were both associated with a lower annual ICU mortality. In contrast to 24-hour intensivist staffing, improvement in team communication is a low-cost, process-targeted intervention strategy that may improve clinical outcomes in ICU patients.

Do speed cameras reduce collisions?

We investigated the effects of speed cameras along a 26 mile segment in metropolitan Phoenix, Arizona. Motor vehicle collisions were retrospectively identified according to three time periods - before cameras were placed, while cameras were in place and after cameras were removed. A 14 mile segment in the same area without cameras was used for control purposes. Five cofounding variables were eliminated. In this study, the placement or removal of interstate highway speed cameras did not independently affect the incidence of motor vehicle collisions.

Risk factors for central line-associated bloodstream infections in the era of best practice.

BACKGROUND: Best clinical practice aims to eliminate central line-associated blood stream infections (CLABSIs). However, CLABSIs still occur. This study's aim was to identify risk factors for CLABSI in the era of best practice. METHODS: Critically ill surgical patients admitted over 2 years to the intensive care unit (ICU) for ≥ 4 days were studied. Patients with CLABSI as cause for ICU admission were excluded. Patients who developed CLABSI (National Healthcare Safety Network definition) were compared with those who did not. Hand hygiene, maximal sterile barriers, chlorhexidine scrub, avoidance of femoral vein, and proper maintenance were emphasized. Variables collected included demographics, diagnosis, and severity of illness using the Acute Physiology and Chronic Health Evaluation (APACHE) IV database and the hospital central data repository. RESULTS: Of 961 patients studied, 51 patients (5.2%) developed 59 CLABSIs. Mean time from ICU admission to CLABSI was 26 days ± 26 days. The CLABSI group was more likely to be male (odds ratio [OR] 1.93, 95% confidence interval [CI] 1.02-3.68), more critically ill on ICU admission (APACHE IV score 85.2 ± 21.9 vs. 65.6 ± 23.2, p < 0.01), more likely admitted to the emergency surgery service (OR 1.92, 95% CI 1.02-3.61), and had an association with reopening of recent laparotomy (OR 2.08, 95% CI 1.10-3.94). CONCLUSION: In the era of best practice, patients who develop CLABSI are clinically distinct from those who do not develop CLABSI. These CLABSIs may be due to deficiencies of the CLABSI definition or represent patient populations requiring enhanced prevention techniques. LEVEL OF EVIDENCE: III, prognostic study.

Effect of glycemic state on hospital mortality in critically ill surgical patients.

Intensive insulin therapy can reduce mortality. Hypoglycemia related to intensive therapy may worsen outcomes. This study compared risk adjusted mortality for different glycemic states. A retrospective review of patients admitted to a surgical intensive care unit over 4 years was performed. Patients were divided into glycemic groups: HYPER (≥1 episode > 180 mg/dL, any <60), HYPO (≥1 episode < 60 mg/dL, any >180), BOTH (≥1 episode < 60 and ≥1 episode > 180 mg/dL), NORMO (all episodes 60-180 mg/dL), HYPER-Only (≥1 episode > 180, none <60 mg/dL), and HYPO-Only (≥1 episode < 60, none >180 mg/dL). Observed to expected Acute Physiology and Chronic Health Evaluation (APACHE) III mortality ratios (O/E) were studied. Number of adverse glycemic events was compared with mortality. Hypoglycemia and hyperglycemia occurred in 18 per cent and 50 per cent of patients. Mortality was 12.4 per cent (O/E = 0.88). BOTH had the highest O/E ratio (1.43) with HYPO the second highest (1.30). Groups excluding hypoglycemia (NORMO and HYPER-only) had the lowest O/E ratios: 0.56 and 0.88. Increasing number of hypoglycemic events were associated with increasing O/E ratio: 0.69 O/E for no events, 1.19 for 1-3 events, 1.35 for 4-6 events, 1.9 for 7-9 events, and 3.13 for ≥ 10 events. Ten or more hyperglycemic events were needed to significantly associate with worse mortality (O/E 1.53). Hyper- and hypoglycemia increase mortality compared with APACHE III expected mortality, with highest mortality risk if both are present. Hypoglycemia is associated with worse risk. Glucose control may need to be loosened to prevent hypoglycemia and reduce glucose variability.

Patient characteristics associated with end-of-life decision making in critically ill surgical patients.

BACKGROUND: Palliative care is an important and necessary humanistic facet of ICU care. Wide variations exist in selection and implementation of palliative care decisions. Understanding patient factors associated with these decisions is crucial. STUDY DESIGN: Consecutive deaths (n = 151 patients) in a tertiary care surgical ICU during a 2-year period were reviewed. All data had been entered into the APACHE IV database. Patients were divided into groups: Withhold (WH), which included patients who had potentially lifesaving therapies withheld or withdrawn, and Full Care (FC), which included patients who had full resuscitative efforts before death. Patient factors including demographics, severity of illness, admission source, and history were compared between groups. RESULTS: Of 151 patients, 111 (74%) had potentially lifesaving therapy withheld or withdrawn (WH group). Forty patients (26%) had full treatment, including CPR, until time of death (FC group). Compared with WH, FC patients had a higher degree of illness at ICU admission (APACHE IV score 103.4 ± 36.6 vs 90.6 ± 29.3; p < 0.02) and were less likely to be male (35% vs 62%; p < 0.005). There were no differences between groups with regard to age, requirement for intubation on admission, medical history, admission source (emergency room vs operating room vs recovery room) or the number of patients admitted status post emergent vs elective surgery or admitted for nonsurgical diagnoses. In a multivariable regression model, male sex (odds ratio = 3.22; 95% CI, 1.45-7.19) and severity of illness (odds ratio = 0.98; 95% CI, 0.97-0.99) retained independent associations with decisions to limit care. CONCLUSIONS: Higher severity of illness and history play no role in the decision to limit care. Sex plays a strong and independent role. Factors influencing end-of-life care require additional study.

Association of 6% hetastarch resuscitation with adverse outcomes in critically ill trauma patients.

BACKGROUND: Six percent hetastarch is used as a volume expander but has been associated with poor outcomes. The aim of this study was to evaluate trauma patients resuscitated with hetastarch. METHODS: A retrospective review was performed of adult trauma patients. Demographics, injury severity, laboratory values, outcomes, and hetastarch use were recorded. RESULTS: A total of 2,225 patients were identified, of whom 497 (22%) received hetastarch. There were no differences in age, gender, injury mechanism, lactate, hematocrit, or creatinine. The mean injury severity score was different: 29.7 ± 12.6 with hetastarch versus 27.5 ± 12.6 without hetastarch. Acute kidney injury developed in 65 hetastarch patients (13%) and in 131 (8%) without hetastarch (relative risk, 1.73; 95% confidence interval [CI], 1.30-2.28). Hetastarch mortality was 21%, compared with 11% without hetastarch (relative risk, 1.84; 95% CI, 1.48-2.29). Multivariate logistic regression demonstrated hetastarch use (odds ratio, 1.96; 95% CI, 1.49-2.58) as independently significant for death. Hetastarch use was independently significant for renal dysfunction as well (odds ratio, 1.70; 95% CI, 1.22-2.36). CONCLUSIONS: Because of the detrimental association with renal function and mortality, hetastarch should be avoided in the resuscitation of trauma patients.

ACS-NSQIP criteria are associated with APACHE severity and outcomes in critically ill surgical patients.

BACKGROUND: Similarity between the ICU patient data acquired by the APACHE system and the patient outcomes data acquired by the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) suggests that variables in NSQIP data could be effective mortality predictors. We theorized that identifying ACS-NSQIP preoperative data points predictive of patient outcomes would assist in identifying potential complications earlier. STUDY DESIGN: Between 2006 and 2008 at the University of Maryland Medical Center, we identified 340 surgical ICU patients included in both databases as our study cohort. Median APACHE score calculation permitted division of study subjects into quartiles from which to examine length of stay, mortality variables, and ACS-NSQIP-recorded postoperative occurrences and preoperative risk factors. Outcomes were compared using each database's percentage of patients who had died. RESULTS: Mortality was positively correlated with APACHE score increases. Initially, the average ICU length of stay increased, then declined. Most common postoperative occurrences were ventilator dependence >48 hours, pneumonia, unplanned intubation, sepsis, and septic shock. It was also noted that preoperative variables, such as American Society of Anesthesiologists classification and serum albumin levels, had an association with a poorer prognosis. CONCLUSIONS: APACHE score predictions are consistent with ACS-NSQIP-recorded postoperative outcomes. Higher APACHE scores correlated with increased incidence of postoperative outcomes and were associated with earlier mortality in the most extremely ill. Poorer states of health before surgery also correlated with poor outcomes postoperatively.

Core temperature correlates with expression of selected stress and immunomodulatory genes in febrile patients with sepsis and noninfectious SIRS.

Environmental hyperthermia and exercise produce extensive changes in gene expression in human blood cells, but it is unknown whether this also happens during febrile-range hyperthermia. We tested the hypothesis that heat shock protein (HSP) and immunomodulatory stress gene expression correlate with fever in intensive care unit patients. Whole blood messenger RNA was obtained over consecutive days from 100 hospitalized patients suffering from sepsis or noninfectious systemic inflammatory response syndrome (SIRS) as defined by conventional criteria. The most abnormal body temperature in the preceding 24 h was recorded for each sample. Expression analysis was performed using the Affymetrix U133 chip. ANCOVA followed by correlation analysis was performed on a subset of 278 prospectively identified sequences of interest. Temperature affected expression of 60 sequences, either independently or as a function of clinical diagnosis. Forty-eight of these (representing 38 genes) were affected by temperature only, including several HSPs, transcription factors heat shock factor (HSF)-1 and HSF-4, cellular adhesion molecules such as ICAM1/CD54 and JAM3, toll receptors TLR-6 and TLR-7, ribosomal proteins, and a number of molecules involved in inflammatory pathways. Twelve sequences demonstrated temperature-dependent responses that differed significantly between patients with sepsis and noninfectious SIRS: CXCL-13; heat shock proteins DNAJB12 and DNAJC4; the F11 receptor; folate hydrolase 1; HSF-2; HSP 70 proteins HSPA1A, HSPA1B, and HSPA1L; interleukin 8; lipopolysaccharide binding protein; and prostaglandin E synthase. Febrile-range temperatures achieved during sepsis and noninfectious SIRS correlate with detectable changes in stress gene expression in vivo, suggesting that fever can activate HSP gene expression and modify innate immune responses. For some genes, it appears that clinical condition can alter temperature-sensitive gene expression. Collectively, these data underscore the potential importance of body temperature in shaping the immune response to infection and injury.