A retrospective multicenter cohort study of the association between anti-Factor Xa values and death, thromboembolism, and bleeding in patients with critical COVID-19.

BACKGROUND: Patients with critical COVID-19 have a high risk of thromboembolism, but intensified thromboprophylaxis has not been proven beneficial. The activity of low-molecular-weight heparins can be monitored by measuring anti-Factor Xa. We aimed to study the association between anti-Factor Xa values and death, thromboembolism, and bleeding in patients with critical COVID-19. METHOD: This retrospective cohort study included adult patients with critical COVID-19 admitted to an intensive care unit at three Swedish hospitals between March 2020 and May 2021 with at least one valid peak and/or trough anti-Factor Xa value. Within the peak and trough categories, patients' minimum, median, and maximum values were determined. Logistic regressions with splines were used to assess associations. RESULTS: In total, 408 patients had at least one valid peak and/or trough anti-Factor Xa measurement, resulting in 153 patients with peak values and 300 patients with trough values. Lower peak values were associated with thromboembolism for patients' minimum (p = 0.01), median (p = 0.005) and maximum (p = 0.001) values. No association was seen between peak values and death or bleeding. Higher trough values were associated with death for median (p = 0.03) and maximum (p = 0.002) values and with both bleeding (p = 0.01) and major bleeding (p = 0.02) for maximum values, but there were no associations with thromboembolism. CONCLUSIONS: Measuring anti-Factor Xa activity may be relevant for administrating low-molecular-weight heparin to patients with critical COVID-19. Lower peak values were associated with an increased risk of thromboembolism, and higher trough values were associated with an increased risk of death and bleeding. Prospective studies are needed to confirm the results. TRIAL REGISTRATION: The study was retrospectively registered at Clinicaltrials.gov, NCT05256524, February 24, 2022.

Treatment Strategies and Perforation Rate of Acute Appendicitis During the Early Phase of the COVID-19 Pandemic: A Swedish Cohort Study.

INTRODUCTION: It is unknown whether the COVID-19 pandemic has had an impact on emergency surgical care in Sweden. This study aimed to compare frequency, treatment strategies, severity, and complication rate of appendicitis during the initial phase of the COVID-19 pandemic with those of previous years. METHODS: In this single-center study, we identified all patients admitted with appendicitis between March 16 and June 16, 2020, at the Stockholm South General Hospital, and compared these with patients hospitalized with appendicitis during the same calendar period the three previous years. We used multivariate logistic regression to calculate Odds Ratios (OR) with 95% confidence intervals as measurement of the association between appendicitis treatment and perforation rate during the COVID-19 period compared to the nonCOVID-19 periods. RESULTS: In all, 892 patients hospitalized with appendicitis were identified, 241 (27%) in 2020 (Covid period group) and the remaining 651 (73%) during the same calendar periods 2017-2019 (nonCovid period group). Appendicitis during the COVID-19 period was associated with double the risk for undergoing conservative treatment (OR 2.15 [95% CI 1.44-3.21]), and a decreased risk for being diagnosed with perforated appendicitis (OR 0.68 [95% CI 0.48-0.98]). CONCLUSIONS: Patients admitted with appendicitis during the early phase of the COVID-19 pandemic in Stockholm, Sweden, were more likely to receive conservative treatment and less likely to suffer from perforated appendicitis compared to patients hospitalized before the pandemic. Hypothetically, this difference could have been due to pandemic-associated resource reallocation, or it may simply reflect an increasing trend towards conservative management of appendicitis.

An observational study of intermediate- or high-dose thromboprophylaxis for critically ill COVID-19 patients.

BACKGROUND: Critically ill COVID-19 patients have a high reported incidence of thromboembolic complications and the optimal dose of thromboprophylaxis is not yet determined. The aim of this study was to investigate if 90-day mortality differed between patients treated with intermediate- or high-dose thromboprophylaxis. METHOD: In this retrospective study, all critically ill COVID-19 patients admitted to intensive care from March 6th until July 15th, 2020, were eligible. Patients were categorized into groups according to daily dose of thromboprophylaxis. Dosing was based on local standardized recommendations, not on degree of critical illness or risk of thrombosis. Cox proportional hazards regression was used to estimate hazard ratios of death within 90 days from ICU admission. Multivariable models were adjusted for sex, age, body-mass index, Simplified Acute Physiology Score III, invasive respiratory support, glucocorticoids, and dosing strategy of thromboprophylaxis. RESULTS: A total of 165 patients were included; 92 intermediate- and 73 high-dose thromboprophylaxis. Baseline characteristics did not differ between groups. The 90-day mortality was 19.6% in patients with intermediate-dose and 19.2% in patients with high-dose thromboprophylaxis. Multivariable hazard ratio of death within 90 days was 0.74 (95% CI, 0.36-1.53) for the high-dose group compared to intermediate-dose group. Multivariable hazard ratio for thromboembolic events and bleedings within 28 days was 0.93 (95% CI 0.37-2.29) and 0.84 (95% CI 0.28-2.54) for high versus intermediate dose, respectively. CONCLUSIONS: A difference in 90-day mortality between intermediate- and high-dose thromboprophylaxis could neither be confirmed nor rejected due to a small sample size.

Perirenal Fat Surface Area and Oncologic Outcome in Elective Colon Cancer Surgery.

BACKGROUND: Central obesity is associated with surgical difficulties, but few studies explore the relationship with long-term results after colon cancer surgery. OBJECTIVE: The purpose of this study was to investigate the association between perirenal fat surface area, a proxy for total visceral fat, and oncologic outcome after intestinal resection for colon cancer. DESIGN: We investigated the association between perirenal fat surface area (exposure) on recurrence and death (outcome) in patients undergoing surgery with curative intent for colon cancer. SETTINGS: The study was conducted at Stockholm South General Hospital, serving a population of 600,000. PATIENTS: Patients (N = 733) without metastases at diagnosis who had a preoperative CT and had undergone elective colon resection between 2006 and 2016 were included. MAIN OUTCOME MEASURES: We compared overall survival, recurrence-free survival, and cause-specific survival by perirenal fat surface area. RESULTS: Patients with high perirenal fat surface area (fourth quartile) had more often left-sided tumors (45% vs 32% in the first quartile) and experienced more postoperative complications (29% vs 13%), but there were no differences in pathologic T and N stage, radicality of surgery, or adjuvant chemotherapy treatment. Overall survival decreased by increasing cancer stage but was not different between perirenal fat surface area categories. The HR for recurrence-free survival per centimeter squared increase in perirenal fat surface area was 1.00 (95% CI, 0.99-1.01) adjusted for age, sex, ASA category, tumor location, and postoperative complication Clavien-Dindo ≥2. The cumulative incidence of recurrence with death as a competing risk was not statistically different between perirenal fat surface area categories (p = 0.06). Subgroup analyses showed a nonsignificant tendency for men with low perirenal fat surface area to have a lower risk of recurrence and women a higher risk. LIMITATIONS: In all register-based studies there can be randomly distributed errors. The results can only be generalized to colon resections. Our cohort ranged over a large year span. CONCLUSIONS: We found no association between perirenal fat surface area and overall survival, recurrence-free survival, or cause-specific cumulative incidence of recurrence in patients undergoing colon resection for cancer. See Video Abstract at http://links.lww.com/DCR/B326. LA SUPERFICIE DE GRASA PERIRRENAL Y EL RESULTADO ONCOLGICO EN CIRUGA ELECTIVA DE CNCER DE COLON: ANTECEDENTES:La obesidad central está asociada con dificultades quirúrgicas, pero pocos estudios exploran la relación de los resultados a largo plazo después de cirugía de cáncer de colon.OBJETIVO:Investigar la asociación entre la superficie de la grasa perirrenal, como un indicador de la grasa visceral total y el resultado oncológico después de una resección intestinal por cáncer de colon.DISEÑO:Se estudió la asociación entre el área de la superficie de la grasa perirrenal (expuesta) con la recurrencia y la muerte (resultado) de pacientes sometidos a cirugía con intención curativa por cáncer de colon.AJUSTES:Atención brindada por el Hospital General del Sur de Estocolmo a una población de 600,000 habitantes.PACIENTES:Aquellos pacientes sin metástasis (n = 733) en el momento del diagnóstico que tuvieron una tomografía computada preoperatoria y que se sometieron a una resección electiva de colon entre 2006-2016.PRINCIPALES MEDIDAS DE RESULTADO:Comparamos la sobrevida general, la sobrevida libre de recurrencia y la sobrevida específica de la causa, por área de superficie de grasa perirrenal.RESULTADOS:Los pacientes con una mayor área de superficie de grasa perirrenal (cuarto cuartil) tuvieron más frecuentemente tumores del lado izquierdo (45% frente a 32% en el primer cuartil) y sufrieron más complicaciones postoperatorias (29% frente a 13%), pero no hubieron diferencias en el Estadío patológico T y N, ni en lo radical de la cirugía o del tratamiento de quimioterapia adyuvante. La supervivencia general disminuyó al aumentar el estadio del cáncer, pero no fue diferente entre las categorías de área de superficie grasa perirrenal. La razón de riesgo para la sobrevida libre de recurrencia por aumento de cm2 en el área de la superficie grasa perirrenal fue de 1.00 (intervalo de confianza del 95%: 0.99-1.01) ajustada por edad, sexo, categoría de la Sociedad Americana de Anestesiólogos, ubicación del tumor y complicación postoperatoria según Clavien-Dindo ≥ 2) La incidencia acumulada de recurrencia con muerte como un riesgo competitivo no fue estadísticamente diferente entre las categorías de área de superficie grasa perirrenal (p = 0.06). Los análisis de subgrupos mostraron una tendencia no significativa para que los hombres con un área de superficie menor en grasa perirrenal tengan un menor riesgo de recurrencia y las mujeres un mayor riesgo.LIMITACIONES:En todos los estudios basados en registros puede haber errores distribuidos aleatoriamente. Los resultados solo pueden generalizarse a resecciones de colon. Nuestra cohorte osciló durante un gran lapso de años.CONCLUSIONES:No se encontró asociación entre el área de superficie de la grasa perirrenal y la sobrevida general, ni con la sobrevida libre de recurrencia o la incidencia acumulada de recurrencia específica de la causa en pacientes sometidos a resección de colon por cáncer. Consulte Video Resumen en http://links.lww.com/DCR/B326. (Traducción-Dr Xavier Delgadillo).

Prone positioning in mechanically ventilated patients with severe acute respiratory distress syndrome and coronavirus disease 2019.

BACKGROUND: The management of COVID-19 ARDS is debated. Although current evidence does not suggest an atypical acute respiratory distress syndrome (ARDS), the physiological response to prone positioning is not fully understood and it is unclear which patients benefit. We aimed to determine whether proning increases oxygenation and to evaluate responders. METHODS: This case series from a single, tertiary university hospital includes all mechanically ventilated patients with COVID-19 and proning between 17 March 2020 and 19 May 2020. The primary measure was change in PaO2 :FiO2 . RESULTS: Forty-four patients, 32 males/12 females, were treated with proning for a total of 138 sessions, with median (range) two (1-8) sessions. Median (IQR) time for the five sessions was 14 (12-17) hours. In the first session, median (IQR) PaO2 :FiO2 increased from 104 (86-122) to 161 (127-207) mm Hg (P < .001). 36/44 patients (82%) improved in PaO2 :FiO2 , with a significant increase in PaO2 :FiO2 in the first three sessions. Median (IQR) FiO2 decreased from 0.7 (0.6-0.8) to 0.5 (0.35-0.6) (<0.001). A significant decrease occurred in the first three sessions. PaO2 , tidal volumes, PEEP, mean arterial pressure (MAP), and norepinephrine infusion did not differ. Primarily, patients with PaO2 :FiO2 approximately < 120 mm Hg before treatment responded to proning. Age, sex, BMI, or SAPS 3 did not predict success in increasing PaO2 :FiO2 . CONCLUSION: Proning increased PaO2 :FiO2 , primarily in patients with PaO2 :FiO2 approximately < 120 mm Hg, with a consistency over three sessions. No characteristic was associated with non-responding, why proning may be considered in most patients. Further study is required to evaluate mortality.

Dosing of thromboprophylaxis and mortality in critically ill COVID-19 patients.

BACKGROUND: A substantial proportion of critically ill COVID-19 patients develop thromboembolic complications, but it is unclear whether higher doses of thromboprophylaxis are associated with lower mortality rates. The purpose of the study was to evaluate the association between initial dosing strategy of thromboprophylaxis in critically ill COVID-19 patients and the risk of death, thromboembolism, and bleeding. METHOD: In this retrospective study, all critically ill COVID-19 patients admitted to two intensive care units in March and April 2020 were eligible. Patients were categorized into three groups according to initial daily dose of thromboprophylaxis: low (2500-4500 IU tinzaparin or 2500-5000 IU dalteparin), medium (> 4500 IU but < 175 IU/kilogram, kg, of body weight tinzaparin or > 5000 IU but < 200 IU/kg of body weight dalteparin), and high dose (≥ 175 IU/kg of body weight tinzaparin or ≥ 200 IU/kg of body weight dalteparin). Thromboprophylaxis dosage was based on local standardized recommendations, not on degree of critical illness or risk of thrombosis. Cox proportional hazards regression was used to estimate hazard ratios with corresponding 95% confidence intervals of death within 28 days from ICU admission. Multivariable models were adjusted for sex, age, body mass index, Simplified Acute Physiology Score III, invasive respiratory support, and initial dosing strategy of thromboprophylaxis. RESULTS: A total of 152 patients were included: 67 received low-, 48 medium-, and 37 high-dose thromboprophylaxis. Baseline characteristics did not differ between groups. For patients who received high-dose prophylaxis, mortality was lower (13.5%) compared to those who received medium dose (25.0%) or low dose (38.8%), p = 0.02. The hazard ratio of death was 0.33 (95% confidence intervals 0.13-0.87) among those who received high dose, and 0.88 (95% confidence intervals 0.43-1.83) among those who received medium dose, as compared to those who received low-dose thromboprophylaxis. There were fewer thromboembolic events in the high (2.7%) vs medium (18.8%) and low-dose thromboprophylaxis (17.9%) groups, p = 0.04. CONCLUSIONS: Among critically ill COVID-19 patients with respiratory failure, high-dose thromboprophylaxis was associated with a lower risk of death and a lower cumulative incidence of thromboembolic events compared with lower doses. TRIAL REGISTRATION: Clinicaltrials.gov NCT04412304 June 2, 2020, retrospectively registered.

Long-Term Results after Anastomotic Leakage following Rectal Cancer Surgery: A Comparison of Treatment with Endo-Sponge and Transanal Irrigation.

OBJECTIVE: We aimed to evaluate long-term results in patients from regular health care treated with endoscopic transanal closure system, that is, endoscopic vacuum-assisted closure system (EVAC) compared to transanal irrigation. METHODS: In this retrospective, medical chart-based, observational study, we included patients with anastomotic leakage after low anterior resection for rectal cancer from 3 Stockholm hospitals 2006-2016 and compared time to first stoma closure in a Kaplan-Meier model and the proportion of patients who were stoma-free at end of follow-up. RESULTS: Anastomotic leakage was found in 81 patients who were followed up in median 5.9 years (min-max: 0.53-13). EVAC was used on 14 (17%) patients and transanal irrigation on 34 (42%) patients. The remaining 33 (41%) patients either got a permanent colostomy or were treated only with antibiotics and percutaneous drainage. Treatment with EVAC or transanal irrigation led to similar rates of stoma closure, both when comparing all patients, and when comparing patients with similar defects. At the end of follow-up, 43% of patients treated with EVAC and 50% of patients treated with repeated irrigation were stoma-free (p = 0.75). CONCLUSIONS: We found no evidence of better outcomes in patients treated with EVAC. The study was, however, limited by small sample size.

Retained sex toys: an increasing and possibly preventable medical condition.

PURPOSE: Retained foreign rectal objects may require surgical removal. To estimate the magnitude of this problem, we report the incidence and treatment of retained rectal objects at a large emergency hospital, and calculate incidence rates at the national level in Sweden. METHODS: All local patient records during 2009-2017 with the diagnosis foreign body in anus and rectum (ICD-10 T185) were accessed and analyzed retrospectively. All Swedish in- and outpatient visits during 2005-2016 with the code T185 were accessed from the National Patient Register. RESULTS: We show an increasing incidence in rectal foreign bodies in Swedish national data. The increase was most noticeable in men, and in our local register there was an overrepresentation of sex toys leading to laparotomy and stoma. CONCLUSIONS: To mitigate surgical cost and comorbidity, policies to decrease the risk of retained sex toys could be considered.

Intraoperative cultures during appendectomy in children are poor predictors of pathogens and resistance patterns in cultures from postoperative abscesses.

BACKGROUND: Intraoperative cultures are commonly sent in complicated appendicitis. Culture-guided antibiotics used to prevent postoperative infectious complications are debated. In this study, we describe the microbial overlap between intraoperative and abscess cultures, and antibiotic resistance patterns. METHOD: A local register of a children's hospital treating children 0-15 years old with appendicitis between 2006 and 2013 was used to find cases with intraoperative cultures, and cultures from drained or aspirated postoperative intraabdominal abscesses. Culture results, administered antibiotics, their nominal coverage of the identified microorganisms, and rationales given for changes in antibiotic regimens were collected from electronic medical records. RESULTS: In 25 of 35 patients who met inclusion criteria, there was no overlap between the intraoperative and abscess cultures. In 33 of 35 patients, all identified intraoperative organisms were covered with postoperative antibiotics. In 14 patients, organisms in the abscess culture were not covered by administered antibiotics. Enterococci not found in the intraoperative culture were found in 12 of 35 abscesses. We found no difference in the antibiotic coverage between rationales given for antibiotic changes. CONCLUSION: The overlap between intraoperative cultures and cultures from subsequent abscesses was small. Lack of antibiotic coverage of intraoperative cultures was not an important factor in abscess formation.

Trends in the Management of Acute Appendicitis in a Single-Center Quality Register Cohort of 5,614 Patients.

Acute appendicitis is one of the most common reasons for emergency surgery. At Stockholm South General Hospital, information on all patients - 15 years or older - undergoing surgery for acute appendicitis is included in a quality register. Data on surgical method, preoperative imaging, hospital stay, intraoperative findings, and 30-day complications were recorded for each patient. From January 2004 to December 2014, 5,614 consecutive patients were registered. The percentage of patients examined with preoperative imaging increased from 30% in 2004 to 93% in 2014. The use of laparoscopic appendectomy increased from 6 to 79%. Negative appendectomies decreased from 7.5-10 to 1.7%. The mean perforation rate was 28.6%. Some form of postoperative complication occurred in 6.6% of those on whom laparoscopy was performed and 10.5% of those who underwent an open surgery, with a significant difference (p < 0.001) in the rate of surgical site infections (surgical site infections, higher in open cases) but with no difference in the number of deep postoperative abscesses. The overall hospital stay decreased from 2004 to 2014 for perforated and non-perforated appendicitis. The overall 30-day mortality rate was 0.12%. Changes in preoperative imaging and treatment strategy for appendicitis during this period resulted in a lower rate of negative appendectomies with acceptable complication rates and shortened hospital stay.

Survival among 148 patients with an incidentally detected appendiceal tumours at surgery for acute appendicitis: a population-based cohort follow-up study.

PURPOSE: To investigate the long-term prognosis of appendiceal tumours incidentally detected at appendicectomy for suspicion of benign appendicitis. METHODS: A retrospective register-based single centre cohort study was carried out, using data from the local acute appendicectomy quality register of cases operated on at the Department of Surgery, South General Hospital, Stockholm, Sweden. The local colorectal cancer register was also used to identify appendix tumours. The study period was between January 2004 and January 2023. Survival was calculated according to the Kaplan-Meier method. RESULTS: A total of 11,888 patients were registered in the acute acute appendicectomy register, 54% males and 46% females, median age 32 (Q1 = 21, Q3 = 47) (with 33.7% were 41 years or older). From the appendicectomy and colorectal registers 148 (1.2% of the total cohort) appendiceal tumours were found; 60% in females and 40% in males, median age 56 (Q1 = 43, Q3 = 70) (with 78.4% being 41 years or older). Tumours found were: Low grade Appendiceal Mucinous Neoplasms (LAMN, N = 64); Neuroendocrine Tumours (NET N = 24); adenocarcinomas or other form of carcinomas (N = 57); and adenomas (N = 3). The overall 5-year survival in patients operated for LAMN was 96.8%, for NET 93.3% and for adenocarcinoma 69.7%. The overall 5-year survival for all tumour patients was 85.7%. For the younger patients (< 51 years) with LAMN and NET, almost all survived to the end of follow-up. Survival of patients in the carcinoma group was statistically significantly lower than for the LAMN and NET groups, especially in females 51 years or older. In the group of tumour patients undergoing surgery (n = 146), primary surgery was laparoscopic in 47% and open in 52%. Two patients did not undergo surgery due to widespread disease. In 64% of cases operation was acute, whereas it was delayed and/or planned in 34%. Most procedures were laparoscopic appendicectomy 36%, followed by open appendicectomy 30%, right-sided hemicolectomy 14.6% (open 11.6% and laparoscopic 3%, acute operation 5.5%), ileocaecal resection 5% (acute operation 3.4%), and staging laparoscopy 7%. In 38% of the operated patients the tumour was discovered incidentally at histopathology examination. Two patients had CRS and HIPEC as the initial operation. Forthy-three per cent of the 146 tumour patients operated underwent a second procedure: CRS and HIPEC in 23.3% and right-sided hemicolectomy in 13.6% (laparoscopic 8.2% open 5.4%). CONCLUSION: Survival was high for patients with incidentally detected appendiceal LAMN or NET, but not so for carcinoma. Survival was lower in the carcinoma group older than 50 years, especially those sick and females.

Increased Incidence and Mortality of Civilian Penetrating Traumatic Brain Injury in Sweden: A Single-Center Registry-Based Study.

BACKGROUND: Penetrating trauma to the head and neck has increased during the past decade in Sweden. The aim of this study was to characterize these injuries and evaluate the outcomes for patients treated at a tertiary trauma center. METHODS: Swedish trauma registry data were extracted on patients with head and neck injuries admitted to Karolinska University Hospital (Stockholm, Sweden) between 2011 and 2019. Outcome information was extracted from hospital records, with the primary endpoints focusing on the physiological outcome measures and the secondary endpoints on the surgical and radiological outcomes. RESULTS: Of 1436 patients with penetrating trauma, 329 with penetrating head and neck injuries were identified. Of the 329 patients, 66 (20%) had suffered a gunshot wound (GSW), 240 (73%) a stab wound (SW), and 23 (7%) an injury from other trauma mechanisms (OTMs). The median age for the corresponding 3 groups of patients was 25, 33, and 21 years, respectively. Assault was the primary intent, with 54 patients experiencing GSWs (81.8%) and 158 SWs (65.8%). Patients with GSWs had more severe injuries, worse admission Glasgow coma scale, motor, scores, and a higher intubation rate at the injury site. Most GSW patients underwent major surgery (59.1%) as the initial procedure and were more likely to have intracranial hemorrhage (21.2%). The 30-day mortality was 45.5% (n = 30) for GSWs, 5.4% (n = 13) for SWs, and 0% (n = 0) for OTMs. There was an annual increase in the incidence and mortality for GSWs and SWs. CONCLUSIONS: Between 2011 and 2019, an increasing annual trend was found in the incidence and mortality from penetrating head and neck trauma in Stockholm, Sweden. GSW patients experienced more severe injuries and intracranial hemorrhage and underwent more surgical interventions compared with patients with SWs and OTMs.

Prehospital transportation of severe penetrating trauma victims in Sweden during the past decade: a police business?

INTRODUCTION: Sweden is facing a surge of gun violence that mandates optimized prehospital transport approaches, and a survey of current practice is fundamental for such optimization. Management of severe, penetrating trauma is time sensitive, and there may be a survival benefit in limiting prehospital interventions. An important aspect is unregulated transportation by police or private vehicles to the hospital, which may decrease time but may also be associated with adverse outcomes. It is not known whether transport of patients with penetrating trauma occurs outside the emergency medical services (EMS) in Sweden and whether it affects outcome. METHOD: This was a retrospective, descriptive nationwide study of all patients with penetrating trauma and injury severity scores (ISSs) ≥ 15 registered in the Swedish national trauma registry (SweTrau) between June 13, 2011, and December 31, 2019. We hypothesized that transport by police and private vehicles occurred and that it affected mortality. RESULT: A total of 657 patients were included. EMS transported 612 patients (93.2%), police 10 patients (1.5%), and private vehicles 27 patients (4.1%). Gunshot wounds (GSWs) were more common in police transport, 80% (n = 8), compared with private vehicles, 59% (n = 16), and EMS, 32% (n = 198). The Glasgow coma scale score (GCS) in the emergency department (ED) was lower for patients transported by police, 11.5 (interquartile range [IQR] 3, 15), in relation to EMS, 15 (IQR 14, 15) and private vehicles 15 (IQR 12.5, 15). The 30-day mortality for EMS was 30% (n = 184), 50% (n = 5) for police transport, and 22% (n = 6) for private vehicles. Transport by private vehicle, odds ratio (OR) 0.65, (confidence interval [CI] 0.24, 1.55, p = 0.4) and police OR 2.28 (CI 0.63, 8.3, p = 0.2) were not associated with increased mortality in relation to EMS. CONCLUSION: Non-EMS transports did occur, however with a low incidence and did not affect mortality. GSWs were more common in police transport, and victims had lower GCS scorescores when arriving at the ED, which warrants further investigations of the operational management of shooting victims in Sweden.

Prehospital and emergency department airway management of severe penetrating trauma in Sweden during the past decade.

BACKGROUND: Prehospital tracheal intubation (TI) is associated with increased mortality in patients with penetrating trauma, and the utility of prehospital advanced airway management is debated. The increased incidence of deadly violence in Sweden warrants a comprehensive evaluation of current airway management for patients with penetrating trauma in the Swedish prehospital environment and on arrival in the emergency department (ED). METHODS: This was an observational, multicenter study of all patients with penetrating trauma and injury severity scores (ISSs) ≥ 15 included in the Swedish national trauma register (SweTrau) between 2011 and 2019. We investigated the frequency and characteristics of prehospital and ED TI, including 30-day mortality and patient characteristics associated with TI. RESULT: Of 816 included patients, 118 (14.5%) were intubated prehospitally, and 248 (30.4%) were intubated in the ED. Patients who were intubated prehospitally had a higher ISS, 33 (interquartile range [IQR] 25, 75), than those intubated in the ED, 25 (IQR 18, 34). Prehospital TI was associated with a higher associated mortality, OR 4.26 (CI 2.57, 7.27, p < 0.001) than TI in the ED, even when adjusted for ISS (OR 2.88 [CI 1.64, 5.14, p < 0.001]). Hemodynamic collapse (≤ 40 mmHg) and low GCS score (≤ 8) were the characteristics most associated with prehospital TI. Traumatic cardiac arrests (TCAs) occurred in 154 (18.9%) patients, of whom 77 (50%) were intubated prehospitally and 56 (36.4%) were intubated in the ED. A subgroup analysis excluding TCA showed that patients with prehospital TI did not have a higher mortality rate than those with ED TI, OR 2.07 (CI 0.93, 4.51, p = 0.068), with OR 1.39 (0.56, 3.26, p = 0.5) when adjusted for ISS. CONCLUSION: Prehospital TI was associated with a higher mortality rate than those with ED TI, which was specifically related to TCA; intubation did not affect mortality in patients without cardiac arrest. Mortality was high when airway management was needed, regardless of cardiac arrest, thereby emphasizing the challenges posed when anesthesia is needed. Several interventions, including whole blood transfusions, the implementation of second-tier EMS units and measures to shorten scene times, have been initiated in Sweden to counteract these challenges.

Improved oxygenation in prone positioning of mechanically ventilated patients with COVID-19 acute respiratory distress syndrome is associated with decreased pulmonary shunt fraction: a prospective multicenter study.

BACKGROUND: Prone position is used in acute respiratory distress syndrome and in coronavirus disease 2019 (Covid-19) acute respiratory distress syndrome (ARDS). However, physiological mechanisms remain unclear. The aim of this study was to determine whether improved oxygenation was related to pulmonary shunt fraction (Q's/Q't), alveolar dead space (Vd/Vtalv) and ventilation/perfusion mismatch (V'A/Q'). METHODS: This was an international, prospective, observational, multicenter, cohort study, including six intensive care units in Sweden and Poland and 71 mechanically ventilated adult patients. RESULTS: Prone position increased PaO2:FiO2 after 30 min, by 78% (83-148 mm Hg). The effect persisted 120 min after return to supine (p < 0.001). The oxygenation index decreased 30 min after prone positioning by 43% (21-12 units). Q's/Q't decreased already after 30 min in the prone position by 17% (0.41-0.34). The effect persisted 120 min after return to supine (p < 0.005). Q's/Q't and PaO2:FiO2 were correlated both in prone (Beta -137) (p < 0.001) and in the supine position (Beta -270) (p < 0.001). V'A/Q' was unaffected and did not correlate to PaO2:FiO2 (p = 0.8). Vd/Vtalv increased at 120 min by 11% (0.55-0.61) (p < 0.05) and did not correlate to PaO2:FiO2 (p = 0.3). The ventilatory ratio increased after 30 min in the prone position by 58% (1.9-3.0) (p < 0.001). PaO2:FiO2 at baseline predicted PaO2:FiO2 at 30 min after proning (Beta 1.3) (p < 0.001). CONCLUSIONS: Improved oxygenation by prone positioning in COVID-19 ARDS patients was primarily associated with a decrease in pulmonary shunt fraction. Dead space remained high and the global V'A/Q' measure could not explain the differences in gas exchange.

Effects of 12 mg vs. 6 mg dexamethasone on thromboembolism and bleeding in patients with critical COVID-19 - a post hoc analysis of the randomized, blinded COVID STEROID 2 trial.

BACKGROUND: Thromboembolism is more common in patients with critical COVID-19 than in other critically ill patients, and inflammation has been proposed as a possible mechanism. The aim of this study was to investigate if 12 mg vs. 6 mg dexamethasone daily reduced the composite outcome of death or thromboembolism in patients with critical COVID-19. METHODS: Using additional data on thromboembolism and bleeding we did a post hoc analysis of Swedish and Danish intensive care unit patients enrolled in the blinded randomized COVID STEROID 2 trial comparing 12 mg vs. 6 mg dexamethasone daily for up to 10 days. The primary outcome was a composite outcome of death or thromboembolism during intensive care. Secondary outcomes were thromboembolism, major bleeding, and any bleeding during intensive care. RESULTS: We included 357 patients. Whilst in intensive care, 53 patients (29%) in the 12 mg group and 53 patients (30%) in the 6 mg group met the primary outcome with an unadjusted absolute risk difference of - 0.5% (95% CI - 10 to 9.5%, p = 1.00) and an adjusted OR of 0.93 (CI 95% 0.58 to 1.49, p = 0.77). We found no firm evidence of differences in any of the secondary outcomes. CONCLUSIONS: Among patients with critical COVID-19, 12 mg vs. 6 mg dexamethasone daily did not result in a statistically significant difference in the composite outcome of death or thromboembolism. However, uncertainty remains due to the limited number of patients.

Incidence, Demographics, and Outcomes of Penetrating Trauma in Sweden During the Past Decade.

Trauma injury is the sixth leading cause of death worldwide, and interpersonal violence is one of the major contributors in particular regarding injuries to the head and neck. The incidence, demographics, and outcomes of penetrating trauma reaching hospitals in Sweden are not known. We report the largest, nationwide epidemiological study of penetrating injuries in Sweden, using the Swedish Trauma Registry (SweTrau). A multi-center retrospective descriptive study of 4,776 patients was conducted with penetrating injuries in Sweden, between 2012 and 2018. Due to the increase in coverage of the SweTrau registry during the same period, we chose to analyze the average number of cases for the time intervals 2013-2015 and 2016-2018 and compare those trends to the reports of the Swedish National Council for Crime Prevention (Brå) as well. A total of 663 patients had Injury Severity Score (ISS) ≥ 15 at admission and were included in the study. Three hundred and sixty-eight (55.5%) were stab wounds (SW), 245 (37.0%) gunshot wounds (GSW), and 50 (7.5%) other traumas. A majority of the cases involved injuries to the head, neck, and face. SW increased from 145 during 2013-2015 to 184 during the second period of 2016-2018. The increase was greater for GSW from 92 to 141 during the same respective periods. This trend of increase over time was also seen in head, neck, and face injuries. The 30-day mortality was unaffected (48-47%) in GSW and trended toward lower in SW (24-21%) when comparing 2013-2015 with 2016-2018. Patients with head trauma had 45% mortality compared to 18% for non-head trauma patients. Head trauma also resulted in worse outcomes, only 13% had Glasgow outcome score (GOS) 5 compared to 27% in non-head trauma. The increasing number of cases of both SW and GSW corresponded well with reports from Brå although further studies also are needed to address deaths outside of hospitals and not registered at the SweTrau. The majority of cases had injuries to the head, neck, and face and were associated with higher mortality and poor outcomes. Further studies are needed to understand the contributing factors to these worse outcomes in Sweden and whether more targeted trauma care of these patients can improve outcomes.

Quantum chemical modeling of the cardiolipin headgroup.

Cardiolipin is a key lipid component in many biological membranes. Proton conduction and proton-lipid interactions on the membrane surface are thought to be central to mitochondrial energy production. However, details on the cardiolipin headgroup structure are lacking and the protonation state of this lipid at physiological pH is not fully established. Here we present ab initio DFT calculations of the cardiolipin (CL) headgroup and its 2'-deoxy derivative (dCL), with the aim of establishing a connection between structure and acid-base equilibrium in CL. Furthermore, we investigate the effects of solvation on the molecular conformations. In our model, both CL and dCL showed a significant gap between the two pK(a) values, with pK(a2) above the physiological range, and intramolecular hydrogen bonds were found to play a central role in the conformations of both molecules. This behavior was also observed experimentally in CL. Structures derived from the DFT calculations were compared with those obtained experimentally, collected for CL in the Protein Data Bank, and conformations from previous as well as new molecular dynamics simulations of cardiolipin bilayers. Transition states for proton transfer in CL were investigated, and we estimate that protons can exchange between phosphate groups with an approximate 4-5 kcal/mol barrier. Computed NMR and IR spectral properties were found to be in reasonable agreement with experimental results available in the literature.

Molecular dynamics simulations of cardiolipin bilayers.

Cardiolipin is a key lipid component in the inner mitochondrial membrane, where the lipid is involved in energy production, cristae structure, and mechanisms in the apoptotic pathway. In this article we used molecular dynamics computer simulations to investigate cardiolipin and its effect on the structure of lipid bilayers. Three cardiolipin/POPC bilayers with different lipid compositions were simulated: 100, 9.2, and 0% cardiolipin. We found strong association of sodium counterions to the carbonyl groups of both lipid types, leaving in the case of 9.2% cardiolipin virtually no ions in the aqueous compartment. Although binding occurred primarily at the carbonyl position, there was a preference to bind to the carbonyl groups of cardiolipin. Ion binding and the small headgroup of cardiolipin gave a strong ordering of the hydrocarbon chains. We found significant effects in the water dipole orientation and water dipole potential which can compensate for the electrostatic repulsion that otherwise should force charged lipids apart. Several parameters relevant for the molecular structure of cardiolipin were calculated and compared with results from analyses of coarse-grained simulations and available X-ray structural data.

Polymorphic phase behavior of cardiolipin derivatives studied by coarse-grained molecular dynamics.

Cardiolipin (CL) is a negatively charged four acyl chain lipid, associated with energy production in bacterial and mitochondrial membranes. Due to the shape of CL, negative curvatures of aggregates are favorable if the charges in the head group can be reduced. The phase polymorphism of CL, and of associated derivatives with 2, 3, 4, or 5 chains, has been determined previously and offers a model system in which micellar, lamellar, and inverse hexagonal phases can be observed. We present an extension to a previously established coarse-grained molecular dynamics model with the aim of reproducing the different CL phases with two adjustable parameters: the number of acyl chains and the effective head group charge. With molecular dynamics simulations of large lipid systems, we observed transitions between different phases on the nanosecond to microsecond time scale. Charge screening by high salt or low pH was successfully modeled by a reduction of phosphate charge, which led to the adoption of aggregates with more negative curvature. Although specific ion binding at the interface and other atomistic details are sacrificed in the coarse-grained model, we found that it captures general phase features over a large range of aggregate geometries.