Trends in Incidence and Outcomes of Cardiac Arrest Occurring in Swedish ICUs.

OBJECTIVE: To determine temporal trends in the incidence of cardiac arrest occurring in the ICU (ICU-CA) and its associated long-term mortality. DESIGN: Retrospective observational study. SETTING: Swedish ICUs, between 2011 and 2017. PATIENTS: Adult patients (≥18 yr old) recorded in the Swedish Intensive Care Registry (SIR). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: ICU-CA was defined as a first episode of cardiopulmonary resuscitation and/or defibrillation following an ICU admission, as recorded in SIR or the Swedish Cardiopulmonary Resuscitation Registry. Annual adjusted ICU-CA incidence trend (all admissions) was estimated using propensity score-weighted analysis. Six-month mortality trends (first admissions) were assessed using multivariable mixed-effects logistic regression. Analyses were adjusted for pre-admission characteristics (sex, age, socioeconomic status, comorbidities, medications, and healthcare utilization), illness severity on ICU admission, and admitting unit. We included 231,427 adult ICU admissions. Crude ICU-CA incidence was 16.1 per 1,000 admissions, with no significant annual trend in the propensity score-weighted analysis. Among 186,530 first admissions, crude 6-month mortality in ICU-CA patients was 74.7% (95% CI, 70.1-78.9) in 2011 and 68.8% (95% CI, 64.4-73.0) in 2017. When controlling for multiple potential confounders, the adjusted 6-month mortality odds of ICU-CA patients decreased by 6% per year (95% CI, 2-10). Patients admitted after out-of-hospital or in-hospital cardiac arrest had the highest ICU-CA incidence (136.1/1,000) and subsequent 6-month mortality (76.0% [95% CI, 73.6-78.4]). CONCLUSIONS: In our nationwide Swedish cohort, the adjusted incidence of ICU-CA remained unchanged between 2011 and 2017. More than two-thirds of patients with ICU-CA did not survive to 6 months following admission, but a slight improvement appears to have occurred over time.

Adverse Events of Peripherally Administered Norepinephrine During Surgery: A Prospective Multicenter Study.

BACKGROUND: Perioperative treatment of hypotension by intravenous administration of norepinephrine in a peripheral vein can lead to adverse events, for example, tissue necrosis. However, the incidence and severity of adverse events during perioperative administration are unknown. METHODS: This was a prospective observational study conducted at 3 Swedish hospitals from 2019 to 2022. A total of 1004 patients undergoing surgery, who met the criteria for perioperative peripheral norepinephrine administration, were included. The infusion site was inspected regularly. If swelling or paleness of skin was detected, the infusion site was changed to a different peripheral line. Systolic blood pressure and pulse frequency were monitored during the infusion time and defined as adverse events at >220 mm Hg and <40 beats•min -1 . In case of adverse events, patients were observed for up to 48 hours. The primary outcome was prevalence of extravasation, defined as swelling around the infusion site. Secondary outcomes were all types of adverse events and associations between predefined clinical variables and risk of adverse events. RESULTS: We observed 2.3% (95% confidence interval [CI], 1.4%-3.2%) extravasation of infusion and 0.9% (95% CI, 0.4%-1.7%) bradycardia. No cases of tissue necrosis or severe hypertension were detected. All adverse events had dissipated spontaneously within 48 hours. Proximal catheter placement was associated with more adverse events. CONCLUSIONS: Extravasation of peripherally administrated norepinephrine in the perioperative period occurred at similar rates as in previous studies in critically ill patients. In our setting, where we regularly inspected the infusion site and shifted site in case of swelling or paleness of skin, we observed no case of severe adverse events. Given that severe adverse events were absent, the potential benefit of this preventive approach requires confirmation in a larger population.

Probing brain tissue microstructure with MRI: principles, challenges, and the role of multidimensional diffusion-relaxation encoding.

Diffusion MRI uses the random displacement of water molecules to sensitize the signal to brain microstructure and to properties such as the density and shape of cells. Microstructure modeling techniques aim to estimate these properties from acquired data by separating the signal between virtual tissue 'compartments' such as the intra-neurite and the extra-cellular space. A key challenge is that the diffusion MRI signal is relatively featureless compared with the complexity of brain tissue. Another challenge is that the tissue microstructure is wildly different within the gray and white matter of the brain. In this review, we use results from multidimensional diffusion encoding techniques to discuss these challenges and their tentative solutions. Multidimensional encoding increases the information content of the data by varying not only the b-value and the encoding direction but also additional experimental parameters such as the shape of the b-tensor and the echo time. Three main insights have emerged from such encoding. First, multidimensional data contradict common model assumptions on diffusion and T2 relaxation, and illustrates how the use of these assumptions cause erroneous interpretations in both healthy brain and pathology. Second, many model assumptions can be dispensed with if data are acquired with multidimensional encoding. The necessary data can be easily acquired in vivo using protocols optimized to minimize Cramér-Rao lower bounds. Third, microscopic diffusion anisotropy reflects the presence of axons but not dendrites. This insight stands in contrast to current 'neurite models' of brain tissue, which assume that axons in white matter and dendrites in gray matter feature highly similar diffusion. Nevertheless, as an axon-based contrast, microscopic anisotropy can differentiate gray and white matter when myelin alterations confound conventional MRI contrasts.

The complexity of kidney disease and diagnosing it - cystatin C, selective glomerular hypofiltration syndromes and proteome regulation.

Estimation of kidney function is often part of daily clinical practice, mostly done by using the endogenous glomerular filtration rate (GFR)-markers creatinine or cystatin C. A recommendation to use both markers in parallel in 2010 has resulted in new knowledge concerning the pathophysiology of kidney disorders by the identification of a new set of kidney disorders, selective glomerular hypofiltration syndromes. These syndromes, connected to strong increases in mortality and morbidity, are characterized by a selective reduction in the glomerular filtration of 5-30 kDa molecules, such as cystatin C, compared to the filtration of small molecules <1 kDa dominating the glomerular filtrate, for example water, urea and creatinine. At least two types of such disorders, shrunken or elongated pore syndrome, are possible according to the pore model for glomerular filtration. Selective glomerular hypofiltration syndromes are prevalent in investigated populations, and patients with these syndromes often display normal measured GFR or creatinine-based GFR-estimates. The syndromes are characterized by proteomic changes promoting the development of atherosclerosis, indicating antibodies and specific receptor-blocking substances as possible new treatment modalities. Presently, the KDIGO guidelines for diagnosing kidney disorders do not recommend cystatin C as a general marker of kidney function and will therefore not allow the identification of a considerable number of patients with selective glomerular hypofiltration syndromes. Furthermore, as cystatin C is uninfluenced by muscle mass, diet or variations in tubular secretion and cystatin C-based GFR-estimation equations do not require controversial race or sex terms, it is obvious that cystatin C should be a part of future KDIGO guidelines.

Glycaemic control and sepsis risk in adults with type 1 diabetes.

AIMS: To study the association between glycated haemoglobin (HbA1c) and sepsis in adults with type 1 diabetes, and to explore the relationship between HbA1c and mortality among individuals who developed sepsis. MATERIALS AND METHODS: We included 33 549 adult individuals with type 1 diabetes recorded in the Swedish National Diabetes Register between January 2005 and December 2015. We used multivariable Cox regression and restricted cubic spline analyses to study the relationship between HbA1c values and sepsis occurrence and association between HbA1c and mortality among those with sepsis. RESULTS: In total, 713 (2.1%) individuals developed sepsis during the study period. Compared with the HbA1c reference interval of 48-52 mmol/mol (6.5-6.9%), the adjusted hazard ratio for sepsis was: 2.50 [95% confidence interval (CI) 1.18-5.29] for HbA1c <43 mmol/mol; 1.88 (95% CI 0.96-3.67) for HbA1c 43-47 mmol/mol; 1.78 (95% CI 1.09-2.89) for HbA1c 53-62 mmol/mol; 1.86 (95% CI 1.14-3.03) for HbA1c 63-72 mmol/mol; 3.15 (95% CI 1.91-5.19) for HbA1c 73-82 mmol/mol; and 4.26 (95% CI 2.53-7.16) for HbA1c >82 mmol/mol. On multivariable restricted cubic spline analysis, we found a J-shaped association between HbA1c and sepsis risk, with the lowest risk observed at HbA1c of approximately 53 mmol/mol. We found no association between HbA1c and mortality among those individuals who developed sepsis. CONCLUSIONS: In our nationwide observational study of adult individuals with type 1 diabetes we found a J-shaped relationship between HbA1c and risk of sepsis, with the lowest risk at HbA1c levels about 53 mmol/mol (7.0%). HbA1c was not associated with mortality in individuals affected by sepsis.

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.

Clinical outcomes during and beyond different COVID-19 critical illness variant periods compared with other lower respiratory tract infections.

BACKGROUND: It is yet to be better understood how outcomes during and after the critical illness potentially differ between severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants from other lower respiratory tract infections (LRTIs). We aimed to compare outcomes in adults admitted to an intensive care unit (ICU) with coronavirus disease 2019 (COVID-19) during the Wild-type, Alpha, Delta, and Omicron periods with individuals admitted with other LRTI. METHODS: Population-based cohort study in Stockholm, Sweden, using health registries with high coverage, including ICU-admitted adults from 1 January 2016 to 15 September 2022. Outcomes were in-hospital mortality, 180-day post-discharge mortality, 180-day hospital readmission, 180-day days alive and at home (DAAH), and incident diagnoses registered during follow-up. RESULTS: The number of ICU admitted individuals were 1421 Wild-type, 551 Alpha, 190 Delta, 223 Omicron, and 2380 LRTI. In-hospital mortality ranged from 28% (n = 665) in the LRTI cohort to 35% (n = 77) in the Delta cohort. The adjusted cause-specific hazard ratio (CSHR) compared with the LRTI cohort was 1.33 (95% confidence interval [CI] 1.16-1.53) in the Wild-type cohort, 1.53 (1.28-1.82) in the Alpha cohort, 1.70 (1.30-2.24) in the Delta cohort, and 1.59 (1.24-2.02) in the Omicron cohort. Among patients discharged alive from their COVID-19 hospitalization, the post-discharge mortality rates were lower (1-3%) compared with the LRTI cohort (9%), and the risk of hospital readmission was lower (CSHRs ranging from 0.42 to 0.68). Moreover, all COVID-19 cohorts had compared with the LRTI cohort more DAAH after compared with before the critical illness. CONCLUSION: Overall, COVID-19 critical was associated with an increased hazard of in-hospital mortality, but among those discharged alive from the hospital, less severe long-term outcomes were observed compared with other LRTIs.

Sodium glucose co-transporter-2 inhibitors in intensive care unit patients with type 2 diabetes: a pilot case control study.

BACKGROUND: Sodium glucose co-transporter-2 (SGLT2) inhibitors improve long-term cardiovascular and renal outcomes in individuals with type 2 diabetes. However, the safety of SGLT2 inhibitors in ICU patients with type 2 diabetes is uncertain. We aimed to perform a pilot study to assess the relationship between empagliflozin therapy and biochemical, and clinical outcomes in such patients. METHODS: We included 18 ICU patients with type 2 diabetes receiving empagliflozin (10 mg daily) and insulin to target glucose range of 10-14 mmol/l according to our liberal glucose control protocol for patients with diabetes (treatment group). Treatment group patients were matched on age, glycated hemoglobin A1c, and ICU duration with 72 ICU patients with type 2 diabetes exposed to the same target glucose range but who did not receive empagliflozin (control group). We compared changes in electrolyte and acid-base parameters, hypoglycemia, ketoacidosis, worsening kidney function, urine culture findings, and hospital mortality between the groups. RESULTS: Median (IQR) maximum increase in sodium and chloride levels were 3 (1-10) mmol/l and 3 (2-8) mmol/l in the control group and 9 (3-12) mmol/l and 8 (3-10) mmol/l in the treatment group (P = 0.045 for sodium, P = 0.059 for chloride). We observed no differences in strong ion difference, pH or base excess. Overall, 6% developed hypoglycemia in each group. No patient in the treatment group and one patient in the control group developed ketoacidosis. Worsening kidney function occurred in 18% and 29% of treatment and control group patients, respectively (P = 0.54). Urine cultures were positive in 22% of treatment group patients and 13% of control group patients (P = 0.28). Overall, 17% of treatment group patients and 19% of control group patients died in hospital (P = 0.79). CONCLUSIONS: In our pilot study of ICU patients with type 2 diabetes, empagliflozin therapy was associated with increases in sodium and chloride levels but was not significantly associated with acid-base changes, hypoglycemia, ketoacidosis, worsening kidney function, bacteriuria, or mortality.

A neurophenomenological fMRI study of a spontaneous automatic writer and a hypnotic cohort.

PURPOSE: To evaluate the neurophenomenology of automatic writing (AW) in a spontaneous automatic writer (NN) and four high hypnotizables (HH). METHODS: During fMRI, NN and the HH were cued to perform spontaneous (NN) or induced (HH) AW, and a comparison task of copying complex symbols, and to rate their experience of control and agency. RESULTS: Compared to copying, for all participants AW was associated with less sense of control and agency and decreased BOLD signal responses in brain regions implicated in the sense of agency (left premotor cortex and insula, right premotor cortex, and supplemental motor area), and increased BOLD signal responses in the left and right temporoparietal junctions and the occipital lobes. During AW, the HH differed from NN in widespread BOLD decreases across the brain and increases in frontal and parietal regions. CONCLUSIONS: Spontaneous and induced AW had similar effects on agency, but only partly overlapping effects on cortical activity.

Glycemic control and blood gas sampling frequency during continuous glucose monitoring in the intensive care unit: A before-and-after study.

BACKGROUND: Whether subcutaneous continuous glucose monitoring (CGM) can safely replace intermittent arterial blood gas glucose analyses in intensive care unit (ICU) patients remains uncertain. We aimed to compare CGM to blood gas glucose values and assess whether CGM use reduces blood gas sampling frequency and glucose variability in ICU patients with type 2 diabetes managed with liberal glucose control. METHODS: We used the FreeStyle Libre CGM in 15 ICU patients and compared their blood glucose metrics with a pre-CGM control population of 105 ICU patients with type 2 diabetes. Both groups received insulin to target glucose range of 10-14 mmol/L. We used linear regression analysis adjusted for illness severity to assess the association of CGM use with blood gas sampling frequency and glucose variability. We used mean absolute relative difference (MARD) and Clarke error grid analysis to assess accuracy of matched CGM-blood glucose values overall, across glucose stata (<10, 10-14, >14 mmol/L), and over time (≤48, 48-96, >96 h). RESULTS: We analyzed 483 matched glucose values. Overall MARD was 11.5 (95% CI, 10.7-12.3)% with 99% of readings in Clarke zones A and B. MARD was 15.5% for glucose values <10 mmol/L, 11.1% at 10-14 mmol/L, and 11.4% >14 mmol/L. MARD was 13.8% in the first 48 h, 10.9% at 48-96 h, and 8.9% beyond 96 h. CGM use was associated with 30% reduction in blood gas sampling frequency. CGM use was not associated with glucose variability as determined by glycemic lability index or standard deviation of blood glucose. CONCLUSIONS: In our cohort of ICU patients with type 2 diabetes receiving liberal glycemic control, CGM showed acceptable accuracy and was associated with a reduction in blood gas sampling frequency without compromising glucose control. Lowest accuracy was observed at glucose values below 10 mmol/L and during the first 48 h of CGM use.

The Effect of a Liberal Approach to Glucose Control in Critically Ill Patients with Type 2 Diabetes: A Multicenter, Parallel-Group, Open-Label Randomized Clinical Trial.

Rationale: Blood glucose concentrations affect outcomes in critically ill patients, but the optimal target blood glucose range in those with type 2 diabetes is unknown. Objectives: To evaluate the effects of a "liberal" approach to targeted blood glucose range during ICU admission. Methods: This mutlicenter, parallel-group, open-label randomized clinical trial included 419 adult patients with type 2 diabetes expected to be in the ICU on at least three consecutive days. In the intervention group intravenous insulin was commenced at a blood glucose >252 mg/dl and titrated to a target range of 180-252 mg/dl. In the comparator group insulin was commenced at a blood glucose >180 mg/dl and titrated to a target range of 108-180 mg/dl. The primary outcome was incident hypoglycemia (<72 mg/dl). Secondary outcomes included glucose metrics and clinical outcomes. Measurements and Main Results: By Day 28, at least one episode of hypoglycemia occurred in 10 of 210 (5%) patients assigned the intervention and 38 of 209 (18%) patients assigned the comparator (incident rate ratio, 0.21 [95% confidence interval (CI), 0.09 to 0.49]; P < 0.001). Those assigned the intervention had greater blood glucose concentrations (daily mean, minimum, maximum), less glucose variability, and less relative hypoglycemia (P < 0.001 for all comparisons). By Day 90, 62 of 210 (29.5%) in the intervention and 52 of 209 (24.9%) in the comparator group had died (absolute difference, 4.6 percentage points [95% CI, -3.9% to 13.2%]; P = 0.29). Conclusions: A liberal approach to blood glucose targets reduced incident hypoglycemia but did not improve patient-centered outcomes. Clinical trial registered with Australian New Zealand Clinical Trials Registry (ACTRN 12616001135404).

Clinical phenotypes and outcomes of SARS-CoV-2, influenza, RSV and seven other respiratory viruses: a retrospective study using complete hospital data.

BACKGROUND: An understanding of differences in clinical phenotypes and outcomes COVID-19 compared with other respiratory viral infections is important to optimise the management of patients and plan healthcare. Herein we sought to investigate such differences in patients positive for SARS-CoV-2 compared with influenza, respiratory syncytial virus (RSV) and other respiratory viruses. METHODS: We performed a retrospective cohort study of hospitalised adults and children (≤15 years) who tested positive for SARS-CoV-2, influenza virus A/B, RSV, rhinovirus, enterovirus, parainfluenza viruses, metapneumovirus, seasonal coronaviruses, adenovirus or bocavirus in a respiratory sample at admission between 2011 and 2020. RESULTS: A total of 6321 adult (1721 SARS-CoV-2) and 6379 paediatric (101 SARS-CoV-2) healthcare episodes were included in the study. In adults, SARS-CoV-2 positivity was independently associated with younger age, male sex, overweight/obesity, diabetes and hypertension, tachypnoea as well as better haemodynamic measurements, white cell count, platelet count and creatinine values. Furthermore, SARS-CoV-2 was associated with higher 30-day mortality as compared with influenza (adjusted HR (aHR) 4.43, 95% CI 3.51 to 5.59), RSV (aHR 3.81, 95% CI 2.72 to 5.34) and other respiratory viruses (aHR 3.46, 95% CI 2.61 to 4.60), as well as higher 90-day mortality, ICU admission, ICU mortality and pulmonary embolism in adults. In children, patients with SARS-CoV-2 were older and had lower prevalence of chronic cardiac and respiratory diseases compared with other viruses. CONCLUSIONS: SARS-CoV-2 is associated with more severe outcomes compared with other respiratory viruses, and although associated with specific patient and clinical characteristics at admission, a substantial overlap precludes discrimination based on these characteristics.

Ventilator-Associated Lower Respiratory Tract Bacterial Infections in COVID-19 Compared With Non-COVID-19 Patients.

OBJECTIVES: Ventilator-associated lower respiratory tract infections (VA-LRTIs) are associated with prolonged length of stay and increased mortality. We aimed to investigate the occurrence of bacterial VA-LRTI among mechanically ventilated COVID-19 patients and compare these findings to non-COVID-19 cohorts throughout the first and second wave of the pandemic. DESIGN: Retrospective cohort study. SETTING: Karolinska University Hospital, Stockholm, Sweden. PATIENTS: All patients greater than or equal to 18 years treated with mechanical ventilation between January 1, 2011, and December 31, 2020. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The cohort consisted of 20,223 ICU episodes (479 COVID-19), with a VA-LRTI incidence proportion of 30% (129/426) in COVID-19 and 18% (1,081/5,907) in non-COVID-19 among patients ventilated greater than or equal to 48 hours. The median length of ventilator treatment for COVID-19 patients was 10 days (interquartile range, 5-18 d), which was significantly longer than for all other investigated specific diagnoses. The VA-LRTI incidence rate per 1,000 ventilator days at risk was 31 (95% CI, 26-37) for COVID-19 and 34 (95% CI, 32-36) for non-COVID-19. With COVID-19 as reference, adjusted subdistribution hazard ratios for VA-LRTI was 0.29-0.50 (95% CI, < 1) for influenza, bacterial pneumonia, acute respiratory distress syndrome, and severe sepsis, but 1.38 (95% CI, 1.15-1.65) for specific noninfectious diagnoses. Compared with COVID-19 in the first wave of the pandemic, COVID-19 in the second wave had adjusted subdistribution hazard ratio of 1.85 (95% CI, 1.14-2.99). In early VA-LRTI Staphylococcus aureus was more common and Streptococcus pneumoniae, Haemophilus influenzae, and Escherichia coli less common in COVID-19 patients, while Serratia species was more often identified in late VA-LRTI. CONCLUSIONS: COVID-19 is associated with exceptionally long durations of mechanical ventilation treatment and high VA-LRTI occurrence proportions. The incidence rate of VA-LRTI was compared with the pooled non-COVID-19 cohort, however, not increased in COVID-19. Significant differences in the incidence of VA-LRTI occurred between the first and second wave of the COVID-19 pandemic.

Patterns and determinants of blood transfusion in intensive care in Sweden between 2010 and 2018: A nationwide, retrospective cohort study.

BACKGROUND: Intensive care unit (ICU) patients are transfused with blood products for a number of reasons, from massive ongoing hemorrhage, to mild anemia following blood sampling, combined with bone marrow depression due to critical illness. There's a paucity of data on transfusions in ICUs and most studies are based on audits or surveys. The aim of this study was to provide a complete picture of ICU-related transfusions in Sweden. METHODS: We conducted a register based retrospective cohort study with data on all adult patient admissions from 82 of 84 Swedish ICUs between 2010 and 2018, as recorded in the Swedish Intensive Care Register. Transfusions were obtained from the SCANDAT-3 database. Descriptive statistics were computed, characterizing transfused and nontransfused patients. The distribution of blood use comparing different ICUs was investigated by computing the observed proportion of ICU stays with a transfusion, as well as the expected proportion. RESULTS: In 330,938 ICU episodes analyzed, at least one transfusion was administered for 106,062 (32%). For both red-cell units and plasma, the fraction of patients who were transfused decreased during the study period from 31.3% in 2010 to 24.6% in 2018 for red-cells, and from 16.6% in 2010 to 9.4% in 2018 for plasma. After adjusting for a range of factors, substantial variation in transfusion frequency remained, especially for plasma units. CONCLUSION: Despite continuous decreases in utilization, transfusions remain common among Swedish ICU patients. There is considerable unexplained variation in transfusion rates. More research is needed to establish stronger critiera for when to transfuse ICU patients.

Cognitive interference processing in adult survivors of childhood acute lymphoblastic leukemia using functional magnetic resonance imaging.

BACKGROUND: Childhood acute lymphoblastic leukemia (ALL) is associated with cognitive impairment in adulthood. Cognitive interference processing and its correlated functional magnetic resonance imaging (fMRI) activity in the brain have not yet been studied in this patient group. MATERIAL: Twenty-six adult childhood ALL survivors (median [interquartile range {IQR}] age, 40.0 [37.0-42.3] years) were investigated at median age (IQR), 35.0 (32.0-37.0) years after treatment with intrathecal and intravenous chemotherapy as well as cranial radiotherapy (24 Gy) and compared with 26 matched controls (median [IQR] age, 37.5 [33.0-41.5] years). METHODS: Cognitive interference processing was investigated in terms of behavioral performance (response times [ms] and accuracy performance [%]) and fMRI activity in the cingulo-fronto-parietal (CFP) attention network as well as other parts of the brain using the multisource interference task (MSIT). RESULTS: ALL survivors had longer response times and reduced accuracy performance during cognitive interference processing (median [IQR] interference effect, 371.9 [314.7-453.3] ms and 6.7 [4.2-14.7]%, respectively) comparedwith controls (303.7 [275.0-376.7] ms and 2.3 [1.6-4.3]%, respectively), but did not exhibit altered fMRI activity in the CFP attention network or elsewhere in the brain. CONCLUSION: Adult childhood ALL survivors demonstrated impaired behavioral performance but no altered fMRI activity when performing cognitive interference processing when compared with controls. The results can be used to better characterize this patient group and to optimize follow-up care and support for these individuals.

Prevalence and impact of early prone position on 30-day mortality in mechanically ventilated patients with COVID-19: a nationwide cohort study.

BACKGROUND: COVID-19 ARDS shares features with non-COVID ARDS but also demonstrates distinct physiological differences. Despite a lack of strong evidence, prone positioning has been advocated as a key therapy for COVID-19 ARDS. The effects of prone position in critically ill patients with COVID-19 are not fully understood, nor is the optimal time of initiation defined. In this nationwide cohort study, we aimed to investigate the association between early initiation of prone position and mortality in mechanically ventilated COVID-19 patients with low oxygenation on ICU admission. METHODS: Using the Swedish Intensive Care Registry (SIR), all Swedish ICU patients ≥ 18 years of age with COVID-19 admitted between March 2020, and April 2021 were identified. A study-population of patients with PaO2/FiO2 ratio ≤ 20 kPa on ICU admission and receiving invasive mechanical ventilation within 24 h from ICU admission was generated. In this study-population, the association between early use of prone position (within 24 h from intubation) and 30-day mortality was estimated using univariate and multivariable logistic regression models. RESULTS: The total study cohort included 6350 ICU patients with COVID-19, of whom 46.4% were treated with prone position ventilation. Overall, 30-day mortality was 24.3%. In the study-population of 1714 patients with lower admission oxygenation (PaO2/FiO2 ratio ≤ 20 kPa), the utilization of early prone increased from 8.5% in March 2020 to 48.1% in April 2021. The crude 30-day mortality was 27.2% compared to 30.2% in patients not receiving early prone positioning. We found no significant association between early use of prone positioning and survival. CONCLUSIONS: During the first three waves of the COVID-19 pandemic, almost half of the patients in Sweden were treated with prone position ventilation. We found no association between early use of prone positioning and survival in patients on mechanical ventilation with severe hypoxemia on ICU admission. To fully elucidate the effect and timing of prone position ventilation in critically ill patients with COVID-19 further studies are desirable.

Renal function during sevoflurane or total intravenous propofol anaesthesia: a single-centre parallel randomised controlled study.

BACKGROUND: The choice of anaesthetic may influence regulation of renal perfusion and function. We investigated renal function in patients anaesthetised with propofol or sevoflurane before surgery and postoperatively. METHODS: Patients with ASA physical status 1-2 planned for spinal surgery were randomised to propofol or sevoflurane anaesthesia. Blood and urine were collected before anaesthesia, during anaesthesia (before surgery), during postoperative care, and the day after surgery. RESULTS: Twenty-seven patients completed the study protocol (average age, 51 yr; average BMI, 28 kg m-2) and 11 were women. Urine output and sodium excretion were lower during sevoflurane anaesthesia (n=14) than during propofol anaesthesia (n=13) (0.3 vs 1.1 ml kg-1 h-1 [P=0.01] and 2.6 vs 6.0 mmol h-1 [P=0.04], respectively). Urinary potassium excretion was lower during anaesthesia than after, without intergroup difference (2.3 vs 5.7 mmol h-1, P<0.001). Sevoflurane anaesthesia increased plasma renin compared with baseline (138 vs 23 mIU L-1, P<0.001) and propofol anaesthesia (138 vs 27 mIU L-1, P=0.008). Plasma arginine-vasopressin did not change significantly during anaesthesia, but was elevated postoperatively compared with baseline irrespective of anaesthetic (21 vs 12 ng L-1, P=0.02). Sevoflurane caused higher postoperative plasma creatinine than propofol (83 vs 66 mmol L-1, P=0.01). Kidney injury molecule-1 and neutrophil gelatinase-associated lipocalin did not change significantly in either group. CONCLUSIONS: Sevoflurane anaesthesia reduced urine output and sodium excretion and increased plasma renin compared with propofol anaesthesia. The impact of this on acute kidney injury and fluid resuscitation during surgery warrants further investigation. CLINICAL TRIAL REGISTRATION: EudraCT: 2017-001646-10; Clinicaltrials.gov: NCT0333680.

Thrombosis and Bleeding After Implementation of an Intermediate-Dose Prophylactic Anticoagulation Protocol in ICU Patients With COVID-19: A Multicenter Screening Study.

Thrombosis and bleeding after implementation of an intermediate-dose prophylactic anticoagulation protocol in intensive care unit (ICU) patients with coronavirus disease 2019 (COVID-19): a multicenter screening study Background: Venous thromboembolism (VTE) is common among critically ill patients with COVID-19. Information regarding VTE prevalence and bleeding complications after implementation of intermediate-dose prophylactic anticoagulation in such patients is, however, limited. Methods: We performed a prospective, observational study in 6 ICUs in 2 university-affiliated teaching hospitals in Sweden. After implementation of an intermediate-dose prophylactic anticoagulation protocol, we performed ultrasound screening for proximal lower-extremity deep vein thrombosis (DVT) and collected routine computed tomography pulmonary angiography exam results. Results: A total of 100 COVID-19 patients were included from June 21, 2020, through February 18, 2021. During a median follow-up of 120 (IQR, 89-134) days, we found VTE in 37 patients with the majority (78.4%) being diagnosed after ICU arrival. Overall, 20 patients had proximal lower-extremity DVT with 95% being detected on ultrasound screening; 22 patients had pulmonary vascular thrombosis; and 4 patients had venous thrombosis at other sites. A total of 6 patients had both proximal lower-extremity DVT and pulmonary vascular thrombosis. On univariate logistic regression analysis of 14 baseline characteristics, only pre-existing heart failure was associated with VTE (OR 4.67, 95% CI 1.13-19.34). Major and non-major bleeding occurred in 10 and 18 patients, respectively. Conclusions: In our cohort of ICU patients with COVID-19, we observed a high prevalence of VTE and bleeding complications after implementation of intermediate-dose anticoagulation. In approximately half of patients, VTE was identified on screening ultrasound.

Chronic dysglycemia and risk of SARS-CoV-2 associated respiratory failure in hospitalized patients.

BACKGROUND: Diabetes is common among patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-induced respiratory failure. We aimed to investigate the relationship between different stages of chronic dysglycemia and development of respiratory failure in hospitalized SARS-CoV-2 positive patients. METHODS: In this retrospective observational study, we included 385 hospitalized SARS-CoV-2 positive patients at Karolinska University Hospital, Sweden with an HbA1c test obtained within 3 months before admission. Based on HbA1c level and previous diabetes history, we classified patients into the following dysglycemia categories: prediabetes, unknown diabetes, controlled diabetes, or uncontrolled diabetes. We used multivariable logistic regression analysis adjusted for age, sex, and body mass index, to assess the association between dysglycemia categories and development of SARS-CoV-2-induced respiratory failure. RESULTS: Of the 385 study patients, 88 (22.9%) had prediabetes, 68 (17.7%) had unknown diabetes, 36 (9.4%) had controlled diabetes, and 83 (21.6%) had uncontrolled diabetes. Overall, 299 (77.7%) patients were admitted with or developed SARS-CoV-2-induced respiratory failure during hospitalization. In multivariable logistic regression analysis compared with no chronic dysglycemia, prediabetes (OR 14.41, 95% CI 5.27-39.43), unknown diabetes (OR 15.86, 95% CI 4.55-55.36), and uncontrolled diabetes (OR 17.61, 95% CI 5.77-53.74) was independently associated with increased risk of SARS-CoV-2-induced respiratory failure. CONCLUSION: In our cohort of hospitalized SARS-CoV-2 positive patients with available HbA1c data, prediabetes, undiagnosed diabetes, and poorly controlled diabetes were associated with a markedly increased risk of SARS-CoV-2-associated respiratory failure.

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.