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BackgroundFrailty, a “syndrome of loss of reserves,” is a decade old concept. Initially it was used mainly in geriatrics but lately its use has been extended into other specialties including surgery. Our main objective was to examine the association between frailty and mortality, between frailty and length of hospital stay (LOS) and frailty and readmission within 30 days in the emergency surgical population.MethodsStudies reporting on frailty in the emergency surgical population were eligible. MEDLINE (via PubMed), EMBASE, Scopus, CENTRAL, and Web of Science were searched with terms related to acute surgery and frail*. We searched for eligible articles without any restrictions on the 2nd of November 2020. Odds ratios (OR) and weighted mean differences (WMD) were calculated with 95% confidence intervals (CI), using a random effect model. Risk of bias assessment was performed according to the recommendations of the Cochrane Collaboration. As the finally selected studies were either prospective or retrospective cohorts, the “Quality In Prognosis Studies” (QUIPS) tool was used.ResultsAt the end of the selection process 21 eligible studies with total 562.070 participants from 8 countries were included in the qualitative and the quantitative synthesis. Patients living with frailty have higher chance of dying within 30 days after an emergency surgical admission (OR: 1.99; CI: 1.76–2.21; p < 0.001). We found a tendency of increased LOS with frailty in acute surgical patients (WMD: 4.75 days; CI: 1.79–7.71; p = 0.002). Patients living with frailty have increased chance of 30-day readmission after discharge (OR: 1.36; CI: 1.06–1.75; p = 0.015).ConclusionsAlthough there is good evidence that living with frailty increases the chance of unfavorable outcomes, further research needs to be done to assess the benefits and costs of frailty screening for emergency surgical patients.Systematic Review RegistrationThe review protocol was registered on the PROSPERO International Prospective Register of Systematic Reviews (CRD42021224689).

Background: The concept of frailty provides an age-independent, easy-to-use tool for risk stratification. We aimed to summarize the evidence regarding the use of frailty tools in COVID-19, assessing the risk of frail patients for in-hospital and 30-day mortality, intensive care unit (ICU) admission, and length of hospitalization (LOH).Methods: The protocol was prospectively registered via PROSPERO (CRD42021241544). Studies reporting on frailty in COVID-19 patients were eligible. We compared in-hospital and 30-day mortality, lengths of stay and ICU admission in frail and non-frail COVID-19 patients. We also compared average frailty in COVID-19 survivors and non-survivors. MEDLINE (via PubMed), EMBASE, Scopus, CENTRAL, and Web of Science were searched up to 3 February 2021 with terms related to COVID-19 and frail*. Search, selection, data extraction and risk of bias assessment were conducted in duplicate by two independent review authors. The QUIPS tool was used for the risk of bias assessment. Odds ratios (OR) and weighted mean differences (WMD) were calculated with 95% confidence intervals (CI) using a random effect model. Heterogeneity was assessed using the I2 and χ2 tests.Results: From 1693 records identified, 27 were included in the qualitative and 21 in the quantitative synthesis. Clinical Frailty Scale (CFS) was used in 24 studies, the Hospital Frailty Risk Score (HFRS) by one and the Frail Non-Disabled questionnaire by another one. One study reported both CFS and HFRS. We found that frail patients (CFS 5–9) compared to non-frail patients (CFS 1–4) have a higher risk for both in-hospital (OR: 2.77; CI: 1.86–4.15) and 30-day mortality (OR: 1.47; CI:1.05–2.06). Frail patients (CFS 5–9) were less likely to be admitted to ICU (OR 0.05, CI: 0.01–0.16). Statistical heterogeneity was not present for CFS 5–9 30-day mortality OR and ICU admission OR (CFS 1–3 vs 4–9), and was moderate for in-hospital mortality WMD. Quantitative synthesis for LOH was not feasible. Most studies carried a high risk of bias.Conclusions: As determined by CFS, frailty is strongly associated with in-hospital and 30-day mortality; hence, investigating its use in deciding on ICU admission further in COVID-19 is warranted.

Objective To characterise the clinical features of children and young people admitted to hospital with laboratory confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in the UK and explore factors associated with admission to critical care, mortality, and development of multisystem inflammatory syndrome in children and adolescents temporarily related to coronavirus disease 2019 (covid-19) (MIS-C). Design Prospective observational cohort study with rapid data gathering and near real time analysis. Setting 260 hospitals in England, Wales, and Scotland between 17 January and 3 July 2020, with a minimum follow-up time of two weeks (to 17 July 2020). Participants 651 children and young people aged less than 19 years admitted to 138 hospitals and enrolled into the International Severe Acute Respiratory and emergency Infections Consortium (ISARIC) WHO Clinical Characterisation Protocol UK study with laboratory confirmed SARS-CoV-2. Main outcome measures Admission to critical care (high dependency or intensive care), in-hospital mortality, or meeting the WHO preliminary case definition for MIS-C. Results Median age was 4.6 (interquartile range 0.3-13.7) years, 35% (225/651) were under 12 months old, and 56% (367/650) were male. 57% (330/576) were white, 12% (67/576) South Asian, and 10% (56/576) black. 42% (276/651) had at least one recorded comorbidity. A systemic mucocutaneous-enteric cluster of symptoms was identified, which encompassed the symptoms for the WHO MIS-C criteria. 18% (116/632) of children were admitted to critical care. On multivariable analysis, this was associated with age under 1 month (odds ratio 3.21, 95% confidence interval 1.36 to 7.66; P=0.008), age 10-14 years (3.23, 1.55 to 6.99; P=0.002), and black ethnicity (2.82, 1.41 to 5.57; P=0.003). Six (1%) of 627 patients died in hospital, all of whom had profound comorbidity. 11% (52/456) met the WHO MIS-C criteria, with the first patient developing symptoms in mid-March. Children meeting MIS-C criteria were older (median age 10.7 (8.3-14.1) v 1.6 (0.2-12.9) years; Pv 42% (148/355); P=0.004). Children with MIS-C were five times more likely to be admitted to critical care (73% (38/52) v 15% (62/404); Pv 28% (86/302); P=0.004), headache (34% (16/47) v 10% (26/263); Pv 8% (21/270); Pv (12% (34/284); P=0.003), and lymphadenopathy (20% (9/46) v 3% (10/318); P9 /L (32% (16/50) v 11% (38/348); P Conclusions Children and young people have less severe acute covid-19 than adults. A systemic mucocutaneous-enteric symptom cluster was also identified in acute cases that shares features with MIS-C. This study provides additional evidence for refining the WHO MIS-C preliminary case definition. Children meeting the MIS-C criteria have different demographic and clinical features depending on whether they have acute SARS-CoV-2 infection (polymerase chain reaction positive) or are post-acute (antibody positive). Study registration ISRCTN66726260.

Rationale: The impact of coronavirus disease (COVID-19) on patients with interstitial lung disease (ILD) has not been established. Objectives: To assess outcomes in patients with ILD hospitalized for COVID-19 versus those without ILD in a contemporaneous age-, sex-, and comorbidity-matched population. Methods: An international multicenter audit of patients with a prior diagnosis of ILD admitted to the hospital with COVID-19 between March 1 and May 1, 2020, was undertaken and compared with patients without ILD, obtained from the ISARIC4C (International Severe Acute Respiratory and Emerging Infection Consortium Coronavirus Clinical Characterisation Consortium) cohort, admitted with COVID-19 over the same period. The primary outcome was survival. Secondary analysis distinguished idiopathic pulmonary fibrosis from non–idiopathic pulmonary fibrosis ILD and used lung function to determine the greatest risks of death. Measurements and Main Results: Data from 349 patients with ILD across Europe were included, of whom 161 were admitted to the hospital with laboratory or clinical evidence of COVID-19 and eligible for propensity score matching. Overall mortality was 49% (79/161) in patients with ILD with COVID-19. After matching, patients with ILD with COVID-19 had significantly poorer survival (hazard ratio [HR], 1.60; confidence interval, 1.17–2.18; P = 0.003) than age-, sex-, and comorbidity-matched controls without ILD. Patients with an FVC of Conclusions: Patients with ILD are at increased risk of death from COVID-19, particularly those with poor lung function and obesity. Stringent precautions should be taken to avoid COVID-19 in patients with ILD.

Perioperative management of high-risk surgical patients is a complex and complicated process. Hemodynamic instability can inflict vital organ hypoperfusion that can have several serious consequences, mainly due to cellular oxygen debt. Therefore, adequate monitoring guided early interventions are inevitable to avoid serious postoperative complications. However, conventional indices, including heart rate, blood pressure, skin temperature and urine output have limited value in diagnosing compensated shock. Therefore, advanced hemodynamic monitoring may become necessary when in addition to cardiac output other measures of oxygen delivery are also taken into account during treatment. However, any alteration that aims to affect macrocirculation only makes sense if it is followed by improved microcirculatory perfusion and adequate oxygen delivery to the cells. Putting the puzzle of hemodynamic stabilization together requires a complex, holistic approach. The purpose of this review is to discuss the holistic approach of multimodal, individualized monitoring that can help to avoid perioperative oxygen debt in high risk surgical patients.

Mortality due to septic-shock-induced respiratory failure remains high. A recent meta-analysis suggested that IgM-enriched immunoglobulin treatment may be beneficial in these patients. In this prospective randomised controlled pilot study we investigated the effects of IgM-enriched immunoglobulin treatment in patients with early septic shock accompanied by severe respiratory failure. 33 patients were randomly allocated to receive 5 ml/kg (predicted body weight) IgM-enriched immunoglobulin (16 patients) or placebo (17 patients), respectively, via 8 h IV-infusion for three consecutive days. Daily Multiple Organ Dysfunction Scores (MODS) were calculated. Serum C-reactive protein (CRP) and procalcitonin (PCT) levels were monitored daily. For statistical analysis two-way ANOVA was used. Daily MODS showed ongoing multiple system organ failure without significant resolution during the 8 days. Median length of ICU stay, mechanical ventilation, vasopressor support during the ICU stay and 28-day mortality were nearly identical in the two groups. Serum PCT levels showed no significant difference between the two groups, however, CRP levels were significantly lower in the IgM-enriched immunoglobulin group on days 4, 5 and 6, respectively. In this study the use of IgM-enriched immunoglobulin preparation failed to produce any improvement in the organ dysfunction as compared to standard sepsis therapy.

To investigate respiratory and hemodynamic changes during lung recruitment and descending optimal positive end-expiratory pressure (PEEP) titration.Prospective auto-control clinical trial.Adult general intensive care unit in a university hospital.Eighteen patients with acute respiratory distress syndrome.Following baseline measurements (T0), PEEP was set at 26 cm H2O and lung recruitment was performed (40/40-maneuver). Then tidal volume was set at 4 mL/kg (T26R) and PEEP was lowered by 2 cm H2O in every 4 mins. Optimal PEEP was defined at 2 cm H2O above the PEEP where Pao2 dropped by10%. After setting the optimal PEEP, the 40/40-maneuver was repeated and tidal volume set at 6 mL/kg (T(end)).Arterial blood gas analysis was done every 4 mins and hemodynamic measurements every 8 mins until T(end), then in 30 (T30) and 60 (T60) mins. The Pao2 increased from T0 to T(end) (203 +/- 108 vs. 322 +/- 101 mm Hg, p.001), but the extravascular lung water (EVLW) did not change significantly. Cardiac index (CI) and the intrathoracic blood volume (ITBV) decreased from T0 to T26R (CI, 3.90 +/- 1.04 vs. 3.62 +/- 0.91 L/min/m2, p.05; ITBVI, 832 +/- 205 vs. 795 +/- 188 m/m2, p.05). There was a positive correlation between CI and ITBVI (r = .699, p.01), a negative correlation between CI and central venous pressure (r = -.294, p.01), and no correlation between CI and mean arterial pressure (MAP).Following lung recruitment and descending optimal PEEP titration, the Pao2 improves significantly, without any change in the EVLW up to 1 hr. This suggests a decrease in atelectasis as a result of recruitment rather than a reduction of EVLW. There is a significant change in CI during the maneuver, but neither central venous pressure, heart rate, nor MAP can reflect these changes.

Alterations of somatostatin-like immunoreactivity (SST-LI) in the plasma of 11 systemic inflammatory response syndrome (SIRS) patients were investigated in correlation with cytokines, adhesion molecules and coagulation markers repeatedly during 4 days. The origin and role of SST were studied in the cecum ligation and puncture (CLP) rat SIRS model. Capsaicin-sensitive peptidergic sensory nerves were defunctionalized by resiniferatoxin (RTX) pretreatment 2 weeks earlier, in a separate group animals were treated with the somatostatin receptor antagonist cyclo-somatostatin (C-SOM). Plasma SST-LI significantly elevated in septic patients compared to healthy volunteers during the whole 4-day period. Significantly decreased Horowitz score showed severe lung injury, increased plasma C-reactive protein and procalcitonin confirmed SIRS. Soluble P-selectin, tissue plasminogen activator and the interleukin 8 and monocyte chemotactic protein-1 significantly increased, interleukin 6 and soluble CD40 ligand did not change, and soluble Vascular Adhesion Molecule-1 decreased. SST-LI significantly increased in rats both in the plasma and the lung 6 h after CLP compared to sham-operation. After RTX pretreatment SST-LI was not altered in intact animals, but the SIRS-induced elevation was absent. Lung MPO activity significantly increased 6 h following CLP compared to sham operation, which was significantly higher both after RTX-desensitization and C-SOM-treatment. Most non-pretreated operated rats survived the 6 h, but 60% of the RTX-pretreated ones died showing a significantly worse survival. This is the first comprehensive study in humans and animal experiments providing evidence that SST is released from the activated peptidergic sensory nerves. It gets into the bloodstream and mediates a potent endogenous protective mechanism.

The activation of poly-ADP-ribose-polymerase enzyme (PARP) plays an important role in the pathophysiology of sepsis [1]. In previous animal models, lipopolysaccharide-induced systemic inflammatory response was significantly reduced by the inhibition of PARP [2]. The aim of our study was to investigate the effect of PARP inhibition on systemic inflammation in a septic animal model.

To compare intrathoracic blood volume (ITBV) guided fluid management and central venous pressure (CVP) guided therapy in ameliorating the progression of early systemic inflammatory response in patients undergoing major surgery.Prospective, randomized clinical trial.Forty patients undergoing major abdominal surgery were randomized into CVP and ITBV groups.In the CVP group the target CVP was 8-12 mmHg while in the ITBV group the goal was to keep the ITBV between 850 and 950 ml/m2 during the operation.Hemodynamic parameters were determined by single arterial thermodilution. Measurements were repeated every 30 min intraoperatively. Serum procalcitonin (PCT) and C-reactive protein (CRP) was monitored preoperatively, on ICU admission, and then daily for 3 days. Serum TNF-alpha levels were measured intraoperatively hourly and then daily for 3 days. There was no significant difference between the two groups regarding hemodynamic parameters at any assessment point. In the overall population changes in the stroke volume index showed a significant correlation with changes in CVP and ITBV. TNF-alpha levels remained in the normal range intraoperatively and during the three postoperative days in both groups. Preoperatively normal PCT and CRP levels increased significantly postoperatively, without significant differences between the groups.ITBV guided fluid therapy did not alter the magnitude of inflammatory response as monitored by serum PCT, CRP, and TNF-alpha in the early postoperative period.