Assessment of Clinical Criteria for Sepsis:For the Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3)

IMPORTANCE: The Third International Consensus Definitions Task Force defined sepsis as “life-threatening organ dysfunction due to a dysregulated host response to infection.” The performance of clinical criteria for this sepsis definition is unknown. OBJECTIVE: To evaluate the validity of clinical criteria to identify patients with suspected infection who are at risk of sepsis. DESIGN, SETTINGS AND POPULATION: Among 1.3 million electronic health record encounters from January 1, 2010, to December 31, 2012, at 12 hospitals in southwestern Pennsylvania, we identified those with suspected infection in whom to compare criteria. Confirmatory analyses were performed in 4 data sets of 706 399 out-of-hospital and hospital encounters at 165 US and non-US hospitals ranging from January 1, 2008, until December 31, 2013. EXPOSURES: Sequential [Sepsis-related] Organ Failure Assessment (SOFA) score, systemic inflammatory response syndrome (SIRS) criteria, Logistic Organ Dysfunction System (LODS) score, and a new model derived using multivariable logistic regression in a split sample, the quick Sequential [Sepsis-related] Organ Failure Assessment (qSOFA) score (range, 0-3 points, with 1 point each for systolic hypotension [≤100 mm Hg], tachypnea [≥22/min], or altered mentation). MAIN OUTCOMES AND MEASURES: For construct validity, pairwise agreement was assessed. For predictive validity, the discrimination for outcomes (primary: in-hospital mortality; secondary: in-hospital mortality or intensive care unit [ICU] length of stay ≥3 days) more common in sepsis than uncomplicated infection was determined. Results were expressed as the fold change in outcome over deciles of baseline risk of death and area under the receiver operating characteristic curve (AUROC). RESULTS: In the primary cohort, 148 907 encounters had suspected infection (n = 74 453 derivation; n = 74 454 validation), of whom 6347 (4%) died. Among ICU encounters in the validation cohort (n = 7932 with suspected infection, of whom 1289 [16%] died), the predictive validity for in-hospital mortality was lower for SIRS (AUROC = 0.64; 95% CI, 0.62-0.66) and qSOFA (AUROC = 0.66; 95% CI, 0.64-0.68) vs SOFA (AUROC = 0.74; 95% CI, 0.73-0.76; P < .001 for both) or LODS (AUROC = 0.75; 95% CI, 0.73-0.76; P < .001 for both). Among non-ICU encounters in the validation cohort (n = 66 522 with suspected infection, of whom 1886 [3%] died), qSOFA had predictive validity (AUROC = 0.81; 95% CI, 0.80-0.82) that was greater than SOFA (AUROC = 0.79; 95% CI, 0.78-0.80; P < .001) and SIRS (AUROC = 0.76; 95% CI, 0.75-0.77; P < .001). Relative to qSOFA scores lower than 2, encounters with qSOFA scores of 2 or higher had a 3- to 14-fold increase in hospital mortality across baseline risk deciles. Findings were similar in external data sets and for the secondary outcome. CONCLUSIONS AND RELEVANCE: Among ICU encounters with suspected infection, the predictive validity for in-hospital mortality of SOFA was not significantly different than the more complex LODS but was statistically greater than SIRS and qSOFA, supporting its use in clinical criteria for sepsis. Among encounters with suspected infection outside of the ICU, the predictive validity for in-hospital mortality of qSOFA was statistically greater than SOFA and SIRS, supporting its use as a prompt to consider possible sepsis

Peripheral artery occlusive disease (PAOD) in chronic phase chronic myeloid leukemia patients treated with nilotinib or Imatinib

Several retrospective studies have described the clinical manifestation of peripheral artery occlusive disease (PAOD) in patients receiving nilotinib. We thus prospectively screened for PAOD in patients with chronic phase chronic myeloid leukemia (CP CML) being treated with tyrosine kinase inhibitors (TKI), including imatinib and nilotinib. One hundred and fifty-nine consecutive patients were evaluated for clinical and biochemical risk factors for cardiovascular disease. Non-invasive assessment for PAOD included determination of the ankle-brachial index (ABI) and duplex ultrasonography. A second cohort consisted of patients with clinically manifest PAOD recruited from additional collaborating centers. Pathological ABI were significantly more frequent in patients on 1st-line nilotinib (7 of 27; 26 %) and in patients on 2nd-line nilotinib (10 of 28; 35.7 %) as compared to patients on 1st-line imatinib (3 of 48; 6.3 %). Clinically manifest PAOD was identified in 5 patients, all with current or previous nilotinib exposure only. Relative risk for PAOD determined by a pathological ABI in 1st-line nilotinib-treated patients as compared to 1st-line imatinib-treated patients was 10.3. PAOD is more frequently observed in patients receiving nilotinib as compared to imatinib. Due to the severe nature of clinically manifest PAOD longitudinal non-invasive monitoring and careful assessment of risk factors is warranted

Deep X-ray and radio observations of the first outburst of the young magnetar Swift J1818.0-1607

Swift J1818.0-1607 is a radio-loud magnetar with a spin period of 1.36 s and a dipolar magnetic field strength of B~3E14 G, which is very young compared to the Galactic pulsar population. We report here on the long-term X-ray monitoring campaign of this young magnetar using XMM-Newton, NuSTAR, and Swift from the activation of its first outburst in March 2020 until October 2021, as well as INTEGRAL upper limits on its hard X-ray emission. The 1-10 keV magnetar spectrum is well modeled by an absorbed blackbody with a temperature of kT_BB~1.1 keV, and apparent reduction in the radius of the emitting region from ~0.6 to ~0.2 km. We also confirm the bright diffuse X-ray emission around the source extending between ~50'' and ~110''. A timing analysis revealed large torque variability, with an average spin-down rate nudot~-2.3E-11 Hz^2 that appears to decrease in magnitude over time. We also observed Swift J1818.0-1607 with the Karl G. Jansky Very Large Array (VLA) on 2021 March 22. We detected the radio counterpart to Swift J1818.0-1607 measuring a flux density of S_v = 4.38+/-0.05 mJy at 3 GHz, and a half ring-like structure of bright diffuse radio emission located at ~90'' to the west of the magnetar. We tentatively suggest that the diffuse X-ray emission is due to a dust scattering halo and that the radio structure may be associated with the supernova remnant of this young pulsar, based on its morphology

Deep X-ray and radio observations of the first outburst of the young magnetar Swift J1818.0-1607

Swift J1818.0-1607 is a radio-loud magnetar with a spin period of 1.36 s and a dipolar magnetic field strength of B~3E14 G, which is very young compared to the Galactic pulsar population. We report here on the long-term X-ray monitoring campaign of this young magnetar using XMM-Newton, NuSTAR, and Swift from the activation of its first outburst in March 2020 until October 2021, as well as INTEGRAL upper limits on its hard X-ray emission. The 1-10 keV magnetar spectrum is well modeled by an absorbed blackbody with a temperature of kT_BB~1.1 keV, and apparent reduction in the radius of the emitting region from ~0.6 to ~0.2 km. We also confirm the bright diffuse X-ray emission around the source extending between ~50'' and ~110''. A timing analysis revealed large torque variability, with an average spin-down rate nudot~-2.3E-11 Hz^2 that appears to decrease in magnitude over time. We also observed Swift J1818.0-1607 with the Karl G. Jansky Very Large Array (VLA) on 2021 March 22. We detected the radio counterpart to Swift J1818.0-1607 measuring a flux density of S_v = 4.38+/-0.05 mJy at 3 GHz, and a half ring-like structure of bright diffuse radio emission located at ~90'' to the west of the magnetar. We tentatively suggest that the diffuse X-ray emission is due to a dust scattering halo and that the radio structure may be associated with the supernova remnant of this young pulsar, based on its morphology