Free flap jaw reconstruction with dental implantation: A single-institution experience.

BACKGROUND: We sought to review our institution's experience with dental implant placement in free flap jaw reconstruction to determine factors impacting restoration of dental occlusion. METHODS: Exactly 48 patients underwent free flap jaw reconstruction with or without dental restoration from 2017 to 2022. Primary outcome was achievement of restored dental occlusion after jaw free flap reconstruction. RESULTS: A total of 48 patients with a mean age of 59.8 ± 16.4 years underwent jaw reconstruction from 2017 to 2022. Ten patients (20.8%) received osteointegrated dental implants. Two patients received a temporary dental prosthesis, 12 ± 4 months after initial reconstruction. Three patients received a final prosthesis, with a mean time to final prosthesis of 17.7 ± 12.4 months. Five patients did not receive any prosthesis despite placement of implants. CONCLUSION: A minority of patients received dental implant placement with free flap jaw reconstruction and only a small subset of these received a definitive dental prosthesis.

Wound healing in the vulnerable: A novel case of postauricular wounds caused by mask ties.

Background: The COVID-19 pandemic has made facial masks an essential part of daily life. While protective facial masks are crucial to help the spread of viral infections, they are common causes of facial skin breakdown, acne, and superficial injuries. Masks with elastic ear loops are also particularly likely to cause ear pressure injuries. Case report: Herein, we present a case of a patient experiencing homelessness found to have significant postauricular wounds due to prolonged mask use in the context of the Covid-19 pandemic. These injuries led to bilateral erosion of the helix with partial avulsion of the ear and mask ear loops eroding into cartilage. Why should an emergency physician be aware of this?: We describe a rare complication of mask use and highlight the difficulties the COVID pandemic has made in providing adequate care for chronic head and neck wounds amongst the homeless population. While PPE remains an important part of decreasing the risk of the spread of infections, it is important to recognize the vulnerabilities of the homeless population during the COVID pandemic and how best to care for novel auricular wounds.

Combination Treatment with Sipuleucel-T and Abiraterone Acetate or Enzalutamide for Metastatic Castration-Resistant Prostate Cancer: STAMP and STRIDE Trials.

PURPOSE: We present long-term outcomes from 2 randomized studies [STAMP (with abiraterone, NCT01487863) and STRIDE (with enzalutamide, NCT01981122)] that were performed to study the impact of sequential or concurrent administration of androgen receptor-targeting agents (ARTAs) on sipuleucel-T immune response and overall survival (OS) in metastatic castration-resistant prostate cancer (mCRPC). PATIENTS AND METHODS: Sipuleucel-T was administered per current prescribing information. Results from STRIDE are presented together with updated STAMP results. Survival status of patients was updated using demographic information to query the National Death Index (NDI). Kaplan-Meier methodology was used to analyze survival. RESULTS: Updated data reduced patient censoring in each study compared with the original analyses; the 95% confidence intervals (CIs) for OS are now estimable. Updated median OS (95% CI) is 33.3 (24.1-40.7) months for STAMP and 32.5 (26.0-45.1) months for STRIDE. There was no notable impact on median OS [HR, 0.727 (0.458-1.155); P = 0.177, reference = STRIDE]. OS with sequential administration was similar to concurrent administration [NDI update: HR, 0.963 (0.639-1.453); P = 0.845, reference = concurrent arm]. Sipuleucel-T potency, measured as antigen-presenting cell (APC) activation, was higher in subsequent infusions compared with the first infusion. Humoral responses (IgG + IgM antibody titers) to PA2024 and prostatic acid phosphatase were significantly elevated versus baseline. No new safety signals were observed. CONCLUSIONS: Median OS was consistent regardless of whether the agents were administered sequentially or concurrently, including after NDI update. Results suggest that sipuleucel-T induces an immunologic prime-boost effect after initial sipuleucel-T exposure, even when combined with ARTAs.

Leave No Stone Unturned: A Case of an Actinomyces Rhinolith Presenting With Chronic Cough and Throat Pain.

Actinomycosis infection in the nasal cavity, especially an actinomyces rhinolith, is extremely rare. It should be considered in cases where a heterogenous calcified mass is found within the nasal cavity on endoscopy and radiographically. Treatment includes surgical debridement and a prolonged course of antibiotics, unique from the more typically encountered fungus ball. This case highlights the broad differential for chronic cough and throat pain and the importance of considering sinonasal contributions to throat symptoms.

A systematic review of suicidal ideation and behaviors among adults with spinal cord injury.

CONTEXT: Suicide is a public health crisis within the United States. Individuals with spinal cord injury (SCI) are vulnerable to negative outcomes such as suicide. OBJECTIVE: This systematic review describes frequency of suicidal ideation (SI) and behaviors (suicide attempt [SA] and deaths) among samples of adults living with SCI. Associated risk and protective factors of SI and suicidal behaviors were also explored. METHODS: On July 7, 2021, OVID Medline, EMBASE, OVID PsycINFO, Web of Science Core Collection, CINAHL, Cochrane Library, and Google Scholar databases were searched for SI, SA, and deaths by suicide among adults with a history of SCI. Risk of bias (RoB) was assessed using the Effective Public Health Practice Project (EPHPP) quality assessment tool. Results were synthesized descriptively considering the likely impact of RoB. The updated Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 reporting method was used. RESULTS: Sixty-nine articles were included. Frequency of SI and SAs within study samples ranged from 4% to 67%, and 0% to approximately 66%, respectively. While assessment methods for SI and SA widely varied, suicide deaths data sources were more consistent. Studies assessing SI and SA generally had high RoB and the overall strength of evidence was low. Stronger observational study designs assessing death by suicide had low RoB and the overall strength of evidence was high. Very few studies examined protective factors. DISCUSSION: Findings support previous work. Quality of evidence, and therefore confidence in the frequency of these outcomes, was impacted by the use of assessment measures without sufficient psychometric properties. The field will benefit from use of psychometrically sound measures to assess for SI, SA and suicide deaths. Furthermore, additional work is needed to elucidate risk and protective factors and to clearly characterize samples to increase generalizability of findings to the larger SCI community, including standardized reporting of SCI characteristics (e.g. use of American Spinal Injury Association classification system). Ultimately, improved suicide assessment and risk management is expected to prevent suicide among those living with SCI. REGISTRATION: CRD42020164686.

Patients with hypothermic sepsis have a unique gene expression profile compared to patients with fever and sepsis.

The pathophysiology of hypothermia during sepsis is unclear. Using genomic profiling of blood leukocytes, we aimed to determine if hypothermia is associated with a different gene expression profile compared to fever during sepsis. Patients with sepsis and either hypothermia or fever within 24 hours after ICU admission were included in the study (n = 168). Hypothermia was defined as body temperature below 36 °C. Fever was defined as body temperature equal to or above 38.3°C. We compared blood gene expression (whole-genome transcriptome in leukocytes) in hypothermic septic compared to febrile septic patients in an unmatched analysis and matched for APACHE IV score and the presence of shock. In total, 67 septic patients were hypothermic and 101 patients were febrile. Hypothermia was associated with a distinct gene expression profile in both unmatched and matched analyses. There were significant differences related to the up- and downregulation of canonical signalling pathways. In the matched analysis, the top upregulated gene was cold-inducible mRNA binding protein (CIRBP) which plays a role in cold-induced suppression of cell proliferation. In addition, we found three signalling pathways significantly upregulated in hypothermic patients compared to febrile patients; tryptophan degradation X, phenylalanine degradation IV and putrescine degradation III. In conclusion, there are distinct signalling pathways and genes associated with hypothermia, including tryptophan degradation and CIRBP expression, providing a possible link to the modulation of body temperature and early immunosuppression. Future studies may focus on the canonical signalling pathways presented in this paper to further investigate spontaneous hypothermia in sepsis.

Physical Frailty is Modifiable in Young Cardiac Rehabilitation Patients.

Frailty is a standardized, quantitative metric used to assess multisystem physiologic reserve and vulnerability to poor health outcomes. Cardiac rehabilitation (CR) positively impacts patient outcomes, including frailty, in adult cardiovascular disease (CVD); however, both the frailty paradigm and CR are understudied in pediatric CVD. This retrospective, single-center cohort study aimed to determine baseline composite frailty for pediatric-onset CVD patients and examine its change throughout CR using a proposed frailty assessment tool. Youth with pediatric-onset CVD participating in CR were stratified into five CVD diagnostic groups: post-heart transplant (HTx) (n = 34), post-ventricular assist device (VAD) (n = 12), single ventricle (n = 20) and biventricular (n = 29) congenital heart disease, and cardiomyopathy (n = 25), and frailty was assessed at baseline and every 30 days during CR. Post-HTx and post-VAD groups had significantly higher median frailty scores at baseline (6/10 and 5.75/10, respectively) driven by reduced strength, gait speed, and functional status. All groups except post-VAD displayed a significant absolute reduction in frailty from baseline to 120 days (HTx: - 3.5; VAD: - 3; SV CHD: - 1; BV CHD: - 1; CM: - 1.5), with similar median post-CR scores (1-3/10 in all groups). These improvements did not significantly correlate with number of CR sessions attended. This study established that frailty exhibits discriminatory utility across pediatric-onset CVD groups at baseline and is significantly modifiable over time. Improvements in frailty and other fitness metrics are likely due to a combination of post-operative recovery, post-diagnosis pharmacological and lifestyle changes, and CR. Further study of this frailty tool is needed to explore its prognostic utility.

Outcomes in men with metastatic castration-resistant prostate cancer who received sipuleucel-T and no immediate subsequent therapy: experience at Dana Farber and in the PROCEED Registry.

BACKGROUND: Sipuleucel-T has demonstrated survival benefit in phase 3 trials but is utilized in few men with metastatic castration-resistant prostate cancer (mCRPC) in part due to low rates of PSA and objective response. Given the requirement to develop immune-mediated antitumor activity as vaccine-based therapy, sipuleucel-T may have delayed clinical activity. We explored this in a cohort of men from PROCEED (NCT01306890), an FDA-requested outcomes registry, and in a separate institutional cohort of mCRPC patients treated with sipuleucel-T at Dana-Farber Cancer Institute (DFCI). METHODS: Men with mCRPC who received 3 infusions of sipuleucel-T and did not initiate a new mCRPC directed therapy for ≥6 months after completion of sipuleucel-T were included. All patients had rising PSA before starting sipuleucel-T and available post-treatment PSA measurements. Clinical outcomes of interest included: PSA50 response rate, time to subsequent mCRPC directed therapy, and overall survival (OS). RESULTS: Of 1902 men with mCRPC treated in PROCEED and 255 patients treated consecutively with sipuleucel-T between 4/2010 and 4/2017 at DFCI, 171 and 28 patients were included, respectively. In the PROCEED sample, PSA50 response was observed in 34 (19.9%) of patients at a median of 5.5 months (IQR: 3.9-9.5) since the last sipuleucel-T infusion; median time to subsequent mCRPC directed therapy was 10 months (95% CI: 9-11); and median OS was 49 months (95% CI: 43-NR). In the DFCI cohort, PSA50 response was observed in 4 (14.3%) of patients at a median of 6.3 months (IQR: 4.7-7.0); median time to subsequent mCRPC directed therapy was 9 months (95% CI: 9-11); and median OS was 60 months (95% CI: 51-74). CONCLUSIONS: In this analysis of mCRPC patients treated with sipuleucel-T who did not immediately initiate subsequent therapy using two datasets, delayed PSA response was observed in a subset of patients indicating delayed clinical activity.

COVID-19 and the Otolaryngology Residency Match: Rising Incidence of Home Matches.

OBJECTIVES/HYPOTHESIS: To quantify the effect of the coronavirus disease 2019 (COVID-19) pandemic upon the 2020 to 2021 residency match for Otolaryngology-Head and Neck Surgery (OHNS). STUDY DESIGN: Retrospective cohort design. METHODS: Residency match outcomes for all applicants to our institution during 2020 to 2021 were collected from the National Residency Matching Program including medical school of origin and matched program. Matches were categorized as to home-program, within-region, or out-of-region and sorted by US geographic region. Matches from the 2020 to 2021 cycle were compared to those from 2019 to 2020, as well as averages and trends from match cycles 2016 to 2020. Statistical analysis included descriptive statistics and chi-square testing. RESULTS: During 2020 to 2021, there were 436 applicants to our single OHNS program. From 2019-2020 to 2020-2021, the match rate decreased significantly for groups studied, including: All applicants (72.0% [268/372] to 64.7% [282/436]; P = .025); all US MD Senior applicants (76.5% [254/332] to 68.9% [262/380]; P = .024); and US MD Seniors specifically without a home program (77.5% [31/40] to 56.4% [22/39]; P = .046). The match rate for US MD Seniors with a home program did not change significantly (76.4% [223/292] to 70.4% [240/341]; P = .09). From 2019-2020 to 2020-2021, the proportion of US MD seniors who matched to home-program increased significantly (22.0% [49/223] to 30.0% [72/240]; P = .05). CONCLUSION: The COVID-19 pandemic saw high volumes of OHNS applicants with an overall decreased rate of matching compared to previous years. These changes particularly affected applicants without home programs. Home-program matching increased significantly, likely as a consequence of the limitations placed on in-person away experiences including interviews. Laryngoscope, 132:1934-1938, 2022.

Induced normothermia ameliorates the procoagulant host response in human endotoxaemia.

BACKGROUND: Dysregulation of coagulation occurs commonly in sepsis, ranging from mild coagulopathy with decreased platelets to disseminated intravascular coagulation (DIC). We investigated the effect of induced normothermia on coagulation during lipopolysaccharide (LPS)-induced endotoxaemia in healthy volunteers. METHODS: Twelve volunteers received an infusion of bacterial lipopolysaccharide (Escherichia coli; 2 ng kg-1) and were assigned to either induced normothermia or control. Induced normothermia to maintain core temperature at 37°C consisted of external surface cooling, cold i.v. fluids, and medication to reduce shivering (buspirone, clonidine, and magnesium sulphate). The primary outcome was the DIC score (International Society on Thrombosis and Haemostasis guideline). Prothrombin time (PT), activated partial thromboplastin time (aPTT), D-dimer, plasma von Willebrand factor (vWf), and rotational thromboelastometry (ROTEM) were measured before and 1, 3, 6, and 8 h after LPS infusion. Differences between groups were tested with a mixed effects model. RESULTS: In control subjects, lipopolysaccharide caused a fever, transiently decreased platelet levels and lowered activated partial thromboplastin time, while prolonging prothrombin time and increasing D-Dimer and vWf levels. Normothermia prevented the DIC-score exceeding 4, which occurred in 50% of control subjects. Normothermia also reduced the fall in platelet count by 67x109 L-1([95%CI:27-107]; p=0.002), aPTT (mean difference:3s [95%CI:1-5]; p=0.005) and lowered vWf levels by 89% ([95%CI:6-172]; p=0.03), compared to the fever group. ROTEM measurements were unaffected by lipopolysaccharide. CONCLUSION: In human endotoxaemia, induced normothermia decreases markers of endothelial activation and DIC. Maintaining normothermia may reduce coagulopathy in hyperinflammatory states.

Correction: Growing a backbone - functional biomaterials and structures for intervertebral disc (IVD) repair and regeneration: challenges, innovations, and future directions.

Correction for 'Growing a backbone - functional biomaterials and structures for intervertebral disc (IVD) repair and regeneration: challenges, innovations, and future directions' by Matthew D. Harmon et al., Biomater. Sci., 2020, 8, 1216-1239, DOI: .

Survival of African-American and Caucasian men after sipuleucel-T immunotherapy: outcomes from the PROCEED registry.

PURPOSE: African Americans experience greater prostate cancer risk and mortality than do Caucasians. An analysis of pooled phase III data suggested differences in overall survival (OS) between African American and Caucasian men receiving sipuleucel-T. We explored this in PROCEED (NCT01306890), an FDA-requested registry in over 1900 patients with metastatic castration-resistant prostate cancer (mCRPC) treated with sipuleucel-T. PATIENTS AND METHODS: OS for patients who received ≥1 sipuleucel-T infusion was compared between African American and Caucasian men using an all patient set and a baseline prostate-specific antigen (PSA)-matched set (two Caucasians to every one African American with baseline PSAs within 10% of each other). Univariable and multivariable analyses were conducted. Survival data were examined using Kaplan-Meier and Cox proportional hazard methodologies. RESULTS: Median follow-up was 46.6 months. Overall survival differed between African American and Caucasian men with hazard ratios (HR) of 0.81 (95% confidence interval [CI]: 0.68-0.97, P = 0.03) in the all patient set and 0.70 (95% CI: 0.57-0.86, P < 0.001) in the PSA-matched set. Median OS was longer in African Americans than in Caucasian men for both analysis sets, e.g., 35.3 and 25.8 months, respectively, in the PSA-matched set. Similar results were observed in the all patient set. Differences were larger when treatment began at lower baseline PSA; curves were more similar among patients with higher baseline PSA. In patients with baseline PSA below the median, the HR was 0.52 (95% CI: 0.37-0.72, P < 0.001), with median OS of 54.3 versus 33.4 months. Known prognostic factors and African American race (multivariable analyses; HR: 0.60, 95% CI: 0.48-0.74, P < 0.001) were independently associated with OS. Use of post-sipuleucel-T anticancer interventions was balanced between races. CONCLUSION: In this exploratory analysis of a registry including nearly 12% African American men with mCRPC, OS was significantly different between African Americans and Caucasians, indicating further research is warranted.

The alliance formation puzzle in contests with capacity-constraints: A test using American football reception-coverage contest data.

We utilize a contest-theoretic model to demonstrate a version of the alliance formation puzzle that aligns with reception-coverage contests in American football. Namely, secondary defenders can opt for single-coverage-1 v 1 contest. Alternatively, they can choose to ally-form double-coverage or 2 v 1 contest with exogenous intra-alliance prize division-when defending a given receiver. In our theoretical treatment, we find that defenses have a lower equilibrium success rate in preventing the receiver from "getting open" under double-coverage than under single-coverage in the absence of capacity constraints. We also find that this success rate paradox is a necessary condition for the alliance formation puzzle. We then test the theoretical treatment by analyzing 8,508 plays of NCAA and NFL game data within a set of fixed effects, logistic regression models that control for receiver, level-of-play, and season-of-play. We find that equilibrium level of defensive success rises significantly and substantially (p-value < 0.01 and marginal effect of between 13 and 17 percentage points) when moving from single-coverage to double-coverage, ceteris paribus. There is strong evidence that the necessary condition for the alliance formation puzzle does not hold in this setting. We conclude that sufficiently-binding physiological and training-based capacity constraints eliminate the alliance formation puzzle in this setting, as was shown theoretically by Konrad and Kovenock (2009). This empirical result suggests that other contest settings that regularly feature alliance, such as liquidity-constrained conflict, may not be puzzling.

Microbiological profile of nosocomial infections following cardiac arrest: Insights from the targeted temperature management (TTM) trial.

AIMS: Infectious complications frequently occur in intensive care unit patients admitted after out-of-hospital cardiac arrest. There is debate on the effects of temperature management on the incidence of infections, as well as on the efficacy and choice of antibiotic prophylaxis. In this substudy of the targeted temperature management (TTM) trial, we describe the microbiological profile of infectious complications in patients with cardiac arrest and examined the impact of TTM at 33 °C compared to TTM at 36 °C. Furthermore we aimed to determine the association between antibiotic prophylaxis and the incidence of infections. METHODS: This is a posthoc analysis of the TTM cohort. Microbiological data was retrospectively collected for the first 14-days of ICU-admission. Logistic regression was used to determine the relationship between antibiotic prophylaxis and pneumonia adjusted for mortality. RESULTS: Of 696 patients included in this analysis, 158 (23%) developed pneumonia and 28 (4%) had bacteremia with a clinically relevant pathogen. Staphylococcus aureus was the most common pathogen isolated in patients with pneumonia (23%) and in patients with bacteremia (24%). Gram-negative pathogens were most common overall. TTM did not have an impact on the microbiological profile. The use of antibiotic prophylaxis was significantly associated with a reduced risk of infection (OR 0.59, 95%CI 0.43-0.79, p = 0.0005). This association remained significant after correcting for confounders (OR 0.64, 95%CI 0.46-0.90; p = 0.01). The association is not present in a model after correction for clustering within centers (aOR 0.55, 95%CI 0.20-1.47, p = 0.22). Adjustment for mortality did not influence the outcome. CONCLUSION: Gram-negative pathogens are the most common causes of nosocomial infections following cardiac arrest. TTM does not impact the microbiological profile. It remains unclear whether patients in ICUs using antibiotic prophylaxis have a reduced risk of pneumonia and bacteremia that is unrelated to center effects.

Growing a backbone - functional biomaterials and structures for intervertebral disc (IVD) repair and regeneration: challenges, innovations, and future directions.

Back pain and associated maladies can account for an immense amount of healthcare cost and loss of productivity in the workplace. In particular, spine related injuries in the US affect upwards of 5.7 million people each year. The degenerative disc disease treatment almost always arises due to a clinical presentation of pain and/or discomfort. Preferred conservative treatment modalities include the use of non-steroidal anti-inflammatory medications, physical therapy, massage, acupuncture, chiropractic work, and dietary supplements like glucosamine and chondroitin. Artificial disc replacement, also known as total disc replacement, is a treatment alternative to spinal fusion. The goal of artificial disc prostheses is to replicate the normal biomechanics of the spine segment, thereby preventing further damage to neighboring sections. Artificial functional disc replacement through permanent metal and polymer-based components continues to evolve, but is far from recapitulating native disc structure and function, and suffers from the risk of unsuccessful tissue integration and device failure. Tissue engineering and regenerative medicine strategies combine novel material structures, bioactive factors and stem cells alone or in combination to repair and regenerate the IVD. These efforts are at very early stages and a more in-depth understanding of IVD metabolism and cellular environment will also lead to a clearer understanding of the native environment which the tissue engineering scaffold should mimic. The current review focusses on the strategies for a successful regenerative scaffold for IVD regeneration and the need for defining new materials, environments, and factors that are so finely tuned in the healthy human intervertebral disc in hopes of treating such a prevalent degenerative process.

Opinions and Management of Hypothermic Sepsis: Results from an Online Survey.

Hypothermia is associated with high mortality in sepsis, but it is now recognized that this association may simply reflect its higher prevalence in sicker patients. Furthermore, there is evidence to suggest that hypothermia may not represent a dysfunction in sepsis. In this study, we conducted a survey to assess how this scientific evidence relates to the perceptions of health care professionals regarding septic hypothermia, and how such perceptions drive clinical conduct concerning the use of active rewarming in this population. A survey with questions on opinions and management of spontaneous hypothermia in sepsis was developed and posted online at the European Society of Intensive Care Medicine (ESICM) website from March 24th, 2017 to the June 26th, 2017 and distributed by electronic email. Respondents were asked to fill in the survey from the perspective of their usual or average practice in their intensive care unit. In total, there were 440 survey respondents. Respondents were predominantly from Europe (66%) The majority of respondents were intensivists (78%) and worked in an academic hospital (66%). One percent of respondents were nurses. Most respondents (96%) reported that there was no protocol for the management of hypothermic sepsis. Of the respondents, 62% actively rewarmed patients with hypothermic sepsis. Hypothermia was defined as a temperature below 36°C (44%) and below 35°C (15%). Rewarming practices showed large variation in terms of the temperature, at which respondents initiate rewarming as well as the target temperature to which patients are rewarmed. The most predominant first-line rewarming method was forced-warm air followed by warm IV fluids. Rewarming decisions were mostly physician driven (58%). Most respondents thought rewarming was beneficial (43%), a small proportion thought rewarming to be harmful (9%). In conclusion, policies, procedures, and beliefs about spontaneous hypothermia and active rewarming in patients with sepsis are variable. This must be taken into consideration in designing future trials. We propose a working group to define hypothermic sepsis to improve comparability of research.

Practice of mechanical ventilation in cardiac arrest patients and effects of targeted temperature management: A substudy of the targeted temperature management trial.

AIMS: Mechanical ventilation practices in patients with cardiac arrest are not well described. Also, the effect of temperature on mechanical ventilation settings is not known. The aims of this study were 1) to describe practice of mechanical ventilation and its relation with outcome 2) to determine effects of different target temperatures strategies (33 °C versus 36 °C) on mechanical ventilation settings. METHODS: This is a substudy of the TTM-trial in which unconscious survivors of a cardiac arrest due to a cardiac cause were randomized to two TTM strategies, 33 °C (TTM33) and 36 °C (TTM36). Mechanical ventilation data were obtained at three time points: 1) before TTM; 2) at the end of TTM (before rewarming) and 3) after rewarming. Logistic regression was used to determine an association between mechanical ventilation variables and outcome. Repeated-measures mixed modelling was performed to determine the effect of TTM on ventilation settings. RESULTS: Mechanical ventilation data was available for 567 of the 950 TTM patients. Of these, 81% was male with a mean (SD) age of 64 (12) years. At the end of TTM median tidal volume was 7.7 ml/kg predicted body weight (PBW)(6.4-8.7) and 60% of patients were ventilated with a tidal volume ≤ 8 ml/kg PBW. Median PEEP was 7.7cmH2O (6.4-8.7) and mean driving pressure was 14.6 cmH2O (±4.3). The median FiO2 fraction was 0.35 (0.30-0.45). Multivariate analysis showed an independent relationship between increased respiratory rate and 28-day mortality. TTM33 resulted in lower end-tidal CO2 (Pgroup = 0.0003) and higher alveolar dead space fraction (Pgroup = 0.003) compared to TTM36, while PCO2 levels and respiratory minute volume were similar between groups. CONCLUSIONS: In the majority of the cardiac arrest patients, protective ventilation settings are applied, including low tidal volumes and driving pressures. High respiratory rate was associated with mortality. TTM33 results in lower end-tidal CO2 levels and a higher alveolar dead space fraction compared to TTTM36.

Induced hypothermia in patients with septic shock and respiratory failure (CASS): a randomised, controlled, open-label trial.

BACKGROUND: Animal models of serious infection suggest that 24 h of induced hypothermia improves circulatory and respiratory function and reduces mortality. We tested the hypothesis that a reduction of core temperature to 32-34°C attenuates organ dysfunction and reduces mortality in ventilator-dependent patients with septic shock. METHODS: In this randomised, controlled, open-label trial, we recruited patients from ten intensive care units (ICUs) in three countries in Europe and North America. Inclusion criteria for patients with severe sepsis or septic shock were a mean arterial pressure of less than 70 mm Hg, mechanical ventilation in an ICU, age at least 50 years, predicted length of stay in the ICU at least 24 h, and recruitment into the study within 6 h of fulfilling inclusion criteria. Exclusion criteria were uncontrolled bleeding, clinically important bleeding disorder, recent open surgery, pregnancy or breastfeeding, or involuntary psychiatric admission. We randomly allocated patients 1:1 (with variable block sizes ranging from four to eight; stratified by predictors of mortality, age, Acute Physiology and Chronic Health Evaluation II score, and study site) to routine thermal management or 24 h of induced hypothermia (target 32-34°C) followed by 48 h of normothermia (36-38°C). The primary endpoint was 30 day all-cause mortality in the modified intention-to-treat population (all randomly allocated patients except those for whom consent was withdrawn or who were discovered to meet an exclusion criterion after randomisation but before receiving the trial intervention). Patients and health-care professionals giving the intervention were not masked to treatment allocation, but assessors of the primary outcome were. This trial is registered with ClinicalTrials.gov, number NCT01455116. FINDINGS: Between Nov 1, 2011, and Nov 4, 2016, we screened 5695 patients. After recruitment of 436 of the planned 560 participants, the trial was terminated for futility (220 [50%] randomly allocated to hypothermia and 216 [50%] to routine thermal management). In the hypothermia group, 96 (44·2%) of 217 died within 30 days versus 77 (35·8%) of 215 in the routine thermal management group (difference 8·4% [95% CI -0·8 to 17·6]; relative risk 1·2 [1·0-1·6]; p=0·07]). INTERPRETATION: Among patients with septic shock and ventilator-dependent respiratory failure, induced hypothermia does not reduce mortality. Induced hypothermia should not be used in patients with septic shock. FUNDING: Trygfonden, Lundbeckfonden, and the Danish National Research Foundation.

Infectious complications after out-of-hospital cardiac arrest-A comparison between two target temperatures.

BACKGROUND: It has been suggested that target temperature management (TTM) increases the probability of infectious complications after cardiac arrest. We aimed to compare the incidence of pneumonia, severe sepsis and septic shock after out-of-hospital cardiac arrest (OHCA) in patients with two target temperatures and to describe changes in biomarkers and possible mortality associated with these infectious complications. METHODS: Post-hoc analysis of the TTM-trial which randomized patients resuscitated from OHCA to a target temperature of 33°C or 36°C. Prospective data on infectious complications were recorded daily during the ICU-stay. Pneumonia, severe sepsis and septic shock were considered infectious complications. Procalcitonin (PCT) and C-reactive-protein (CRP) levels were measured at 24h, 48h and 72h after cardiac arrest. RESULTS: There were 939 patients in the modified intention-to-treat population. Five-hundred patients (53%) developed pneumonia, severe sepsis or septic shock which was associated with mortality in multivariate analysis (Hazard ratio [HR] 1.39; 95%CI 1.13-1.70; p=0.001). There was no statistically significant difference in the incidence of infectious complications between temperature groups (sub-distribution hazard ratio [SHR] 0.88; 95%CI 0.75-1.03; p=0.12). PCT and CRP were significantly higher for patients with infections at all times (p<0.001), but there was considerable overlap. CONCLUSIONS: Patients who develop pneumonia, severe sepsis or septic shock after OHCA might have an increased mortality. A target temperature of 33°C after OHCA was not associated with an increased risk of infectious complications compared to a target temperature of 36°C. PCT and CRP are of limited value for diagnosing infectious complications after cardiac arrest.