Global patient outcomes after elective surgery: prospective cohort study in 27 low-, middle- and high-income countries.

BACKGROUND: As global initiatives increase patient access to surgical treatments, there remains a need to understand the adverse effects of surgery and define appropriate levels of perioperative care. METHODS: We designed a prospective international 7-day cohort study of outcomes following elective adult inpatient surgery in 27 countries. The primary outcome was in-hospital complications. Secondary outcomes were death following a complication (failure to rescue) and death in hospital. Process measures were admission to critical care immediately after surgery or to treat a complication and duration of hospital stay. A single definition of critical care was used for all countries. RESULTS: A total of 474 hospitals in 19 high-, 7 middle- and 1 low-income country were included in the primary analysis. Data included 44 814 patients with a median hospital stay of 4 (range 2-7) days. A total of 7508 patients (16.8%) developed one or more postoperative complication and 207 died (0.5%). The overall mortality among patients who developed complications was 2.8%. Mortality following complications ranged from 2.4% for pulmonary embolism to 43.9% for cardiac arrest. A total of 4360 (9.7%) patients were admitted to a critical care unit as routine immediately after surgery, of whom 2198 (50.4%) developed a complication, with 105 (2.4%) deaths. A total of 1233 patients (16.4%) were admitted to a critical care unit to treat complications, with 119 (9.7%) deaths. Despite lower baseline risk, outcomes were similar in low- and middle-income compared with high-income countries. CONCLUSIONS: Poor patient outcomes are common after inpatient surgery. Global initiatives to increase access to surgical treatments should also address the need for safe perioperative care. STUDY REGISTRATION: ISRCTN5181700

Effect of aliskiren on post-discharge outcomes among diabetic and non-diabetic patients hospitalized for heart failure: insights from the ASTRONAUT trial

Aims The objective of the Aliskiren Trial on Acute Heart Failure Outcomes (ASTRONAUT) was to determine whether aliskiren, a direct renin inhibitor, would improve post-discharge outcomes in patients with hospitalization for heart failure (HHF) with reduced ejection fraction. Pre-specified subgroup analyses suggested potential heterogeneity in post-discharge outcomes with aliskiren in patients with and without baseline diabetes mellitus (DM). Methods and results ASTRONAUT included 953 patients without DM (aliskiren 489; placebo 464) and 662 patients with DM (aliskiren 319; placebo 343) (as reported by study investigators). Study endpoints included the first occurrence of cardiovascular death or HHF within 6 and 12 months, all-cause death within 6 and 12 months, and change from baseline in N-terminal pro-B-type natriuretic peptide (NT-proBNP) at 1, 6, and 12 months. Data regarding risk of hyperkalaemia, renal impairment, and hypotension, and changes in additional serum biomarkers were collected. The effect of aliskiren on cardiovascular death or HHF within 6 months (primary endpoint) did not significantly differ by baseline DM status (P = 0.08 for interaction), but reached statistical significance at 12 months (non-DM: HR: 0.80, 95% CI: 0.64-0.99; DM: HR: 1.16, 95% CI: 0.91-1.47; P = 0.03 for interaction). Risk of 12-month all-cause death with aliskiren significantly differed by the presence of baseline DM (non-DM: HR: 0.69, 95% CI: 0.50-0.94; DM: HR: 1.64, 95% CI: 1.15-2.33; P < 0.01 for interaction). Among non-diabetics, aliskiren significantly reduced NT-proBNP through 6 months and plasma troponin I and aldosterone through 12 months, as compared to placebo. Among diabetic patients, aliskiren reduced plasma troponin I and aldosterone relative to placebo through 1 month only. There was a trend towards differing risk of post-baseline potassium ≥6 mmol/L with aliskiren by underlying DM status (non-DM: HR: 1.17, 95% CI: 0.71-1.93; DM: HR: 2.39, 95% CI: 1.30-4.42; P = 0.07 for interaction). Conclusion This pre-specified subgroup analysis from the ASTRONAUT trial generates the hypothesis that the addition of aliskiren to standard HHF therapy in non-diabetic patients is generally well-tolerated and improves post-discharge outcomes and biomarker profiles. In contrast, diabetic patients receiving aliskiren appear to have worse post-discharge outcomes. Future prospective investigations are needed to confirm potential benefits of renin inhibition in a large cohort of HHF patients without D

Effect of Hydrocortisone on Mortality and Organ Support in Patients With Severe COVID-19: The REMAP-CAP COVID-19 Corticosteroid Domain Randomized Clinical Trial.

Importance: Evidence regarding corticosteroid use for severe coronavirus disease 2019 (COVID-19) is limited. Objective: To determine whether hydrocortisone improves outcome for patients with severe COVID-19. Design, Setting, and Participants: An ongoing adaptive platform trial testing multiple interventions within multiple therapeutic domains, for example, antiviral agents, corticosteroids, or immunoglobulin. Between March 9 and June 17, 2020, 614 adult patients with suspected or confirmed COVID-19 were enrolled and randomized within at least 1 domain following admission to an intensive care unit (ICU) for respiratory or cardiovascular organ support at 121 sites in 8 countries. Of these, 403 were randomized to open-label interventions within the corticosteroid domain. The domain was halted after results from another trial were released. Follow-up ended August 12, 2020. Interventions: The corticosteroid domain randomized participants to a fixed 7-day course of intravenous hydrocortisone (50 mg or 100 mg every 6 hours) (n = 143), a shock-dependent course (50 mg every 6 hours when shock was clinically evident) (n = 152), or no hydrocortisone (n = 108). Main Outcomes and Measures: The primary end point was organ support-free days (days alive and free of ICU-based respiratory or cardiovascular support) within 21 days, where patients who died were assigned -1 day. The primary analysis was a bayesian cumulative logistic model that included all patients enrolled with severe COVID-19, adjusting for age, sex, site, region, time, assignment to interventions within other domains, and domain and intervention eligibility. Superiority was defined as the posterior probability of an odds ratio greater than 1 (threshold for trial conclusion of superiority >99%). Results: After excluding 19 participants who withdrew consent, there were 384 patients (mean age, 60 years; 29% female) randomized to the fixed-dose (n = 137), shock-dependent (n = 146), and no (n = 101) hydrocortisone groups; 379 (99%) completed the study and were included in the analysis. The mean age for the 3 groups ranged between 59.5 and 60.4 years; most patients were male (range, 70.6%-71.5%); mean body mass index ranged between 29.7 and 30.9; and patients receiving mechanical ventilation ranged between 50.0% and 63.5%. For the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively, the median organ support-free days were 0 (IQR, -1 to 15), 0 (IQR, -1 to 13), and 0 (-1 to 11) days (composed of 30%, 26%, and 33% mortality rates and 11.5, 9.5, and 6 median organ support-free days among survivors). The median adjusted odds ratio and bayesian probability of superiority were 1.43 (95% credible interval, 0.91-2.27) and 93% for fixed-dose hydrocortisone, respectively, and were 1.22 (95% credible interval, 0.76-1.94) and 80% for shock-dependent hydrocortisone compared with no hydrocortisone. Serious adverse events were reported in 4 (3%), 5 (3%), and 1 (1%) patients in the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively. Conclusions and Relevance: Among patients with severe COVID-19, treatment with a 7-day fixed-dose course of hydrocortisone or shock-dependent dosing of hydrocortisone, compared with no hydrocortisone, resulted in 93% and 80% probabilities of superiority with regard to the odds of improvement in organ support-free days within 21 days. However, the trial was stopped early and no treatment strategy met prespecified criteria for statistical superiority, precluding definitive conclusions. Trial Registration: ClinicalTrials.gov Identifier: NCT02735707

The Properties of Planck Galactic Cold Clumps in the L1495 Dark Cloud

Planck Galactic Cold Clumps (PGCCs) possibly represent the early stages of star formation. To understand better the properties of PGCCs, we studied 16 PGCCs in the L1495 cloud with molecular lines and continuum data from Herschel, JCMT/SCUBA-2, and the PMO 13.7 m telescope. Thirty dense cores were identified in 16 PGCCs from 2D Gaussian fitting. The dense cores have dust temperatures of T d = 11–14 K, and H2 column densities of ${N}_{{{\rm{H}}}_{2}}$ = (0.36–2.5) × 1022 cm−2. We found that not all PGCCs contain prestellar objects. In general, the dense cores in PGCCs are usually at their earliest evolutionary stages. All the dense cores have non-thermal velocity dispersions larger than the thermal velocity dispersions from molecular line data, suggesting that the dense cores may be turbulence-dominated. We have calculated the virial parameter α and found that 14 of the dense cores have α 2. This suggests that some of the dense cores are not bound in the absence of external pressure and magnetic fields. The column density profiles of dense cores were fitted. The sizes of the flat regions and core radii decrease with the evolution of dense cores. CO depletion was found to occur in all the dense cores, but is more significant in prestellar core candidates than in protostellar or starless cores. The protostellar cores inside the PGCCs are still at a very early evolutionary stage, sharing similar physical and chemical properties with the prestellar core candidates

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

Aseptic Loosening Rates in Distal Femoral Endoprostheses: Does Stem Size Matter?

BACKGROUND: Long-term survival of distal femoral endoprosthetic replacements is largely affected by aseptic loosening. It is unclear whether and to what degree surgical technique and component selection influence the risk of loosening. QUESTIONS/PURPOSES: We (1) established the overall failure and aseptic loosening rates in a tumor population and asked (2) whether stem diameter and specifically the diaphysis-to-stem ratio predicts loosening, and (3) whether resection percentage correlates with failure. METHODS: We retrospectively reviewed the charts of all 93 patients in whom 104 distal femoral replacements had been performed from 1985 to 2008. We extracted the following data: age, need for revision surgeries, tumor diagnosis, adjunct treatment, and implant characteristics. We reviewed radiographs and determined stem size, bone diaphyseal width, and resection percentage of the femur. Kaplan-Meier survivorship was calculated for all implant failures and failures resulting from aseptic loosening. We evaluated radiolucent lines in patients with radiographic followup over 5 years. We identified independent risk factors for loosening. The minimum followup for radiographic evaluation was 5 years (mean, 12.7 years; range, 5.4–23.5 years). RESULTS: Overall implant survival for 104 stems in 93 patients was 73.3% at 10 years, 62.8% at 15 years, and 46.1% at 20 years. Survival from aseptic loosening was 94.6% at 10 and 15 years and 86.5% at 20 years. Of the variables analyzed, only bone:stem ratio independently predicted aseptic failure. Patients with stable implants had larger stem sizes and lower bone:stem ratios than those with loose implants (14.5 mm versus 10.7 mm and 2.02 versus 2.81, respectively). CONCLUSIONS: Our data suggest durability relates to selecting stems that fill the canal. LEVEL OF EVIDENCE: Level III, therapeutic study. See Guidelines for Authors for a complete description of levels of evidence

Aseptic loosening rates in distal femoral endoprostheses: Does stem size matter?

Background: Long-term survival of distal femoral endoprosthetic replacements is largely affected by aseptic loosening. It is unclear whether and to what degree surgical technique and component selection influence the risk of loosening. Questions/purposes: We (1) established the overall failure and aseptic loosening rates in a tumor population and asked (2) whether stem diameter and specifically the diaphysis-to-stem ratio predicts loosening, and (3) whether resection percentage correlates with failure. Methods: We retrospectively reviewed the charts of all 93 patients in whom 104 distal femoral replacements had been performed from 1985 to 2008. We extracted the following data: age, need for revision surgeries, tumor diagnosis, adjunct treatment, and implant characteristics. We reviewed radiographs and determined stem size, bone diaphyseal width, and resection percentage of the femur. Kaplan-Meier survivorship was calculated for all implant failures and failures resulting from aseptic loosening. We evaluated radiolucent lines in patients with radiographic followup over 5 years. We identified independent risk factors for loosening. The minimum followup for radiographic evaluation was 5 years (mean, 12.7 years; range, 5.4-23.5 years). Results: Overall implant survival for 104 stems in 93 patients was 73.3% at 10 years, 62.8% at 15 years, and 46.1% at 20 years. Survival from aseptic loosening was 94.6% at 10 and 15 years and 86.5% at 20 years. Of the variables analyzed, only bone:stem ratio independently predicted aseptic failure. Patients with stable implants had larger stem sizes and lower bone:stem ratios than those with loose implants (14.5 mm versus 10.7 mm and 2.02 versus 2.81, respectively). Conclusions: Our data suggest durability relates to selecting stems that fill the canal. Level of Evidence: Level III, therapeutic study. See Guidelines for Authors for a complete description of levels of evidence. © 2011 The Association of Bone and Joint Surgeons®